CSNK1D

UniProt ID: P48730
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

Casein kinase I isoform delta (CK1delta) is a constitutively active, monomeric serine/threonine protein kinase of the casein kinase 1 (CK1) family. It uses ATP and is magnesium-dependent, and is operationally defined as a "casein kinase" by its preference for acidic substrates; it performs both primed (phospho-directed) and unprimed phosphorylation. Its activity is autoinhibited by C-terminal autophosphorylation and reactivated by phosphatase (PP1)-mediated dephosphorylation. CK1delta is a central component of the circadian clock, phosphorylating PERIOD proteins PER1 and PER2 to control their stability and nuclear entry and thereby set circadian period; missense variants (e.g. T44A, H46R) reduce kinase activity and cause familial advanced sleep phase syndrome and familial migraine. CK1delta also phosphorylates Dishevelled (DVL2/DVL3) and other components to modulate Wnt/beta-catenin signaling, acts at the centrosome and Golgi to promote microtubule nucleation, Golgi organization and primary (non-motile) ciliogenesis, and regulates the mitotic spindle. It phosphorylates a large and diverse set of additional substrates including p53/TP53, MDM2, YAP1, HIF1A, TOP2A, connexin-43/GJA1, PKD2, eIF6, DCK and tau/MAPT, linking it to DNA-damage responses, Hippo signaling, vesicle trafficking and (via tau hyperphosphorylation) neurodegeneration. It localizes to the cytoplasm/cytosol, nucleus, centrosome, perinuclear region, spindle and spindle microtubules, Golgi apparatus, ciliary basal body and plasma membrane, with correct localization dependent on kinase activity.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005876 spindle microtubule
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) transfer of spindle microtubule localization. CK1delta does localize to spindle microtubules upon DNA damage by direct experimental evidence, so this CC term is supported.
Reason: Consistent with experimental IDA evidence (PMID:10826492) showing CK1delta localization at spindle microtubules; a genuine, if context-dependent (DNA-damage), location.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: IBA transfer of a role in promoting proteasomal degradation. CK1delta phosphorylates phosphodegrons that prime substrates (YAP1, MDM2) for SCF(beta-TRCP)-mediated ubiquitination and degradation, so the process is real but is a downstream, substrate-driven consequence of kinase activity rather than a core function.
Reason: Supported by experimental data on YAP1 and MDM2 degron phosphorylation, but this is one of many substrate-specific downstream effects rather than the gene's core function.
Supporting Evidence:
PMID:20048001
A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).
PMID:20708156
Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.
GO:0042752 regulation of circadian rhythm
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA transfer of regulation of circadian rhythm. This is a hallmark, well-established physiological role of CK1delta via PER1/PER2 phosphorylation; disease variants cause familial advanced sleep phase.
Reason: Core biological process; strongly supported by direct interaction with and phosphorylation of PER1/PER2 and by FASPS2/migraine disease variants.
Supporting Evidence:
PMID:23636092
Casein kinase idelta mutations in familial migraine and advanced sleep phase.
GO:0051225 spindle assembly
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: IBA transfer of a spindle assembly role. CK1delta is recruited to the spindle/centrosome and its inhibition alters mitotic spindle formation, so the process has direct experimental support.
Reason: Supported experimentally (PMID:10826492, PMID:16027726) but represents a context-specific (mitotic/trophoblast) role rather than the core kinase/circadian function.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0090263 positive regulation of canonical Wnt signaling pathway
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA transfer of positive regulation of canonical Wnt signaling. CK1delta/CK1 phosphorylates DVL2/DVL3 and other Wnt components; a well-supported signaling role of the gene.
Reason: Core signaling process supported by experimental data on DVL phosphorylation and Wnt-3a-dependent neurite outgrowth.
Supporting Evidence:
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
GO:1905515 non-motile cilium assembly
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA transfer of a primary (non-motile) cilium assembly role, also directly demonstrated by loss-of-function in human RPE cells and Csnk1d-null mouse cells.
Reason: Supported by direct IMP evidence (PMID:24648492) that CK1delta is required for primary ciliogenesis; a well-established cell-biological role.
Supporting Evidence:
PMID:24648492
Casein kinase 1delta functions at the centrosome and Golgi to promote ciliogenesis.
GO:0006897 endocytosis
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: IBA transfer of an endocytosis role, derived largely from distant yeast CK1 paralogs (Yck1/Yck2, SGD). Human CK1delta has no direct experimental support for a role in endocytosis.
Reason: Over-transfer from divergent fungal paralogs; the WITH/FROM evidence (SGD:S000001177, SGD:S000005098) is from yeast CK1 enzymes whose endocytic role is not established for human CK1delta.
GO:0004672 protein kinase activity
IEA
GO_REF:0000120 		MODIFY
Summary: Electronic annotation of generic protein kinase activity. Correct but superseded by the more specific protein serine/threonine kinase activity, which is experimentally established.
Reason: Term is correct but too general; CK1delta is specifically a serine/threonine kinase.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000003 		ACCEPT
Summary: Electronic (EC-based) annotation of protein serine/threonine kinase activity. This is the core molecular function, directly demonstrated for many substrates.
Reason: Core molecular function, abundantly supported by experimental (EXP/IDA) evidence and structural data.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
EC=2.7.11.1 {ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092};
GO:0005524 ATP binding
IEA
GO_REF:0000002 		ACCEPT
Summary: ATP binding is a core feature of this ATP-dependent kinase, supported by numerous co-crystal structures with ATP-competitive inhibitors bound in the ATP pocket.
Reason: Essential for catalysis; supported by InterPro kinase domain signatures and over 30 PDB structures of the ATP-binding site.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: Nuclear localization from UniProt subcellular location mapping. CK1delta shuttles to the nucleus where it acts on nuclear substrates (e.g. p53, PER nuclear transport).
Reason: Consistent with documented nuclear localization in UniProt and nuclear substrate biology.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Cytoplasmic localization from UniProt mapping; CK1delta is predominantly cytoplasmic.
Reason: Well-supported primary location of this kinase.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044 		ACCEPT
Summary: Golgi localization from UniProt mapping, also directly demonstrated; CK1delta acts at the Golgi (with AKAP450) for microtubule nucleation and ciliogenesis.
Reason: Supported by experimental IDA (PMID:10826492) and functional ciliogenesis data (PMID:24648492).
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005813 centrosome
IEA
GO_REF:0000044 		ACCEPT
Summary: Centrosome localization from UniProt mapping, directly demonstrated and functionally important; CK1delta is anchored at the centrosome via AKAP9/AKAP450.
Reason: Strongly supported by experimental IDA evidence and a defined centrosomal localization signal required for ciliogenesis.
Supporting Evidence:
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
GO:0005819 spindle
IEA
GO_REF:0000044 		ACCEPT
Summary: Spindle localization from UniProt mapping, also directly demonstrated (recruited to the spindle apparatus upon DNA damage).
Reason: Consistent with experimental IDA evidence (PMID:10826492).
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005886 plasma membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Plasma membrane localization from UniProt mapping; CK1delta is reported at the cell membrane, also supported by IDA and HPA.
Reason: Consistent with UniProt subcellular location and experimental evidence.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
Cell membrane.
GO:0030111 regulation of Wnt signaling pathway
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA machine-learning annotation of Wnt signaling regulation. Generic but correct; captured more specifically by the canonical Wnt annotations.
Reason: A genuine, well-supported role of CK1delta in Wnt signaling (DVL phosphorylation).
Supporting Evidence:
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Perinuclear region localization from UniProt mapping, also directly demonstrated.
Reason: Consistent with experimental IDA evidence (PMID:16027726).
Supporting Evidence:
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
GO:0050321 tau-protein kinase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Tau-protein kinase activity (EC 2.7.11.26), a specific molecular function of CK1delta directly demonstrated in vitro.
Reason: Experimentally established specific MF; CK1delta phosphorylates tau and disrupts microtubule binding.
Supporting Evidence:
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116 		ACCEPT
Summary: Rhea/EC-based electronic annotation of protein serine kinase activity, a core CK1delta function.
Reason: Core molecular function abundantly supported by experimental evidence.
Supporting Evidence:
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a high-throughput interactome (with DVL3). The term is uninformative about molecular function.
Reason: Bare "protein binding" conveys no specific function; relevant interactions (e.g. DVL3) are captured by the Wnt-signaling and kinase annotations.
GO:0005515 protein binding
IPI
PMID:20708156
Phosphorylation by casein kinase I promotes the turnover of ... 		MARK AS OVER ANNOTATED
Summary: Protein binding evidenced by interaction with MDM2 (Q00987). The MDM2 interaction is functionally meaningful (phosphodegron priming) but the bare term is uninformative.
Reason: Uninformative MF term; the functional MDM2 relationship is captured by the proteasomal degradation BP annotation.
GO:0005515 protein binding
IPI
PMID:21179498
High-throughput chemical screen identifies a novel potent mo... 		MARK AS OVER ANNOTATED
Summary: Protein binding evidenced by interaction with PER2 (O15055). Functionally central to circadian biology but the bare term is uninformative.
Reason: Uninformative MF term; the PER2 interaction is captured by circadian regulation and kinase annotations.
GO:0005515 protein binding
IPI
PMID:22609948
Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated prim... 		MARK AS OVER ANNOTATED
Summary: Protein binding evidenced by interaction with mouse Dvl2 (Q60838). The bare term is uninformative.
Reason: Uninformative MF term; the DVL2 relationship is captured by Wnt-signaling and cilium annotations.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a proteome-scale interactome map (DVL3, LURAP1, TRIM9). Uninformative about function.
Reason: Bare "protein binding" from high-throughput interactome; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a binary interactome reference map (multiple partners). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:32707033
Kinase Interaction Network Expands Functional and Disease Ro... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a kinase interaction network (GAPVD1). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a neurodegenerative-disease interactome (APP). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a cell-specific interactome remodeling study (PER2, GAPVD1, ZNF618). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from OpenCell endogenous-tagging interactome (GAPVD1). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0005515 protein binding
IPI
PMID:36931259
A central chaperone-like role for 14-3-3 proteins in human c... 		MARK AS OVER ANNOTATED
Summary: Protein binding evidenced by interaction with 14-3-3 epsilon/YWHAE (P62258). Uninformative bare term.
Reason: Bare "protein binding"; no specific molecular function conveyed.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding from a multimodal cell-map study (PER2, GAPVD1). Uninformative.
Reason: Bare "protein binding" from high-throughput screen; no specific function conveyed.
GO:0048208 COPII vesicle coat assembly
TAS
Reactome:R-HSA-204005 		KEEP AS NON CORE
Summary: Reactome annotation linking CK1delta to COPII vesicle formation via SEC23 phosphorylation. A narrow substrate-driven role.
Reason: Real but specialized substrate-driven role (CSNK1D phosphorylates SEC23, Reactome R-HSA-5694441); not a core function.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
Golgi apparatus.
GO:0004674 protein serine/threonine kinase activity
TAS
Reactome:R-HSA-5694441 		ACCEPT
Summary: Reactome (TAS) annotation of protein serine/threonine kinase activity in the context of SEC23 phosphorylation. Core MF.
Reason: Core molecular function, consistent with all experimental evidence.
Supporting Evidence:
PMID:10606744
Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15.
GO:0005829 cytosol
IDA
GO_REF:0000052 		ACCEPT
Summary: Cytosol localization from immunofluorescence (HPA). CK1delta is a predominantly cytosolic kinase.
Reason: Direct IDA evidence for a genuine cytosolic location.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm.
GO:0005886 plasma membrane
IDA
GO_REF:0000052 		ACCEPT
Summary: Plasma membrane localization from immunofluorescence (HPA), concordant with UniProt cell membrane annotation.
Reason: Direct IDA evidence consistent with documented cell membrane location.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
Cell membrane.
GO:0050321 tau-protein kinase activity
EXP
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its bi... 		ACCEPT
Summary: Direct experimental demonstration that CK1delta phosphorylates tau, a specific molecular function (EC 2.7.11.26).
Reason: Strong EXP evidence; CK1delta phosphorylates tau and disrupts its microtubule binding.
Supporting Evidence:
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
GO:0050321 tau-protein kinase activity
EXP
PMID:17562708
Novel phosphorylation sites in tau from Alzheimer brain supp... 		ACCEPT
Summary: Experimental support for tau-protein kinase activity; CK1 phosphorylates novel tau sites found in Alzheimer brain.
Reason: EXP evidence corroborating the specific tau-kinase MF.
Supporting Evidence:
PMID:17562708
Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis.
GO:0106310 protein serine kinase activity
EXP
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its bi... 		ACCEPT
Summary: Experimental support for protein serine kinase activity (tau phosphorylation).
Reason: Core MF; strong EXP evidence.
Supporting Evidence:
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
GO:0106310 protein serine kinase activity
EXP
PMID:17562708
Novel phosphorylation sites in tau from Alzheimer brain supp... 		ACCEPT
Summary: Experimental support for protein serine kinase activity (tau phosphorylation at novel sites).
Reason: Core MF; EXP evidence.
Supporting Evidence:
PMID:17562708
Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis.
GO:0106310 protein serine kinase activity
EXP
PMID:17962809
Phosphorylation at Ser244 by CK1 determines nuclear localiza... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via PKD2 Ser244 phosphorylation.
Reason: Core MF; EXP evidence (PKD2 substrate).
Supporting Evidence:
PMID:17962809
Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2.
GO:0106310 protein serine kinase activity
EXP
PMID:19591487
3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibit... 		ACCEPT
Summary: Experimental support for protein serine kinase activity in an inhibitor characterization study of CK1delta.
Reason: Core MF; EXP/inhibitor-based evidence of catalytic activity.
Supporting Evidence:
PMID:19591487
3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta.
GO:0106310 protein serine kinase activity
EXP
PMID:20041275
Isoform specific phosphorylation of p53 by protein kinase CK... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via isoform-specific p53 phosphorylation.
Reason: Core MF; EXP evidence (p53 substrate).
Supporting Evidence:
PMID:20041275
Isoform specific phosphorylation of p53 by protein kinase CK1.
GO:0106310 protein serine kinase activity
EXP
PMID:20048001
A coordinated phosphorylation by Lats and CK1 regulates YAP ... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via YAP1 phosphodegron phosphorylation.
Reason: Core MF; EXP evidence (YAP1 substrate).
Supporting Evidence:
PMID:20048001
A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).
GO:0106310 protein serine kinase activity
EXP
PMID:20637175
Casein kinase 1delta activates human recombinant deoxycytidi... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via DCK Ser-74 phosphorylation (in vitro; per UniProt CAUTION, probably not physiological in vivo).
Reason: The MF is directly demonstrated in vitro; the caveat applies to the in vivo DCK regulation, not to the kinase activity itself.
Supporting Evidence:
PMID:20637175
Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity.
GO:0106310 protein serine kinase activity
EXP
PMID:20699359
Casein kinase 1 regulates human hypoxia-inducible factor HIF... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via HIF-1alpha phosphorylation.
Reason: Core MF; EXP evidence (HIF-1 substrate).
Supporting Evidence:
PMID:20699359
Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
GO:0106310 protein serine kinase activity
EXP
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via DVL2/DVL3 phosphorylation.
Reason: Core MF; EXP evidence (DVL substrates, Wnt signaling).
Supporting Evidence:
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
GO:0106310 protein serine kinase activity
EXP
PMID:23636092
Casein kinase iδ mutations in familial migraine and advanced... 		ACCEPT
Summary: Experimental support for protein serine kinase activity via PER2 peptide phosphorylation; FASPS2/migraine variants reduce activity.
Reason: Core MF; EXP evidence directly tied to circadian biology and disease.
Supporting Evidence:
PMID:23636092
Casein kinase idelta mutations in familial migraine and advanced sleep phase.
GO:1904948 midbrain dopaminergic neuron differentiation
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: ISS transfer from the mouse ortholog (Q9DC28) of a role in midbrain dopaminergic neuron differentiation. Plausible developmental/pleiotropic role but not core and without direct human evidence.
Reason: Inferred by sequence similarity from mouse; a pleiotropic developmental role, not a core function.
GO:2000052 positive regulation of non-canonical Wnt signaling pathway
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: ISS transfer from mouse ortholog of a non-canonical Wnt role. CK1delta acts in Wnt signaling broadly; the non-canonical specificity is inferred.
Reason: Sequence-similarity-based; Wnt signaling involvement is supported overall, but the non-canonical-specific role is inferred rather than directly shown in human.
GO:0050321 tau-protein kinase activity
IDA
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective... 		ACCEPT
Summary: Direct assay (IDA) of CK1delta catalytic activity (tau/casein kinase activity) in the context of DBNDD2 binding.
Reason: Supports the specific tau-protein kinase MF with direct evidence.
Supporting Evidence:
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.
GO:0106310 protein serine kinase activity
IDA
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective... 		ACCEPT
Summary: Direct assay (IDA) of CK1delta protein serine kinase activity.
Reason: Core MF; direct evidence.
Supporting Evidence:
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.
GO:0004672 protein kinase activity
IMP
PMID:19591487
3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibit... 		MODIFY
Summary: Generic protein kinase activity from inhibitor characterization. Correct but superseded by the specific serine/threonine kinase term.
Reason: Too general; CK1delta is specifically a serine/threonine kinase.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:10606744
Protein kinase CK1 is a p53-threonine 18 kinase which requir... 		ACCEPT
Summary: Direct demonstration that CK1 phosphorylates p53 at Thr18, a serine/threonine kinase activity.
Reason: Core MF; direct experimental evidence (p53 Thr18 kinase).
Supporting Evidence:
PMID:10606744
Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:20041275
Isoform specific phosphorylation of p53 by protein kinase CK... 		ACCEPT
Summary: Direct demonstration of isoform-specific p53 phosphorylation by CK1.
Reason: Core MF; direct experimental evidence.
Supporting Evidence:
PMID:20041275
Isoform specific phosphorylation of p53 by protein kinase CK1.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:20637175
Casein kinase 1delta activates human recombinant deoxycytidi... 		ACCEPT
Summary: Direct demonstration of CK1delta serine/threonine kinase activity (DCK Ser-74 phosphorylation in vitro).
Reason: Core MF; direct in vitro kinase assay.
Supporting Evidence:
PMID:20637175
Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity.
GO:0106310 protein serine kinase activity
IDA
PMID:12270943
Casein kinase 1 regulates connexin-43 gap junction assembly. 		ACCEPT
Summary: Direct demonstration that CK1 phosphorylates connexin-43/GJA1 (serine kinase activity).
Reason: Core MF; direct experimental evidence (connexin-43 substrate).
Supporting Evidence:
PMID:12270943
Casein kinase 1 regulates connexin-43 gap junction assembly.
GO:0106310 protein serine kinase activity
IMP
PMID:19043076
Casein kinase I delta/epsilon phosphorylates topoisomerase I... 		ACCEPT
Summary: CK1delta/epsilon phosphorylates TOP2A at Ser-1106, supporting protein serine kinase activity.
Reason: Core MF; supported by substrate phosphorylation evidence (TOP2A).
Supporting Evidence:
PMID:19043076
Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity.
GO:0106310 protein serine kinase activity
IDA
PMID:21084295
Opposing action of casein kinase 1 and calcineurin in nucleo... 		ACCEPT
Summary: Direct demonstration of eIF6 phosphorylation by CK1, supporting protein serine kinase activity.
Reason: Core MF; direct experimental evidence (eIF6 substrate).
Supporting Evidence:
PMID:21084295
Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6.
GO:0036064 ciliary basal body
IDA
PMID:29257953
Evolutionary Proteomics Uncovers Ancient Associations of Cil... 		ACCEPT
Summary: Direct localization to the ciliary basal body, consistent with CK1delta's established centrosome/basal-body role in ciliogenesis.
Reason: Direct IDA evidence; concordant with the functional ciliogenesis data.
Supporting Evidence:
PMID:29257953
Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
GO:0045296 cadherin binding
HDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by... 		MARK AS OVER ANNOTATED
Summary: Cadherin binding from a high-throughput E-cadherin interactome proximity dataset. CK1delta is not an established cadherin-binding adaptor.
Reason: High-throughput proximity-based annotation; no specific cadherin-binding function is established for CK1delta and it is not supported by focused studies.
GO:0004672 protein kinase activity
ISS
GO_REF:0000024 		MODIFY
Summary: Generic protein kinase activity inferred by sequence similarity from mouse ortholog. Superseded by the specific serine/threonine kinase term.
Reason: Too general; CK1delta is specifically a serine/threonine kinase.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:25500533
Phosphorylation of LRRK2 by casein kinase 1α regulates trans... 		ACCEPT
Summary: This paper is primarily about CK1alpha/CSNK1A1 as the LRRK2 kinase; for CK1delta it shows only moderate in vitro phosphorylation of LRRK2 at S955. It nonetheless documents CK1delta serine/threonine kinase activity in vitro.
Reason: Supports the generic Ser/Thr kinase MF in vitro; the LRRK2-specific physiological role belongs to CK1alpha and should not be over-transferred to CK1delta.
Supporting Evidence:
PMID:25500533
we found that CK1δ/ε and CK1γ isoforms could moderately phosphorylate S955 and S935 in vitro, respectively
GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane
TAS
Reactome:R-HSA-5694441 		KEEP AS NON CORE
Summary: Reactome localization to the ERGIC membrane in the context of SEC23 phosphorylation during COPII vesicle formation. Plausible given the Golgi/secretory role.
Reason: Pathway-specific Reactome localization tied to the SEC23/COPII substrate role; consistent with Golgi association but specialized.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
Golgi apparatus.
GO:0007020 microtubule nucleation
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		ACCEPT
Summary: Loss-of-function evidence that CK1delta is required for microtubule nucleation at the Golgi (via AKAP450), part of its ciliogenesis function.
Reason: Direct IMP evidence; a well-supported cell-biological role.
Supporting Evidence:
PMID:24648492
CK1δ was required for microtubule nucleation at the Golgi and maintenance of Golgi integrity.
GO:0034067 protein localization to Golgi apparatus
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		KEEP AS NON CORE
Summary: CK1delta loss disperses Golgi/centrosomal proteins (AKAP450, IFT20), supporting a role in protein localization to the Golgi.
Reason: Supported by IMP evidence but a downstream component of the broader Golgi-organization/ciliogenesis function.
Supporting Evidence:
PMID:24648492
the Golgi distribution of its binding partner, A-kinase anchor protein 450 (AKAP450)
GO:0007030 Golgi organization
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		ACCEPT
Summary: CK1delta is required for maintenance of Golgi integrity and the polarized Golgi ribbon, supporting Golgi organization.
Reason: Direct IMP evidence; CK1delta inhibition disrupts cis-Golgi organization.
Supporting Evidence:
PMID:24648492
where it is important for maintaining Golgi organization and polarized trafficking
GO:0061512 protein localization to cilium
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		KEEP AS NON CORE
Summary: CK1delta is required for correct ciliary distribution of transport proteins (Rab8a, polycystin-2), supporting protein localization to cilium.
Reason: Supported by IMP evidence; a component of the ciliogenesis function rather than an independent core role.
Supporting Evidence:
PMID:24648492
alters pericentrosomal or ciliary distribution of several proteins involved in ciliary transport
GO:0071539 protein localization to centrosome
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		KEEP AS NON CORE
Summary: CK1delta is required for pericentrosomal positioning of CEP290/PCM1, supporting protein localization to the centrosome.
Reason: Supported by IMP evidence; part of the centrosome/ciliogenesis function.
Supporting Evidence:
PMID:24648492
CK1δ is required for proper positioning of these centriolar satellite proteins
GO:1905515 non-motile cilium assembly
IMP
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to pr... 		ACCEPT
Summary: Direct loss-of-function evidence (siRNA, kinase inhibitor, Csnk1d-null cells) that CK1delta is required for primary (non-motile) ciliogenesis.
Reason: Strong IMP evidence across multiple models; a well-established role.
Supporting Evidence:
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2574840 		ACCEPT
Summary: Cytosol localization from Reactome (AURKA pathway reaction). Cytosol is a genuine CK1delta location; one of many redundant Reactome citations.
Reason: The cytosol CC term is correct; redundant with other cytosol annotations differing only by Reactome reference.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2574845 		ACCEPT
Summary: Cytosol localization from Reactome (AURKA pathway reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-3000310 		ACCEPT
Summary: Cytosol localization from Reactome (AURKA/PLK1 reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-3000319 		ACCEPT
Summary: Cytosol localization from Reactome (BORA/PLK1/AURKA reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380272 		ACCEPT
Summary: Cytosol localization from Reactome (centrosome maturation reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380283 		ACCEPT
Summary: Cytosol localization from Reactome (gamma-TuRC recruitment reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380294 		ACCEPT
Summary: Cytosol localization from Reactome (centrosome reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380303 		ACCEPT
Summary: Cytosol localization from Reactome (Nlp dissociation reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380311 		ACCEPT
Summary: Cytosol localization from Reactome (Plk1 recruitment reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380316 		ACCEPT
Summary: Cytosol localization from Reactome (NuMA/microtubule reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380455 		ACCEPT
Summary: Cytosol localization from Reactome (CDK11p58 recruitment reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380508 		ACCEPT
Summary: Cytosol localization from Reactome (NuMA translocation reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5617816 		ACCEPT
Summary: Cytosol localization from Reactome (RAB3IP/RAB8A reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626220 		ACCEPT
Summary: Cytosol localization from Reactome (C2CD3 centriole reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626223 		ACCEPT
Summary: Cytosol localization from Reactome (distal appendage protein reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626227 		ACCEPT
Summary: Cytosol localization from Reactome (CP110/CEP97 dissociation reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626228 		ACCEPT
Summary: Cytosol localization from Reactome (TTBK2 recruitment reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626681 		ACCEPT
Summary: Cytosol localization from Reactome (transition zone protein reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626699 		ACCEPT
Summary: Cytosol localization from Reactome (MARK4/ODF2 reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5638009 		ACCEPT
Summary: Cytosol localization from Reactome (CEP164/RAB3IP vesicle reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-6791223 		ACCEPT
Summary: Cytosol localization from Reactome (pre-40S rRNA processing reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853405 		ACCEPT
Summary: Cytosol localization from Reactome (TPX2/AURKA reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853419 		ACCEPT
Summary: Cytosol localization from Reactome (TPX2/AURKA autophosphorylation reaction). Redundant but correct CC term.
Reason: Cytosol is a genuine location; redundant Reactome citation.
GO:0005794 Golgi apparatus
IDA
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Go... 		ACCEPT
Summary: Direct demonstration of CK1delta association with post-Golgi structures.
Reason: Direct IDA evidence; concordant with the Golgi/secretory role.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005813 centrosome
IDA
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate... 		ACCEPT
Summary: Direct demonstration of centrosomal localization, functionally required for Wnt-3a-dependent neurite outgrowth.
Reason: Direct IDA evidence; a functionally important location.
Supporting Evidence:
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
GO:0005819 spindle
IDA
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Go... 		ACCEPT
Summary: Direct demonstration of CK1delta localization at the spindle apparatus.
Reason: Direct IDA evidence.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005876 spindle microtubule
IDA
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Go... 		ACCEPT
Summary: Direct demonstration of CK1delta localization at spindle microtubules.
Reason: Direct IDA evidence.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005886 plasma membrane
IDA
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle f... 		ACCEPT
Summary: Direct demonstration of plasma membrane localization in trophoblast cells.
Reason: Direct IDA evidence consistent with the cell membrane annotation.
Supporting Evidence:
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
GO:0048471 perinuclear region of cytoplasm
IDA
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle f... 		ACCEPT
Summary: Direct demonstration of perinuclear localization.
Reason: Direct IDA evidence.
Supporting Evidence:
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
GO:0051225 spindle assembly
IDA
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Go... 		KEEP AS NON CORE
Summary: CK1delta associates with the spindle apparatus; functional involvement in spindle formation is supported by inhibitor studies in trophoblasts.
Reason: Supported experimentally but a context-specific (mitotic) role, not the core function.
Supporting Evidence:
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6791223 		ACCEPT
Summary: Nucleoplasm localization from Reactome (pre-rRNA processing reaction); consistent with documented nuclear localization.
Reason: Consistent with nuclear localization of CK1delta.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0005813 centrosome
IDA
PMID:21399614
Novel asymmetrically localizing components of human centroso... 		ACCEPT
Summary: Centrosome localization from a proteomic study of asymmetrically localizing centrosome components.
Reason: Direct evidence corroborating the well-established centrosomal location.
Supporting Evidence:
PMID:21399614
Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods.
GO:0090263 positive regulation of canonical Wnt signaling pathway
IMP
PMID:20412773
The Hippo pathway regulates Wnt/beta-catenin signaling. 		ACCEPT
Summary: Loss/gain-of-function evidence linking CK1 to canonical Wnt/beta-catenin signaling in the context of Hippo-Wnt crosstalk (CK1delta/epsilon-mediated DVL phosphorylation).
Reason: Supported by IMP evidence; a core signaling role of CK1delta.
Supporting Evidence:
PMID:20412773
The Hippo pathway regulates Wnt/beta-catenin signaling.
GO:0005634 nucleus
ISS
GO_REF:0000024 		ACCEPT
Summary: Nuclear localization inferred by sequence similarity from mouse ortholog; concordant with the experimentally and UniProt-documented nuclear location.
Reason: Consistent with documented nuclear localization.
Supporting Evidence:
file:human/CSNK1D/CSNK1D-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
GO:0004672 protein kinase activity
IDA
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective... 		MODIFY
Summary: Generic protein kinase activity from a direct assay. Correct but superseded by the specific serine/threonine kinase term.
Reason: Too general; CK1delta is specifically a serine/threonine kinase.
GO:0005515 protein binding
IPI
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective... 		MARK AS OVER ANNOTATED
Summary: Protein binding evidenced by interaction with DBNDD2/CK1BP (Q9BQY9), an isoform-selective binding partner. Bare term is uninformative.
Reason: Uninformative MF term; the specific DBNDD2 interaction is documented in UniProt but the bare "protein binding" conveys no function.
GO:0006468 protein phosphorylation
IDA
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective... 		ACCEPT
Summary: Protein phosphorylation as a biological process, directly demonstrated; this is the core enzymatic activity of CK1delta expressed as a BP.
Reason: Core process directly supported; CK1delta phosphorylates numerous protein substrates.
Supporting Evidence:
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: ISS transfer (from mouse ortholog) of a role in promoting proteasomal degradation; supported in human by YAP1/MDM2 degron phosphorylation.
Reason: A genuine substrate-driven downstream effect (degron priming), not a core function.
Supporting Evidence:
PMID:20708156
Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.
GO:0032922 circadian regulation of gene expression
ISS
GO_REF:0000024 		ACCEPT
Summary: ISS transfer of circadian regulation of gene expression. CK1delta controls PER stability/nuclear entry and thus the transcriptional clock; a core role.
Reason: Core circadian function; CK1delta regulates PER-mediated transcriptional feedback.
Supporting Evidence:
PMID:23636092
Casein kinase idelta mutations in familial migraine and advanced sleep phase.
GO:0042752 regulation of circadian rhythm
ISS
GO_REF:0000024 		ACCEPT
Summary: ISS transfer of regulation of circadian rhythm; a hallmark, disease-linked role of CK1delta.
Reason: Core biological process supported by PER phosphorylation and FASPS2/migraine variants.
Supporting Evidence:
PMID:23636092
Casein kinase idelta mutations in familial migraine and advanced sleep phase.
GO:0004672 protein kinase activity
TAS
PMID:8786104
Sequence analysis of the cDNA for the human casein kinase I ... 		MODIFY
Summary: Generic protein kinase activity from the original CSNK1D cDNA characterization. Correct but superseded by the specific serine/threonine kinase term.
Reason: Too general; CK1delta is specifically a serine/threonine kinase.

Core Functions

Constitutively active protein serine/threonine kinase (ATP- and Mg2+-dependent) that phosphorylates a broad range of substrates, including via primed (phospho-directed) and unprimed mechanisms.

Molecular Function:
protein serine/threonine kinase activity
Supporting Evidence:
  • PMID:10606744
    Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15.

Phosphorylates PER1 and PER2 to control their stability and nuclear transport, acting as a central component of the circadian clock that sets period length; loss-of-function variants cause familial advanced sleep phase syndrome and migraine.

Molecular Function:
protein serine/threonine kinase activity
Directly Involved In:
regulation of circadian rhythm circadian regulation of gene expression
Supporting Evidence:
  • PMID:23636092
    Casein kinase idelta mutations in familial migraine and advanced sleep phase.

Phosphorylates Dishevelled (DVL2/DVL3) and other components to regulate canonical Wnt/beta-catenin signaling and Wnt-3a-dependent neurite outgrowth.

Molecular Function:
protein serine/threonine kinase activity
Directly Involved In:
positive regulation of canonical Wnt signaling pathway
Supporting Evidence:
  • PMID:21422228
    Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.

Acts at the centrosome and Golgi (anchored via AKAP9/AKAP450) to promote microtubule nucleation, Golgi organization and primary (non-motile) ciliogenesis.

Molecular Function:
protein serine/threonine kinase activity
Directly Involved In:
non-motile cilium assembly Golgi organization microtubule nucleation
Supporting Evidence:
  • PMID:24648492
    Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000003
Gene Ontology annotation based on Enzyme Commission mapping
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000116
Automatic Gene Ontology annotation based on Rhea mapping
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10606744
Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15.
PMID:10826492
Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus.
PMID:12270943
Casein kinase 1 regulates connexin-43 gap junction assembly.
PMID:14761950
Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
PMID:16027726
Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
PMID:16189514
Towards a proteome-scale map of the human protein-protein interaction network.
PMID:16618118
Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.
PMID:17562708
Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis.
PMID:17962809
Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2.
PMID:19043076
Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity.
PMID:19591487
3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta.
PMID:20041275
Isoform specific phosphorylation of p53 by protein kinase CK1.
PMID:20048001
A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).
PMID:20412773
The Hippo pathway regulates Wnt/beta-catenin signaling.
PMID:20637175
Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity.
PMID:20699359
Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
PMID:20708156
Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.
PMID:21084295
Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6.
PMID:21179498
High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIα as a clock regulatory kinase.
PMID:21399614
Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods.
PMID:21422228
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
PMID:22609948
Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated primary cilia disassembly pathway.
PMID:23636092
Casein kinase iδ mutations in familial migraine and advanced sleep phase.
PMID:24648492
Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:25468996
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
PMID:25500533
Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7.
PMID:29257953
Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32707033
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:36931259
A central chaperone-like role for 14-3-3 proteins in human cells.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
PMID:8786104
Sequence analysis of the cDNA for the human casein kinase I delta (CSNK1D) gene and its chromosomal localization.
Reactome:R-HSA-204005
COPII-mediated vesicle transport
Reactome:R-HSA-2574840
AJUBA facilitates AURKA autophosphorylation
Reactome:R-HSA-2574845
AJUBA binds centrosome-associated AURKA
Reactome:R-HSA-3000310
AURKA phosphorylates PLK1
Reactome:R-HSA-3000319
BORA binds PLK1 and AURKA
Reactome:R-HSA-380272
Plk1-mediated phosphorylation of Nlp
Reactome:R-HSA-380283
Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome
Reactome:R-HSA-380294
Loss of C-Nap-1 from centrosomes
Reactome:R-HSA-380303
Dissociation of Phospho-Nlp from the centrosome
Reactome:R-HSA-380311
Recruitment of Plk1 to centrosomes
Reactome:R-HSA-380316
Association of NuMA with microtubules
Reactome:R-HSA-380455
Recruitment of CDK11p58 to the centrosomes
Reactome:R-HSA-380508
Translocation of NuMA to the centrosomes
Reactome:R-HSA-5617816
RAB3IP stimulates nucleotide exchange on RAB8A
Reactome:R-HSA-5626220
C2CD3 binds the mother centriole
Reactome:R-HSA-5626223
C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole
Reactome:R-HSA-5626227
CP110 and CEP97 dissociate from the centriole
Reactome:R-HSA-5626228
The distal appendage proteins recruit TTBK2
Reactome:R-HSA-5626681
Recruitment of transition zone proteins
Reactome:R-HSA-5626699
MARK4 binds ODF2 in the centriole
Reactome:R-HSA-5638009
CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
Reactome:R-HSA-5694441
CSNK1D phosphorylates SEC23
Reactome:R-HSA-6791223
18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation from the nucleus to the cytosol
Reactome:R-HSA-8853405
TPX2 binds AURKA at centrosomes
Reactome:R-HSA-8853419
TPX2 promotes AURKA autophosphorylation

Suggested Questions for Experts

Q: Which CK1delta substrates and biological roles are truly delta-specific versus shared with the highly similar CK1epsilon, given their frequent co-redundancy?

Q: To what extent are the many in vitro substrate phosphorylations (e.g. DCK, eIF6, TOP2A) physiologically relevant in vivo, as opposed to reflecting CK1delta's broad acidic-substrate preference?

Suggested Experiments

Experiment: Acute, isoform-selective degradation (e.g. dTAG/AID) of CK1delta versus CK1epsilon followed by phosphoproteomics to define the delta-specific substrate repertoire and disentangle redundancy.

Experiment: Structure-guided separation-of-function CSNK1D alleles (catalytic-dead vs centrosomal-localization-deficient) in human cells and mice to dissect the kinase-dependent versus scaffolding contributions to ciliogenesis and circadian period.

📚 Additional Documentation

Notes

(CSNK1D-notes.md)

CSNK1D (Casein kinase I isoform delta, CK1δ) review notes

UniProt: P48730 (KC1D_HUMAN). 415 aa. EC 2.7.11.1 (protein Ser/Thr kinase) and EC 2.7.11.26 (tau-protein kinase). HGNC: CSNK1D. Chr 17q25.3.

Summary of biology

CK1δ is a constitutively active, monomeric (PubMed:22168824, PubMed:23106386) serine/threonine
protein kinase of the casein kinase 1 (CK1) family. It uses ATP and is magnesium-dependent
(catalytic mechanism shared by the CK1 family). It is a "casein kinase" operationally defined by
preferential phosphorylation of acidic substrates, and characteristically performs both primed
(phospho-directed) and unprimed phosphorylation. Activity is autoinhibited by C-terminal
autophosphorylation (a "futile cycle") and reactivated by phosphatases (PP1) [UniProt PTM;
PMID:9632646].

Core molecular function

  • Protein-serine/threonine kinase activity (ATP binding). Directly demonstrated in vitro for
    many substrates [PMID:10606744 p53/TP53 Thr18; PMID:20041275 p53 S20; PMID:12270943 connexin-43/GJA1;
    PMID:14761950 + PMID:17562708 MAPT/tau; PMID:19043076 TOP2A Ser-1106; PMID:20637175 DCK Ser-74;
    PMID:20699359 HIF-1α Ser247; PMID:21084295 eIF6 Ser174/175; PMID:21422228 DVL2/DVL3;
    PMID:17962809 PKD2 Ser244; PMID:20048001 YAP1 phosphodegron; PMID:23636092 PER2 peptide]. This is
    the unambiguous core function and is supported by EXP/IDA evidence and abundant structural data
    (>30 PDB entries).
  • Tau-protein kinase activity (GO:0050321) is a valid, more specific MF directly shown
    [PMID:14761950 "Casein kinase 1 delta phosphorylates tau"; PMID:17562708 novel tau sites].

Core biological processes

  • Circadian rhythm / regulation of circadian rhythm (GO:0042752; GO:0032922 circadian regulation
    of gene expression)    . CK1δ phosphorylates PER1/PER2, controlling their stability, nuclear entry
    and thus the clock period. FASPS2 (familial advanced sleep phase) and familial migraine are caused
    by CSNK1D missense variants (T44A, H46R) that reduce kinase activity [PMID:23636092; PMID:15800623].
    This is a hallmark, well-established physiological role. Interacts directly with PER1/PER2
    [PubMed:11165242].
  • Wnt signaling (regulation of Wnt signaling pathway; canonical Wnt). CK1δ phosphorylates DVL2/DVL3
    to mediate Wnt-3a-dependent neurite outgrowth PMID:21422228. Hippo-Wnt crosstalk: TAZ inhibits
    CK1δ/ε-mediated DVL phosphorylation [PMID:20412773 — note this is a Hippo→Wnt paper where CK1δ acts
    on DVL]. CK1 family broadly phosphorylates LRP6, APC, β-catenin in canonical Wnt (family-level,
    largely from orthologs/IBA).
  • Centrosome / ciliogenesis / Golgi / microtubules. CK1δ localizes to the centrosome (anchored via
    AKAP9/AKAP450 [PubMed:12270714]) and Golgi; required for primary (non-motile) ciliogenesis, Golgi-derived
    microtubule nucleation and Golgi organization [PMID:24648492 IMP for GO:0007020 microtubule nucleation,
    GO:0034067 protein localization to Golgi, GO:0007030 Golgi organization, GO:0061512 protein localization
    to cilium, GO:0071539 protein localization to centrosome, GO:1905515 non-motile cilium assembly].
    Localizes to spindle/spindle microtubules upon DNA damage; involved in mitotic spindle formation in
    trophoblasts [PMID:10826492; PMID:16027726].

Substrate-driven roles (real but mostly non-core / downstream of kinase activity)

Many BP annotations are transferred from individual substrate phosphorylation events:
- p53/MDM2: phosphorylates p53 Thr18/S20 and promotes MDM2 turnover via SCF(β-TRCP) [PMID:10606744;
PMID:20041275; PMID:20708156]. Linked to GO:0032436 positive regulation of proteasomal ubiquitin-
dependent protein catabolic process (YAP1, MDM2 degron priming).
- HIF-1α regulation PMID:20699359; TOP2A/DNA cleavage PMID:19043076; DCK activation (in vitro only,
CAUTION: probably not in vivo per UniProt) PMID:20637175; eIF6 nucleo-cytoplasmic shuttling
PMID:21084295; PKD2 nuclear localization PMID:17962809; YAP1 stability/Hippo PMID:20048001;
connexin-43 gap junction assembly PMID:12270943.

Subcellular location

Cytoplasm, nucleus, centrosome (MOC), perinuclear region, cell/plasma membrane, spindle/spindle
microtubule, Golgi apparatus, cytosol, ciliary basal body (GO:0036064 IDA PMID:29257953), ERGIC
membrane (Reactome). Correct localization requires kinase activity [PubMed:11161704].

Annotation-review reasoning highlights

  • protein binding (GO:0005515, IPI x many): bare "protein binding" is uninformative →
    MARK_AS_OVER_ANNOTATED. Several partners are biologically meaningful (PER2 O15055; DVL3/Q92997;
    MDM2 Q00987; YWHAE/14-3-3ε P62258) but the term itself conveys no function. Real binding functions
    (PER, DVL) are captured better elsewhere via the kinase/circadian/Wnt annotations.
  • cadherin binding (GO:0045296, HDA PMID:25468996): high-throughput E-cadherin interactome
    proximity dataset; CK1δ is not an established cadherin-binding adaptor → MARK_AS_OVER_ANNOTATED.
  • Many GO:0005829 cytosol TAS Reactome annotations point at numerous centrosome/ciliogenesis
    reactions; cytosol localization is correct but each is a separate Reactome reaction citation →
    ACCEPT location (cytosol is a true location) but redundant; keep representative as ACCEPT.
  • COPII vesicle coat assembly (GO:0048208 TAS Reactome R-HSA-204005) / CSNK1D phosphorylates SEC23
    (R-HSA-5694441)    : CK1δ phosphorylates SEC23A in COPII vesicle formation (Reactome). Real but a
    narrow substrate-driven role → KEEP_AS_NON_CORE.
  • endocytosis (GO:0006897 IBA): transferred from yeast CK1 orthologs (Yck1/Yck2, SGD) — these
    yeast paralogs regulate endocytosis, but human CK1δ has no direct experimental support for endocytosis
    → MARK_AS_OVER_ANNOTATED (over-transfer from distant paralogs).
  • midbrain dopaminergic neuron differentiation (GO:1904948 ISS) / positive regulation of non-canonical
    Wnt (GO:2000052 ISS)    : ISS from mouse ortholog Q9DC28 (ParkinsonsUK-UCL). Plausible developmental/
    pleiotropic roles but not core → KEEP_AS_NON_CORE.
  • DCK (PMID:20637175): UniProt CAUTION says in vitro only, probably not in vivo. Still supports the
    MF (protein serine kinase activity) since phosphorylation was directly demonstrated → ACCEPT for MF.

Provenance for key claims

  • Monomer, constitutively active: PubMed:22168824, PubMed:23106386; UniProt SUBUNIT.
  • FASPS2 disease & migraine, reduced kinase activity of T44A/H46R: PMID:23636092, [PMID:15800623 FASPS2 A44].
  • Autoinhibition by autophosphorylation: UniProt PTM; PMID:9632646.
  • Ciliogenesis mechanism: PMID:24648492.

Caveat on PMID:25500533 (GO:0004674 IDA)

PMID:25500533 (Chia et al.) is primarily about CK1α/CSNK1A1, identified by a kinome siRNA screen as
the kinase responsible for constitutive LRRK2 phosphorylation at S910/S935. For CK1δ specifically, the
paper reports only that "CK1δ/ε and CK1γ isoforms could moderately phosphorylate S955 and S935 in vitro"
[PMID:25500533, Suppl. Fig. 5c,d]. So this paper does support that CK1δ has protein Ser/Thr kinase
activity in vitro, but the headline physiological LRRK2-Golgi finding is a CK1α function, not CK1δ. The
GO:0004674 IDA annotation on CSNK1D from this reference is therefore retained as ACCEPT for the generic
MF (it does show in-vitro Ser/Thr kinase activity of CK1δ) but is weak; the LRRK2-specific biology should
not be over-transferred to CK1δ.

Reactome cytosol/centrosome reactions (GO:0005829 TAS x many)

The ~25 GO:0005829 cytosol TAS annotations each cite a distinct Reactome reaction (centrosome maturation,
ciliogenesis, rRNA processing, AURKA/PLK1 cascades). Cytosol is a genuine CK1δ location, so the location
term is correct, but the long list is redundant Reactome pathway-membership inflation. Keep one
representative as ACCEPT (core cytosolic kinase); mark the remainder ACCEPT as well since the CC term
itself is not wrong (they differ only by reference, not by term).

Pn Notes

(CSNK1D-pn-notes.md)

CSNK1D PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: P48730
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: Casein kinase I isoform delta (CK1delta) is a constitutively active, monomeric serine/threonine protein kinase of the casein kinase 1 (CK1) family. It uses ATP and is magnesium-dependent, and is operationally defined as a "casein kinase" by its preference for acidic substrates; it performs both primed (phospho-directed) and unprimed phosphorylation. Its activity is autoinhibited by C-terminal autophosphorylation and reactivated by phosphatase (PP1)-mediated dephosphorylation. CK1delta is a central component of the circadian clock, phosphorylating PERIOD proteins PER1 and PER2 to control their stability and nuclear entry and thereby set circadian period; missense variants (e.g. T44A, H46R) reduce kinase activity and cause familial advanced sleep phase syndrome and familial migraine. CK1delta also phosphorylates Dishevelled (DVL2/DVL3) and other components to modulate Wnt/beta-catenin signaling, acts at the centrosome and Golgi to promote microtubule nucleation, Golgi organization and primary (non-motile) ciliogenesis, and regulates the mitotic spindle. It phosphorylates a large and diverse set of additional substrates including p53/TP53, MDM2, YAP1, HIF1A, TOP2A, connexin-43/GJA1, PKD2, eIF6, DCK and tau/MAPT, linking it to DNA-damage responses, Hippo signaling, vesicle trafficking and (via tau hyperphosphorylation) neurodegeneration. It localizes to the cytoplasm/cytosol, nucleus, centrosome, perinuclear region, spindle and spindle microtubules, Golgi apparatus, ciliary basal body and plasma membrane, with correct localization dependent on kinase activity.
  • Existing/core annotation action counts: ACCEPT: 80; KEEP_AS_NON_CORE: 11; MARK_AS_OVER_ANNOTATED: 15; MODIFY: 5

PN Consistency Summary

  • Consistency: GAP. The review treats CK1δ's COPII/SEC23 phosphorylation (Reactome GO:0048208 COPII vesicle coat assembly; R-HSA-5694441) as a generic, non-core secretory role and has NO autophagy annotation — it never mentions RAB1-directed autophagosome closure or COPII-regulated autophagophore membrane input. The PN frames the SAME COPII/RAB1 biology as autophagy-directed (RAB1 effector → phosphorylates COPII coat → autophagosome closure), citing CK1δ/Hrr25 autophagosome-completion papers absent from the review. So review and PN are not contradictory but interpret overlapping evidence (Golgi/COPII/RAB1) in different pathways; the autophagy reading is under-captured in the review.
  • PN story / NEW pressure: PN asserts an autophagosome-closure/sealing role not in existing GO or the review. GO:0000045 "autophagosome assembly" verified real (OLS) and confirmed new_to_goa (no autophagy term in CSNK1D-goa.tsv). Defensible ADD if the Hrr25/CK1δ autophagosome-completion literature (Frontiers/JCB titles in PN row) holds for human CK1δ — but PN supplies only article titles, not verified PMIDs; much of the primary evidence is yeast Hrr25. Treat as defensible-but-needs-PMID-verification.
  • Evidence alignment: No overlap. PN cites autophagosome-closure review + Ypt1/Rab1-Hrr25 JCB + CK1δ/Hrr25 autophagosome-completion Frontiers (titles only). Review cites COPII via Reactome (R-HSA-204005, R-HSA-5694441) only, framed as secretory. The autophagy PMIDs are missing from the review.
  • Verdict: UNDER-CAPTURED autophagy role; PN ADD (GO:0000045) plausible but PMID-unverified. Recommended edits: [REF] resolve the PN row's title-only citations to PMIDs and confirm human (not just yeast Hrr25) evidence; [YAML] if confirmed, add GO:0000045 (involved_in) and reframe the SEC23/COPII annotations to note an autophagosome-membrane-input role alongside secretion.

Full Consistency Review

  • UniProt: P48730 · batch: proteostasis-batch-2026-06-07 · review status: COMPLETE
  • PN placement: row1 ALP|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ER membrane input|COPII vesicle component regulator; row2 ALP|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|...unknown ; PN-node mapping: Sealing group→GO:0000045 autophagosome assembly (new_to_goa); all other ALP nodes no_mapping; ALP class context_only→GO:0016236.
  • Consistency: GAP. The review treats CK1δ's COPII/SEC23 phosphorylation (Reactome GO:0048208 COPII vesicle coat assembly; R-HSA-5694441) as a generic, non-core secretory role and has NO autophagy annotation — it never mentions RAB1-directed autophagosome closure or COPII-regulated autophagophore membrane input. The PN frames the SAME COPII/RAB1 biology as autophagy-directed (RAB1 effector → phosphorylates COPII coat → autophagosome closure), citing CK1δ/Hrr25 autophagosome-completion papers absent from the review. So review and PN are not contradictory but interpret overlapping evidence (Golgi/COPII/RAB1) in different pathways; the autophagy reading is under-captured in the review.
  • PN story / NEW pressure: PN asserts an autophagosome-closure/sealing role not in existing GO or the review. GO:0000045 "autophagosome assembly" verified real (OLS) and confirmed new_to_goa (no autophagy term in CSNK1D-goa.tsv). Defensible ADD if the Hrr25/CK1δ autophagosome-completion literature (Frontiers/JCB titles in PN row) holds for human CK1δ — but PN supplies only article titles, not verified PMIDs; much of the primary evidence is yeast Hrr25. Treat as defensible-but-needs-PMID-verification.
  • Mapping strategy: GO:0000045 from the "Sealing of autophagophore membrane" group is appropriately specific (assembly, not autophagosome-lysosome fusion); the "unknown" leaf and COPII-regulator leaf are correctly no_mapping. Reasonable; not over-broad.
  • Evidence alignment: No overlap. PN cites autophagosome-closure review + Ypt1/Rab1-Hrr25 JCB + CK1δ/Hrr25 autophagosome-completion Frontiers (titles only). Review cites COPII via Reactome (R-HSA-204005, R-HSA-5694441) only, framed as secretory. The autophagy PMIDs are missing from the review.
  • Verdict: UNDER-CAPTURED autophagy role; PN ADD (GO:0000045) plausible but PMID-unverified. Recommended edits: [REF] resolve the PN row's title-only citations to PMIDs and confirm human (not just yeast Hrr25) evidence; [YAML] if confirmed, add GO:0000045 (involved_in) and reframe the SEC23/COPII annotations to note an autophagosome-membrane-input role alongside secretion.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07
  • review_yaml: genes/human/CSNK1D/CSNK1D-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Regulation of autophagophore membrane composition | ER membrane input | COPII vesicle component regulator

  • UniProt: P48730
  • In branches: ALP
  • Notes: RAB1 effector that is directed to autophagosomes by RAB1, then phosphorylates the COPII coat to promote autophagy. Important for autophagosome closure.
  • PN references (titles):
    • Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
    • Ypt1/Rab1 regulates Hrr25/CK1δ kinase activity in ER–Golgi traffic and macroautophagy | Journal of Cell Biology | Rockefeller University Press (rupress.org)
    • Frontiers | Casein Kinase 1 Family Member CK1δ/Hrr25 Is Required for Autophagosome Completion | Cell and Developmental Biology (frontiersin.org)
  • PN-node mapping records (path + ancestors):
    • [subtype] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ER membrane input|COPII vesicle component regulator
      status=no_mapping scope= GO=[]
      rationale: This PN leaf groups upstream regulators of COPII contribution to autophagophore membrane input. The two-member set does not support one crisp shared GO term beyond broad vesicle-coating or kinase context.
    • [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition|ER membrane input
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
    • [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Regulation of autophagophore membrane composition
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Specific function in sealing of autophagophore membrane unknown

  • UniProt: P48730
  • In branches: ALP
  • Notes: RAB1 effector that is directed to autophagosomes by RAB1, then phosphorylates the COPII coat to promote autophagy. Important for autophagosome closure.
  • PN references (titles):
    • Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
    • Ypt1/Rab1 regulates Hrr25/CK1δ kinase activity in ER–Golgi traffic and macroautophagy | Journal of Cell Biology | Rockefeller University Press (rupress.org)
    • Frontiers | Casein Kinase 1 Family Member CK1δ/Hrr25 Is Required for Autophagosome Completion | Cell and Developmental Biology (frontiersin.org)
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Specific function in sealing of autophagophore membrane unknown
      status=no_mapping scope= GO=[]
      rationale: This PN leaf is explicitly an unknown-function residual bucket and does not support a defensible shared GO mapping.
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
      rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: P48730
gene_symbol: CSNK1D
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Casein kinase I isoform delta (CK1delta) is a constitutively active,
  monomeric serine/threonine protein kinase of the casein kinase 1 (CK1) family. It
  uses ATP and is magnesium-dependent, and is operationally defined as a "casein kinase"
  by its preference for acidic substrates; it performs both primed (phospho-directed)
  and unprimed phosphorylation. Its activity is autoinhibited by C-terminal autophosphorylation
  and reactivated by phosphatase (PP1)-mediated dephosphorylation. CK1delta is a central
  component of the circadian clock, phosphorylating PERIOD proteins PER1 and PER2 to
  control their stability and nuclear entry and thereby set circadian period; missense
  variants (e.g. T44A, H46R) reduce kinase activity and cause familial advanced sleep
  phase syndrome and familial migraine. CK1delta also phosphorylates Dishevelled (DVL2/DVL3)
  and other components to modulate Wnt/beta-catenin signaling, acts at the centrosome
  and Golgi to promote microtubule nucleation, Golgi organization and primary (non-motile)
  ciliogenesis, and regulates the mitotic spindle. It phosphorylates a large and diverse
  set of additional substrates including p53/TP53, MDM2, YAP1, HIF1A, TOP2A, connexin-43/GJA1,
  PKD2, eIF6, DCK and tau/MAPT, linking it to DNA-damage responses, Hippo signaling,
  vesicle trafficking and (via tau hyperphosphorylation) neurodegeneration. It localizes
  to the cytoplasm/cytosol, nucleus, centrosome, perinuclear region, spindle and spindle
  microtubules, Golgi apparatus, ciliary basal body and plasma membrane, with correct
  localization dependent on kinase activity.
alternative_products:
- name: '1'
  id: P48730-1
- name: '2'
  id: P48730-2
  sequence_note: VSP_010253
existing_annotations:
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) transfer of spindle microtubule localization. CK1delta
      does localize to spindle microtubules upon DNA damage by direct experimental
      evidence, so this CC term is supported.
    action: ACCEPT
    reason: Consistent with experimental IDA evidence (PMID:10826492) showing CK1delta
      localization at spindle microtubules; a genuine, if context-dependent (DNA-damage),
      location.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic
      process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of a role in promoting proteasomal degradation. CK1delta
      phosphorylates phosphodegrons that prime substrates (YAP1, MDM2) for SCF(beta-TRCP)-mediated
      ubiquitination and degradation, so the process is real but is a downstream,
      substrate-driven consequence of kinase activity rather than a core function.
    action: KEEP_AS_NON_CORE
    reason: Supported by experimental data on YAP1 and MDM2 degron phosphorylation,
      but this is one of many substrate-specific downstream effects rather than the
      gene's core function.
    supported_by:
    - reference_id: PMID:20048001
      supporting_text: A coordinated phosphorylation by Lats and CK1 regulates YAP
        stability through SCF(beta-TRCP).
    - reference_id: PMID:20708156
      supporting_text: Phosphorylation by casein kinase I promotes the turnover of
        the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.
- term:
    id: GO:0042752
    label: regulation of circadian rhythm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of regulation of circadian rhythm. This is a hallmark, well-established
      physiological role of CK1delta via PER1/PER2 phosphorylation; disease variants
      cause familial advanced sleep phase.
    action: ACCEPT
    reason: Core biological process; strongly supported by direct interaction with
      and phosphorylation of PER1/PER2 and by FASPS2/migraine disease variants.
    supported_by:
    - reference_id: PMID:23636092
      supporting_text: Casein kinase idelta mutations in familial migraine and advanced
        sleep phase.
- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of a spindle assembly role. CK1delta is recruited to the
      spindle/centrosome and its inhibition alters mitotic spindle formation, so the
      process has direct experimental support.
    action: KEEP_AS_NON_CORE
    reason: Supported experimentally (PMID:10826492, PMID:16027726) but represents
      a context-specific (mitotic/trophoblast) role rather than the core kinase/circadian
      function.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of positive regulation of canonical Wnt signaling. CK1delta/CK1
      phosphorylates DVL2/DVL3 and other Wnt components; a well-supported signaling
      role of the gene.
    action: ACCEPT
    reason: Core signaling process supported by experimental data on DVL phosphorylation
      and Wnt-3a-dependent neurite outgrowth.
    supported_by:
    - reference_id: PMID:21422228
      supporting_text: Casein kinase 1 delta functions at the centrosome to mediate
        Wnt-3a-dependent neurite outgrowth.
- term:
    id: GO:1905515
    label: non-motile cilium assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of a primary (non-motile) cilium assembly role, also directly
      demonstrated by loss-of-function in human RPE cells and Csnk1d-null mouse cells.
    action: ACCEPT
    reason: Supported by direct IMP evidence (PMID:24648492) that CK1delta is required
      for primary ciliogenesis; a well-established cell-biological role.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: Casein kinase 1delta functions at the centrosome and Golgi
        to promote ciliogenesis.
- term:
    id: GO:0006897
    label: endocytosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA transfer of an endocytosis role, derived largely from distant yeast
      CK1 paralogs (Yck1/Yck2, SGD). Human CK1delta has no direct experimental support
      for a role in endocytosis.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-transfer from divergent fungal paralogs; the WITH/FROM evidence (SGD:S000001177,
      SGD:S000005098) is from yeast CK1 enzymes whose endocytic role is not established
      for human CK1delta.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of generic protein kinase activity. Correct but
      superseded by the more specific protein serine/threonine kinase activity, which
      is experimentally established.
    action: MODIFY
    reason: Term is correct but too general; CK1delta is specifically a serine/threonine
      kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: Electronic (EC-based) annotation of protein serine/threonine kinase activity.
      This is the core molecular function, directly demonstrated for many substrates.
    action: ACCEPT
    reason: Core molecular function, abundantly supported by experimental (EXP/IDA)
      evidence and structural data.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: EC=2.7.11.1 {ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:17562708,
        ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:21422228,
        ECO:0000269|PubMed:23636092};
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding is a core feature of this ATP-dependent kinase, supported
      by numerous co-crystal structures with ATP-competitive inhibitors bound in the
      ATP pocket.
    action: ACCEPT
    reason: Essential for catalysis; supported by InterPro kinase domain signatures
      and over 30 PDB structures of the ATP-binding site.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein
        kinase family. Casein kinase I subfamily.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization from UniProt subcellular location mapping. CK1delta
      shuttles to the nucleus where it acts on nuclear substrates (e.g. p53, PER nuclear
      transport).
    action: ACCEPT
    reason: Consistent with documented nuclear localization in UniProt and nuclear
      substrate biology.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization from UniProt mapping; CK1delta is predominantly
      cytoplasmic.
    action: ACCEPT
    reason: Well-supported primary location of this kinase.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Golgi localization from UniProt mapping, also directly demonstrated; CK1delta
      acts at the Golgi (with AKAP450) for microtubule nucleation and ciliogenesis.
    action: ACCEPT
    reason: Supported by experimental IDA (PMID:10826492) and functional ciliogenesis
      data (PMID:24648492).
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Centrosome localization from UniProt mapping, directly demonstrated and
      functionally important; CK1delta is anchored at the centrosome via AKAP9/AKAP450.
    action: ACCEPT
    reason: Strongly supported by experimental IDA evidence and a defined centrosomal
      localization signal required for ciliogenesis.
    supported_by:
    - reference_id: PMID:21422228
      supporting_text: Casein kinase 1 delta functions at the centrosome to mediate
        Wnt-3a-dependent neurite outgrowth.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Spindle localization from UniProt mapping, also directly demonstrated
      (recruited to the spindle apparatus upon DNA damage).
    action: ACCEPT
    reason: Consistent with experimental IDA evidence (PMID:10826492).
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Plasma membrane localization from UniProt mapping; CK1delta is reported
      at the cell membrane, also supported by IDA and HPA.
    action: ACCEPT
    reason: Consistent with UniProt subcellular location and experimental evidence.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: Cell membrane.
- term:
    id: GO:0030111
    label: regulation of Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning annotation of Wnt signaling regulation. Generic
      but correct; captured more specifically by the canonical Wnt annotations.
    action: ACCEPT
    reason: A genuine, well-supported role of CK1delta in Wnt signaling (DVL phosphorylation).
    supported_by:
    - reference_id: PMID:21422228
      supporting_text: Casein kinase 1 delta functions at the centrosome to mediate
        Wnt-3a-dependent neurite outgrowth.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Perinuclear region localization from UniProt mapping, also directly demonstrated.
    action: ACCEPT
    reason: Consistent with experimental IDA evidence (PMID:16027726).
    supported_by:
    - reference_id: PMID:16027726
      supporting_text: Inhibition of casein kinase I delta alters mitotic spindle formation
        and induces apoptosis in trophoblast cells.
- term:
    id: GO:0050321
    label: tau-protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Tau-protein kinase activity (EC 2.7.11.26), a specific molecular function
      of CK1delta directly demonstrated in vitro.
    action: ACCEPT
    reason: Experimentally established specific MF; CK1delta phosphorylates tau and
      disrupts microtubule binding.
    supported_by:
    - reference_id: PMID:14761950
      supporting_text: Casein kinase 1 delta phosphorylates tau and disrupts its binding
        to microtubules.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Rhea/EC-based electronic annotation of protein serine kinase activity,
      a core CK1delta function.
    action: ACCEPT
    reason: Core molecular function abundantly supported by experimental evidence.
    supported_by:
    - reference_id: PMID:14761950
      supporting_text: Casein kinase 1 delta phosphorylates tau and disrupts its binding
        to microtubules.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Generic protein binding from a high-throughput interactome (with DVL3).
      The term is uninformative about molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" conveys no specific function; relevant interactions
      (e.g. DVL3) are captured by the Wnt-signaling and kinase annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20708156
  qualifier: enables
  review:
    summary: Protein binding evidenced by interaction with MDM2 (Q00987). The MDM2
      interaction is functionally meaningful (phosphodegron priming) but the bare
      term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the functional MDM2 relationship is captured by
      the proteasomal degradation BP annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179498
  qualifier: enables
  review:
    summary: Protein binding evidenced by interaction with PER2 (O15055). Functionally
      central to circadian biology but the bare term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the PER2 interaction is captured by circadian regulation
      and kinase annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22609948
  qualifier: enables
  review:
    summary: Protein binding evidenced by interaction with mouse Dvl2 (Q60838). The
      bare term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the DVL2 relationship is captured by Wnt-signaling
      and cilium annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic protein binding from a proteome-scale interactome map (DVL3,
      LURAP1, TRIM9). Uninformative about function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput interactome; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein binding from a binary interactome reference map (multiple
      partners). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Generic protein binding from a kinase interaction network (GAPVD1). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Generic protein binding from a neurodegenerative-disease interactome (APP).
      Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding from a cell-specific interactome remodeling study
      (PER2, GAPVD1, ZNF618). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding from OpenCell endogenous-tagging interactome (GAPVD1).
      Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36931259
  qualifier: enables
  review:
    summary: Protein binding evidenced by interaction with 14-3-3 epsilon/YWHAE (P62258).
      Uninformative bare term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding"; no specific molecular function conveyed.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein binding from a multimodal cell-map study (PER2, GAPVD1).
      Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare "protein binding" from high-throughput screen; no specific function
      conveyed.
- term:
    id: GO:0048208
    label: COPII vesicle coat assembly
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-204005
  qualifier: involved_in
  review:
    summary: Reactome annotation linking CK1delta to COPII vesicle formation via SEC23
      phosphorylation. A narrow substrate-driven role.
    action: KEEP_AS_NON_CORE
    reason: Real but specialized substrate-driven role (CSNK1D phosphorylates SEC23,
      Reactome R-HSA-5694441); not a core function.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: Golgi apparatus.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694441
  qualifier: enables
  review:
    summary: Reactome (TAS) annotation of protein serine/threonine kinase activity
      in the context of SEC23 phosphorylation. Core MF.
    action: ACCEPT
    reason: Core molecular function, consistent with all experimental evidence.
    supported_by:
    - reference_id: PMID:10606744
      supporting_text: Protein kinase CK1 is a p53-threonine 18 kinase which requires
        prior phosphorylation of serine 15.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosol localization from immunofluorescence (HPA). CK1delta is a predominantly
      cytosolic kinase.
    action: ACCEPT
    reason: Direct IDA evidence for a genuine cytosolic location.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Plasma membrane localization from immunofluorescence (HPA), concordant
      with UniProt cell membrane annotation.
    action: ACCEPT
    reason: Direct IDA evidence consistent with documented cell membrane location.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: Cell membrane.
- term:
    id: GO:0050321
    label: tau-protein kinase activity
  evidence_type: EXP
  original_reference_id: PMID:14761950
  qualifier: enables
  review:
    summary: Direct experimental demonstration that CK1delta phosphorylates tau, a
      specific molecular function (EC 2.7.11.26).
    action: ACCEPT
    reason: Strong EXP evidence; CK1delta phosphorylates tau and disrupts its microtubule
      binding.
    supported_by:
    - reference_id: PMID:14761950
      supporting_text: Casein kinase 1 delta phosphorylates tau and disrupts its binding
        to microtubules.
- term:
    id: GO:0050321
    label: tau-protein kinase activity
  evidence_type: EXP
  original_reference_id: PMID:17562708
  qualifier: enables
  review:
    summary: Experimental support for tau-protein kinase activity; CK1 phosphorylates
      novel tau sites found in Alzheimer brain.
    action: ACCEPT
    reason: EXP evidence corroborating the specific tau-kinase MF.
    supported_by:
    - reference_id: PMID:17562708
      supporting_text: Novel phosphorylation sites in tau from Alzheimer brain support
        a role for casein kinase 1 in disease pathogenesis.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:14761950
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity (tau phosphorylation).
    action: ACCEPT
    reason: Core MF; strong EXP evidence.
    supported_by:
    - reference_id: PMID:14761950
      supporting_text: Casein kinase 1 delta phosphorylates tau and disrupts its binding
        to microtubules.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:17562708
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity (tau phosphorylation
      at novel sites).
    action: ACCEPT
    reason: Core MF; EXP evidence.
    supported_by:
    - reference_id: PMID:17562708
      supporting_text: Novel phosphorylation sites in tau from Alzheimer brain support
        a role for casein kinase 1 in disease pathogenesis.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:17962809
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via PKD2 Ser244
      phosphorylation.
    action: ACCEPT
    reason: Core MF; EXP evidence (PKD2 substrate).
    supported_by:
    - reference_id: PMID:17962809
      supporting_text: Phosphorylation at Ser244 by CK1 determines nuclear localization
        and substrate targeting of PKD2.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:19591487
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity in an inhibitor
      characterization study of CK1delta.
    action: ACCEPT
    reason: Core MF; EXP/inhibitor-based evidence of catalytic activity.
    supported_by:
    - reference_id: PMID:19591487
      supporting_text: 3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors
        of p38alpha mitogen activated protein kinase and casein kinase 1delta.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:20041275
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via isoform-specific
      p53 phosphorylation.
    action: ACCEPT
    reason: Core MF; EXP evidence (p53 substrate).
    supported_by:
    - reference_id: PMID:20041275
      supporting_text: Isoform specific phosphorylation of p53 by protein kinase CK1.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:20048001
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via YAP1 phosphodegron
      phosphorylation.
    action: ACCEPT
    reason: Core MF; EXP evidence (YAP1 substrate).
    supported_by:
    - reference_id: PMID:20048001
      supporting_text: A coordinated phosphorylation by Lats and CK1 regulates YAP
        stability through SCF(beta-TRCP).
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:20637175
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via DCK Ser-74
      phosphorylation (in vitro; per UniProt CAUTION, probably not physiological in
      vivo).
    action: ACCEPT
    reason: The MF is directly demonstrated in vitro; the caveat applies to the in
      vivo DCK regulation, not to the kinase activity itself.
    supported_by:
    - reference_id: PMID:20637175
      supporting_text: Casein kinase 1delta activates human recombinant deoxycytidine
        kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation
        of its activity.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:20699359
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via HIF-1alpha
      phosphorylation.
    action: ACCEPT
    reason: Core MF; EXP evidence (HIF-1 substrate).
    supported_by:
    - reference_id: PMID:20699359
      supporting_text: Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:21422228
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via DVL2/DVL3
      phosphorylation.
    action: ACCEPT
    reason: Core MF; EXP evidence (DVL substrates, Wnt signaling).
    supported_by:
    - reference_id: PMID:21422228
      supporting_text: Casein kinase 1 delta functions at the centrosome to mediate
        Wnt-3a-dependent neurite outgrowth.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:23636092
  qualifier: enables
  review:
    summary: Experimental support for protein serine kinase activity via PER2 peptide
      phosphorylation; FASPS2/migraine variants reduce activity.
    action: ACCEPT
    reason: Core MF; EXP evidence directly tied to circadian biology and disease.
    supported_by:
    - reference_id: PMID:23636092
      supporting_text: Casein kinase idelta mutations in familial migraine and advanced
        sleep phase.
- term:
    id: GO:1904948
    label: midbrain dopaminergic neuron differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer from the mouse ortholog (Q9DC28) of a role in midbrain dopaminergic
      neuron differentiation. Plausible developmental/pleiotropic role but not core
      and without direct human evidence.
    action: KEEP_AS_NON_CORE
    reason: Inferred by sequence similarity from mouse; a pleiotropic developmental
      role, not a core function.
- term:
    id: GO:2000052
    label: positive regulation of non-canonical Wnt signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer from mouse ortholog of a non-canonical Wnt role. CK1delta
      acts in Wnt signaling broadly; the non-canonical specificity is inferred.
    action: KEEP_AS_NON_CORE
    reason: Sequence-similarity-based; Wnt signaling involvement is supported overall,
      but the non-canonical-specific role is inferred rather than directly shown in
      human.
- term:
    id: GO:0050321
    label: tau-protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:16618118
  qualifier: enables
  review:
    summary: Direct assay (IDA) of CK1delta catalytic activity (tau/casein kinase
      activity) in the context of DBNDD2 binding.
    action: ACCEPT
    reason: Supports the specific tau-protein kinase MF with direct evidence.
    supported_by:
    - reference_id: PMID:16618118
      supporting_text: Dysbindin structural homologue CK1BP is an isoform-selective
        binding partner of human casein kinase-1.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:16618118
  qualifier: enables
  review:
    summary: Direct assay (IDA) of CK1delta protein serine kinase activity.
    action: ACCEPT
    reason: Core MF; direct evidence.
    supported_by:
    - reference_id: PMID:16618118
      supporting_text: Dysbindin structural homologue CK1BP is an isoform-selective
        binding partner of human casein kinase-1.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IMP
  original_reference_id: PMID:19591487
  qualifier: enables
  review:
    summary: Generic protein kinase activity from inhibitor characterization. Correct
      but superseded by the specific serine/threonine kinase term.
    action: MODIFY
    reason: Too general; CK1delta is specifically a serine/threonine kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:10606744
  qualifier: enables
  review:
    summary: Direct demonstration that CK1 phosphorylates p53 at Thr18, a serine/threonine
      kinase activity.
    action: ACCEPT
    reason: Core MF; direct experimental evidence (p53 Thr18 kinase).
    supported_by:
    - reference_id: PMID:10606744
      supporting_text: Protein kinase CK1 is a p53-threonine 18 kinase which requires
        prior phosphorylation of serine 15.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:20041275
  qualifier: enables
  review:
    summary: Direct demonstration of isoform-specific p53 phosphorylation by CK1.
    action: ACCEPT
    reason: Core MF; direct experimental evidence.
    supported_by:
    - reference_id: PMID:20041275
      supporting_text: Isoform specific phosphorylation of p53 by protein kinase CK1.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:20637175
  qualifier: enables
  review:
    summary: Direct demonstration of CK1delta serine/threonine kinase activity (DCK
      Ser-74 phosphorylation in vitro).
    action: ACCEPT
    reason: Core MF; direct in vitro kinase assay.
    supported_by:
    - reference_id: PMID:20637175
      supporting_text: Casein kinase 1delta activates human recombinant deoxycytidine
        kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation
        of its activity.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:12270943
  qualifier: enables
  review:
    summary: Direct demonstration that CK1 phosphorylates connexin-43/GJA1 (serine
      kinase activity).
    action: ACCEPT
    reason: Core MF; direct experimental evidence (connexin-43 substrate).
    supported_by:
    - reference_id: PMID:12270943
      supporting_text: Casein kinase 1 regulates connexin-43 gap junction assembly.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:19043076
  qualifier: enables
  review:
    summary: CK1delta/epsilon phosphorylates TOP2A at Ser-1106, supporting protein
      serine kinase activity.
    action: ACCEPT
    reason: Core MF; supported by substrate phosphorylation evidence (TOP2A).
    supported_by:
    - reference_id: PMID:19043076
      supporting_text: Casein kinase I delta/epsilon phosphorylates topoisomerase
        IIalpha at serine-1106 and modulates DNA cleavage activity.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21084295
  qualifier: enables
  review:
    summary: Direct demonstration of eIF6 phosphorylation by CK1, supporting protein
      serine kinase activity.
    action: ACCEPT
    reason: Core MF; direct experimental evidence (eIF6 substrate).
    supported_by:
    - reference_id: PMID:21084295
      supporting_text: Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic
        shuttling of mammalian translation initiation factor eIF6.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:29257953
  qualifier: located_in
  review:
    summary: Direct localization to the ciliary basal body, consistent with CK1delta's
      established centrosome/basal-body role in ciliogenesis.
    action: ACCEPT
    reason: Direct IDA evidence; concordant with the functional ciliogenesis data.
    supported_by:
    - reference_id: PMID:29257953
      supporting_text: Evolutionary Proteomics Uncovers Ancient Associations of Cilia
        with Signaling Pathways.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  qualifier: enables
  review:
    summary: Cadherin binding from a high-throughput E-cadherin interactome proximity
      dataset. CK1delta is not an established cadherin-binding adaptor.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput proximity-based annotation; no specific cadherin-binding
      function is established for CK1delta and it is not supported by focused studies.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: Generic protein kinase activity inferred by sequence similarity from mouse
      ortholog. Superseded by the specific serine/threonine kinase term.
    action: MODIFY
    reason: Too general; CK1delta is specifically a serine/threonine kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:25500533
  qualifier: enables
  review:
    summary: This paper is primarily about CK1alpha/CSNK1A1 as the LRRK2 kinase; for
      CK1delta it shows only moderate in vitro phosphorylation of LRRK2 at S955. It
      nonetheless documents CK1delta serine/threonine kinase activity in vitro.
    action: ACCEPT
    reason: Supports the generic Ser/Thr kinase MF in vitro; the LRRK2-specific physiological
      role belongs to CK1alpha and should not be over-transferred to CK1delta.
    supported_by:
    - reference_id: PMID:25500533
      supporting_text: we found that CK1δ/ε and CK1γ isoforms could moderately phosphorylate
        S955 and S935 in vitro, respectively
- term:
    id: GO:0033116
    label: endoplasmic reticulum-Golgi intermediate compartment membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694441
  qualifier: located_in
  review:
    summary: Reactome localization to the ERGIC membrane in the context of SEC23 phosphorylation
      during COPII vesicle formation. Plausible given the Golgi/secretory role.
    action: KEEP_AS_NON_CORE
    reason: Pathway-specific Reactome localization tied to the SEC23/COPII substrate
      role; consistent with Golgi association but specialized.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: Golgi apparatus.
- term:
    id: GO:0007020
    label: microtubule nucleation
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: Loss-of-function evidence that CK1delta is required for microtubule nucleation
      at the Golgi (via AKAP450), part of its ciliogenesis function.
    action: ACCEPT
    reason: Direct IMP evidence; a well-supported cell-biological role.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: CK1δ was required for microtubule nucleation at the Golgi and
        maintenance of Golgi integrity.
- term:
    id: GO:0034067
    label: protein localization to Golgi apparatus
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: CK1delta loss disperses Golgi/centrosomal proteins (AKAP450, IFT20),
      supporting a role in protein localization to the Golgi.
    action: KEEP_AS_NON_CORE
    reason: Supported by IMP evidence but a downstream component of the broader Golgi-organization/ciliogenesis
      function.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: the Golgi distribution of its binding partner, A-kinase anchor
        protein 450 (AKAP450)
- term:
    id: GO:0007030
    label: Golgi organization
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: CK1delta is required for maintenance of Golgi integrity and the polarized
      Golgi ribbon, supporting Golgi organization.
    action: ACCEPT
    reason: Direct IMP evidence; CK1delta inhibition disrupts cis-Golgi organization.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: where it is important for maintaining Golgi organization and
        polarized trafficking
- term:
    id: GO:0061512
    label: protein localization to cilium
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: CK1delta is required for correct ciliary distribution of transport proteins
      (Rab8a, polycystin-2), supporting protein localization to cilium.
    action: KEEP_AS_NON_CORE
    reason: Supported by IMP evidence; a component of the ciliogenesis function rather
      than an independent core role.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: alters pericentrosomal or ciliary distribution of several proteins
        involved in ciliary transport
- term:
    id: GO:0071539
    label: protein localization to centrosome
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: CK1delta is required for pericentrosomal positioning of CEP290/PCM1,
      supporting protein localization to the centrosome.
    action: KEEP_AS_NON_CORE
    reason: Supported by IMP evidence; part of the centrosome/ciliogenesis function.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: CK1δ is required for proper positioning of these centriolar
        satellite proteins
- term:
    id: GO:1905515
    label: non-motile cilium assembly
  evidence_type: IMP
  original_reference_id: PMID:24648492
  qualifier: acts_upstream_of_or_within
  review:
    summary: Direct loss-of-function evidence (siRNA, kinase inhibitor, Csnk1d-null
      cells) that CK1delta is required for primary (non-motile) ciliogenesis.
    action: ACCEPT
    reason: Strong IMP evidence across multiple models; a well-established role.
    supported_by:
    - reference_id: PMID:24648492
      supporting_text: Casein kinase 1δ functions at the centrosome and Golgi to promote
        ciliogenesis.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2574840
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (AURKA pathway reaction). Cytosol is
      a genuine CK1delta location; one of many redundant Reactome citations.
    action: ACCEPT
    reason: The cytosol CC term is correct; redundant with other cytosol annotations
      differing only by Reactome reference.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2574845
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (AURKA pathway reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000310
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (AURKA/PLK1 reaction). Redundant but
      correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000319
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (BORA/PLK1/AURKA reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380272
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (centrosome maturation reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380283
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (gamma-TuRC recruitment reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380294
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (centrosome reaction). Redundant but
      correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380303
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (Nlp dissociation reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380311
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (Plk1 recruitment reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380316
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (NuMA/microtubule reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380455
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (CDK11p58 recruitment reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380508
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (NuMA translocation reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617816
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (RAB3IP/RAB8A reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626220
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (C2CD3 centriole reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626223
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (distal appendage protein reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626227
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (CP110/CEP97 dissociation reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626228
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (TTBK2 recruitment reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626681
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (transition zone protein reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626699
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (MARK4/ODF2 reaction). Redundant but
      correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5638009
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (CEP164/RAB3IP vesicle reaction). Redundant
      but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6791223
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (pre-40S rRNA processing reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8853405
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (TPX2/AURKA reaction). Redundant but
      correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8853419
  qualifier: located_in
  review:
    summary: Cytosol localization from Reactome (TPX2/AURKA autophosphorylation reaction).
      Redundant but correct CC term.
    action: ACCEPT
    reason: Cytosol is a genuine location; redundant Reactome citation.
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:10826492
  qualifier: located_in
  review:
    summary: Direct demonstration of CK1delta association with post-Golgi structures.
    action: ACCEPT
    reason: Direct IDA evidence; concordant with the Golgi/secretory role.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:21422228
  qualifier: located_in
  review:
    summary: Direct demonstration of centrosomal localization, functionally required
      for Wnt-3a-dependent neurite outgrowth.
    action: ACCEPT
    reason: Direct IDA evidence; a functionally important location.
    supported_by:
    - reference_id: PMID:21422228
      supporting_text: Casein kinase 1 delta functions at the centrosome to mediate
        Wnt-3a-dependent neurite outgrowth.
- term:
    id: GO:0005819
    label: spindle
  evidence_type: IDA
  original_reference_id: PMID:10826492
  qualifier: located_in
  review:
    summary: Direct demonstration of CK1delta localization at the spindle apparatus.
    action: ACCEPT
    reason: Direct IDA evidence.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005876
    label: spindle microtubule
  evidence_type: IDA
  original_reference_id: PMID:10826492
  qualifier: located_in
  review:
    summary: Direct demonstration of CK1delta localization at spindle microtubules.
    action: ACCEPT
    reason: Direct IDA evidence.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16027726
  qualifier: located_in
  review:
    summary: Direct demonstration of plasma membrane localization in trophoblast cells.
    action: ACCEPT
    reason: Direct IDA evidence consistent with the cell membrane annotation.
    supported_by:
    - reference_id: PMID:16027726
      supporting_text: Inhibition of casein kinase I delta alters mitotic spindle formation
        and induces apoptosis in trophoblast cells.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16027726
  qualifier: located_in
  review:
    summary: Direct demonstration of perinuclear localization.
    action: ACCEPT
    reason: Direct IDA evidence.
    supported_by:
    - reference_id: PMID:16027726
      supporting_text: Inhibition of casein kinase I delta alters mitotic spindle formation
        and induces apoptosis in trophoblast cells.
- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: IDA
  original_reference_id: PMID:10826492
  qualifier: involved_in
  review:
    summary: CK1delta associates with the spindle apparatus; functional involvement
      in spindle formation is supported by inhibitor studies in trophoblasts.
    action: KEEP_AS_NON_CORE
    reason: Supported experimentally but a context-specific (mitotic) role, not the
      core function.
    supported_by:
    - reference_id: PMID:10826492
      supporting_text: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi
        structures, microtubules and the spindle apparatus.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6791223
  qualifier: located_in
  review:
    summary: Nucleoplasm localization from Reactome (pre-rRNA processing reaction);
      consistent with documented nuclear localization.
    action: ACCEPT
    reason: Consistent with nuclear localization of CK1delta.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:21399614
  qualifier: located_in
  review:
    summary: Centrosome localization from a proteomic study of asymmetrically localizing
      centrosome components.
    action: ACCEPT
    reason: Direct evidence corroborating the well-established centrosomal location.
    supported_by:
    - reference_id: PMID:21399614
      supporting_text: Novel asymmetrically localizing components of human centrosomes
        identified by complementary proteomics methods.
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20412773
  qualifier: involved_in
  review:
    summary: Loss/gain-of-function evidence linking CK1 to canonical Wnt/beta-catenin
      signaling in the context of Hippo-Wnt crosstalk (CK1delta/epsilon-mediated DVL
      phosphorylation).
    action: ACCEPT
    reason: Supported by IMP evidence; a core signaling role of CK1delta.
    supported_by:
    - reference_id: PMID:20412773
      supporting_text: The Hippo pathway regulates Wnt/beta-catenin signaling.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Nuclear localization inferred by sequence similarity from mouse ortholog;
      concordant with the experimentally and UniProt-documented nuclear location.
    action: ACCEPT
    reason: Consistent with documented nuclear localization.
    supported_by:
    - reference_id: file:human/CSNK1D/CSNK1D-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm. Nucleus.'
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:16618118
  qualifier: enables
  review:
    summary: Generic protein kinase activity from a direct assay. Correct but superseded
      by the specific serine/threonine kinase term.
    action: MODIFY
    reason: Too general; CK1delta is specifically a serine/threonine kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16618118
  qualifier: enables
  review:
    summary: Protein binding evidenced by interaction with DBNDD2/CK1BP (Q9BQY9),
      an isoform-selective binding partner. Bare term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the specific DBNDD2 interaction is documented in
      UniProt but the bare "protein binding" conveys no function.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:16618118
  qualifier: involved_in
  review:
    summary: Protein phosphorylation as a biological process, directly demonstrated;
      this is the core enzymatic activity of CK1delta expressed as a BP.
    action: ACCEPT
    reason: Core process directly supported; CK1delta phosphorylates numerous protein
      substrates.
    supported_by:
    - reference_id: PMID:16618118
      supporting_text: Dysbindin structural homologue CK1BP is an isoform-selective
        binding partner of human casein kinase-1.
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic
      process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer (from mouse ortholog) of a role in promoting proteasomal
      degradation; supported in human by YAP1/MDM2 degron phosphorylation.
    action: KEEP_AS_NON_CORE
    reason: A genuine substrate-driven downstream effect (degron priming), not a core
      function.
    supported_by:
    - reference_id: PMID:20708156
      supporting_text: Phosphorylation by casein kinase I promotes the turnover of
        the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.
- term:
    id: GO:0032922
    label: circadian regulation of gene expression
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer of circadian regulation of gene expression. CK1delta controls
      PER stability/nuclear entry and thus the transcriptional clock; a core role.
    action: ACCEPT
    reason: Core circadian function; CK1delta regulates PER-mediated transcriptional
      feedback.
    supported_by:
    - reference_id: PMID:23636092
      supporting_text: Casein kinase idelta mutations in familial migraine and advanced
        sleep phase.
- term:
    id: GO:0042752
    label: regulation of circadian rhythm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer of regulation of circadian rhythm; a hallmark, disease-linked
      role of CK1delta.
    action: ACCEPT
    reason: Core biological process supported by PER phosphorylation and FASPS2/migraine
      variants.
    supported_by:
    - reference_id: PMID:23636092
      supporting_text: Casein kinase idelta mutations in familial migraine and advanced
        sleep phase.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: TAS
  original_reference_id: PMID:8786104
  qualifier: enables
  review:
    summary: Generic protein kinase activity from the original CSNK1D cDNA characterization.
      Correct but superseded by the specific serine/threonine kinase term.
    action: MODIFY
    reason: Too general; CK1delta is specifically a serine/threonine kinase.
    proposed_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
core_functions:
- description: Constitutively active protein serine/threonine kinase (ATP- and Mg2+-dependent)
    that phosphorylates a broad range of substrates, including via primed (phospho-directed)
    and unprimed mechanisms.
  supported_by:
  - reference_id: PMID:10606744
    supporting_text: Protein kinase CK1 is a p53-threonine 18 kinase which requires
      prior phosphorylation of serine 15.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
- description: Phosphorylates PER1 and PER2 to control their stability and nuclear
    transport, acting as a central component of the circadian clock that sets period
    length; loss-of-function variants cause familial advanced sleep phase syndrome
    and migraine.
  supported_by:
  - reference_id: PMID:23636092
    supporting_text: Casein kinase idelta mutations in familial migraine and advanced
      sleep phase.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0042752
    label: regulation of circadian rhythm
  - id: GO:0032922
    label: circadian regulation of gene expression
- description: Phosphorylates Dishevelled (DVL2/DVL3) and other components to regulate
    canonical Wnt/beta-catenin signaling and Wnt-3a-dependent neurite outgrowth.
  supported_by:
  - reference_id: PMID:21422228
    supporting_text: Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent
      neurite outgrowth.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
- description: Acts at the centrosome and Golgi (anchored via AKAP9/AKAP450) to promote
    microtubule nucleation, Golgi organization and primary (non-motile) ciliogenesis.
  supported_by:
  - reference_id: PMID:24648492
    supporting_text: Casein kinase 1δ functions at the centrosome and Golgi to promote
      ciliogenesis.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:1905515
    label: non-motile cilium assembly
  - id: GO:0007030
    label: Golgi organization
  - id: GO:0007020
    label: microtubule nucleation
proposed_new_terms: []
suggested_questions:
- question: Which CK1delta substrates and biological roles are truly delta-specific versus shared with the highly similar CK1epsilon, given their frequent co-redundancy?
- question: To what extent are the many in vitro substrate phosphorylations (e.g. DCK, eIF6, TOP2A) physiologically relevant in vivo, as opposed to reflecting CK1delta's broad acidic-substrate preference?
suggested_experiments:
- description: Acute, isoform-selective degradation (e.g. dTAG/AID) of CK1delta versus CK1epsilon followed by phosphoproteomics to define the delta-specific substrate repertoire and disentangle redundancy.
- description: Structure-guided separation-of-function CSNK1D alleles (catalytic-dead vs centrosomal-localization-deficient) in human cells and mice to dissect the kinase-dependent versus scaffolding contributions to ciliogenesis and circadian period.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10606744
  title: Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation
    of serine 15.
  findings: []
- id: PMID:10826492
  title: Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures,
    microtubules and the spindle apparatus.
  findings: []
- id: PMID:12270943
  title: Casein kinase 1 regulates connexin-43 gap junction assembly.
  findings: []
- id: PMID:14761950
  title: Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules.
  findings: []
- id: PMID:16027726
  title: Inhibition of casein kinase I delta alters mitotic spindle formation and
    induces apoptosis in trophoblast cells.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16618118
  title: Dysbindin structural homologue CK1BP is an isoform-selective binding partner
    of human casein kinase-1.
  findings: []
- id: PMID:17562708
  title: Novel phosphorylation sites in tau from Alzheimer brain support a role for
    casein kinase 1 in disease pathogenesis.
  findings: []
- id: PMID:17962809
  title: Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate
    targeting of PKD2.
  findings: []
- id: PMID:19043076
  title: Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106
    and modulates DNA cleavage activity.
  findings: []
- id: PMID:19591487
  title: 3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha
    mitogen activated protein kinase and casein kinase 1delta.
  findings: []
- id: PMID:20041275
  title: Isoform specific phosphorylation of p53 by protein kinase CK1.
  findings: []
- id: PMID:20048001
  title: A coordinated phosphorylation by Lats and CK1 regulates YAP stability through
    SCF(beta-TRCP).
  findings: []
- id: PMID:20412773
  title: The Hippo pathway regulates Wnt/beta-catenin signaling.
  findings: []
- id: PMID:20637175
  title: Casein kinase 1delta activates human recombinant deoxycytidine kinase by
    Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity.
  findings: []
- id: PMID:20699359
  title: Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
  findings: []
- id: PMID:20708156
  title: Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein
    via the SCF(beta-TRCP) ubiquitin ligase.
  findings: []
- id: PMID:21084295
  title: Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic
    shuttling of mammalian translation initiation factor eIF6.
  findings: []
- id: PMID:21179498
  title: High-throughput chemical screen identifies a novel potent modulator of cellular
    circadian rhythms and reveals CKIα as a clock regulatory kinase.
  findings: []
- id: PMID:21399614
  title: Novel asymmetrically localizing components of human centrosomes identified
    by complementary proteomics methods.
  findings: []
- id: PMID:21422228
  title: Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent
    neurite outgrowth.
  findings: []
- id: PMID:22609948
  title: Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated primary cilia disassembly
    pathway.
  findings: []
- id: PMID:23636092
  title: Casein kinase iδ mutations in familial migraine and advanced sleep phase.
  findings: []
- id: PMID:24648492
  title: Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by quantitative
    proteomics.
  findings: []
- id: PMID:25500533
  title: Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering
    via differential interaction with ARHGEF7.
  findings: []
- id: PMID:29257953
  title: Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling
    Pathways.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human
    Kinases.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:36931259
  title: A central chaperone-like role for 14-3-3 proteins in human cells.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8786104
  title: Sequence analysis of the cDNA for the human casein kinase I delta (CSNK1D)
    gene and its chromosomal localization.
  findings: []
- id: Reactome:R-HSA-204005
  title: COPII-mediated vesicle transport
  findings: []
- id: Reactome:R-HSA-2574840
  title: AJUBA facilitates AURKA autophosphorylation
  findings: []
- id: Reactome:R-HSA-2574845
  title: AJUBA binds centrosome-associated AURKA
  findings: []
- id: Reactome:R-HSA-3000310
  title: AURKA phosphorylates PLK1
  findings: []
- id: Reactome:R-HSA-3000319
  title: BORA binds PLK1 and AURKA
  findings: []
- id: Reactome:R-HSA-380272
  title: Plk1-mediated phosphorylation of Nlp
  findings: []
- id: Reactome:R-HSA-380283
  title: Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome
  findings: []
- id: Reactome:R-HSA-380294
  title: Loss of C-Nap-1 from centrosomes
  findings: []
- id: Reactome:R-HSA-380303
  title: Dissociation of Phospho-Nlp from the centrosome
  findings: []
- id: Reactome:R-HSA-380311
  title: Recruitment of Plk1 to centrosomes
  findings: []
- id: Reactome:R-HSA-380316
  title: Association of NuMA with microtubules
  findings: []
- id: Reactome:R-HSA-380455
  title: Recruitment of CDK11p58 to the centrosomes
  findings: []
- id: Reactome:R-HSA-380508
  title: Translocation of NuMA to the centrosomes
  findings: []
- id: Reactome:R-HSA-5617816
  title: RAB3IP stimulates nucleotide exchange on RAB8A
  findings: []
- id: Reactome:R-HSA-5626220
  title: C2CD3 binds the mother centriole
  findings: []
- id: Reactome:R-HSA-5626223
  title: C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole
  findings: []
- id: Reactome:R-HSA-5626227
  title: CP110 and CEP97 dissociate from the centriole
  findings: []
- id: Reactome:R-HSA-5626228
  title: The distal appendage proteins recruit TTBK2
  findings: []
- id: Reactome:R-HSA-5626681
  title: Recruitment of transition zone proteins
  findings: []
- id: Reactome:R-HSA-5626699
  title: MARK4 binds ODF2 in the centriole
  findings: []
- id: Reactome:R-HSA-5638009
  title: CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
  findings: []
- id: Reactome:R-HSA-5694441
  title: CSNK1D phosphorylates SEC23
  findings: []
- id: Reactome:R-HSA-6791223
  title: 18SE pre-rRNA in pre-40S particles is nucleolytically processed during translocation
    from the nucleus to the cytosol
  findings: []
- id: Reactome:R-HSA-8853405
  title: TPX2 binds AURKA at centrosomes
  findings: []
- id: Reactome:R-HSA-8853419
  title: TPX2 promotes AURKA autophosphorylation
  findings: []