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Protein

Cyclin-dependent kinase 5 activator 1

Gene

CDK5R1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publication

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • cyclin-dependent protein kinase 5 activator activity Source: Ensembl
  • cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  • kinase activity Source: UniProtKB
  • protein kinase activity Source: ProtInc
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Biological rhythms

Enzyme and pathway databases

ReactomeiR-HSA-399956. CRMPs in Sema3A signaling.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ15078.
SIGNORiQ15078.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 5 activator 1
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:1775. CDK5R1.

Subcellular locationi

Cyclin-dependent kinase 5 activator 1, p35 :
Cyclin-dependent kinase 5 activator 1, p25 :
  • Nucleus
  • Cytoplasmperinuclear region

  • Note: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions. In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 21G → A: Absent from the cell periphery. 2 Publications
Mutagenesisi8 – 81S → A: Increased susceptibility to calpain. 1 Publication
Mutagenesisi8 – 81S → E: Reduced susceptibility to calpain. 1 Publication
Mutagenesisi138 – 1381T → A: Increased susceptibility to calpain. 1 Publication
Mutagenesisi138 – 1381T → E: Reduced susceptibility to calpain. 1 Publication

Organism-specific databases

PharmGKBiPA26311.

Chemistry

ChEMBLiCHEMBL1907600.

Polymorphism and mutation databases

BioMutaiCDK5R1.
DMDMi2498217.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 307306Cyclin-dependent kinase 5 activator 1, p35PRO_0000004794Add
BLAST
Chaini99 – 307209Cyclin-dependent kinase 5 activator 1, p25PRO_0000004795Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei8 – 81Phosphoserine; by CDK51 Publication
Modified residuei138 – 1381Phosphothreonine; by CDK51 Publication

Post-translational modificationi

The p35 form is proteolytically cleaved by calpain, giving rise to the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25. The conversion results in deregulation of the CDK5 kinase: p25/CDK5 kinase displays an increased and altered tau phosphorylation in comparison to the p35/CDK5 kinase in vivo (By similarity).By similarity
Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35.2 Publications
Ubiquitinated. Degradation of p35 by proteasome results in down-regulation of CDK5 activity. During this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation.1 Publication
Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei98 – 992Cleavage; by calpainBy similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15078.
PaxDbiQ15078.
PRIDEiQ15078.

PTM databases

iPTMnetiQ15078.
PhosphoSiteiQ15078.

Miscellaneous databases

PMAP-CutDBQ15078.

Expressioni

Tissue specificityi

Brain and neuron specific.

Gene expression databases

BgeeiENSG00000176749.
CleanExiHS_CDK5R1.
ExpressionAtlasiQ15078. baseline and differential.
GenevisibleiQ15078. HS.

Organism-specific databases

HPAiHPA000252.

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. Only the heterodimer shows kinase activity. Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4 (By similarity). Interacts with RASGRF2. The complex p35/CDK5 interacts with CLOCK.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AATKQ6ZMQ8-12EBI-746189,EBI-2008436
AATKQ6ZMQ8-26EBI-746189,EBI-2008441
CDK5Q005356EBI-746189,EBI-1041567
MTUS2Q5JR593EBI-746189,EBI-742948

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114376. 39 interactions.
DIPiDIP-24222N.
IntActiQ15078. 14 interactions.
MINTiMINT-128009.
STRINGi9606.ENSP00000318486.

Chemistry

BindingDBiQ15078.

Structurei

Secondary structure

1
307
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi148 – 16215Combined sources
Helixi172 – 18716Combined sources
Helixi198 – 21114Combined sources
Helixi219 – 23719Combined sources
Beta strandi239 – 2413Combined sources
Helixi246 – 2483Combined sources
Helixi254 – 27724Combined sources
Helixi279 – 29012Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4LX-ray2.65D/E147-293[»]
1UNGX-ray2.30D/E100-307[»]
1UNHX-ray2.35D/E100-307[»]
1UNLX-ray2.20D/E100-307[»]
3O0GX-ray1.95D/E145-293[»]
ProteinModelPortaliQ15078.
SMRiQ15078. Positions 145-293.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15078.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiQ15078.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG091G0OB3.
PhylomeDBiQ15078.
TreeFamiTF101036.

Family and domain databases

Gene3Di1.10.472.10. 1 hit.
InterProiIPR004944. CDK5_activator.
IPR013763. Cyclin-like.
[Graphical view]
PANTHERiPTHR23401. PTHR23401. 1 hit.
PfamiPF03261. CDK5_activator. 1 hit.
[Graphical view]
PIRSFiPIRSF009324. Cdk5_activator. 1 hit.
SUPFAMiSSF47954. SSF47954. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15078-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:307
Mass (Da):34,060
Last modified:November 1, 1997 - v1
Checksum:iD1C29A07AFF1B644
GO

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.
CCDSiCCDS11273.1.
PIRiS50861.
RefSeqiNP_003876.1. NM_003885.2.
XP_011523740.1. XM_011525438.2.
UniGeneiHs.500015.

Genome annotation databases

EnsembliENST00000313401; ENSP00000318486; ENSG00000176749.
GeneIDi8851.
KEGGihsa:8851.
UCSCiuc002hhn.4. human.

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.
CCDSiCCDS11273.1.
PIRiS50861.
RefSeqiNP_003876.1. NM_003885.2.
XP_011523740.1. XM_011525438.2.
UniGeneiHs.500015.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4LX-ray2.65D/E147-293[»]
1UNGX-ray2.30D/E100-307[»]
1UNHX-ray2.35D/E100-307[»]
1UNLX-ray2.20D/E100-307[»]
3O0GX-ray1.95D/E145-293[»]
ProteinModelPortaliQ15078.
SMRiQ15078. Positions 145-293.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114376. 39 interactions.
DIPiDIP-24222N.
IntActiQ15078. 14 interactions.
MINTiMINT-128009.
STRINGi9606.ENSP00000318486.

Chemistry

BindingDBiQ15078.
ChEMBLiCHEMBL1907600.

PTM databases

iPTMnetiQ15078.
PhosphoSiteiQ15078.

Polymorphism and mutation databases

BioMutaiCDK5R1.
DMDMi2498217.

Proteomic databases

EPDiQ15078.
PaxDbiQ15078.
PRIDEiQ15078.

Protocols and materials databases

DNASUi8851.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000313401; ENSP00000318486; ENSG00000176749.
GeneIDi8851.
KEGGihsa:8851.
UCSCiuc002hhn.4. human.

Organism-specific databases

CTDi8851.
GeneCardsiCDK5R1.
HGNCiHGNC:1775. CDK5R1.
HPAiHPA000252.
MIMi603460. gene.
neXtProtiNX_Q15078.
PharmGKBiPA26311.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiQ15078.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG091G0OB3.
PhylomeDBiQ15078.
TreeFamiTF101036.

Enzyme and pathway databases

ReactomeiR-HSA-399956. CRMPs in Sema3A signaling.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ15078.
SIGNORiQ15078.

Miscellaneous databases

EvolutionaryTraceiQ15078.
GeneWikiiCDK5R1.
GenomeRNAii8851.
PMAP-CutDBQ15078.
PROiQ15078.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176749.
CleanExiHS_CDK5R1.
ExpressionAtlasiQ15078. baseline and differential.
GenevisibleiQ15078. HS.

Family and domain databases

Gene3Di1.10.472.10. 1 hit.
InterProiIPR004944. CDK5_activator.
IPR013763. Cyclin-like.
[Graphical view]
PANTHERiPTHR23401. PTHR23401. 1 hit.
PfamiPF03261. CDK5_activator. 1 hit.
[Graphical view]
PIRSFiPIRSF009324. Cdk5_activator. 1 hit.
SUPFAMiSSF47954. SSF47954. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCD5R1_HUMAN
AccessioniPrimary (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: September 7, 2016
This is version 172 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

Cleavage of p35 to p25 may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases. The p25 form accumulates in neurons in the brain of patients with Alzheimer disease, but not in normal brain. This accumulation correlates with an increase in CDK5 kinase activity. Application of amyloid beta peptide A-beta(1-42) induced the conversion of p35 to p25 in primary cortical neurons. Expression of the p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.