UniProtKB - Q15078 (CD5R1_HUMAN)
Cyclin-dependent kinase 5 activator 1
CDK5R1
Functioni
p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.
1 PublicationMiscellaneous
GO - Molecular functioni
- actin filament binding Source: Ensembl
- alpha-tubulin binding Source: ARUK-UCL
- beta-tubulin binding Source: ARUK-UCL
- cadherin binding Source: UniProtKB
- calcium ion binding Source: UniProtKB
- cyclin-dependent protein serine/threonine kinase activator activity Source: GO_Central
- ephrin receptor binding Source: Ensembl
- ionotropic glutamate receptor binding Source: Ensembl
- kinase activity Source: UniProtKB
- protease binding Source: Ensembl
- protein kinase activator activity Source: GO_Central
- protein kinase activity Source: ProtInc
- protein kinase binding Source: UniProtKB
- protein serine/threonine kinase activator activity Source: UniProtKB
GO - Biological processi
- activation of protein kinase activity Source: GO_Central
- axonal fasciculation Source: UniProtKB
- axon guidance Source: UniProtKB
- brain development Source: UniProtKB
- cerebellum development Source: Ensembl
- embryo development ending in birth or egg hatching Source: Ensembl
- ephrin receptor signaling pathway Source: UniProtKB
- G1 to G0 transition involved in cell differentiation Source: Ensembl
- G protein-coupled acetylcholine receptor signaling pathway Source: UniProtKB
- hippocampus development Source: Ensembl
- ionotropic glutamate receptor signaling pathway Source: UniProtKB
- layer formation in cerebral cortex Source: Ensembl
- microtubule cytoskeleton organization Source: ARUK-UCL
- negative regulation of axon extension Source: Ensembl
- negative regulation of transcription, DNA-templated Source: DFLAT
- neuron cell-cell adhesion Source: UniProtKB
- neuron differentiation Source: UniProtKB
- neuron migration Source: UniProtKB
- neuron projection development Source: UniProtKB
- peptidyl-serine phosphorylation Source: UniProtKB
- peptidyl-threonine phosphorylation Source: UniProtKB
- positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
- positive regulation of MHC class II biosynthetic process Source: ARUK-UCL
- positive regulation of microtubule polymerization Source: ARUK-UCL
- positive regulation of neuron apoptotic process Source: UniProtKB
- positive regulation of protein targeting to membrane Source: Ensembl
- positive regulation of signaling receptor activity Source: ARUK-UCL
- regulation of actin cytoskeleton organization Source: Ensembl
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
- regulation of dendritic spine morphogenesis Source: UniProtKB
- regulation of macroautophagy Source: ParkinsonsUK-UCL
- regulation of neuron differentiation Source: UniProtKB
- regulation of synaptic vesicle cycle Source: Ensembl
- rhythmic process Source: UniProtKB-KW
- serine phosphorylation of STAT protein Source: Ensembl
- superior olivary nucleus maturation Source: Ensembl
Keywordsi
Biological process | Biological rhythms |
Enzyme and pathway databases
PathwayCommonsi | Q15078 |
Reactomei | R-HSA-399956, CRMPs in Sema3A signaling R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9031628, NGF-stimulated transcription R-HSA-9032845, Activated NTRK2 signals through CDK5 |
SignaLinki | Q15078 |
SIGNORi | Q15078 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclin-dependent kinase 5 activator 1Short name: CDK5 activator 1 Alternative name(s): Cyclin-dependent kinase 5 regulatory subunit 1 TPKII regulatory subunit Cleaved into the following 2 chains: Alternative name(s): Tau protein kinase II 23 kDa subunit Short name: p23 |
Gene namesi | Name:CDK5R1 Synonyms:CDK5R, NCK5A |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1775, CDK5R1 |
MIMi | 603460, gene |
neXtProti | NX_Q15078 |
VEuPathDBi | HostDB:ENSG00000176749 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Lipid-anchor 1 Publication; Cytoplasmic side Curated
Other locations
- neuron projection 1 Publication
Note: In the primary cortical neurons, p35 is present in the peripheries and nerve terminals.1 Publication
Nucleus
- Nucleus 1 Publication
Other locations
- perinuclear region 1 Publication
- Perikaryon 1 Publication
Note: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions (PubMed:18507738). In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites (PubMed:18507738).1 Publication
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- axon Source: UniProtKB
- contractile fiber Source: UniProtKB
- cyclin-dependent protein kinase holoenzyme complex Source: ComplexPortal
- cytoplasm Source: UniProtKB
- dendrite Source: UniProtKB
- dendritic spine Source: UniProtKB
- growth cone Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- membrane Source: UniProtKB
- neuromuscular junction Source: UniProtKB
- neuron projection Source: ARUK-UCL
- neuronal cell body Source: UniProtKB
- perikaryon Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: UniProtKB
- postsynaptic density Source: UniProtKB
- presynapse Source: Ensembl
- protein kinase 5 complex Source: Ensembl
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 | G → A: Absent from the cell periphery. 2 Publications | 1 | |
Mutagenesisi | 8 | S → A: Increased susceptibility to calpain. 1 Publication | 1 | |
Mutagenesisi | 8 | S → E: Reduced susceptibility to calpain. 1 Publication | 1 | |
Mutagenesisi | 138 | T → A: Increased susceptibility to calpain. 1 Publication | 1 | |
Mutagenesisi | 138 | T → E: Reduced susceptibility to calpain. 1 Publication | 1 | |
Mutagenesisi | 305 | L → A in L-3A mutant; abolished recognition and ubiquitination by the CRL2(FEM1B) complex. 1 Publication | 1 | |
Mutagenesisi | 305 | L → R in L-3R mutant; abolished recognition and ubiquitination by the CRL2(FEM1B) complex, while promoting recognition and ubiquitination by the CRL2(FEM1B) complex. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8851 |
OpenTargetsi | ENSG00000176749 |
PharmGKBi | PA26311 |
Miscellaneous databases
Pharosi | Q15078, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2783 |
DrugBanki | DB07364, 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE DB02052, Indirubin-3'-monoxime |
DrugCentrali | Q15078 |
Genetic variation databases
BioMutai | CDK5R1 |
DMDMi | 2498217 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed | |||
ChainiPRO_0000004794 | 2 – 307 | Cyclin-dependent kinase 5 activator 1, p35Add BLAST | 306 | |
ChainiPRO_0000004795 | 99 – 307 | Cyclin-dependent kinase 5 activator 1, p25Add BLAST | 209 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycine1 Publication | 1 | |
Modified residuei | 8 | Phosphoserine; by CDK51 Publication | 1 | |
Modified residuei | 138 | Phosphothreonine; by CDK51 Publication | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 98 – 99 | Cleavage; by calpainBy similarity | 2 |
Keywords - PTMi
Lipoprotein, Myristate, Phosphoprotein, Ubl conjugationProteomic databases
MassIVEi | Q15078 |
PaxDbi | Q15078 |
PeptideAtlasi | Q15078 |
PRIDEi | Q15078 |
ProteomicsDBi | 60429 |
PTM databases
iPTMneti | Q15078 |
PhosphoSitePlusi | Q15078 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000176749, Expressed in neocortex and 195 other tissues |
ExpressionAtlasi | Q15078, baseline and differential |
Genevisiblei | Q15078, HS |
Organism-specific databases
HPAi | ENSG00000176749, Tissue enriched (brain) |
Interactioni
Subunit structurei
Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3 (PubMed:16039528, PubMed:17671990, PubMed:15689152). Only the heterodimer shows kinase activity (PubMed:16039528, PubMed:17671990, PubMed:15689152).
Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4 (By similarity).
Interacts with RASGRF2 (PubMed:15128856). The complex p35/CDK5 interacts with CLOCK (PubMed:24235147).
By similarity5 PublicationsBinary interactionsi
Q15078
GO - Molecular functioni
- actin filament binding Source: Ensembl
- alpha-tubulin binding Source: ARUK-UCL
- beta-tubulin binding Source: ARUK-UCL
- cadherin binding Source: UniProtKB
- ephrin receptor binding Source: Ensembl
- ionotropic glutamate receptor binding Source: Ensembl
- protease binding Source: Ensembl
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114376, 54 interactors |
ComplexPortali | CPX-2201, Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant CPX-3142, Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant |
DIPi | DIP-24222N |
ELMi | Q15078 |
IntActi | Q15078, 42 interactors |
MINTi | Q15078 |
STRINGi | 9606.ENSP00000318486 |
Chemistry databases
BindingDBi | Q15078 |
Miscellaneous databases
RNActi | Q15078, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q15078 |
SMRi | Q15078 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q15078 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 97 – 136 | DisorderedSequence analysisAdd BLAST | 40 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 111 – 129 | Polar residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3932, Eukaryota |
GeneTreei | ENSGT00390000008812 |
HOGENOMi | CLU_034132_2_0_1 |
InParanoidi | Q15078 |
OMAi | EVATDHE |
OrthoDBi | 1492547at2759 |
PhylomeDBi | Q15078 |
TreeFami | TF101036 |
Family and domain databases
InterProi | View protein in InterPro IPR004944, CDK5_activator IPR036915, Cyclin-like_sf |
PANTHERi | PTHR23401, PTHR23401, 1 hit |
Pfami | View protein in Pfam PF03261, CDK5_activator, 1 hit |
PIRSFi | PIRSF009324, Cdk5_activator, 1 hit |
SUPFAMi | SSF47954, SSF47954, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL
60 70 80 90 100
PWKRIVAVSA KKKNSKKVQP NSSYQNNITH LNNENLKKSL SCANLSTFAQ
110 120 130 140 150
PPPAQPPAPP ASQLSGSQTG GSSSVKKAPH PAVTSAGTPK RVIVQASTSE
160 170 180 190 200
LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS VDRSLLLQGW QDQGFITPAN
210 220 230 240 250
VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYMGNE ISYPLKPFLV
260 270 280 290 300
ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQVFSDLK NESGQEDKKR
LLLGLDR
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketJ3QRB5 | J3QRB5_HUMAN | Cyclin-dependent kinase 5 activator... | CDK5R1 | 115 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X80343 mRNA Translation: CAA56587.1 AY376350 Genomic DNA Translation: AAQ74776.1 BT019573 mRNA Translation: AAV38380.1 CH471147 Genomic DNA Translation: EAW80227.1 CH471147 Genomic DNA Translation: EAW80228.1 BC020580 mRNA Translation: AAH20580.1 |
CCDSi | CCDS11273.1 |
PIRi | S50861 |
RefSeqi | NP_003876.1, NM_003885.2 XP_011523740.1, XM_011525438.2 XP_016880770.1, XM_017025281.1 |
Genome annotation databases
Ensembli | ENST00000313401.4; ENSP00000318486.3; ENSG00000176749.9 |
GeneIDi | 8851 |
KEGGi | hsa:8851 |
MANE-Selecti | ENST00000313401.4; ENSP00000318486.3; NM_003885.3; NP_003876.1 |
UCSCi | uc002hhn.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X80343 mRNA Translation: CAA56587.1 AY376350 Genomic DNA Translation: AAQ74776.1 BT019573 mRNA Translation: AAV38380.1 CH471147 Genomic DNA Translation: EAW80227.1 CH471147 Genomic DNA Translation: EAW80228.1 BC020580 mRNA Translation: AAH20580.1 |
CCDSi | CCDS11273.1 |
PIRi | S50861 |
RefSeqi | NP_003876.1, NM_003885.2 XP_011523740.1, XM_011525438.2 XP_016880770.1, XM_017025281.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1H4L | X-ray | 2.65 | D/E | 147-293 | [»] | |
1UNG | X-ray | 2.30 | D/E | 100-307 | [»] | |
1UNH | X-ray | 2.35 | D/E | 100-307 | [»] | |
1UNL | X-ray | 2.20 | D/E | 100-307 | [»] | |
3O0G | X-ray | 1.95 | D/E | 145-293 | [»] | |
6LDP | X-ray | 2.35 | A/B | 298-307 | [»] | |
7CNG | X-ray | 3.49 | A/B | 298-307 | [»] | |
AlphaFoldDBi | Q15078 | |||||
SMRi | Q15078 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114376, 54 interactors |
ComplexPortali | CPX-2201, Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant CPX-3142, Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant |
DIPi | DIP-24222N |
ELMi | Q15078 |
IntActi | Q15078, 42 interactors |
MINTi | Q15078 |
STRINGi | 9606.ENSP00000318486 |
Chemistry databases
BindingDBi | Q15078 |
ChEMBLi | CHEMBL2783 |
DrugBanki | DB07364, 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE DB02052, Indirubin-3'-monoxime |
DrugCentrali | Q15078 |
PTM databases
iPTMneti | Q15078 |
PhosphoSitePlusi | Q15078 |
Genetic variation databases
BioMutai | CDK5R1 |
DMDMi | 2498217 |
Proteomic databases
MassIVEi | Q15078 |
PaxDbi | Q15078 |
PeptideAtlasi | Q15078 |
PRIDEi | Q15078 |
ProteomicsDBi | 60429 |
Protocols and materials databases
ABCDi | Q15078, 1 sequenced antibody |
Antibodypediai | 15411, 284 antibodies from 34 providers |
DNASUi | 8851 |
Genome annotation databases
Ensembli | ENST00000313401.4; ENSP00000318486.3; ENSG00000176749.9 |
GeneIDi | 8851 |
KEGGi | hsa:8851 |
MANE-Selecti | ENST00000313401.4; ENSP00000318486.3; NM_003885.3; NP_003876.1 |
UCSCi | uc002hhn.4, human |
Organism-specific databases
CTDi | 8851 |
DisGeNETi | 8851 |
GeneCardsi | CDK5R1 |
HGNCi | HGNC:1775, CDK5R1 |
HPAi | ENSG00000176749, Tissue enriched (brain) |
MIMi | 603460, gene |
neXtProti | NX_Q15078 |
OpenTargetsi | ENSG00000176749 |
PharmGKBi | PA26311 |
VEuPathDBi | HostDB:ENSG00000176749 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3932, Eukaryota |
GeneTreei | ENSGT00390000008812 |
HOGENOMi | CLU_034132_2_0_1 |
InParanoidi | Q15078 |
OMAi | EVATDHE |
OrthoDBi | 1492547at2759 |
PhylomeDBi | Q15078 |
TreeFami | TF101036 |
Enzyme and pathway databases
PathwayCommonsi | Q15078 |
Reactomei | R-HSA-399956, CRMPs in Sema3A signaling R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation R-HSA-8862803, Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9031628, NGF-stimulated transcription R-HSA-9032845, Activated NTRK2 signals through CDK5 |
SignaLinki | Q15078 |
SIGNORi | Q15078 |
Miscellaneous databases
BioGRID-ORCSi | 8851, 7 hits in 1078 CRISPR screens |
EvolutionaryTracei | Q15078 |
GeneWikii | CDK5R1 |
GenomeRNAii | 8851 |
Pharosi | Q15078, Tchem |
PROi | PR:Q15078 |
RNActi | Q15078, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000176749, Expressed in neocortex and 195 other tissues |
ExpressionAtlasi | Q15078, baseline and differential |
Genevisiblei | Q15078, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004944, CDK5_activator IPR036915, Cyclin-like_sf |
PANTHERi | PTHR23401, PTHR23401, 1 hit |
Pfami | View protein in Pfam PF03261, CDK5_activator, 1 hit |
PIRSFi | PIRSF009324, Cdk5_activator, 1 hit |
SUPFAMi | SSF47954, SSF47954, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CD5R1_HUMAN | |
Accessioni | Q15078Primary (citable) accession number: Q15078 Secondary accession number(s): E1P664, Q5U0G3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1997 | |
Last modified: | May 25, 2022 | |
This is version 211 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families