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Protein

Cyclin-dependent kinase 5 activator 1

Gene

Cdk5r1

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • cyclin-dependent protein kinase 5 activator activity Source: RGD
  • cyclin-dependent protein serine/threonine kinase activity Source: RGD
  • ephrin receptor binding Source: UniProtKB
  • kinase activity 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-RNO-399956. CRMPs in Sema3A signaling.
R-RNO-6804756. Regulation of TP53 Activity through Phosphorylation.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi629472. Cdk5r1.

Subcellular locationi

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

  • Note: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions.By similarity

GO - Cellular componenti

  • axon Source: UniProtKB
  • contractile fiber Source: UniProtKB
  • cyclin-dependent protein kinase 5 holoenzyme complex Source: RGD
  • cytoplasm Source: UniProtKB
  • dendrite Source: UniProtKB
  • dendritic spine Source: UniProtKB
  • growth cone Source: UniProtKB
  • membrane Source: UniProtKB
  • neuromuscular junction Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • nucleoplasm Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
  • postsynaptic density Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi138 – 1381T → A: Increased susceptibility to calpain cleavage. 1 Publication
Mutagenesisi138 – 1381T → E: Decreased susceptibility to calpain cleavage. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 307306Cyclin-dependent kinase 5 activator 1, p35PRO_0000004798Add
BLAST
Chaini99 – 307209Cyclin-dependent kinase 5 activator 1, p25PRO_0000004799Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei8 – 81Phosphoserine; by CDK5By similarity
Modified residuei138 – 1381Phosphothreonine; by CDK5By similarity

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.2 Publications
Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35 (By similarity).By similarity
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 (By similarity).By similarity
Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.By similarity

Sites

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

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP61810.

PTM databases

iPTMnetiP61810.
PhosphoSiteiP61810.

Expressioni

Tissue specificityi

Brain and neuron specific.

Gene expression databases

GenevisibleiP61810. RN.

Interactioni

Subunit structurei

Heterodimer composed of CDK5 and CDK5R (p25) and macromolecular complex composed of at least CDK5, CDK5R (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity (By similarity). Interacts with RASGRF2. Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4. The complex p35/CDK5 interacts with CLOCK.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Fzr1B1WCA13EBI-2008489,EBI-8078743

GO - Molecular functioni

  • cadherin binding Source: UniProtKB
  • ephrin receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi250555. 2 interactions.
DIPiDIP-29352N.
IntActiP61810. 5 interactions.
MINTiMINT-3376450.
STRINGi10116.ENSRNOP00000062473.

Structurei

3D structure databases

ProteinModelPortaliP61810.
SMRiP61810. Positions 145-293.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiP61810.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG7GTT4Q.
PhylomeDBiP61810.
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.

P61810-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL
60 70 80 90 100
PWKRIVAVSA KKKNSKKAQP NSSYQSNIAH LNNENLKKSL SCANLSTFAQ
110 120 130 140 150
PPPAQPPAPP ASQLSGSQTG VSSSVKKAPH PAITSAGTPK 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):34,031
Last modified:June 7, 2004 - v1
Checksum:i165AA0747410B0C0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50707 mRNA. Translation: AAC52611.1.
RefSeqiNP_446343.1. NM_053891.1.
UniGeneiRn.11213.

Genome annotation databases

EnsembliENSRNOT00000031746; ENSRNOP00000062473; ENSRNOG00000021685.
GeneIDi116671.
KEGGirno:116671.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50707 mRNA. Translation: AAC52611.1.
RefSeqiNP_446343.1. NM_053891.1.
UniGeneiRn.11213.

3D structure databases

ProteinModelPortaliP61810.
SMRiP61810. Positions 145-293.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250555. 2 interactions.
DIPiDIP-29352N.
IntActiP61810. 5 interactions.
MINTiMINT-3376450.
STRINGi10116.ENSRNOP00000062473.

PTM databases

iPTMnetiP61810.
PhosphoSiteiP61810.

Proteomic databases

PaxDbiP61810.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000031746; ENSRNOP00000062473; ENSRNOG00000021685.
GeneIDi116671.
KEGGirno:116671.

Organism-specific databases

CTDi8851.
RGDi629472. Cdk5r1.

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiP61810.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG7GTT4Q.
PhylomeDBiP61810.
TreeFamiTF101036.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP61810.

Gene expression databases

GenevisibleiP61810. RN.

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...

Publicationsi

  1. "Phosphorylation of the high molecular weight neurofilament protein (NF-H) by Cdk5 and p35."
    Sun D., Leung C.L., Liem R.K.H.
    J. Biol. Chem. 271:14245-14250(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells."
    Nath R., Davis M., Probert A.W., Kupina N.C., Ren X., Schielke G.P., Wang K.K.
    Biochem. Biophys. Res. Commun. 274:16-21(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC CLEAVAGE BY CALPAIN.
  3. "p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent extracellular signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons."
    Kesavapany S., Amin N., Zheng Y.-L., Nijhara R., Jaffe H., Sihag R., Gutkind J.S., Takahashi S., Kulkarni A., Grant P., Pant H.C.
    J. Neurosci. 24:4421-4431(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RASGRF2.
  4. "Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 by site-specific phosphorylation."
    Kamei H., Saito T., Ozawa M., Fujita Y., Asada A., Bibb J.A., Saido T.C., Sorimachi H., Hisanaga S.
    J. Biol. Chem. 282:1687-1694(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-8 AND THR-138, MUTAGENESIS OF THR-138.
  5. "Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
    Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
    Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHA4.

Entry informationi

Entry nameiCD5R1_RAT
AccessioniPrimary (citable) accession number: P61810
Secondary accession number(s): Q62938
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: June 8, 2016
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.