logo CaMPDB: Calpain for Modulatory Proteolysis Database

SB0076 : p35, cyclin-dependent kinase 5, regulatory subunit 1

[ CaMP Format ]

* Basic Information

OrganismHomo sapiens (human)
Protein Namescyclin-dependent kinase 5 activator 1 [Homo sapiens]; cyclin-dependent kinase 5 activator 1; TPKII regulatory subunit; regulatory partner for CDK5 kinase; CDK5 activator 1; tau protein kinase II 23kDa subunit; neuronal CDK5 activator; cyclin-dependent kinase 5 regulatory subunit 1; Cyclin-dependent kinase 5 activator 1; Cyclin-dependent kinase 5 regulatory subunit 1; Cyclin-dependent kinase 5 activator 1, p35; p35; Cyclin-dependent kinase 5 activator 1, p25; p25; Tau protein kinase II 23 kDa subunit; p23
Gene NamesCDK5R1; CDK5R, NCK5A; CDK5R; NCK5A; cyclin-dependent kinase 5, regulatory subunit 1 (p35)
Gene Locus17q11.2; chromosome 17
GO FunctionNot available
Entrez Protein Entrez Nucleotide Entrez Gene UniProt OMIM HGNC HPRD KEGG
NP_003876 NM_003885 8851 Q15078 603460 HGNC:1775 04586 hsa:8851

* Information From OMIM

Function: CDK5 is required for proper development of the mammalian central nervous system. To be activated, CDK5 must associate with its regulatory subunit, p35. Patrick et al. (1999) showed that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer disease (OMIM:104300). This accumulation correlated with an increase in CDK5 kinase activity. Unlike p35, p25 was not readily degraded, and binding of p25 to CDK5 constitutively activated CDK5, changed its cellular location, and altered its substrate specificity. In vivo, the p25/CDK5 complex hyperphosphorylated tau (OMIM:157140), which reduced tau's ability to associate with microtubules. Moreover, expression of the p25/CDK5 complex in cultured primary neurons induced cytoskeletal disruption, morphologic degeneration, and apoptosis. Patrick et al. (1999) concluded that cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases.

* Structure Information

1. Primary Information

Length: 307 aa

Average Mass: 34.060 kDa

Monoisotopic Mass: 34.039 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain namebeginendscoree-value
Cyclin-dependent kinase 5 activator protein 1. 75293135.01.7
--- cleavage 98 (inside Cyclin-dependent kinase 5 activator protein 75..293) ---

3. Sequence Information

Fasta Sequence: SB0076.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 1H4L (X-ray; 265 A; D/E=147-293), 1UNG (X-ray; 230 A; D/E=100-307), 1UNH (X-ray; 235 A; D/E=100-307), 1UNL (X-ray; 220 A; D/E=100-307), 3O0G (X-ray; 195 A; D/E=145-293)

* Cleavage Information

1 [sites] cleaved by Calpain 2

Source Reference: [PubMed ID: 10830966] Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH, Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature. 2000 May 18;405(6784):360-4.

Cleavage sites (±10aa)


Phe98 Ala

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'

Sequence conservation (by blast)

* References

[PubMed ID: 24085300] Saito T, Yano M, Kawai Y, Asada A, Wada M, Doi H, Hisanaga S, Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators. J Biol Chem. 2013 Nov 8;288(45):32433-9. doi: 10.1074/jbc.M113.512293. Epub 2013

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