CCND1 encodes cyclin D1, a 295-residue, non-catalytic D-type cyclin that couples mitogenic signalling to cell-cycle commitment. Its cyclin box binds CDK4 or CDK6 to form a serine/threonine kinase holoenzyme in which cyclin D1 supplies the activating conformational change and the substrate specificity; the assembled complex phosphorylates the retinoblastoma family pocket proteins RB1, RBL1 and RBL2 in G1, releasing E2F transcription factors and licensing the G1/S transition, after which cyclin E-CDK2 completes RB inactivation. Cyclin D1 itself has no kinase activity. Its abundance, rather than its intrinsic activity, is the regulated variable: RAS-RAF-MEK-ERK signalling induces CCND1 transcription while PI3K-AKT supports translation and complex assembly, and CIP/KIP proteins (p21, p27) promote holoenzyme assembly and carry it through the nuclear membrane into the nucleus. At the G1/S boundary, GSK3-dependent phosphorylation of Thr286 drives XPO1-mediated nuclear export followed by ubiquitination - chiefly by CRL4(AMBRA1), and by SCF(FBXO4), SCF(FBXO31) after DNA damage, APC/C-CDC27 and UHRF2 - and proteasomal degradation, while USP2 deubiquitination and FBXO32-mediated K27-linked ubiquitination stabilise it. Beyond the kinase, cyclin D1 has CDK-independent activities as a transcriptional corepressor: tethered by INSM1 it delivers HDAC1/HDAC3 to the NEUROD1 and insulin promoters, and it restrains the androgen receptor and NRF1. Cyclin D1 is nuclear, cytoplasmic and nuclear-membrane associated, is required in a tissue-restricted way for retinal and pregnancy-associated mammary development, and is a prominent oncogene: it is amplified or overexpressed in many carcinomas and is placed under immunoglobulin-locus control by t(11;14)(q13;q32) in mantle-cell lymphoma and multiple myeloma.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:19412162 F-box protein FBXO31 mediates cyclin D1 degradation to induc... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:19412162 ectopic expression of FBXO31 acts through a proteasome-directed pathway to mediate the degradation of cyclin D1, an important regulator of progression from G1 to S phase, resulting in arrest in G1 PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:33854232 AMBRA1 regulates cyclin D to guard S-phase entry and genomic... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:33854232 we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:33854235 CRL4(AMBRA1) is a master regulator of D-type cyclins. | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:33854235 we identify CRL4AMBRA1 (also known as CRL4DCAF3) as the ubiquitin ligase that targets all three D-type cyclins for degradation PMID:33854235 loss of Ambra1 induces the accumulation of D-type cyclins and retinoblastoma (RB) hyperphosphorylation and hyperproliferation |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:33854239 The AMBRA1 E3 ligase adaptor regulates the stability of cycl... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. PMID:33854239 D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:0000082 G1/S transition of mitotic cell cycle | NAS PMID:7603984 Growth suppression by p16ink4 requires functional retinoblas... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle |
| GO:0000082 G1/S transition of mitotic cell cycle | NAS PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene PMID:8114739 This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression. |
| GO:0000082 G1/S transition of mitotic cell cycle | TAS PMID:18483258 UVA-induced cell cycle progression is mediated by a disinteg... | ACCEPT | Summary: Core process. Cyclin D1 drives the G1/S transition as the activating subunit of cyclin D1-CDK4/CDK6. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:18483258 siRNA knockdown of cyclin D1 blocked the UVA-induced cell cycle progression, indicating that this process is mediated by cyclin D1 PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:16569215 INSM1 functions as a transcriptional repressor of the neuroD... | ACCEPT | Summary: Cyclin D1 cooperates with INSM1 to repress the NEUROD1/beta2 promoter, a CDK-independent corepressor role. Reason: Genuine, CDK-independent second function, curated by UniProt: "Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner". Cyclin D1 is recruited to these promoters by INSM1 and brings in HDAC1/HDAC3, so it performs part of the repression rather than merely being required for it. Supporting Evidence: PMID:16569215 Cyclin D1 co-operates with INSM1 and suppresses neuroD/beta2 promoter activity. PMID:16569215 we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:18417529 Identification of an INSM1-binding site in the insulin promo... | ACCEPT | Summary: Cyclin D1 is recruited with HDAC3 to the insulin promoter and represses insulin gene transcription. Reason: Genuine, CDK-independent second function, curated by UniProt: "Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner". Cyclin D1 is recruited to these promoters by INSM1 and brings in HDAC1/HDAC3, so it performs part of the repression rather than merely being required for it. Supporting Evidence: PMID:18417529 The mechanism for transcriptional repression of the insulin gene by INSM1 is mediated through the recruitment of cyclin D1 and histone deacetylase-3 to the insulin promoter. PMID:18417529 Anti-INSM1 or anti-cyclin D1 morpholino treatment of fetal mouse pancreas enhances the insulin promoter activity. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D-CDK4/CDK6 kinase holoenzyme. Reason: Cyclin D1 is an obligate subunit of the CDK4 and CDK6 holoenzymes: complex formation is what confers kinase activity and substrate specificity on the catalytic partner, and the cyclin D1-CDK4 heterodimer has been solved crystallographically. UniProt: "Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex". Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:17420273 CDK4 and CDK6 delay senescence by kinase-dependent and p16IN... | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D-CDK4/CDK6 kinase holoenzyme. Reason: Cyclin D1 is an obligate subunit of the CDK4 and CDK6 holoenzymes: complex formation is what confers kinase activity and substrate specificity on the catalytic partner, and the cyclin D1-CDK4 heterodimer has been solved crystallographically. UniProt: "Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex". Supporting Evidence: PMID:17420273 catalytically inactive versions of these kinases are unable to extend the replicative life span PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D-CDK4/CDK6 kinase holoenzyme. Reason: Cyclin D1 is an obligate subunit of the CDK4 and CDK6 holoenzymes: complex formation is what confers kinase activity and substrate specificity on the catalytic partner, and the cyclin D1-CDK4 heterodimer has been solved crystallographically. UniProt: "Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex". Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IEA GO_REF:0000107 | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D-CDK4/CDK6 kinase holoenzyme. Reason: Cyclin D1 is an obligate subunit of the CDK4 and CDK6 holoenzymes: complex formation is what confers kinase activity and substrate specificity on the catalytic partner, and the cyclin D1-CDK4 heterodimer has been solved crystallographically. UniProt: "Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex". Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0001889 liver development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-transferred rat annotation for involvement in liver development. Reason: Plausible and worth retaining, but downstream of the core activity: cyclin D1 supports hepatoblast/hepatocyte proliferation via CDK4/6-RB, and organ-level developmental phenotypes follow from that single G1 function rather than from a liver-specific activity. Non-core for a pleiotropic proliferation driver. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0003714 transcription corepressor activity | IDA PMID:16569215 INSM1 functions as a transcriptional repressor of the neuroD... | ACCEPT | Summary: Cyclin D1 acts as a transcriptional corepressor with INSM1 at the NEUROD1 promoter. Reason: Directly demonstrated: cyclin D1 does not bind DNA itself but is tethered by INSM1 and delivers HDAC activity to the promoter, repressing transcription independently of the cell cycle. UniProt curates this as a distinct function of CCND1. Supporting Evidence: PMID:16569215 we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity PMID:16569215 INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1 |
| GO:0003714 transcription corepressor activity | IDA PMID:18417529 Identification of an INSM1-binding site in the insulin promo... | ACCEPT | Summary: Cyclin D1 acts as a transcriptional corepressor with INSM1 and HDAC3 at the insulin promoter. Reason: Directly demonstrated: cyclin D1 does not bind DNA itself but is tethered by INSM1 and delivers HDAC activity to the promoter, repressing transcription independently of the cell cycle. UniProt curates this as a distinct function of CCND1. Supporting Evidence: PMID:18417529 The mechanism for transcriptional repression of the insulin gene by INSM1 is mediated through the recruitment of cyclin D1 and histone deacetylase-3 to the insulin promoter. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000107 | REMOVE | Summary: Orthology-transferred assertion that cyclin D1 enables protein kinase activity. Reason: Wrong in kind: cyclin D1 is a non-catalytic regulatory subunit with no kinase domain (UniProt describes it as the "Regulatory component of the cyclin D1-CDK4 (DC) complex", and the only domain annotated is the cyclin N-terminal domain, residues 28-152). The phosphotransfer chemistry is performed by CDK4/CDK6; cyclin D1 contributes activation and substrate specificity, which is already annotated as GO:0061575/GO:0016538. The donor mouse Ccnd1 annotation is itself a role conflation between the holoenzyme and its regulatory subunit. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P25322 · Ccnd1 SOURCE BAD Mouse Ccnd1 is likewise a non-catalytic cyclin; the transferred catalytic term is wrong at source. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene file:human/CCND1/CCND1-deep-research-falcon.md catalysis is performed by CDK4/6, with RB1 and related pocket proteins serving as prominent holoenzyme substrates |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:15681588 Structural and biochemical studies of human proliferating ce... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:15681588 Structural and biochemical studies of human proliferating ce... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:16431923 N protein could directly bind to cyclin D and inhibit the activity of CDK4-cyclin D complex |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | REMOVE | Summary: Curated physical interaction between cyclin D1 and SARS-CoV nucleoprotein, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function. The finding is that a viral nucleoprotein binds cyclin D and inhibits CDK4-cyclin D activity, i.e. a property of the virus rather than a molecular function of cyclin D1. Supporting Evidence: PMID:16431923 N protein could directly bind to cyclin D and inhibit the activity of CDK4-cyclin D complex |
| GO:0005515 protein binding | IPI PMID:16461912 Cyclin D1b variant influences prostate cancer growth through... | MODIFY | Summary: Curated interaction between cyclin D1 and the histone deacetylase HDAC3. Reason: Bare protein binding is uninformative; the cited interaction is with a histone deacetylase, and HDAC recruitment is the mechanism of cyclin D1 corepressor function. Replace with histone deacetylase binding (GO:0042826), which CCND1 already carries by IPI from PMID:18417529. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:16569215 INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1 |
| GO:0005515 protein binding | IPI PMID:16461912 Cyclin D1b variant influences prostate cancer growth through... | MODIFY | Summary: Curated interaction between cyclin D1 and the androgen receptor (AR). Reason: Bare protein binding is uninformative. Cyclin D1 binds AR and restrains its transcriptional activity (an LxxLL-dependent, CDK-independent corepressor role), so nuclear receptor binding (GO:0035257) is the informative term. GO:0050681 "nuclear androgen receptor binding" is obsolete (QuickGO) and is therefore not proposed. Proposed replacements: nuclear receptor binding Supporting Evidence: PMID:16461912 In the prostate, cyclin D1a acts through discrete mechanisms to negatively regulate androgen receptor (AR) activity and thus limit androgen-dependent proliferation. |
| GO:0005515 protein binding | IPI PMID:16569215 INSM1 functions as a transcriptional repressor of the neuroD... | MODIFY | Summary: Curated interaction between cyclin D1 and the transcription factor INSM1. Reason: Bare protein binding is uninformative. Cyclin D1 is recruited by/binds the transcription factor INSM1 and modulates its activity, so transcription factor binding (GO:0008134) captures the evidence; the functional consequence is separately annotated as transcription corepressor activity. Proposed replacements: transcription factor binding Supporting Evidence: PMID:19124461 The cyclin box of cyclin D1 is essential for INSM1 binding. |
| GO:0005515 protein binding | IPI PMID:16864783 Cyclin D1 repression of nuclear respiratory factor 1 integra... | MODIFY | Summary: Curated interaction between cyclin D1 and the transcription factor NRF1. Reason: Bare protein binding is uninformative. Cyclin D1 is recruited by/binds the transcription factor NRF1 and modulates its activity, so transcription factor binding (GO:0008134) captures the evidence; the functional consequence is separately annotated as transcription corepressor activity. Proposed replacements: transcription factor binding Supporting Evidence: PMID:16864783 Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:17334399 Functional consequences of cyclin D1/BRCA1 interaction in br... | REMOVE | Summary: Curated physical interaction between cyclin D1 and BRCA1, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function and the cited evidence does not support a specific informative MF for cyclin D1. Removal reflects the uninformativeness of the term, not doubt about the reported interaction. |
| GO:0005515 protein binding | IPI PMID:17517622 Functional characterization of human PFTK1 as a cyclin-depen... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | MODIFY | Summary: Curated interaction between cyclin D1 and the transcription factor INSM1. Reason: Bare protein binding is uninformative. Cyclin D1 is recruited by/binds the transcription factor INSM1 and modulates its activity, so transcription factor binding (GO:0008134) captures the evidence; the functional consequence is separately annotated as transcription corepressor activity. Proposed replacements: transcription factor binding Supporting Evidence: PMID:19124461 The cyclin box of cyclin D1 is essential for INSM1 binding. |
| GO:0005515 protein binding | IPI PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:19409388 Isolation and characterization of cytoplasmic cyclin D1 muta... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase mouse Cdk4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds mouse Cdk4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:19412162 F-box protein FBXO31 mediates cyclin D1 degradation to induc... | MODIFY | Summary: Curated physical interaction between cyclin D1 and FBXO31, a component of a ubiquitin-ligase complex that targets cyclin D1. Reason: Bare protein binding is uninformative. The evidence-supported molecular function is binding of a ubiquitin-ligase component (FBXO31), i.e. ubiquitin protein ligase binding (GO:0031625). Note the directionality: cyclin D1 is the substrate here, which is why no ubiquitination process term is proposed for cyclin D1 itself. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19412162 Cyclin D1 degradation results from a direct interaction with FBXO31 and is dependent on the F-box motif of FBXO31 and phosphorylation of cyclin D1 at Thr 286 |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:20399237 TM4SF5 accelerates G1/S phase progression via cytosolic p27K... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005515 protein binding | IPI PMID:20439707 C/EBP{delta} targets cyclin D1 for proteasome-mediated degra... | MODIFY | Summary: Curated physical interaction between cyclin D1 and CDC27/APC3, a component of a ubiquitin-ligase complex that targets cyclin D1. Reason: Bare protein binding is uninformative. The evidence-supported molecular function is binding of a ubiquitin-ligase component (CDC27/APC3), i.e. ubiquitin protein ligase binding (GO:0031625). Note the directionality: cyclin D1 is the substrate here, which is why no ubiquitination process term is proposed for cyclin D1 itself. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20439707 C/EBPdelta induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1 |
| GO:0005515 protein binding | IPI PMID:21242975 Cyclin D1 interacts and collaborates with Ral GTPases enhanc... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:21242975 Cyclin D1 interacts and collaborates with Ral GTPases enhanc... | REMOVE | Summary: Curated physical interaction between cyclin D1 and rat Ralbp1, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function and the cited evidence does not support a specific informative MF for cyclin D1. Removal reflects the uninformativeness of the term, not doubt about the reported interaction. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:21952639 NIRF constitutes a nodal point in the cell cycle network and... | MODIFY | Summary: Curated physical interaction between cyclin D1 and UHRF2, a component of a ubiquitin-ligase complex that targets cyclin D1. Reason: Bare protein binding is uninformative. The evidence-supported molecular function is binding of a ubiquitin-ligase component (UHRF2), i.e. ubiquitin protein ligase binding (GO:0031625). Note the directionality: cyclin D1 is the substrate here, which is why no ubiquitination process term is proposed for cyclin D1 itself. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:21952639 interacts with multiple cell cycle proteins including cyclins (A2, B1, D1 and E1), p53 and pRB, and ubiquitinates cyclins D1 and E1 |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:24218572 CDK10/cyclin M is a protein kinase that controls ETS2 degrad... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:24855949 A code for RanGDP binding in ankyrin repeats defines a nucle... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:24855949 A code for RanGDP binding in ankyrin repeats defines a nucle... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein CDKN1B (isoform entry), recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:31217276 The DNA deaminase APOBEC3B interacts with the cell-cycle pro... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31217276 A3B is capable of disrupting the CDK4-dependent nuclear import of Cyclin D1 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Curated physical interaction between cyclin D1 and SMARCA4, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function, and this row comes from a screen for mutation-directed neo-interactions, so it is doubly unsuitable as evidence for a wild-type molecular function of cyclin D1. Removal does not assert that the reported interaction is false. Supporting Evidence: PMID:35512704 Systematic discovery of mutation-directed neo-protein-protein interactions in cancer |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Curated physical interaction between cyclin D1 and SMAD4, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function, and this row comes from a screen for mutation-directed neo-interactions, so it is doubly unsuitable as evidence for a wild-type molecular function of cyclin D1. Removal does not assert that the reported interaction is false. Supporting Evidence: PMID:35512704 Systematic discovery of mutation-directed neo-protein-protein interactions in cancer |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Curated physical interaction between cyclin D1 and FBXW7, recorded as bare "protein binding". Reason: GO:0005515 conveys no molecular function, and this row comes from a screen for mutation-directed neo-interactions, so it is doubly unsuitable as evidence for a wild-type molecular function of cyclin D1. Removal does not assert that the reported interaction is false. Supporting Evidence: PMID:35512704 Systematic discovery of mutation-directed neo-protein-protein interactions in cancer |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK6, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK6 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. |
| GO:0005515 protein binding | IPI PMID:7568034 Identification of human cyclin-dependent kinase 8, a putativ... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK4, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK4 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p21/CDKN1A, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | REMOVE | Summary: Curated physical interaction between cyclin D1 and the CIP/KIP protein p27/CDKN1B, recorded as bare "protein binding". Reason: The interaction is not in doubt, but GO:0005515 is uninformative and no specific molecular-function term is supported by an interaction alone. The functional consequence of CIP/KIP binding - assembly and nuclear import of the cyclin D1-CDK4 holoenzyme - is already captured by GO:0000307/GO:0097128 and the nuclear/nuclear-membrane localisation annotations. Removal does not assert that the interaction is false. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005515 protein binding | IPI PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of... | MODIFY | Summary: Curated physical interaction between cyclin D1 and the protein kinase CDK2, recorded with the uninformative term "protein binding". Reason: The interaction is real and central, but bare protein binding conveys no function. Cyclin D1 binds CDK2 as its catalytic partner, so the informative molecular function is protein kinase binding (GO:0019901), which is already independently annotated to CCND1 from other references. Proposed replacements: protein kinase binding |
| GO:0005634 nucleus | EXP PMID:40307251 F-box protein FBXO32 ubiquitinates and stabilizes D-type cyc... | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:40307251 FBXO32 catalyzes the lysine (Lys/K)27-linked polyubiquitination of cyclin D1 at the K58 site and subsequent stabilization. PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus |
| GO:0005634 nucleus | EXP PMID:9106657 New functional activities for the p21 family of CDK inhibito... | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus |
| GO:0005634 nucleus | IDA PMID:11793365 Expression of frizzled-related protein and Wnt-signalling mo... | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:11793365 both c-myc and cyclin D1 were markedly elevated in all tumour tissues PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus |
| GO:0005634 nucleus | IDA PMID:20399237 TM4SF5 accelerates G1/S phase progression via cytosolic p27K... | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005634 nucleus | IDA PMID:29279382 Structural basis of the phosphorylation-independent recognit... | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin D1 localises to the nucleus, where the cyclin D1-CDK4/6 holoenzyme phosphorylates RB-family proteins. Reason: Well established. UniProt gives "SUBCELLULAR LOCATION: Nucleus" with experimental support, and this is where cyclin D1-CDK4/6 acts on RB-family proteins; CIP/KIP proteins carry the complex into the nucleus. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226094 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226095 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3215385 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3215426 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5205799 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5205861 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5216234 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5661117 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6790036 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69227 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75822 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75823 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942836 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8952058 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8952062 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8952069 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9008412 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9754129 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9754130 | ACCEPT | Summary: Cyclin D1 acts in the nucleoplasm as part of the cyclin D1-CDK4/6 holoenzyme. Reason: Consistent with the experimentally supported nuclear localisation and with the site of action on RB-family pocket proteins; the Reactome-sourced rows describe cyclin D-CDK4/6 reactions (RB1/RBL1/RBL2 phosphorylation) that take place in the nucleoplasm. A more granular restatement of the accepted nuclear localisation. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:16864783 Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. |
| GO:0005737 cytoplasm | EXP PMID:9106657 New functional activities for the p21 family of CDK inhibito... | ACCEPT | Summary: Cyclin D1 is also cytoplasmic; complex assembly and Thr286-dependent export/degradation occur there. Reason: Genuine second pool rather than contamination: cyclin D1 is exported from the nucleus after Thr286 phosphorylation and is ubiquitinated and degraded in the cytoplasm, and UniProt lists "Cytoplasm" with experimental support. Cytoplasmic cyclin D1-CDK4 also assembles there before import. Supporting Evidence: PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cyclin D1 is also cytoplasmic; complex assembly and Thr286-dependent export/degradation occur there. Reason: Genuine second pool rather than contamination: cyclin D1 is exported from the nucleus after Thr286 phosphorylation and is ubiquitinated and degraded in the cytoplasm, and UniProt lists "Cytoplasm" with experimental support. Cytoplasmic cyclin D1-CDK4 also assembles there before import. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:29279382 Structural basis of the phosphorylation-independent recognit... | ACCEPT | Summary: Cyclin D1 is also cytoplasmic; complex assembly and Thr286-dependent export/degradation occur there. Reason: Genuine second pool rather than contamination: cyclin D1 is exported from the nucleus after Thr286 phosphorylation and is ubiquitinated and degraded in the cytoplasm, and UniProt lists "Cytoplasm" with experimental support. Cytoplasmic cyclin D1-CDK4 also assembles there before import. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin D1 is also cytoplasmic; complex assembly and Thr286-dependent export/degradation occur there. Reason: Genuine second pool rather than contamination: cyclin D1 is exported from the nucleus after Thr286 phosphorylation and is ubiquitinated and degraded in the cytoplasm, and UniProt lists "Cytoplasm" with experimental support. Cytoplasmic cyclin D1-CDK4 also assembles there before import. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | REMOVE | Summary: Phylogenetically propagated claim that cyclin D1 is active at the microtubule organizing center. Reason: Arguing the node placement rather than a similarity score: every traceable donor for this IBA is a mitotic cyclin - human CCNB1 (P14635), CCNB2 (O95067) and CCNF (P41002), the fission yeast cyclins SPBC2G2.09c and SPBC582.03, and budding yeast S000006323 - for which centrosome/spindle-pole-body association is a class-specific property tied to mitotic entry and spindle function. The assertion therefore sits at a node ancestral to the D-type cyclins while describing a B/F-cyclin behaviour. D-type cyclins perform a different job (mitogen-dependent CDK4/6 activation in G1), and no human, mouse or rat literature places cyclin D1 activity at the MTOC; UniProt lists only nucleus, cytoplasm and nuclear membrane. The target is outside the clade in which the annotated behaviour arose. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN007424001 SUPPORTS SOURCE BUT NOT TARGET Ancestral cyclin node; the MTOC behaviour it carries is attested only in the mitotic-cyclin descendants. UniProtKB:P14635 · CCNB1 SUPPORTS SOURCE BUT NOT TARGET Mitotic B-type cyclin; centrosomal localisation is specific to its mitotic role. UniProtKB:P41002 · CCNF SUPPORTS SOURCE BUT NOT TARGET Cyclin F, another non-D-type cyclin with centrosomal function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75822 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75823 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75824 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75825 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848414 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848436 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8853956 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8941895 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8941915 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942607 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8951443 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9009378 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9623355 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9858645 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9929482 | ACCEPT | Summary: Reactome-derived cytosolic localisation, reflecting cyclin D1 export, ubiquitination and proteasomal degradation and cytoplasmic holoenzyme assembly. Reason: Consistent with the experimentally supported cytoplasmic pool: Thr286-phosphorylated cyclin D1 is relocalised to the cytoplasm and degraded there, and cyclin D-CDK4/6 complexes form in the cytosol before nuclear import. A finer-grained restatement of the accepted cytoplasm annotation. Supporting Evidence: PMID:29279382 cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm PMID:20399237 TM4SF5 enhanced trafficking of CDK4 and cyclin D1 into the nucleus and induced complex formation between them. |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Orthology-transferred localisation of cyclin D1 to bicellular tight junctions. Reason: Not supportable for human cyclin D1: UniProt records only nucleus, cytoplasm and nuclear membrane, and no human study places cyclin D1 at tight junctions or gives it a junctional activity. The donor mouse annotation could not be traced from the cached record, so the claim is left in place but flagged rather than removed outright. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P25322 · Ccnd1 UNRESOLVED Donor annotation not traceable in the cached record; no human evidence for a tight-junction pool of cyclin D1. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-transferred general involvement in regulation of RNA polymerase II transcription. Reason: Broader than, but consistent with, the experimentally documented CDK-independent corepressor role of cyclin D1 at the NEUROD1, insulin, NRF1 and AR-dependent promoters. An IEA that is more general than the literature-level terms is acceptable. Supporting Evidence: PMID:16569215 we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity PMID:16864783 Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. |
| GO:0006974 DNA damage response | IDA PMID:19412162 F-box protein FBXO31 mediates cyclin D1 degradation to induc... | MARK AS OVER ANNOTATED | Summary: Cyclin D1 is the substrate whose FBXO31-mediated degradation implements G1 arrest after DNA damage. Reason: Participation test: in the cited work DNA damage stabilises FBXO31, which then ubiquitinates and degrades cyclin D1, and the G1 arrest follows from cyclin D1 disappearing. Cyclin D1 is the terminal target acted on by the response, not a transducer of it - being required for, consumed by, or acted on by a process is not participation. The observation is sound, so the row is flagged rather than removed; a CDK-independent role for cyclin D1 in RAD51-dependent repair is reported elsewhere but is a different claim and is not evidenced by this reference. Supporting Evidence: PMID:19412162 ectopic expression of FBXO31 acts through a proteasome-directed pathway to mediate the degradation of cyclin D1, an important regulator of progression from G1 to S phase, resulting in arrest in G1 PMID:19412162 Cyclin D1 degradation results from a direct interaction with FBXO31 and is dependent on the F-box motif of FBXO31 and phosphorylation of cyclin D1 at Thr 286 |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin D1 positively regulates cell population proliferation. Reason: Direct consequence of the core activity and independently supported in human cells: cyclin D1 activates CDK4/6, RB is inactivated, and cells commit to S phase; knockdown blocks proliferative responses. A broad but correct term for a mitogen-responsive G1 cyclin. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. PMID:18483258 siRNA knockdown of cyclin D1 blocked the UVA-induced cell cycle progression, indicating that this process is mediated by cyclin D1 |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to xenobiotic stimulus; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18291362 Sulindac suppresses beta-catenin expression in human cancer ... | MARK AS OVER ANNOTATED | Summary: IEP annotation from a study in which sulindac treatment downregulates cyclin D1 along with other beta-catenin targets. Reason: CCND1 is a transcriptional target of beta-catenin, so its downregulation is a readout of the drug response rather than an activity of cyclin D1 within it. Expression-change (IEP) evidence cannot distinguish being regulated by a stimulus from participating in the response; the same call was made for CDK4 on this reference. Supporting Evidence: PMID:18291362 The transcriptional targets of beta-catenin, c-myc, cyclin D1 and cdk 4 were also dramatically downregulated. |
| GO:0010039 response to iron ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to iron ion; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0010165 response to X-ray | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to X-ray; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IDA PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | MODIFY | Summary: IDA for positive regulation of the G2/M transition, taken from a study of INSM1 binding cyclin D1 and arresting cells in G1. Reason: The essence - cyclin D1 positively regulates a mitotic cell-cycle phase transition - is right, but the phase is wrong. The cited experiments show that INSM1 sequestration of cyclin D1 blocks CDK4 binding and leaves RB hypophosphorylated, i.e. they concern the G1/S transition; nothing in them addresses G2/M. Replace with positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), which CCND1 already carries by IBA. Proposed replacements: positive regulation of G1/S transition of mitotic cell cycle Supporting Evidence: PMID:19124461 INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein PMID:19124461 The cyclin box of cyclin D1 is essential for INSM1 binding. |
| GO:0016301 kinase activity | IEA GO_REF:0000107 | REMOVE | Summary: Orthology-transferred assertion that cyclin D1 enables kinase activity. Reason: Wrong in kind: cyclin D1 is a non-catalytic regulatory subunit with no kinase domain (UniProt describes it as the "Regulatory component of the cyclin D1-CDK4 (DC) complex", and the only domain annotated is the cyclin N-terminal domain, residues 28-152). The phosphotransfer chemistry is performed by CDK4/CDK6; cyclin D1 contributes activation and substrate specificity, which is already annotated as GO:0061575/GO:0016538. The donor mouse Ccnd1 annotation is itself a role conflation between the holoenzyme and its regulatory subunit. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P25322 · Ccnd1 SOURCE BAD Mouse Ccnd1 is likewise a non-catalytic cyclin; the transferred catalytic term is wrong at source. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene file:human/CCND1/CCND1-deep-research-falcon.md catalysis is performed by CDK4/6, with RB1 and related pocket proteins serving as prominent holoenzyme substrates |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cyclin D1 enables cyclin-dependent protein serine/threonine kinase regulator activity. Reason: Core molecular function. Cyclin D1 has no catalytic activity of its own; it binds CDK4/CDK6, drives the conformational change that renders the kinase competent, and imparts substrate specificity. This is the activity assigned to CCND1 in the cached GO-CAM models. Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IEA GO_REF:0000107 | ACCEPT | Summary: Cyclin D1 enables cyclin-dependent protein serine/threonine kinase regulator activity. Reason: Core molecular function. Cyclin D1 has no catalytic activity of its own; it binds CDK4/CDK6, drives the conformational change that renders the kinase competent, and imparts substrate specificity. This is the activity assigned to CCND1 in the cached GO-CAM models. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. |
| GO:0017053 transcription repressor complex | IDA PMID:16569215 INSM1 functions as a transcriptional repressor of the neuroD... | ACCEPT | Summary: Cyclin D1 is part of an INSM1-HDAC transcription repressor complex on the NEUROD1 and insulin promoters. Reason: Co-immunoprecipitation and ChIP place cyclin D1, INSM1 and HDAC1/HDAC3 together on the target promoters, with cyclin D1 bridging INSM1 to the deacetylases. Component assignment follows directly from the evidence. Supporting Evidence: PMID:16569215 INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1 PMID:16569215 we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity |
| GO:0017053 transcription repressor complex | IDA PMID:18417529 Identification of an INSM1-binding site in the insulin promo... | ACCEPT | Summary: Cyclin D1 is part of an INSM1-HDAC transcription repressor complex on the NEUROD1 and insulin promoters. Reason: Co-immunoprecipitation and ChIP place cyclin D1, INSM1 and HDAC1/HDAC3 together on the target promoters, with cyclin D1 bridging INSM1 to the deacetylases. Component assignment follows directly from the evidence. Supporting Evidence: PMID:16569215 INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1 PMID:16569215 we conclude that INSM1 recruits cyclin D1 and HDACs, which confer transcriptional repressor activity |
| GO:0019899 enzyme binding | IPI PMID:19412162 F-box protein FBXO31 mediates cyclin D1 degradation to induc... | MODIFY | Summary: Generic enzyme-binding annotation whose WITH entry is the deubiquitinase USP2 (O75604). Reason: "Enzyme binding" is uninformative. The partner recorded in WITH/FROM is USP2, the deubiquitinase that opposes cyclin D1 turnover (UniProt SUBUNIT: "Interacts with USP2"), so the informative child term is ubiquitin-specific protease binding (GO:1990381). Proposed replacements: ubiquitin-specific protease binding |
| GO:0019901 protein kinase binding | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin D1 binds protein kinases (CDK4/CDK6). Reason: Correct and informative for a cyclin: binding CDK4/CDK6 is the molecular event that creates the active holoenzyme, and it is supported both structurally and biochemically. This is also the term to which the bare "protein binding" rows with CDK partners should be resolved. Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0019901 protein kinase binding | IPI PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | ACCEPT | Summary: Cyclin D1 binds CDK4; INSM1 competes for the same surface. Reason: Correct and informative for a cyclin: binding CDK4/CDK6 is the molecular event that creates the active holoenzyme, and it is supported both structurally and biochemically. This is also the term to which the bare "protein binding" rows with CDK partners should be resolved. Supporting Evidence: PMID:19124461 INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A |
| GO:0019901 protein kinase binding | IPI PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | ACCEPT | Summary: Cyclin D1 binds and activates CDK6. Reason: Correct and informative for a cyclin: binding CDK4/CDK6 is the molecular event that creates the active holoenzyme, and it is supported both structurally and biochemically. This is also the term to which the bare "protein binding" rows with CDK partners should be resolved. Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene |
| GO:0031100 animal organ regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-transferred involvement in animal organ regeneration (rat). Reason: Defensible but contextual: cyclin D1 is induced during regenerative proliferation (classically in liver) and drives the resulting G1/S transitions, so its contribution is the same single core activity deployed in a regenerative context rather than a distinct regeneration function. Keep as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0031571 mitotic G1 DNA damage checkpoint signaling | IDA PMID:19412162 F-box protein FBXO31 mediates cyclin D1 degradation to induc... | MARK AS OVER ANNOTATED | Summary: Same FBXO31 experiments, framed as mitotic G1 DNA damage checkpoint signaling. Reason: Participation test: in the cited work DNA damage stabilises FBXO31, which then ubiquitinates and degrades cyclin D1, and the G1 arrest follows from cyclin D1 disappearing. Cyclin D1 is the terminal target acted on by the response, not a transducer of it - being required for, consumed by, or acted on by a process is not participation. The observation is sound, so the row is flagged rather than removed; a CDK-independent role for cyclin D1 in RAD51-dependent repair is reported elsewhere but is a different claim and is not evidenced by this reference. Checkpoint *signalling* in particular is carried out by ATM and FBXO31 here, not by cyclin D1. Supporting Evidence: PMID:19412162 RNAi-mediated knockdown of FBXO31 prevents cells from undergoing efficient arrest in G1 after gamma-irradiation PMID:19412162 Cyclin D1 degradation results from a direct interaction with FBXO31 and is dependent on the F-box motif of FBXO31 and phosphorylation of cyclin D1 at Thr 286 |
| GO:0031965 nuclear membrane | EXP PMID:9106657 New functional activities for the p21 family of CDK inhibito... | ACCEPT | Summary: Cyclin D-CDK4 complexes accumulate at the nuclear membrane before nuclear import. Reason: Explicitly curated by UniProt from the same experimental work: "Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members". A genuine staging location on the route to the nuclear site of action. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0031965 nuclear membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin D-CDK4 complexes accumulate at the nuclear membrane before nuclear import. Reason: Explicitly curated by UniProt from the same experimental work: "Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members". A genuine staging location on the route to the nuclear site of action. Supporting Evidence: PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to the nucleus PMID:9106657 cyclin D1 and p21 bind concomitantly to cdk4 during the in vivo assembly of cdk4/cyclin D1 complexes |
| GO:0032026 response to magnesium ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to magnesium ion; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to estradiol; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0033197 response to vitamin E | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to vitamin E; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0033327 Leydig cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-transferred involvement in Leydig cell differentiation (rat). Reason: Plausible tissue-level contribution mediated by proliferation control rather than by a differentiation-specific activity of cyclin D1; D-cyclin loss gives tissue-restricted developmental phenotypes because different tissues depend on different D-cyclins for their G1 progression. Non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0042826 histone deacetylase binding | IPI PMID:18417529 Identification of an INSM1-binding site in the insulin promo... | ACCEPT | Summary: Cyclin D1 binds HDAC3, the deacetylase it delivers to INSM1-bound promoters. Reason: Informative and mechanistically central to the corepressor function: the INSM1-HDAC interaction is mediated through cyclin D1, and HDAC3 occupies the repressed promoters with INSM1 and cyclin D1. Supporting Evidence: PMID:18417529 The mechanism for transcriptional repression of the insulin gene by INSM1 is mediated through the recruitment of cyclin D1 and histone deacetylase-3 to the insulin promoter. PMID:16569215 INSM1 interacts with HDAC-1 and -3 and that this interaction is mediated through cyclin D1 |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | MODIFY | Summary: Cyclin D1 activates a protein serine/threonine kinase (CDK6), annotated with the generic activator term. Reason: The essence is correct but the term is one level too general: the kinases cyclin D1 activates are cyclin-dependent kinases, so the precise term is cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), which CCND1 already carries from independent evidence and which the cached GO-CAM models use for this activity. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene |
| GO:0043627 response to estrogen | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to estrogen; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0044321 response to leptin | IDA PMID:17344214 leptin-induced growth stimulation of breast cancer cells inv... | MARK AS OVER ANNOTATED | Summary: Annotation for involvement in the response to leptin, from a study of leptin-induced CCND1 promoter activation. Reason: The experiments identify CCND1 as the promoter acted upon: activated STAT3, SRC1 and Med1 are recruited to the CYCLIN D1 promoter and drive its expression. Cyclin D1 is therefore the output of leptin signalling rather than a component of the response machinery; the proliferation that follows is its ordinary G1/S function. Supporting Evidence: PMID:17344214 leptin induced increase in CYCLIN D1 promoter activity is mediated through binding of activated Stat3 at the Stat binding sites |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic protein-containing complex binding, transferred from rat Ccnd1. Reason: True in a trivial sense but uninformative: it conveys no molecular function beyond what the specific complex and binding annotations (GO:0000307, GO:0097128, GO:0097131, GO:0019901) already state precisely. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to ethanol; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0048545 response to steroid hormone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to steroid hormone; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to glucocorticoid; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0051412 response to corticosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to corticosterone; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0051592 response to calcium ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in response to calcium ion; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IDA PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | ACCEPT | Summary: Core molecular function: cyclin D1 is the activating subunit of CDK4/CDK6. Reason: Core molecular function. Cyclin D1 has no catalytic activity of its own; it binds CDK4/CDK6, drives the conformational change that renders the kinase competent, and imparts substrate specificity. This is the activity assigned to CCND1 in the cached GO-CAM models. Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IEA GO_REF:0000117 | ACCEPT | Summary: Core molecular function: cyclin D1 is the activating subunit of CDK4/CDK6. Reason: Core molecular function. Cyclin D1 has no catalytic activity of its own; it binds CDK4/CDK6, drives the conformational change that renders the kinase competent, and imparts substrate specificity. This is the activity assigned to CCND1 in the cached GO-CAM models. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | TAS PMID:33854239 The AMBRA1 E3 ligase adaptor regulates the stability of cycl... | ACCEPT | Summary: Core molecular function: cyclin D1 is the activating subunit of CDK4/CDK6. Reason: Core molecular function. Cyclin D1 has no catalytic activity of its own; it binds CDK4/CDK6, drives the conformational change that renders the kinase competent, and imparts substrate specificity. This is the activity assigned to CCND1 in the cached GO-CAM models. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. PMID:33854239 D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication |
| GO:0070064 proline-rich region binding | IDA PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | ACCEPT | Summary: Cyclin D1 binds the proline-rich N-terminal region of INSM1 through its cyclin box. Reason: Directly mapped: the proline-rich N terminus of INSM1 is required for cyclin D1 binding and mutation of those proline residues abolishes it, while the cyclin box of cyclin D1 provides the binding surface. An informative, evidence-matched molecular function underlying the corepressor role. Supporting Evidence: PMID:19124461 The proline-rich N-terminal portion of INSM1 is required for cyclin D1 binding. PMID:19124461 The cyclin box of cyclin D1 is essential for INSM1 binding. |
| GO:0070141 response to UV-A | IDA PMID:18483258 UVA-induced cell cycle progression is mediated by a disinteg... | KEEP AS NON CORE | Summary: Cyclin D1 mediates UVA-induced cell-cycle progression in keratinocytes downstream of ADAM17-EGFR-AKT. Reason: Kept rather than flagged as an expression artefact because loss of function, not only induction, was tested: siRNA knockdown of cyclin D1 abolished the UVA-induced progression, so cyclin D1 executes the proliferative arm of this stress response. It does so through its ordinary CDK4/6-activating activity in a specific context, hence non-core. Supporting Evidence: PMID:18483258 siRNA knockdown of cyclin D1 blocked the UVA-induced cell cycle progression, indicating that this process is mediated by cyclin D1 |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transferred rat Ccnd1 annotation asserting involvement in cellular response to hypoxia; the underlying observation is that CCND1 expression changes with the stimulus. Reason: CCND1 transcription is the canonical downstream readout of mitogenic, hormonal and stress signalling, so a change in cyclin D1 abundance after this stimulus does not establish that cyclin D1 executes a step of the response. Cyclin D1 acts only through activation of CDK4/CDK6 in G1; the stimulus-specific machinery lies upstream. Not wrong that levels respond, but an over-annotation of an expression change. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK ROLE CONFLATION Sources checked: UniProtKB:P39948 · Ccnd1 SUPPORTS SOURCE BUT NOT TARGET Rat Ccnd1 expression-response annotation; induction of the donor gene does not make cyclin D1 an executor of the response. |
| GO:0097128 cyclin D1-CDK4 complex | IEA GO_REF:0000107 | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D1-CDK4 complex. Reason: The most precisely specified complex annotation available for this gene product, and the one used for CCND1 in the cached GO-CAM models; established biochemically and by the 2.3 A crystal structure of the heterodimer. Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. |
| GO:0097128 cyclin D1-CDK4 complex | IPI PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D1-CDK4 complex. Reason: The most precisely specified complex annotation available for this gene product, and the one used for CCND1 in the cached GO-CAM models; established biochemically and by the 2.3 A crystal structure of the heterodimer. Supporting Evidence: PMID:19237565 we report the crystal structure of CDK4 in complex with cyclin D1 at a resolution of 2.3 A PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the transition through the G(1) phase of the cell cycle. |
| GO:0097131 cyclin D1-CDK6 complex | IPI PMID:15232106 Self-assembling protein microarrays. | ACCEPT | Summary: Cyclin D1 is a subunit of the cyclin D1-CDK6 complex. Reason: The cyclin D1-CDK6 pairing is long established biochemically - CDK6 associates with cyclins D1, D2 and D3 in human cell lysates and is activated by them - so although the cited reference is a proteome-array method paper, the complex assignment is correct and independently supported. Supporting Evidence: PMID:8114739 The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Core process, with the correct regulatory direction: cyclin D1 positively regulates the G1/S transition. Reason: Defining biological process for cyclin D1: as the regulatory subunit of cyclin D1-CDK4/CDK6 it activates the kinase that phosphorylates RB-family pocket proteins in G1, relieving repression of E2F and licensing S-phase gene expression. Supported concordantly by structure, biochemistry, genetics and phylogeny; the GO-CAM models that include CCND1 (gocams/61e0e55600000624, gocams/680ad14200006016) place its activity in exactly this process. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle |
| GO:1901992 positive regulation of mitotic cell cycle phase transition | IEA GO_REF:0000117 | ACCEPT | Summary: Broad ARBA term for positive regulation of a mitotic cell-cycle phase transition. Reason: Correct but less specific than the G1/S terms CCND1 already carries; an IEA that is more general than the literature-supported annotation is acceptable and needs no change. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: Broad ARBA term for regulation of the G1/S transition. Reason: Correct parent of the positively-signed, experimentally supported annotation; harmless generality from an automated model. Supporting Evidence: PMID:33854239 Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. |
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Download this section (compressed HTML)Q: Should cyclin D1's role as the substrate of CRL4(AMBRA1), SCF(FBXO31), APC/C-CDC27 and FBXO32 be made machine-readable as has_input on those ligase activities, rather than left implicit? At present the substrate relationship surfaces only as bare protein-binding rows on CCND1 and as over-annotated DNA-damage-response process terms.
Suggested experts: Pagano M, Sage J
Q: Is the reported CDK-independent contribution of cyclin D1 to homologous recombination (RAD51 loading at damage sites, not reproduced by CDK4/6 inhibition) a distinct molecular function that warrants its own annotation, or a consequence of altered cell-cycle distribution?
Q: Cyclin D1b differs from canonical cyclin D1a in its C terminus, lacking the Thr286 degron, and behaves differently towards the androgen receptor. Should AR-related and localisation annotations derived from cyclin D1b studies carry an isoform qualifier rather than being asserted for P24385 as a whole?
Suggested experts: Knudsen KE
Experiment: Compare endogenous-locus knock-in of a kinase-dead-binding cyclin D1 (e.g. the K112E-equivalent allele that cannot activate CDK4/6) with a cyclin-box mutant that cannot bind INSM1, then measure nascent transcription (TT-seq) and promoter occupancy (ChIP-seq for cyclin D1, INSM1, HDAC3) at NEUROD1 and INS in a neuroendocrine line.
Hypothesis: The transcriptional corepressor function of cyclin D1 is separable from CDK4/6 activation and does not require kinase activity.
Type: separation-of-function genetics with nascent transcriptomics and ChIP-seq
Experiment: Acute degron-mediated depletion of endogenous cyclin D1 with quantitative imaging of centrosome composition and duplication, plus centrosome-fraction proteomics comparing cyclin D1 with CCNB1 and CCNF as positive controls.
Hypothesis: Cyclin D1 has no activity of its own at the microtubule organizing center, contrary to the phylogenetically propagated GO:0005815 annotation.
Type: targeted protein degradation with imaging and organelle proteomics
Experiment: For a panel of the annotated stimuli (estradiol, glucocorticoid, calcium, hypoxia), compare wild-type cells with cells in which CCND1 promoter induction is blocked but cyclin D1 protein is supplied constitutively, and test whether the stimulus-specific downstream response is preserved.
Hypothesis: The rat-derived "response to X" annotations reflect CCND1 transcription rather than participation of cyclin D1 in each response.
Type: promoter-uncoupling/complementation assay
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