DB code: M00196

RLCP classification 3.103.126600.1165 : Transfer
CATH domain 3.30.200.20 : Phosphorylase Kinase; domain 1 Catalytic domain
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
-.-.-.- :
1.10.472.10 : Cyclin A; domain 1
E.C. 2.7.11.22
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 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 1 M00125 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
Q00535 Cyclin-dependent kinase 5
EC 2.7.11.22
Cell division protein kinase 5
Serine/threonine-protein kinase PSSALRE
Tau protein kinase II catalytic subunit
TPKII catalytic subunit
None NP_001157882.1 (Protein)
NM_001164410.1 (DNA/RNA sequence)
NP_004926.1 (Protein)
NM_004935.3 (DNA/RNA sequence)
PF00069 (Pkinase)
[Graphical View]
Q15078 Cyclin-dependent kinase 5 activator 1
CDK5 activator 1
Cyclin-dependent kinase 5 regulatory subunit 1
TPKII regulatory subunit
Cyclin-dependent kinase 5 activator 1, p35
(p35)
Cyclin-dependent kinase 5 activator 1, p25
(p25)
Tau protein kinase II 23 kDa subunit
(p23)
NP_003876.1 (Protein)
NM_003885.2 (DNA/RNA sequence)
PF03261 (CDK5_activator)
[Graphical View]

KEGG enzyme name
cyclin-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q00535 CDK5_HUMAN ATP + a protein = ADP + a phosphoprotein. Heterodimer 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. Cytoplasm (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).
Q15078 CD5R1_HUMAN 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. 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.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00017 C00008 C00562
E.C.
Compound Magnesium ATP Protein ADP Phosphoprotein
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide peptide/protein amine group,nucleotide peptide/protein,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
1h4lA01 Unbound Unbound Unbound Unbound Unbound
1h4lB01 Unbound Unbound Unbound Unbound Unbound
1ungA01 Unbound Unbound Unbound Analogue:ALH Unbound
1ungB01 Unbound Unbound Unbound Analogue:ALH Unbound
1unhA01 Unbound Unbound Unbound Analogue:IXM Unbound
1unhB01 Unbound Unbound Unbound Analogue:IXM Unbound
1unlA01 Unbound Unbound Unbound Analogue:RRC Unbound
1unlB01 Unbound Unbound Unbound Analogue:RRC Unbound
1h4lA02 Unbound Unbound Unbound Unbound Unbound
1h4lB02 Unbound Unbound Unbound Unbound Unbound
1ungA02 Unbound Unbound Unbound Unbound Unbound
1ungB02 Unbound Unbound Unbound Unbound Unbound
1unhA02 Unbound Unbound Unbound Unbound Unbound
1unhB02 Unbound Unbound Unbound Unbound Unbound
1unlA02 Unbound Unbound Unbound Unbound Unbound
1unlB02 Unbound Unbound Unbound Unbound Unbound
1h4lD Unbound Unbound Unbound Unbound Unbound
1h4lE Unbound Unbound Unbound Unbound Unbound
1ungD Unbound Unbound Unbound Unbound Unbound
1ungE Unbound Unbound Unbound Unbound Unbound
1unhD Unbound Unbound Unbound Unbound Unbound
1unhE Unbound Unbound Unbound Unbound Unbound
1unlD Unbound Unbound Unbound Unbound Unbound
1unlE Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1h4lA01 LYS 33 ;TYR 15;GLY 16 invisible 11-14, 39-42
1h4lB01 LYS 33 ;TYR 15;GLY 16 invisible 11-14, 39-42
1ungA01 LYS 33 ;TYR 15;GLY 16 invisible 11-14
1ungB01 LYS 33 ; ; invisible 10-16, 22-28, 39-42
1unhA01 LYS 33 ;TYR 15;GLY 16 invisible 11-14, 25-26, 39-42
1unhB01 LYS 33 ;TYR 15;GLY 16 invisible 11-14, 25-26, 39-42
1unlA01 LYS 33 THR 14;TYR 15;GLY 16
1unlB01 LYS 33 THR 14;TYR 15;GLY 16
1h4lA02 ASP 126;LYS 128 ASN 131;ASP 144(Magnesium binding)
1h4lB02 ASP 126;LYS 128 ASN 131;ASP 144(Magnesium binding)
1ungA02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1ungB02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1unhA02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1unhB02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1unlA02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1unlB02 ASP 126;LYS 128 ASN 131; (Magnesium binding) mutant D144N
1h4lD
1h4lE
1ungD
1ungE
1unhD
1unhE
1unlD
1unlE

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 11437375
Journal Biochem Biophys Res Commun
Year 2001
Volume 285
Pages 77-83
Authors Lim HY, Seow KT, Li Q, Kesuma D, Wang JH, Qi RZ
Title Structural Insights into Cdk5 activation by a neuronal Cdk5 activator.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11604388
Journal J Biol Chem
Year 2001
Volume 276
Pages 48292-9
Authors Clare PM, Poorman RA, Kelley LC, Watenpaugh KD, Bannow CA, Leach KL
Title The cyclin-dependent kinases cdk2 and cdk5 act by a random, anticooperative kinetic mechanism.
Related PDB 1jsv
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11583627
Journal Mol Cell
Year 2001
Volume 8
Pages 657-69
Authors Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A
Title Structure and regulation of the CDK5-p25(nck5a) complex.
Related PDB 1h4l
Related UniProtKB
[4]
Resource
Comments INTERACTION WITH AATK.
Medline ID
PubMed ID 14521924
Journal Biochem Biophys Res Commun
Year 2003
Volume 310
Pages 398-404
Authors Honma N, Asada A, Takeshita S, Enomoto M, Yamakawa E, Tsutsumi K, Saito T, Satoh T, Itoh H, Kaziro Y, Kishimoto T, Hisanaga S
Title Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein.
Related PDB
Related UniProtKB Q00535
[5]
Resource
Comments
Medline ID
PubMed ID 14673202
Journal Neurosignals
Year 2003
Volume 12
Pages 164-72
Authors Mapelli M, Musacchio A
Title The structural perspective on CDK5.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15689152
Journal J Med Chem
Year 2005
Volume 48
Pages 671-9
Authors Mapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai LH, Meijer L, Musacchio A
Title Mechanism of CDK5/p25 binding by CDK inhibitors.
Related PDB 1ung 1unh 1unl
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16236519
Journal Trends Biochem Sci
Year 2005
Volume 30
Pages 630-41
Authors Malumbres M, Barbacid M
Title Mammalian cyclin-dependent kinases.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 16407256
Journal J Biol Chem
Year 2006
Volume 281
Pages 7271-81
Authors Otyepka M, Bartova I, Kriz Z, Koca J
Title Different mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics.
Related PDB
Related UniProtKB

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).

Created Updated
2004-03-25 2009-02-26