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Protein

Cyclin-dependent kinase 5 activator 1

Gene

Cdk5r1

Organism
Mus musculus (Mouse)
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.2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processBiological rhythms

Enzyme and pathway databases

ReactomeiR-MMU-399956 CRMPs in Sema3A signaling
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:101764 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi157E → Q: Abolishes the binding to CDK5RAP1, CDK5RAP2, CDKRAP3, but not to CDK5. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3885555

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000047962 – 307Cyclin-dependent kinase 5 activator 1, p35Add BLAST306
ChainiPRO_000000479799 – 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.1 Publication
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 calpain2

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP61809
PRIDEiP61809

PTM databases

iPTMnetiP61809
PhosphoSitePlusiP61809

Expressioni

Tissue specificityi

Brain and neuron specific.

Gene expression databases

BgeeiENSMUSG00000048895 Expressed in 257 organ(s), highest expression level in striatum
ExpressionAtlasiP61809 baseline and differential
GenevisibleiP61809 MM

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 (By similarity). Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4. The complex p35/CDK5 interacts with CLOCK.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198647, 2 interactors
ComplexPortaliCPX-3143 Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant
CPX-3144 Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant
CORUMiP61809
DIPiDIP-29354N
IntActiP61809, 7 interactors
MINTiP61809
STRINGi10090.ENSMUSP00000099514

Structurei

3D structure databases

ProteinModelPortaliP61809
SMRiP61809
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3932 Eukaryota
ENOG410YFUI LUCA
GeneTreeiENSGT00390000008812
HOVERGENiHBG050853
InParanoidiP61809
KOiK11716
OMAiDHELQAI
OrthoDBiEOG091G0OB3
PhylomeDBiP61809
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P61809-1 [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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1AQH0B1AQH0_MOUSE
Cyclin-dependent kinase 5 activator...
Cdk5r1
138Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89527 mRNA Translation: AAB49474.1
Y11335 Genomic DNA Translation: CAA72176.1
S82819 Genomic DNA Translation: AAB46777.1
BC046823 mRNA Translation: AAH46823.1
BC050768 mRNA Translation: AAH50768.1
BC058697 mRNA Translation: AAH58697.1
CCDSiCCDS25134.1
RefSeqiNP_034001.1, NM_009871.3
UniGeneiMm.142275
Mm.474282

Genome annotation databases

EnsembliENSMUST00000053413; ENSMUSP00000099514; ENSMUSG00000048895
GeneIDi12569
KEGGimmu:12569
UCSCiuc007kmg.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89527 mRNA Translation: AAB49474.1
Y11335 Genomic DNA Translation: CAA72176.1
S82819 Genomic DNA Translation: AAB46777.1
BC046823 mRNA Translation: AAH46823.1
BC050768 mRNA Translation: AAH50768.1
BC058697 mRNA Translation: AAH58697.1
CCDSiCCDS25134.1
RefSeqiNP_034001.1, NM_009871.3
UniGeneiMm.142275
Mm.474282

3D structure databases

ProteinModelPortaliP61809
SMRiP61809
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198647, 2 interactors
ComplexPortaliCPX-3143 Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant
CPX-3144 Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant
CORUMiP61809
DIPiDIP-29354N
IntActiP61809, 7 interactors
MINTiP61809
STRINGi10090.ENSMUSP00000099514

Chemistry databases

ChEMBLiCHEMBL3885555

PTM databases

iPTMnetiP61809
PhosphoSitePlusiP61809

Proteomic databases

PaxDbiP61809
PRIDEiP61809

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000053413; ENSMUSP00000099514; ENSMUSG00000048895
GeneIDi12569
KEGGimmu:12569
UCSCiuc007kmg.1 mouse

Organism-specific databases

CTDi8851
MGIiMGI:101764 Cdk5r1

Phylogenomic databases

eggNOGiKOG3932 Eukaryota
ENOG410YFUI LUCA
GeneTreeiENSGT00390000008812
HOVERGENiHBG050853
InParanoidiP61809
KOiK11716
OMAiDHELQAI
OrthoDBiEOG091G0OB3
PhylomeDBiP61809
TreeFamiTF101036

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiCdk5r1 mouse
PROiPR:P61809
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000048895 Expressed in 257 organ(s), highest expression level in striatum
ExpressionAtlasiP61809 baseline and differential
GenevisibleiP61809 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiCD5R1_MOUSE
AccessioniPrimary (citable) accession number: P61809
Secondary accession number(s): Q62938
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 7, 2018
This is version 141 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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