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P61809 (CD5R1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Cyclin-dependent kinase 5 activator 1, p35
    Short name=p35
  2. Cyclin-dependent kinase 5 activator 1, p25
    Short name=p25
    Alternative name(s):
    Tau protein kinase II 23 kDa subunit
    Short name=p23
Gene names
Name:Cdk5r1
Synonyms:Cdk5r, Nck5a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length307 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7

Subunit structure

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. Ref.5 Ref.6 Ref.7

Subcellular location

Cyclin-dependent kinase 5 activator 1, p35: Cell membrane; Lipid-anchor; Cytoplasmic side By similarity Ref.6.

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. Ref.6

Tissue specificity

Brain and neuron specific.

Post-translational modification

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. Ref.4

Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35 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.

Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis By similarity.

Sequence similarities

Belongs to the cyclin-dependent kinase 5 activator family.

Ontologies

Keywords
   Biological processBiological rhythms
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   PTMLipoprotein
Myristate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled acetylcholine receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

axon guidance

Inferred from mutant phenotype PubMed 10545161. Source: UniProtKB

axonal fasciculation

Inferred from mutant phenotype PubMed 10545161. Source: UniProtKB

brain development

Inferred from mutant phenotype PubMed 10545161. Source: UniProtKB

cerebellum development

Inferred from mutant phenotype PubMed 11226314. Source: MGI

cerebral cortex radially oriented cell migration

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

embryo development

Inferred from sequence or structural similarity. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from mutant phenotype Ref.6. Source: UniProtKB

hippocampus development

Inferred from genetic interaction PubMed 11517264. Source: MGI

ionotropic glutamate receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

layer formation in cerebral cortex

Inferred from genetic interaction PubMed 11517264. Source: MGI

negative regulation of axon extension

Inferred from genetic interaction PubMed 22573681. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

neuron cell-cell adhesion

Inferred from mutant phenotype PubMed 10753743. Source: UniProtKB

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from direct assay PubMed 9010203. Source: UniProtKB

neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from genetic interaction PubMed 11517264. Source: MGI

positive regulation of protein targeting to membrane

Inferred from direct assay PubMed 18054859. Source: MGI

regulation of actin cytoskeleton organization

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

regulation of dendritic spine morphogenesis

Inferred from mutant phenotype Ref.6. Source: UniProtKB

regulation of microtubule cytoskeleton organization

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

serine phosphorylation of STAT3 protein

Inferred from direct assay PubMed 15096606. Source: MGI

superior olivary nucleus maturation

Inferred from genetic interaction PubMed 11517264. Source: MGI

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

contractile fiber

Inferred from sequence or structural similarity. Source: UniProtKB

cyclin-dependent protein kinase 5 holoenzyme complex

Inferred from electronic annotation. Source: InterPro

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine

Inferred from sequence or structural similarity. Source: UniProtKB

growth cone

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncadherin binding

Inferred from sequence or structural similarity. Source: UniProtKB

calcium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

cyclin-dependent protein kinase 5 activator activity

Inferred from mutant phenotype PubMed 11517264. Source: MGI

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

cytoskeletal protein binding

Traceable author statement PubMed 12496365. Source: MGI

kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11276227Ref.6. Source: UniProtKB

protein serine/threonine kinase activator activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 307306Cyclin-dependent kinase 5 activator 1, p35
PRO_0000004796
Chain99 – 307209Cyclin-dependent kinase 5 activator 1, p25
PRO_0000004797

Sites

Site98 – 992Cleavage; by calpain

Amino acid modifications

Modified residue81Phosphoserine; by CDK5 By similarity
Modified residue1381Phosphothreonine; by CDK5 By similarity
Lipidation21N-myristoyl glycine By similarity

Experimental info

Mutagenesis1571E → Q: Abolishes the binding to CDK5RAP1, CDK5RAP2, CDKRAP3, but not to CDK5. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P61809 [UniParc].

Last modified June 7, 2004. Version 1.
Checksum: 165AA0747410B0C0

FASTA30734,031
        10         20         30         40         50         60 
MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL PWKRIVAVSA 

        70         80         90        100        110        120 
KKKNSKKAQP NSSYQSNIAH LNNENLKKSL SCANLSTFAQ PPPAQPPAPP ASQLSGSQTG 

       130        140        150        160        170        180 
VSSSVKKAPH PAITSAGTPK RVIVQASTSE LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS 

       190        200        210        220        230        240 
VDRSLLLQGW QDQGFITPAN VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYMGNE 

       250        260        270        280        290        300 
ISYPLKPFLV ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQVFSDLK NESGQEDKKR 


LLLGLDR 

« Hide

References

« Hide 'large scale' references
[1]"Differential mRNA expression of the CDK5 activators P35 and P39 in the developing mouse brain."
Nilden F., Backstrom A., Bark I.C.
Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: 129/Sv.
[2]"Molecular cloning and chromosomal mapping of the mouse gene encoding cyclin-dependent kinase 5 regulatory subunit p35."
Ohshima T., Kozak C.A., Nagle J.W., Pant H.C., Brady R.O., Kulkarni A.B.
Genomics 35:372-375(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/SvJ.
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[4]"Neurotoxicity induces cleavage of p35 to p25 by calpain."
Lee M.-S., Kwon Y.T., Li M., Peng J., Friedlander R.M., Tsai L.-H.
Nature 405:360-364(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC CLEAVAGE BY CALPAIN.
[5]"Identification of a neuronal Cdk5 activator-binding protein as Cdk5 inhibitor."
Ching Y.-P., Pang A.S.H., Lam W.-H., Qi R.Z., Wang J.H.
J. Biol. Chem. 277:15237-15240(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDK5; CDK5RAP1; CDK5RAP2 AND CDK5RAP3, MUTAGENESIS OF GLU-157.
[6]"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: FUNCTION IN DENDRITIC SPINE MORPHOGENESIS, INTERACTION WITH NGEF, SUBCELLULAR LOCATION.
[7]"Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation."
Kwak Y., Jeong J., Lee S., Park Y.U., Lee S.A., Han D.H., Kim J.H., Ohshima T., Mikoshiba K., Suh Y.H., Cho S., Park S.K.
J. Biol. Chem. 288:36878-36889(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CLOCK.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS25134.1.
RefSeqNP_034001.1. NM_009871.2.
UniGeneMm.142275.
Mm.474282.

3D structure databases

ProteinModelPortalP61809.
SMRP61809. Positions 145-293.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198647. 2 interactions.
DIPDIP-29354N.
IntActP61809. 2 interactions.

PTM databases

PhosphoSiteP61809.

Proteomic databases

PRIDEP61809.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000053413; ENSMUSP00000099514; ENSMUSG00000048895.
GeneID12569.
KEGGmmu:12569.
UCSCuc007kmg.1. mouse.

Organism-specific databases

CTD8851.
MGIMGI:101764. Cdk5r1.

Phylogenomic databases

eggNOGNOG283789.
HOVERGENHBG050853.
InParanoidP61809.
KOK11716.
OMACANLSSF.
PhylomeDBP61809.
TreeFamTF101036.

Gene expression databases

BgeeP61809.
GenevestigatorP61809.

Family and domain databases

Gene3D1.10.472.10. 1 hit.
InterProIPR004944. CDK5_activator.
IPR013763. Cyclin-like.
[Graphical view]
PANTHERPTHR23401. PTHR23401. 1 hit.
PfamPF03261. CDK5_activator. 1 hit.
[Graphical view]
PIRSFPIRSF009324. Cdk5_activator. 1 hit.
SUPFAMSSF47954. SSF47954. 1 hit.
ProtoNetSearch...

Other

NextBio281670.
PROP61809.
SOURCESearch...

Entry information

Entry nameCD5R1_MOUSE
AccessionPrimary (citable) accession number: P61809
Secondary accession number(s): Q62938
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: July 9, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot