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Protein

Cyclin-dependent kinase 5 activator 1

Gene

CDK5R1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processBiological 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

Organism-specific databases

VGNCiVGNC:27128 CDK5R1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin filament binding Source: Ensembl
  • alpha-tubulin binding Source: ARUK-UCL
  • beta-tubulin binding Source: ARUK-UCL
  • cadherin binding Source: UniProtKB
  • ionotropic glutamate receptor binding Source: Ensembl
  • protease binding Source: Ensembl
  • protein kinase binding Source: Ensembl

Protein-protein interaction databases

BioGridi159447, 6 interactors
CORUMiQ28199
IntActiQ28199, 4 interactors
MINTiQ28199
STRINGi9913.ENSBTAP00000052270

Structurei

3D structure databases

ProteinModelPortaliQ28199
SMRiQ28199
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR004944 CDK5_activator
IPR036915 Cyclin-like_sf
PfamiView protein in Pfam
PF03261 CDK5_activator, 1 hit
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

Similar proteinsi

Entry informationi

Entry nameiCD5R1_BOVIN
AccessioniPrimary (citable) accession number: Q28199
Secondary accession number(s): Q0II69, Q28865, Q29462
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: March 28, 2018
This is version 145 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health