EzCatDB: M00196
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DB codeM00196
RLCP classification3.103.126600.1165 : Transfer
CATH domainDomain 13.30.200.20 : Phosphorylase Kinase; domain 1Catalytic domain
Domain 21.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 3-.-.-.-
Domain 41.10.472.10 : Cyclin A; domain 1
E.C.2.7.11.22

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
3.30.200.20 : Phosphorylase Kinase; domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

Q00535Q15078
Protein nameCyclin-dependent kinase 5Cyclin-dependent kinase 5 activator 1cyclin-dependent kinase
Bur1
Bur1 Cdk
Cak1
Cak1p
cdc2
cdc2 kinase
Cdc28p
CDK
cdk-activating kinase
Cdk-activating protein kinase
cdk1
cdk2
Cdk2
cdk3
cdk4
cdk5
cdk6
cdk7
cdk8
cdk9
cyclin A-activated cdc2
cyclin A-activated cdk2
cyclin D-cdk6 kinase
cyclin D-dependent kinase
cyclin E kinase
cyclin-A associated kinase
cyclin-dependent kinase 6
cyclin-dependent kinase-2
cyclin-dependent kinase-4
cyclin-dependent protein kinase activating kinase
cyk
D-type cyclin kinase
nclk
neuronal cdc2-like kinase
PCTAIRE-1
STK25
SynonymsEC 2.7.11.22
Cell division protein kinase 5
Serine/threonine-protein kinase PSSALRE
Tau protein kinase II catalytic subunit
TPKII catalytic subunit
CDK5 activator 1
Cyclin-dependent kinase 5 regulatory subunit 1
TPKII regulatory subunit
ContainsNoneCyclin-dependent kinase 5 activator 1, p35
(p35)
Cyclin-dependent kinase 5 activator 1, p25
(p25)
Tau protein kinase II 23 kDa subunit
(p23)
RefSeqNP_001157882.1 (Protein)
NM_001164410.1 (DNA/RNA sequence)
NP_004926.1 (Protein)
NM_004935.3 (DNA/RNA sequence)
NP_003876.1 (Protein)
NM_003885.2 (DNA/RNA sequence)
PfamPF00069 (Pkinase)
[Graphical view]
PF03261 (CDK5_activator)
[Graphical view]


UniProtKB:Accession NumberQ00535Q15078
Entry nameCDK5_HUMANCD5R1_HUMAN
ActivityATP + a protein = ADP + a phosphoprotein.
SubunitHeterodimer of a catalytic subunit and a regulatory subunit (p35). Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 (By similarity). Interacts with AATK.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 (By similarity). Interacts with RASGRF2.
Subcellular locationCytoplasm (By similarity). Cell projection, lamellipodium (By similarity). Cell projection, growth cone (By similarity). Note=In axonal growth cone with extension to the peripheral lamellipodia (By similarity).Cyclin-dependent kinase 5 activator 1, p35: Cell membrane, Lipid-anchor, Cytoplasmic side (Probable). Note=In the primary cortical neurons, p35 is present in the peripheries and nerve terminals.,Cyclin-dependent kinase 5 activator 1, p25: Nucleus. Cytoplasm, perinuclear region. Note=The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions. In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00017C00008C00562
CompoundMagnesiumATPProteinADPPhosphoprotein
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidepeptide/proteinamine group,nucleotidepeptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
1h4lA01UnboundUnboundUnboundUnboundUnbound
1h4lB01UnboundUnboundUnboundUnboundUnbound
1ungA01UnboundUnboundUnboundAnalogue:ALHUnbound
1ungB01UnboundUnboundUnboundAnalogue:ALHUnbound
1unhA01UnboundUnboundUnboundAnalogue:IXMUnbound
1unhB01UnboundUnboundUnboundAnalogue:IXMUnbound
1unlA01UnboundUnboundUnboundAnalogue:RRCUnbound
1unlB01UnboundUnboundUnboundAnalogue:RRCUnbound
1h4lA02UnboundUnboundUnboundUnboundUnbound
1h4lB02UnboundUnboundUnboundUnboundUnbound
1ungA02UnboundUnboundUnboundUnboundUnbound
1ungB02UnboundUnboundUnboundUnboundUnbound
1unhA02UnboundUnboundUnboundUnboundUnbound
1unhB02UnboundUnboundUnboundUnboundUnbound
1unlA02UnboundUnboundUnboundUnboundUnbound
1unlB02UnboundUnboundUnboundUnboundUnbound
1h4lDUnboundUnboundUnboundUnboundUnbound
1h4lEUnboundUnboundUnboundUnboundUnbound
1ungDUnboundUnboundUnboundUnboundUnbound
1ungEUnboundUnboundUnboundUnboundUnbound
1unhDUnboundUnboundUnboundUnboundUnbound
1unhEUnboundUnboundUnboundUnboundUnbound
1unlDUnboundUnboundUnboundUnboundUnbound
1unlEUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [2], [3]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
1h4lA01LYS 33
 
      ;TYR 15;GLY 16
invisible 11-14, 39-42
1h4lB01LYS 33
 
      ;TYR 15;GLY 16
invisible 11-14, 39-42
1ungA01LYS 33
 
      ;TYR 15;GLY 16
invisible 11-14
1ungB01LYS 33
 
      ;      ;      
invisible 10-16, 22-28, 39-42
1unhA01LYS 33
 
      ;TYR 15;GLY 16
invisible 11-14, 25-26, 39-42
1unhB01LYS 33
 
      ;TYR 15;GLY 16
invisible 11-14, 25-26, 39-42
1unlA01LYS 33
 
THR 14;TYR 15;GLY 16
 
1unlB01LYS 33
 
THR 14;TYR 15;GLY 16
 
1h4lA02ASP 126;LYS 128
ASN 131;ASP 144(Magnesium binding)
 
 
1h4lB02ASP 126;LYS 128
ASN 131;ASP 144(Magnesium binding)
 
 
1ungA02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1ungB02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1unhA02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1unhB02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1unlA02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1unlB02ASP 126;LYS 128
ASN 131;       (Magnesium binding)
 
mutant D144N
1h4lD 
 
 
 
1h4lE 
 
 
 
1ungD 
 
 
 
1ungE 
 
 
 
1unhD 
 
 
 
1unhE 
 
 
 
1unlD 
 
 
 
1unlE 
 
 
 


references
[1]
PubMed ID11437375
JournalBiochem Biophys Res Commun
Year2001
Volume285
Pages77-83
AuthorsLim HY, Seow KT, Li Q, Kesuma D, Wang JH, Qi RZ
TitleStructural Insights into Cdk5 activation by a neuronal Cdk5 activator.
[2]
CommentsX-ray crystallography
PubMed ID11604388
JournalJ Biol Chem
Year2001
Volume276
Pages48292-9
AuthorsClare PM, Poorman RA, Kelley LC, Watenpaugh KD, Bannow CA, Leach KL
TitleThe cyclin-dependent kinases cdk2 and cdk5 act by a random, anticooperative kinetic mechanism.
Related PDB1jsv
[3]
CommentsX-ray crystallography
PubMed ID11583627
JournalMol Cell
Year2001
Volume8
Pages657-69
AuthorsTarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A
TitleStructure and regulation of the CDK5-p25(nck5a) complex.
Related PDB1h4l
[4]
CommentsINTERACTION WITH AATK.
PubMed ID14521924
JournalBiochem Biophys Res Commun
Year2003
Volume310
Pages398-404
AuthorsHonma N, Asada A, Takeshita S, Enomoto M, Yamakawa E, Tsutsumi K, Saito T, Satoh T, Itoh H, Kaziro Y, Kishimoto T, Hisanaga S
TitleApoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein.
Related UniProtKBQ00535
[5]
PubMed ID14673202
JournalNeurosignals
Year2003
Volume12
Pages164-72
AuthorsMapelli M, Musacchio A
TitleThe structural perspective on CDK5.
[6]
CommentsX-ray crystallography
PubMed ID15689152
JournalJ Med Chem
Year2005
Volume48
Pages671-9
AuthorsMapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai LH, Meijer L, Musacchio A
TitleMechanism of CDK5/p25 binding by CDK inhibitors.
Related PDB1ung,1unh,1unl
[7]
PubMed ID16236519
JournalTrends Biochem Sci
Year2005
Volume30
Pages630-41
AuthorsMalumbres M, Barbacid M
TitleMammalian cyclin-dependent kinases.
[8]
PubMed ID16407256
JournalJ Biol Chem
Year2006
Volume281
Pages7271-81
AuthorsOtyepka M, Bartova I, Kriz Z, Koca J
TitleDifferent mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics.

comments
The E.C. was transferred from 2.7.1.37 to 2.7.11.22.
This enzyme is homologous to phosphorylase b (M00198 of EzCatDB) with conserved catalytic residues, suggesting the same catalytic mechanism.
Cyclin-dependent kinase 5(CDK5) in this entry is homologous to other CDKs in M00195, and catalytic mechanisms of this enzyme seem same as M00195.
Although it is called cyclin-dependent kinase 5, it is not activated by cyclins(reguratory subunits of other CDKs).
The regulatory subunits of this enzyme are p35(swiss-prot;CD5R1_HUMAN;Q15078) or p39(CD5R2_HUMAN;Q13319). The N-terminal truncated form of p35 also activate this enzyme and called p25. The chains, D and E, of 1h4l, 1ung, 1unh and 1unl (in PDB) are C-terminal fragments of p35 (i.e. p25). The structures of N-terminal fragment of p35 or p39 are undetermined. These regulatory subunits (p25, p35, p39) have single cyclin-like domain(CATH:1.10.472.10) while cyclins have two domains(CATH:1.10.472.10, 1.10.472.10).

createdupdated
2004-03-252009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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