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Protein

Cyclin-dependent kinase 5 activator 1

Gene

CDK5R1

Organism
Bos taurus (Bovine)
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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Biological rhythms

Enzyme and pathway databases

ReactomeiR-BTA-399956. CRMPs in Sema3A signaling.
R-BTA-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, NCK5A
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 19

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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000047922 – 307Cyclin-dependent kinase 5 activator 1, p35Add BLAST306
ChainiPRO_000000479399 – 307Cyclin-dependent kinase 5 activator 1, p25Add BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei8Phosphoserine; by CDK5By similarity1
Modified residuei138Phosphothreonine; by CDK5By similarity1

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 (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)DescriptionActionsGraphical viewLength
Sitei98 – 99Cleavage; by calpainBy similarity2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ28199.
PRIDEiQ28199.

Expressioni

Tissue specificityi

Brain and neuron specific.

Gene expression databases

BgeeiENSBTAG00000004475.

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. Interacts with RASGRF2. Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4. The complex p35/CDK5 interacts with CLOCK (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi159447. 6 interactors.
IntActiQ28199. 3 interactors.
MINTiMINT-1173378.
STRINGi9913.ENSBTAP00000052270.

Structurei

3D structure databases

ProteinModelPortaliQ28199.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiQ28199.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG091G0OB3.
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.

Q28199-1 [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 VSSSVKKAPH PAVSSAGTPK 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):34,088
Last modified:November 1, 1997 - v1
Checksum:i738F24F3F458EE68
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114L → V in CAA55481 (PubMed:8143878).Curated1
Sequence conflicti177 – 178WL → CV in CAA55534 (PubMed:7957957).Curated2
Sequence conflicti177 – 178WL → CV in CAA55481 (PubMed:8143878).Curated2
Sequence conflicti180S → R in AAI22780 (Ref. 3) Curated1
Sequence conflicti270S → T in AAI22780 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78934 mRNA. Translation: CAA55534.1.
S73375 mRNA. Translation: AAB31984.1.
BC122779 mRNA. Translation: AAI22780.1.
X78883 mRNA. Translation: CAA55481.1.
PIRiS50850.
S51373.
RefSeqiNP_776937.2. NM_174512.3.
UniGeneiBt.103335.

Genome annotation databases

EnsembliENSBTAT00000056064; ENSBTAP00000052270; ENSBTAG00000004475.
GeneIDi282173.
KEGGibta:282173.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78934 mRNA. Translation: CAA55534.1.
S73375 mRNA. Translation: AAB31984.1.
BC122779 mRNA. Translation: AAI22780.1.
X78883 mRNA. Translation: CAA55481.1.
PIRiS50850.
S51373.
RefSeqiNP_776937.2. NM_174512.3.
UniGeneiBt.103335.

3D structure databases

ProteinModelPortaliQ28199.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159447. 6 interactors.
IntActiQ28199. 3 interactors.
MINTiMINT-1173378.
STRINGi9913.ENSBTAP00000052270.

Proteomic databases

PaxDbiQ28199.
PRIDEiQ28199.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000056064; ENSBTAP00000052270; ENSBTAG00000004475.
GeneIDi282173.
KEGGibta:282173.

Organism-specific databases

CTDi8851.

Phylogenomic databases

eggNOGiKOG3932. Eukaryota.
ENOG410YFUI. LUCA.
GeneTreeiENSGT00390000008812.
HOGENOMiHOG000063677.
HOVERGENiHBG050853.
InParanoidiQ28199.
KOiK11716.
OMAiLSIINLM.
OrthoDBiEOG091G0OB3.
TreeFamiTF101036.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000004475.

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_BOVIN
AccessioniPrimary (citable) accession number: Q28199
Secondary accession number(s): Q0II69, Q28865, Q29462
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 5, 2016
This is version 134 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, Direct protein sequencing, 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.