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P61809

- CD5R1_MOUSE

UniProt

P61809 - CD5R1_MOUSE

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Protein

Cyclin-dependent kinase 5 activator 1

Gene

Cdk5r1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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.2 Publications

Sites

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

GO - Molecular functioni

  1. cadherin binding Source: UniProtKB
  2. calcium ion binding Source: UniProtKB
  3. cyclin-dependent protein kinase 5 activator activity Source: MGI
  4. cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  5. cytoskeletal protein binding Source: MGI
  6. kinase activity Source: UniProtKB
  7. protein serine/threonine kinase activator activity Source: UniProtKB

GO - Biological processi

  1. axonal fasciculation Source: UniProtKB
  2. axon guidance Source: UniProtKB
  3. brain development Source: UniProtKB
  4. cerebellum development Source: MGI
  5. cerebral cortex radially oriented cell migration Source: DFLAT
  6. embryo development Source: UniProtKB
  7. ephrin receptor signaling pathway Source: UniProtKB
  8. G-protein coupled acetylcholine receptor signaling pathway Source: UniProtKB
  9. hippocampus development Source: MGI
  10. ionotropic glutamate receptor signaling pathway Source: UniProtKB
  11. layer formation in cerebral cortex Source: MGI
  12. negative regulation of axon extension Source: MGI
  13. negative regulation of transcription, DNA-templated Source: Ensembl
  14. neuron cell-cell adhesion Source: UniProtKB
  15. neuron differentiation Source: UniProtKB
  16. neuron migration Source: UniProtKB
  17. neuron projection development Source: UniProtKB
  18. peptidyl-threonine phosphorylation Source: Ensembl
  19. positive regulation of cell cycle arrest Source: MGI
  20. positive regulation of neuron apoptotic process Source: UniProtKB
  21. positive regulation of protein kinase activity Source: MGI
  22. positive regulation of protein targeting to membrane Source: MGI
  23. regulation of actin cytoskeleton organization Source: DFLAT
  24. regulation of dendritic spine morphogenesis Source: UniProtKB
  25. regulation of microtubule cytoskeleton organization Source: DFLAT
  26. rhythmic process Source: UniProtKB-KW
  27. serine phosphorylation of STAT3 protein Source: MGI
  28. superior olivary nucleus maturation Source: MGI
Complete GO annotation...

Keywords - Biological processi

Biological rhythms

Enzyme and pathway databases

ReactomeiREACT_244852. CRMPs in Sema3A signaling.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:101764. Cdk5r1.

Subcellular locationi

Chain 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

  1. axon Source: UniProtKB
  2. contractile fiber Source: UniProtKB
  3. cyclin-dependent protein kinase 5 holoenzyme complex Source: InterPro
  4. cytoplasm Source: UniProtKB
  5. dendrite Source: UniProtKB
  6. dendritic spine Source: UniProtKB
  7. growth cone Source: UniProtKB
  8. membrane Source: UniProtKB
  9. neuromuscular junction Source: UniProtKB
  10. neuronal cell body Source: UniProtKB
  11. nucleus Source: UniProtKB
  12. perinuclear region of cytoplasm Source: Ensembl
  13. plasma membrane Source: UniProtKB-KW
  14. postsynaptic density Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi157 – 1571E → Q: Abolishes the binding to CDK5RAP1, CDK5RAP2, CDKRAP3, but not to CDK5. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 307306Cyclin-dependent kinase 5 activator 1, p35PRO_0000004796Add
BLAST
Chaini99 – 307209Cyclin-dependent kinase 5 activator 1, p25PRO_0000004797Add
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.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

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP61809.
PRIDEiP61809.

PTM databases

PhosphoSiteiP61809.

Expressioni

Tissue specificityi

Brain and neuron specific.

Gene expression databases

BgeeiP61809.
ExpressionAtlasiP61809. baseline and differential.
GenevestigatoriP61809.

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

WithEntry#Exp.IntActNotes
Cdh1P098032EBI-7840438,EBI-984420
Cdk5P496152EBI-7840438,EBI-6510052

Protein-protein interaction databases

BioGridi198647. 2 interactions.
DIPiDIP-29354N.
IntActiP61809. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliP61809.
SMRiP61809. Positions 145-293.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG283789.
HOVERGENiHBG050853.
InParanoidiP61809.
KOiK11716.
OMAiCANLSSF.
PhylomeDBiP61809.
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.

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

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_009871.2.
UniGeneiMm.142275.
Mm.474282.

Genome annotation databases

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

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 .
CCDSi CCDS25134.1.
RefSeqi NP_034001.1. NM_009871.2.
UniGenei Mm.142275.
Mm.474282.

3D structure databases

ProteinModelPortali P61809.
SMRi P61809. Positions 145-293.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198647. 2 interactions.
DIPi DIP-29354N.
IntActi P61809. 2 interactions.

PTM databases

PhosphoSitei P61809.

Proteomic databases

MaxQBi P61809.
PRIDEi P61809.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000053413 ; ENSMUSP00000099514 ; ENSMUSG00000048895 .
GeneIDi 12569.
KEGGi mmu:12569.
UCSCi uc007kmg.1. mouse.

Organism-specific databases

CTDi 8851.
MGIi MGI:101764. Cdk5r1.

Phylogenomic databases

eggNOGi NOG283789.
HOVERGENi HBG050853.
InParanoidi P61809.
KOi K11716.
OMAi CANLSSF.
PhylomeDBi P61809.
TreeFami TF101036.

Enzyme and pathway databases

Reactomei REACT_244852. CRMPs in Sema3A signaling.

Miscellaneous databases

ChiTaRSi Cdk5r1. mouse.
NextBioi 281670.
PROi P61809.
SOURCEi Search...

Gene expression databases

Bgeei P61809.
ExpressionAtlasi P61809. baseline and differential.
Genevestigatori P61809.

Family and domain databases

Gene3Di 1.10.472.10. 1 hit.
InterProi IPR004944. CDK5_activator.
IPR013763. Cyclin-like.
[Graphical view ]
PANTHERi PTHR23401. PTHR23401. 1 hit.
Pfami PF03261. CDK5_activator. 1 hit.
[Graphical view ]
PIRSFi PIRSF009324. Cdk5_activator. 1 hit.
SUPFAMi SSF47954. SSF47954. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiCD5R1_MOUSE
AccessioniPrimary (citable) accession number: P61809
Secondary accession number(s): Q62938
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 26, 2014
This is version 105 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3