SKP2 (also known as FBXL1 or p45-SKP2) is the F-box/leucine-rich-repeat substrate-recognition subunit of an SCF cullin-RING E3 ubiquitin ligase (SKP1-CUL1-RBX1-SKP2). Its N-terminal F-box binds SKP1, which tethers it to the CUL1 scaffold, while its C-terminal leucine-rich-repeat solenoid, together with the accessory subunit CKS1B, forms a composite receptor for phosphorylated degrons. SKP2 has no catalytic activity itself: it selects substrates and positions them near the RBX1-bound, ubiquitin-charged E2 enzyme. Its best-characterised substrate is the CDK inhibitor p27/CDKN1B phosphorylated on Thr187 by cyclin E/A-CDK2; its K48-linked polyubiquitination and proteasomal destruction in late G1 releases CDK2 activity and commits the cell to S phase, forming a positive-feedback switch at the G1/S transition. Other substrates include p21/CDKN1A, p57, p130/RBL2, the replication factors CDT1 and ORC1, FOXO1, MYC, MKP-1/DUSP1, RAG2 and E-cadherin, and the protein is itself degraded by APC/C-CDH1 during G1 so that its abundance peaks at S phase. SKP2 also has a non-degradative activity: after DNA double-strand breaks it catalyses K63-linked ubiquitination of NBN/NBS1, which is required for NBS1-ATM interaction, ATM recruitment to damage foci and homologous-recombination repair. SKP2 acts mainly in the nucleoplasm; p300-mediated acetylation of lysines in its nuclear localisation signal, and AKT-dependent phosphorylation, redistribute a pool to the cytoplasm where it directs degradation of substrates such as E-cadherin. SKP2 abundance is frequently elevated in human tumours, where it correlates with low p27 levels and increased proliferation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: SKP2 drives the G1/S transition as the SCF substrate receptor that removes Thr187-phosphorylated p27/CDKN1B (with CKS1B), releasing cyclin E/A-CDK2 activity. Reason: Core biological process. SCF(SKP2)-dependent destruction of p27 (and p21) at late G1 is the best-established SKP2 mechanism, supported by structure, reconstituted ubiquitination and loss-of-function experiments that block S-phase entry. The ARBA electronic assignment agrees with the experimental literature. Supporting Evidence: PMID:7553852 prevented entry into S phase in both normal and transformed cells. file:human/SKP2/SKP2-deep-research-falcon.md p27 ubiquitination and proteasomal degradation promote G1/S progression. |
| GO:0000082 G1/S transition of mitotic cell cycle | NAS PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga... | ACCEPT | Summary: SKP2 drives the G1/S transition as the SCF substrate receptor that removes Thr187-phosphorylated p27/CDKN1B (with CKS1B), releasing cyclin E/A-CDK2 activity. Reason: Core biological process. SCF(SKP2)-dependent destruction of p27 (and p21) at late G1 is the best-established SKP2 mechanism, supported by structure, reconstituted ubiquitination and loss-of-function experiments that block S-phase entry. The author statement accompanies the SCF(SKP2) crystal structure, which defines SKP2 as the substrate-recognition module of the ligase that controls G1/S regulators. Supporting Evidence: PMID:11961546 binds the Skp1-F boxSkp2 protein file:human/SKP2/SKP2-deep-research-falcon.md p27 ubiquitination and proteasomal degradation promote G1/S progression. |
| GO:0000082 G1/S transition of mitotic cell cycle | TAS PMID:7553852 p19Skp1 and p45Skp2 are essential elements of the cyclin A-C... | ACCEPT | Summary: SKP2 drives the G1/S transition as the SCF substrate receptor that removes Thr187-phosphorylated p27/CDKN1B (with CKS1B), releasing cyclin E/A-CDK2 activity. Reason: Core biological process. SCF(SKP2)-dependent destruction of p27 (and p21) at late G1 is the best-established SKP2 mechanism, supported by structure, reconstituted ubiquitination and loss-of-function experiments that block S-phase entry. The founding p45(SKP2) paper showed that interfering with p45 function blocks S-phase entry. Supporting Evidence: PMID:7553852 prevented entry into S phase in both normal and transformed cells. |
| GO:0005515 protein binding | IPI PMID:11931757 Human origin recognition complex large subunit is degraded b... | MODIFY | Summary: SKP2 recognises ORC1 as an SCF(SKP2) substrate, signalling its proteasomal destruction after replication initiation. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:11931757 hOrc1p destruction occurs through the proteasome file:human/SKP2/SKP2-deep-research-falcon.md Proteolytic regulation of p21, p57, p130, FOXO1, BRCA2, CDT1 and other substrates. |
| GO:0005515 protein binding | IPI PMID:12504026 CAND1 binds to unneddylated CUL1 and regulates the formation... | MODIFY | Summary: SKP2 binds the CUL1 scaffold via SKP1; CAND1 competes for this interaction and thereby regulates SCF(SKP2) assembly. Reason: The informative function is binding of the CUL1 scaffold (through SKP1), for which GO:0097602 cullin family protein binding is the specific term; bare protein binding is uninformative. Proposed replacements: cullin family protein binding Supporting Evidence: PMID:12504026 Both in vivo and in vitro, CAND1 prevents the binding of SKP1 and SKP2 to CUL1 |
| GO:0005515 protein binding | IPI PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | MODIFY | Summary: SKP2 engages SKP1, the adaptor that couples the F-box receptor to CUL1; TIP120A interferes with this loading step. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:12609982 but interfered with the binding of Skp1 and F-box proteins PMID:23911321 Skp2 directly interacts with Skp1 via its F-box domain and indirectly |
| GO:0005515 protein binding | IPI PMID:12609982 TIP120A associates with cullins and modulates ubiquitin liga... | MODIFY | Summary: SKP2 associates with CUL1 in the SCF complex; TIP120A/cullin binding antagonises F-box protein loading. Reason: The informative function is binding of the CUL1 scaffold (through SKP1), for which GO:0097602 cullin family protein binding is the specific term; bare protein binding is uninformative. Proposed replacements: cullin family protein binding Supporting Evidence: PMID:12609982 but interfered with the binding of Skp1 and F-box proteins |
| GO:0005515 protein binding | IPI PMID:12813041 A negatively charged amino acid in Skp2 is required for Skp2... | MODIFY | Summary: SKP2 binds the accessory subunit CKS1 through Asp-331, creating the composite receptor for Thr187-phosphorylated p27. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:12813041 Mutation of Asp-331 to Ala disrupts the interaction between Skp2 and Cks1. PMID:12813041 Ubiquitination of p27 requires the SCFSkp2 ubiquitin ligase and Skp2 |
| GO:0005515 protein binding | IPI PMID:12813041 A negatively charged amino acid in Skp2 is required for Skp2... | MODIFY | Summary: SKP2 functions within the SKP1-containing SCF ligase that ubiquitinates p27. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:12813041 Ubiquitination of p27 requires the SCFSkp2 ubiquitin ligase and Skp2 |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | MODIFY | Summary: SKP2, with CKS1, forms the composite phosphodegron receptor for Thr187-phosphorylated p27/CDKN1B. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16209941 whereas p27(Kip1) binds to both Cks1 and Skp2. PMID:16209941 p27(Kip1) ubiquitination also requires the accessory protein Cks1. |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | MODIFY | Summary: CKS1 binds the SKP2 LRR domain and C-terminal tail, completing the p27 phosphodegron-binding surface. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16209941 p27(Kip1) ubiquitination also requires the accessory protein Cks1. PMID:16209941 whereas p27(Kip1) binds to both Cks1 and Skp2. |
| GO:0005515 protein binding | IPI PMID:16286470 Cooperation of ERK and SCFSkp2 for MKP-1 destruction provide... | MODIFY | Summary: SKP2 recognises ERK-phosphorylated MKP-1/DUSP1 as an SCF(SKP2) substrate, sustaining ERK signalling. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16286470 active ERK-promoted phospho-Ser(296) MKP-1 bound to SCF(Skp2) ubiquitin ligase |
| GO:0005515 protein binding | IPI PMID:16376880 The X protein of hepatitis B virus binds to the F box protei... | MODIFY | Summary: SKP2 acts as the substrate receptor for CIP/KIP CDK inhibitors including p21/CDKN1A. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. p21/CDKN1A is a documented SCF(SKP2) substrate (recognised together with cyclin E-CDK2). Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Proteolytic regulation of p21, p57, p130, FOXO1, BRCA2, CDT1 and other substrates. PMID:16209941 p27(Kip1) ubiquitination also requires the accessory protein Cks1. |
| GO:0005515 protein binding | IPI PMID:16376880 The X protein of hepatitis B virus binds to the F box protei... | MODIFY | Summary: SKP2 binds SKP1 through its F-box; HBx destabilises this SCF(SKP2) complex to protect c-Myc. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16376880 through a direct interaction with the F box region of Skp2 and PMID:23911321 Skp2 directly interacts with Skp1 via its F-box domain and indirectly |
| GO:0005515 protein binding | IPI PMID:16376880 The X protein of hepatitis B virus binds to the F box protei... | REMOVE | Summary: Interaction with the hepatitis B virus X protein, which binds the SKP2 F-box and inhibits SCF(SKP2)-dependent c-Myc ubiquitination. Reason: Here SKP2 is the target of a viral inhibitor rather than exercising an activity on HBx, so no informative SKP2 molecular function follows. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:16376880 through a direct interaction with the F box region of Skp2 and |
| GO:0005515 protein binding | IPI PMID:16865698 Acute myelogenous leukemia-derived SMAD4 mutations target th... | REMOVE | Summary: Interaction record with SMAD4 from a study of leukaemia-derived SMAD4 mutants. Reason: The cited study attributes degradation of the mutant SMAD4 proteins to SCF(beta-TrCP1), not to SCF(SKP2), so it supports no specific SKP2 activity. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:16865698 interacts with and acts as a critical determinant for degradation of both |
| GO:0005515 protein binding | IPI PMID:16880511 Regulation of p27 degradation and S-phase progression by Ro5... | REMOVE | Summary: Interaction with TRIM21/Ro52, a RING protein that can replace RBX1 in a CUL1-based ligase core containing SKP2. Reason: This is complex membership rather than an SKP2 activity, and it is already captured by the GO:0019005 SCF ubiquitin ligase complex IDA from the same paper. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:16880511 Here we identify Skp2 as a component |
| GO:0005515 protein binding | IPI PMID:17157259 SNIP1 is a candidate modifier of the transcriptional activit... | MODIFY | Summary: SKP2 recognises c-MYC, promoting its ubiquitination (a modification that also modulates MYC transcriptional output). Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. MYC ubiquitination by SKP2 is documented in the cited interaction context and in focused studies. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16376880 through a direct interaction with the F box region of Skp2 and PMID:23277542 ARF inhibits the interaction of c-Myc with the E3 ubiquitin ligase Skp2. |
| GO:0005515 protein binding | IPI PMID:18239684 Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect... | REMOVE | Summary: Interaction record annotated with cadherin-1 from the study of Skp2 phosphorylation and APC/C-Cdh1-mediated Skp2 degradation. Reason: The cited paper concerns SKP2 as a substrate of APC/C-Cdh1 (FZR1), i.e. an activity exercised on SKP2, so no informative SKP2 molecular function follows. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:18239684 regulated by the APC(Cdh1), which targets Skp2 for degradation. |
| GO:0005515 protein binding | IPI PMID:18239684 Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect... | MODIFY | Summary: SKP2 associates with CKS1B as part of the p27 ubiquitin-ligase receptor whose abundance is timed by phosphorylation. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:18239684 The p27(Kip1) ubiquitin ligase receptor Skp2 is often overexpressed in human PMID:12813041 Ubiquitination of p27 requires the SCFSkp2 ubiquitin ligase and Skp2 |
| GO:0005515 protein binding | IPI PMID:18239684 Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect... | REMOVE | Summary: Interaction with the RING subunit RBX1 of the SCF core. Reason: RBX1 contact reflects SKP2 membership of the SCF holoenzyme, already annotated as GO:0019005, and GO does not provide an informative SKP2-side binding term here. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:11961546 Cul1 serves as a rigid scaffold that |
| GO:0005515 protein binding | IPI PMID:18239684 Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect... | MODIFY | Summary: SKP2 binds SKP1 within SCF(SKP2), whose activity toward p27 is timed by Ser64/Ser72 phosphorylation. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:18239684 The p27(Kip1) ubiquitin ligase receptor Skp2 is often overexpressed in human PMID:23911321 Skp2 directly interacts with Skp1 via its F-box domain and indirectly |
| GO:0005515 protein binding | IPI PMID:18239684 Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect... | MODIFY | Summary: SKP2 associates with the CUL1 scaffold in SCF(SKP2). Reason: The informative function is binding of the CUL1 scaffold (through SKP1), for which GO:0097602 cullin family protein binding is the specific term; bare protein binding is uninformative. Proposed replacements: cullin family protein binding Supporting Evidence: PMID:18239684 The p27(Kip1) ubiquitin ligase receptor Skp2 is often overexpressed in human PMID:11961546 Cul1 serves as a rigid scaffold that |
| GO:0005515 protein binding | IPI PMID:18805092 Structural insights into NEDD8 activation of cullin-RING lig... | MODIFY | Summary: In reconstituted neddylated SCF assays, SKP2 (as SKP1-SKP2) delivers p27/CDKN1B for ubiquitination. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. The biochemical reconstitution used SKP1-SKP2 with CKS1 and cyclin A-CDK2 to ubiquitinate p27. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:18805092 Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved PMID:16209941 p27(Kip1) ubiquitination also requires the accessory protein Cks1. |
| GO:0005515 protein binding | IPI PMID:18818696 Structural and functional coupling of Hsp90- and Sgt1-centre... | REMOVE | Summary: Interaction with SGT1 from the Hsp90-Sgt1 structural study. Reason: The paper establishes that SGT1 bridges Hsp90 to the substrate-specific arm of SCF ligases; SKP2 is the recipient of this chaperone coupling, so no specific SKP2 activity is defined. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:18818696 We show that Sgt1 bridges the Hsp90 |
| GO:0005515 protein binding | IPI PMID:21119685 Notch-induced Asb2 expression promotes protein ubiquitinatio... | REMOVE | Summary: Interaction with ASB2, which bridges ECS and SCF(SKP2) into non-canonical dimeric ligase complexes. Reason: The activity described belongs to ASB2 (bridging two cullin complexes); for SKP2 the record remains an uninformative binding statement. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:21119685 binds Jak2 directly but associates with E2A through Skp2. |
| GO:0005515 protein binding | IPI PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by... | REMOVE | Summary: CUL1 association detected in a systematic quantitative (AQUA) survey of cullin-RING ligase stoichiometry. Reason: A proteome-scale stoichiometry survey; SKP2-CUL1 complex membership is already captured by GO:0019005 and the focused CUL1-binding annotations. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:21145461 Examination of CRL complex stoichiometry |
| GO:0005515 protein binding | IPI PMID:21856198 JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 hi... | MODIFY | Summary: SKP2 recognises CDT1 (a licensing factor whose stability is controlled by phosphorylation) as an SCF(SKP2) substrate. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. CDT1 is a documented SCF(SKP2) substrate; PCNA co-occurs in the replication-licensing context. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:21856198 JNK phosphorylates Cdt1 on threonine file:human/SKP2/SKP2-deep-research-falcon.md Proteolytic regulation of p21, p57, p130, FOXO1, BRCA2, CDT1 and other substrates. |
| GO:0005515 protein binding | IPI PMID:22632967 Cyclin F-mediated degradation of ribonucleotide reductase M2... | REMOVE | Summary: p27/CDKN1B interaction recorded in the cyclin F-RRM2 study. Reason: The mechanism established in this paper belongs to SCF(cyclin F) and RRM2; SKP2-p27 recognition is annotated more informatively from the focused structural studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:22632967 F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box |
| GO:0005515 protein binding | IPI PMID:22632967 Cyclin F-mediated degradation of ribonucleotide reductase M2... | REMOVE | Summary: SKP1 interaction recorded in the cyclin F-RRM2 F-box interactome study. Reason: Generic F-box/SKP1 co-purification in a study whose mechanism concerns SCF(cyclin F); SKP2-SKP1 engagement is captured by the focused annotations and GO:0019005. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:22632967 F-box proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | MODIFY | Summary: Cytoplasmic SKP2 recognises casein kinase I-phosphorylated E-cadherin, promoting its ubiquitination and destruction. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. This is the cytoplasmic, acetylation-gated branch of SKP2 activity. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:22770219 ubiquitination and destruction of E-cadherin. PMID:22770219 acetylation of Skp2 in the nuclear localization signal (NLS) promotes its |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | REMOVE | Summary: Interaction with the acetyltransferase EP300/p300, which acetylates SKP2 at K68/K71. Reason: p300 acts on SKP2 (acetylating its NLS); SKP2 exercises no activity on p300, so the binding record is uninformative. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:22770219 Skp2 is acetylated by p300 at K68 and K71, which is a process that |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | REMOVE | Summary: Interaction with the deacetylase SIRT3, which reverses SKP2 K68/K71 acetylation. Reason: SIRT3 acts on SKP2; no SKP2 molecular function follows from the interaction. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:22770219 Skp2 is acetylated by p300 at K68 and K71, which is a process that |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | REMOVE | Summary: Interaction with FZR1/Cdh1, the APC/C coactivator that targets SKP2 for degradation. Reason: SKP2 is the substrate of APC/C-Cdh1 in this relationship, so the binding record defines no SKP2 activity. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:18239684 regulated by the APC(Cdh1), which targets Skp2 for degradation. |
| GO:0005515 protein binding | IPI PMID:23911321 Pharmacological inactivation of Skp2 SCF ubiquitin ligase re... | MODIFY | Summary: SKP2 binds SKP1 through its F-box domain; small molecules that block this interface abolish SCF(SKP2) ligase activity. Reason: The interaction is part of the recognition bridge SKP2 forms between the SCF core and its substrates, i.e. ubiquitin-like ligase-substrate adaptor activity (GO:1990756); bare protein binding is uninformative. The pharmacological study shows the SKP1 interface is what confers SCF(SKP2) ligase function. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:23911321 Skp2 directly interacts with Skp1 via its F-box domain and indirectly PMID:23911321 Skp2 is an F-box protein, constituting one of the four subunits of the Skp1-Cullin-1-F-Box (SCF) ubiquitin E3 ligase complex. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: p21/CDKN1A interaction detected in a systematic in situ proximity-ligation survey of pathway interactions. Reason: High-throughput PLA survey; the informative SKP2-CIP/KIP relationship is annotated from the focused studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:25241761 investigate 1204 endogenous PPIs in HeLa cells, and 557 PPIs of them tested |
| GO:0005515 protein binding | IPI PMID:27194766 ISG12a Restricts Hepatitis C Virus Infection through the Ubi... | MODIFY | Summary: SKP2 acts as the E3 ligase receptor for hepatitis C virus NS5A, which the ISG12a/IFI27 adaptor delivers for ubiquitin-dependent degradation. Reason: The informative molecular function behind this interaction is SKP2 acting as the substrate-recognition adaptor that brings a substrate to the SCF(SKP1-CUL1-RBX1) ligase (GO:1990756); bare protein binding does not capture it. Replacing rather than removing because the cited study establishes the substrate-receptor relationship. The antiviral effect requires SKP2 ligase activity, so the interaction is substrate recognition. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:27194766 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. PMID:27194766 Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity |
| GO:0005515 protein binding | IPI PMID:27542266 DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and c... | MODIFY | Summary: SKP2 associates with CUL1, whose DCUN1D3-dependent neddylation is required for SCF(SKP2) assembly and activity. Reason: The informative function is binding of the CUL1 scaffold (through SKP1), for which GO:0097602 cullin family protein binding is the specific term; bare protein binding is uninformative. Proposed replacements: cullin family protein binding Supporting Evidence: PMID:27542266 DCUN1D3 can inhibit the formation of SCFSKP2 complex by reducing Cullin-1 PMID:27542266 Given that p27 is the primary target of SCFSKP2 complex |
| GO:0005515 protein binding | IPI PMID:27705803 A High-Density Map for Navigating the Human Polycomb Complex... | REMOVE | Summary: SKP1 interaction detected in an affinity-purification map of the human Polycomb complexome. Reason: Proteome-scale complexome mapping; SKP2-SKP1 engagement is annotated from the focused structural work and GO:0019005. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:27705803 Here, we systematically mapped the human |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: CKS1B interaction from the BioPlex 2.0 affinity-purification interactome. Reason: High-throughput interactome record; the informative SKP2-CKS1B relationship is captured from the focused mechanistic studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:28514442 With more than 56,000 candidate interactions, |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: CUL1 interaction from the BioPlex 2.0 affinity-purification interactome. Reason: High-throughput interactome record; CUL1 binding is annotated from focused SCF-assembly studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:28514442 With more than 56,000 candidate interactions, |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | REMOVE | Summary: SKP1 interaction measured as a benchmark pair in the LuTHy two-hybrid technology paper. Reason: Methodological benchmark interaction; adds no functional information beyond the focused SKP1-binding annotations. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:29997244 The double-readout procedure detects interactions with higher sensitivity than |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | REMOVE | Summary: p21/CDKN1A interaction from a mass-spectrometry survey of interferon-stimulated gene interactions. Reason: Proteome-scale ISG interaction survey; the SKP2-CIP/KIP substrate relationship is annotated from focused studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:30833792 We identified interactions between 104 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: CDKN1A interaction from the BioPlex 3.0/HCT116 proteome-scale interactome. Reason: Proteome-scale affinity-purification network; SCF membership and the informative substrate/adaptor relationships are annotated elsewhere in this review. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: CKS1B interaction from the BioPlex 3.0/HCT116 proteome-scale interactome. Reason: Proteome-scale affinity-purification network; SCF membership and the informative substrate/adaptor relationships are annotated elsewhere in this review. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: RBX1 interaction from the BioPlex 3.0/HCT116 proteome-scale interactome. Reason: Proteome-scale affinity-purification network; SCF membership and the informative substrate/adaptor relationships are annotated elsewhere in this review. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: SKP1 interaction from the BioPlex 3.0/HCT116 proteome-scale interactome. Reason: Proteome-scale affinity-purification network; SCF membership and the informative substrate/adaptor relationships are annotated elsewhere in this review. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: FZR1 interaction from the BioPlex 3.0/HCT116 proteome-scale interactome. Reason: Proteome-scale affinity-purification network; SCF membership and the informative substrate/adaptor relationships are annotated elsewhere in this review. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:33961781 Thousands of interactions assemble proteins into modules that impart spatial and |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: AKT1 interaction from a systematic screen for mutation-directed neo-interactions in cancer. Reason: High-throughput neoPPI screen; no SKP2 activity on AKT1 is established here (the reported SKP2-AKT K63 branch rests on other studies). Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:35512704 prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: SMAD4 interaction from the same mutation-directed neo-interaction screen. Reason: High-throughput screen record with no established SKP2 activity on SMAD4. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). Supporting Evidence: PMID:35512704 prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: SKP1 interaction used within an AI-guided protein-interaction drug-discovery pipeline. Reason: Methodological/high-throughput record; SKP2-SKP1 binding is annotated from the focused structural studies. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: SKP1 interaction from a multimodal cell-map (interactome plus imaging) resource. Reason: Proteome-scale mapping resource; adds no functional resolution beyond the focused SKP1-binding annotations. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: FZR1 interaction from the same multimodal cell-map resource. Reason: Proteome-scale mapping resource; FZR1/APC-Cdh1 acts on SKP2 rather than the reverse. Bare protein binding carries no functional information about SKP2, so the annotation is removed as uninformative; removal does not imply the reported physical interaction is false (it remains recorded in the interaction databases). |
| GO:0005634 nucleus | EXP PMID:22770219 Acetylation-dependent regulation of Skp2 function. | ACCEPT | Summary: SKP2 acts in the nucleus, where SCF(SKP2) ubiquitinates nuclear substrates such as p27, p21, p130, CDT1 and ORC1. Reason: Core localisation: canonical Thr187-dependent p27 turnover and the other cell-cycle substrate degradations are nuclear events, and SKP2 carries a functional NLS whose acetylation shifts a pool to the cytoplasm. Supporting Evidence: PMID:22770219 acetylation of Skp2 in the nuclear localization signal (NLS) promotes its file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: SKP2 acts in the nucleus, where SCF(SKP2) ubiquitinates nuclear substrates such as p27, p21, p130, CDT1 and ORC1. Reason: Core localisation: canonical Thr187-dependent p27 turnover and the other cell-cycle substrate degradations are nuclear events, and SKP2 carries a functional NLS whose acetylation shifts a pool to the cytoplasm. The UniProt subcellular-location mapping agrees with the experimental data. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localisation of SKP2 by immunofluorescence. Reason: Consistent with the nuclear site of SCF(SKP2) action on cell-cycle regulators; nucleoplasm is the specific compartment of the core activity. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1363328 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Phosphorylated p130 (RBL2) binds SCF(Skp2):Cks1 complex". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1363331 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Ubiquitination of p130 (RBL2) by SCF (Skp2)". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187545 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Association of Cks1 with SCF(Skp2) complex". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187552 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187574 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Degradation of ubiquitinated p27/p21 by the 26S proteasome". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187575 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Ubiquitination of phospho-p27/p21". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-188191 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "APC/C:Cdh1-mediated degradation of Skp2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6781922 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "USP13 binds UFD1L:SKP2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-68946 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Phosphorylated Orc1 is ubiquitinated while still associated with chromatin". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8939688 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "SCF(SKP2) complex binds RUNX2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8939706 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "SCF(SKP2) polyubiquitinates RUNX2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686969 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "APC/C:Cdh1 polyubiquitinates SKP2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9686980 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "RB1 recruits APC/C:Cdh1 complex to SKP2". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9687377 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "Defective RB1 does not form a complex with SKP2 and FZR1". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708517 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "FBXL17 ubiquitinates BACH1 (in BACH1:FBXL17:SCF (SKP2))". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9708525 | ACCEPT | Summary: Nucleoplasmic SKP2 in the curated Reactome reaction "BACH1:FBXL17 binds SCF(SKP2) complex". Reason: Core localisation: the Reactome reaction places SKP2 (or SCF(SKP2)) in the nucleoplasm, which is where the canonical CDK-inhibitor and replication-factor degradations occur. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: A nucleolar pool of SKP2 detected by immunofluorescence. Reason: Accepted as observed localisation but kept non-core: no nucleolar SKP2 substrate or function has been defined, and the canonical activity is nucleoplasmic. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Canonical activity is predominantly nuclear and oscillates with the cell cycle. |
| GO:0005737 cytoplasm | EXP PMID:22770219 Acetylation-dependent regulation of Skp2 function. | KEEP AS NON CORE | Summary: A cytoplasmic pool of SKP2 exists and is functional, degrading substrates such as E-cadherin; it is promoted by NLS acetylation and AKT-dependent signalling. Reason: Kept as a real but non-core localisation: cytoplasmic SKP2 is generated by regulated modification (p300 acetylation of the NLS, AKT/14-3-3) and drives context-specific functions (migration), whereas the core cell-cycle activity is nuclear. Supporting Evidence: PMID:22770219 acetylation of Skp2 in the nuclear localization signal (NLS) promotes its PMID:22770219 ubiquitination and destruction of E-cadherin. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A cytoplasmic pool of SKP2 exists and is functional, degrading substrates such as E-cadherin; it is promoted by NLS acetylation and AKT-dependent signalling. Reason: Kept as a real but non-core localisation: cytoplasmic SKP2 is generated by regulated modification (p300 acetylation of the NLS, AKT/14-3-3) and drives context-specific functions (migration), whereas the core cell-cycle activity is nuclear. The UniProt location mapping reflects the same experimental observation. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Cytosolic SKP2 detected by immunofluorescence. Reason: Kept as a real but non-core localisation: cytoplasmic SKP2 is generated by regulated modification (p300 acetylation of the NLS, AKT/14-3-3) and drives context-specific functions (migration), whereas the core cell-cycle activity is nuclear. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952618 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8952620 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955241 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "CAND1 binds cytosolic CRL E3 ubiquitin ligases". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8955289 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8956040 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8956200 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983140 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "Transfer of Ub from E2 to substrate and release of E2". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983147 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "Release of E3 from polyubiquitinated substrate". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983156 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "Polyubiquitination of substrate". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-983157 | KEEP AS NON CORE | Summary: Cytosolic SCF(SKP2) in the curated Reactome reaction "Interaction of E3 with substrate and E2-Ub complex". Reason: Retained but non-core: these reactions describe cytosolic CRL1 handling (neddylation, CAND1/COMMD exchange, deneddylation) and generic E3 chemistry rather than the nuclear substrate-degradation activity that defines SKP2. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md Phosphorylation and acetylation can stabilize it and redistribute a fraction to the cytoplasm |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: SKP2 directs ubiquitin-dependent proteolysis of its substrates. Reason: Correct but general; the specific child term GO:0031146 (SCF-dependent proteasomal ubiquitin-dependent protein catabolic process) is separately annotated and better captures the mechanism. Acceptable as a broader electronic mapping. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md p27 ubiquitination and proteasomal degradation promote G1/S progression. PMID:11931757 hOrc1p destruction occurs through the proteasome |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | ACCEPT | Summary: SKP2 participates in protein ubiquitination as the substrate-recognition subunit of an SCF ligase. Reason: Correct but general (UniPathway mapping); the specific SCF-dependent catabolic and K63-linked ubiquitination terms carry the mechanism. UniProt records the same pathway assignment. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md SKP2 is the substrate receptor of SCF^SKP2 rather than an autonomous catalytic enzyme. PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked |
| GO:0019005 SCF ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Summary: SKP2 is the F-box substrate-receptor subunit of the SCF(SKP1-CUL1-RBX1-SKP2) ubiquitin ligase complex. Reason: Core cellular component, established by the Cul1-Rbx1-Skp1-F box(Skp2) crystal structure and by biochemical reconstitution; SKP2 has no activity outside this (or a TRIM21-substituted) complex. The PAINT node (PANTHER:PTN009029653) places SCF membership deep in the F-box/LRR family, consistent with plant, fly and rodent members; SKP2's own experimental annotation appearing in WITH/FROM is expected for an IBD seeded partly by this gene. Supporting Evidence: PMID:11961546 binds the Skp1-F boxSkp2 protein PMID:23911321 Skp2 is an F-box protein, constituting one of the four subunits of the Skp1-Cullin-1-F-Box (SCF) ubiquitin E3 ligase complex. |
| GO:0019005 SCF ubiquitin ligase complex | IDA PMID:16880511 Regulation of p27 degradation and S-phase progression by Ro5... | ACCEPT | Summary: SKP2 is the F-box substrate-receptor subunit of the SCF(SKP1-CUL1-RBX1-SKP2) ubiquitin ligase complex. Reason: Core cellular component, established by the Cul1-Rbx1-Skp1-F box(Skp2) crystal structure and by biochemical reconstitution; SKP2 has no activity outside this (or a TRIM21-substituted) complex. This paper directly identified SKP2 in an SKP1-cullin-F-box complex (including a Cul1-Ro52 core) active on Thr187-phosphorylated p27. Supporting Evidence: PMID:16880511 Here we identify Skp2 as a component PMID:16880511 is mediated by SCF(Skp2) E3 ligase that captures |
| GO:0019005 SCF ubiquitin ligase complex | IDA PMID:22464731 Skp2 E3 ligase integrates ATM activation and homologous reco... | ACCEPT | Summary: SKP2 is the F-box substrate-receptor subunit of the SCF(SKP1-CUL1-RBX1-SKP2) ubiquitin ligase complex. Reason: Core cellular component, established by the Cul1-Rbx1-Skp1-F box(Skp2) crystal structure and by biochemical reconstitution; SKP2 has no activity outside this (or a TRIM21-substituted) complex. The NBS1 study used the assembled SKP2 SCF ligase to show K63-linked ubiquitination activity. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked |
| GO:0019005 SCF ubiquitin ligase complex | IEA GO_REF:0000120 | ACCEPT | Summary: SKP2 is the F-box substrate-receptor subunit of the SCF(SKP1-CUL1-RBX1-SKP2) ubiquitin ligase complex. Reason: Core cellular component, established by the Cul1-Rbx1-Skp1-F box(Skp2) crystal structure and by biochemical reconstitution; SKP2 has no activity outside this (or a TRIM21-substituted) complex. The combined electronic/orthology assignment (mouse Skp2, Q9Z0Z3) agrees with the human experimental data. Supporting Evidence: PMID:11961546 binds the Skp1-F boxSkp2 protein |
| GO:0019005 SCF ubiquitin ligase complex | IPI PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga... | ACCEPT | Summary: SKP2 is the F-box substrate-receptor subunit of the SCF(SKP1-CUL1-RBX1-SKP2) ubiquitin ligase complex. Reason: Core cellular component, established by the Cul1-Rbx1-Skp1-F box(Skp2) crystal structure and by biochemical reconstitution; SKP2 has no activity outside this (or a TRIM21-substituted) complex. The crystal structure of Cul1-Rbx1-Skp1-F box(Skp2) is the defining evidence. Supporting Evidence: PMID:11961546 binds the Skp1-F boxSkp2 protein PMID:11961546 Cul1 serves as a rigid scaffold that |
| GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: SKP2 targets substrates (p27/CDKN1B, p21, p130/RBL2, CDT1, ORC1, FOXO1 and others) for SCF-dependent proteasomal degradation. Reason: Core biological process: this is what SCF(SKP2) does, demonstrated by reconstituted ubiquitination, degron mutants and loss-of-function accumulation of p27. The phylogenetic assignment through PANTHER:PTN009029653 is sound: SCF-dependent degradation is the ancestral role of this F-box/LRR clade, and the target lies inside it. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md p27 ubiquitination and proteasomal degradation promote G1/S progression. PMID:11931757 hOrc1p destruction occurs through the proteasome |
| GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | NAS PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga... | ACCEPT | Summary: SKP2 targets substrates (p27/CDKN1B, p21, p130/RBL2, CDT1, ORC1, FOXO1 and others) for SCF-dependent proteasomal degradation. Reason: Core biological process: this is what SCF(SKP2) does, demonstrated by reconstituted ubiquitination, degron mutants and loss-of-function accumulation of p27. The author statement accompanies the SCF(SKP2) structure that explains how substrate and E2 are positioned. Supporting Evidence: PMID:11961546 binds the Skp1-F boxSkp2 protein PMID:11961546 Cul1 serves as a rigid scaffold that |
| GO:0042802 identical protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | KEEP AS NON CORE | Summary: SKP2 self-associates (dimerises) in an acetylation-dependent manner; p300-mediated K68/K71 acetylation promotes dimerisation and NLS deletion or K68/K71 mutation prevents it. Reason: Unlike bare protein binding, identical protein binding is a specific, directly demonstrated property. It is retained but non-core: dimerisation is a regulatory feature of the F-box protein rather than the substrate-receptor activity itself, and its functional consequences for substrate choice are not yet resolved. Supporting Evidence: PMID:22770219 We found that p300-mediated Skp2 acetylation promotes Skp2 dimerization PMID:22770219 Skp2 is acetylated by p300 at K68 and K71, which is a process that |
| GO:0042981 regulation of apoptotic process | IDA PMID:23277542 Domain-specific c-Myc ubiquitylation controls c-Myc transcri... | KEEP AS NON CORE | Summary: By ubiquitinating the c-MYC transcriptional domain, SKP2 suppresses the ARF-dependent, p53-independent apoptotic programme; SKP2 overexpression inhibits c-Myc-induced apoptosis. Reason: Retained as a genuine but indirect, context-dependent consequence of MYC ubiquitination rather than a core SKP2 function: the term is generic, the effect is mediated through a substrate's transcriptional output, and the experiments rely on SKP2 overexpression. Supporting Evidence: PMID:23277542 Overexpression of Skp2, which occurs in many human tumors, inhibits the PMID:23277542 ARF inhibits the interaction of c-Myc with the E3 ubiquitin ligase Skp2. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IMP PMID:27194766 ISG12a Restricts Hepatitis C Virus Infection through the Ubi... | ACCEPT | Summary: SKP2 is required for ubiquitin-dependent proteasomal degradation of its substrates; here, of hepatitis C virus NS5A delivered by ISG12a/IFI27. Reason: Core process (and a parent of the SCF-specific GO:0031146 also annotated). The requirement was shown by loss of the antiviral effect when SKP2 ligase function is lost. Supporting Evidence: PMID:27194766 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. PMID:27194766 Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity |
| GO:0045087 innate immune response | IMP PMID:27194766 ISG12a Restricts Hepatitis C Virus Infection through the Ubi... | KEEP AS NON CORE | Summary: SKP2 contributes to an interferon-induced antiviral effector arm by degrading a viral protein delivered by the ISG ISG12a/IFI27. Reason: Kept non-core: SKP2 is a general SCF substrate receptor recruited by an ISG adaptor in this one setting, not a dedicated innate-immune component. Evidence rests on a single HCV study (cached record is abstract-only). Supporting Evidence: PMID:27194766 ISG12a recruits an E3 ligase, SKP2, for ubiquitination and degradation of viral PMID:27194766 Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity |
| GO:0051607 defense response to virus | IMP PMID:27194766 ISG12a Restricts Hepatitis C Virus Infection through the Ubi... | KEEP AS NON CORE | Summary: SKP2-dependent degradation of HCV NS5A restricts viral replication, giving SKP2 an antiviral activity in this context. Reason: Kept non-core for the same reason as the innate-immune term: a context-specific, adaptor-dependent use of the general substrate-receptor activity, supported by one study. UniProt records the same HCV-restricted antiviral function. Supporting Evidence: PMID:27194766 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. PMID:27194766 Moreover, the antiviral effect of ISG12a is dependent on the E3 ligase activity |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:22464731 Skp2 E3 ligase integrates ATM activation and homologous reco... | ACCEPT | Summary: Following DNA damage, SKP2 directs K63-linked (non-degradative) ubiquitination of NBN/NBS1, which is required for NBS1-ATM interaction. Reason: Core, mechanistically distinct second activity of SCF(SKP2): the linkage is signalling rather than degradative, directly demonstrated for NBS1, and modelled as such in the production GO-CAM gomodel:65a1f4f800001029. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked file:human/SKP2/SKP2-deep-research-falcon.md SKP2 can also support **nonproteolytic K63-linked ubiquitination**. |
| GO:0070534 protein K63-linked ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: Following DNA damage, SKP2 directs K63-linked (non-degradative) ubiquitination of NBN/NBS1, which is required for NBS1-ATM interaction. Reason: Core, mechanistically distinct second activity of SCF(SKP2): the linkage is signalling rather than degradative, directly demonstrated for NBS1, and modelled as such in the production GO-CAM gomodel:65a1f4f800001029. The combined electronic/orthology assignment (mouse Skp2) agrees with the human IDA. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked |
| GO:0070936 protein K48-linked ubiquitination | IMP PMID:27194766 ISG12a Restricts Hepatitis C Virus Infection through the Ubi... | ACCEPT | Summary: SKP2-dependent degradation of its substrates proceeds through K48-linked polyubiquitin chains, shown here for hepatitis C virus NS5A. Reason: K48 chains are the canonical degradative output of SCF ligases, and the annotating curator read the full text (our cached record is abstract-only and states only that degradation is ubiquitination- and proteasome-dependent). Accepting rather than second-guessing; the claim is also consistent with all SCF(SKP2) proteolytic substrates. Supporting Evidence: PMID:27194766 (SKP2) is identified as an ubiquitin E3 ligase for NS5A. PMID:27194766 ISG12a recruits an E3 ligase, SKP2, for ubiquitination and degradation of viral |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: By K63-ubiquitinating NBN, SKP2 promotes ATM recruitment and activation at double-strand breaks and is required for efficient homologous-recombination repair. Reason: Core process for the DNA-damage branch: SKP2 performs the ubiquitination step that licenses NBS1-ATM interaction, and its loss causes an HR defect and IR sensitivity. The IBD at PANTHER:PTN002700216 is grounded on mouse Skp2 and on this gene's own experimental annotation; SKP2 appearing in its own WITH/FROM marks direct experimental support, not circularity. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked PMID:22464731 we show that Skp2 deficiency exhibits a defect in homologous |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IDA PMID:22464731 Skp2 E3 ligase integrates ATM activation and homologous reco... | ACCEPT | Summary: By K63-ubiquitinating NBN, SKP2 promotes ATM recruitment and activation at double-strand breaks and is required for efficient homologous-recombination repair. Reason: Core process for the DNA-damage branch: SKP2 performs the ubiquitination step that licenses NBS1-ATM interaction, and its loss causes an HR defect and IR sensitivity. Supporting Evidence: PMID:22464731 we show that Skp2 deficiency exhibits a defect in homologous PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IEA GO_REF:0000120 | ACCEPT | Summary: By K63-ubiquitinating NBN, SKP2 promotes ATM recruitment and activation at double-strand breaks and is required for efficient homologous-recombination repair. Reason: Core process for the DNA-damage branch: SKP2 performs the ubiquitination step that licenses NBS1-ATM interaction, and its loss causes an HR defect and IR sensitivity. The electronic/orthology assignment from mouse Skp2 agrees with the human IDA. Supporting Evidence: PMID:22464731 we show that Skp2 deficiency exhibits a defect in homologous |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: SKP2 is the substrate-recognition adaptor that brings substrates to the CUL1-RBX1 catalytic core: its F-box binds SKP1 and its LRR domain (with CKS1B for phospho-p27) binds the substrate. Reason: Core molecular function. SKP2 has no catalytic activity of its own; the structures of Cul1-Rbx1-Skp1-F box(Skp2) and Skp1-Skp2-Cks1/phospho-p27 define exactly this adaptor role. The IBD (PANTHER:PTN009029653, with mouse Skp2 and this gene) places adaptor activity at the ancestral F-box node, which is where it belongs for an F-box/LRR receptor; the target's own presence in WITH/FROM reflects its experimental grounding. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md SKP2 is the substrate receptor of SCF^SKP2 rather than an autonomous catalytic enzyme. PMID:11961546 binds the Skp1-F boxSkp2 protein |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IDA PMID:22464731 Skp2 E3 ligase integrates ATM activation and homologous reco... | ACCEPT | Summary: SKP2 is the substrate-recognition adaptor that brings substrates to the CUL1-RBX1 catalytic core: its F-box binds SKP1 and its LRR domain (with CKS1B for phospho-p27) binds the substrate. Reason: Core molecular function. SKP2 has no catalytic activity of its own; the structures of Cul1-Rbx1-Skp1-F box(Skp2) and Skp1-Skp2-Cks1/phospho-p27 define exactly this adaptor role. Directly demonstrated for NBS1 recognition and K63-linked ubiquitination, and used with this term in the production GO-CAM gomodel:65a1f4f800001029. Supporting Evidence: PMID:22464731 Skp2 interacts with NBS1 and triggers K63-linked file:human/SKP2/SKP2-deep-research-falcon.md SKP2 is the substrate receptor of SCF^SKP2 rather than an autonomous catalytic enzyme. |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: SKP2 is the substrate-recognition adaptor that brings substrates to the CUL1-RBX1 catalytic core: its F-box binds SKP1 and its LRR domain (with CKS1B for phospho-p27) binds the substrate. Reason: Core molecular function. SKP2 has no catalytic activity of its own; the structures of Cul1-Rbx1-Skp1-F box(Skp2) and Skp1-Skp2-Cks1/phospho-p27 define exactly this adaptor role. The combined electronic/orthology assignment agrees with the experimental and phylogenetic evidence. Supporting Evidence: file:human/SKP2/SKP2-deep-research-falcon.md SKP2 is the substrate receptor of SCF^SKP2 rather than an autonomous catalytic enzyme. |
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Download this section (compressed HTML)Q: Should the many SKP2 substrate interactions currently recorded as bare protein binding (p27/CDKN1B, p21/CDKN1A, CDT1, ORC1, MYC, DUSP1, E-cadherin, HCV NS5A) be re-curated as has_input on the SCF(SKP2) ligase activity in GO-CAM, rather than as GO:0005515 rows on SKP2?
Q: Which reported SKP2 substrates meet a GO-CAM standard of evidence (reconstituted ubiquitination plus degron mutant plus loss-of-function stabilisation), and which rest only on co-immunoprecipitation or overexpression and should stay uncurated?
Q: Is the acetylation-dependent SKP2 dimerisation a functional requirement for substrate selection (as suggested for other F-box proteins), and if so should a homodimerisation activity be modelled alongside the adaptor activity?
Experiment: Rescue SKP2-null cells with separation-of-function alleles (D331A, LRR-surface mutants) and quantify the stability and ubiquitination of a panel of candidate substrates by pulse-chase and ubiquitin-remnant proteomics.
Hypothesis: The CKS1B-dependent phosphodegron pocket is required only for a defined subset of SKP2 substrates (p27 and other CIP/KIP proteins), while LRR-only contacts suffice for others.
Type: separation-of-function rescue with degradation proteomics
Experiment: Compare NBN ubiquitin-site mutants and an SKP2 allele defective for K63 chain output (E2 pairing) for ATM autophosphorylation, ATM foci, HR reporter activity and IR survival, with p27 turnover measured in parallel as a specificity control.
Hypothesis: SKP2-dependent K63-linked ubiquitination of NBN, and not its proteolytic activity, is what confers resistance to ionising radiation.
Type: linkage-specific ubiquitination and DNA-repair assay
Experiment: Compare the ubiquitinated proteomes of cells expressing NLS-acetylation-mimetic (K68/K71) and non-acetylatable SKP2 alleles after compartment fractionation, to test whether E-cadherin and other cytoplasmic substrates are specifically enriched.
Hypothesis: Cytoplasmic relocalisation of SKP2 driven by NLS acetylation re-targets the ligase to a distinct substrate set.
Type: compartment-resolved ubiquitinome comparison
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