Reviewed, UniProtKB/Swiss-Prot Q00535 (CDK5_HUMAN)

Names and origin

Protein names

Recommended name:
    Cell division protein kinase 5
    EC=2.7.11.22
Alternative name(s):
    Cyclin-dependent kinase 5
    Tau protein kinase II catalytic subunit
      Short name=TPKII catalytic subunit
    Serine/threonine-protein kinase PSSALRE

Gene names

Name:

CDK5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	292 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probably involved in the control of the cell cycle. Interacts with D1 and D3-type G1 cyclins. Can phosphorylate histone H1, tau, MAP2 and NF-H and NF-M. Also interacts with p35 which activates the kinase.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	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.
Subcellular location	CytoplasmBy similarity. Cell projection › lamellipodiumBy similarity. Cell projection › growth coneBy similarity. Note= In axonal growth cone with extension to the peripheral lamellipodia By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cell projection Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement. Source: ProtInc embryonic development Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron apoptosis Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	axon Inferred from sequence or structural similarity. Source: UniProtKB cell soma Inferred from sequence or structural similarity. Source: UniProtKB dendrite 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 nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro ErbB-2 class receptor binding Inferred from sequence or structural similarity. Source: UniProtKB ErbB-3 class receptor binding Inferred from sequence or structural similarity. Source: UniProtKB acetylcholine receptor activator activity Inferred from sequence or structural similarity. Source: UniProtKB cyclin-dependent protein kinase activity Traceable author statement. Source: ProtInc tau-protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AATK	Q6ZMQ8-1	1	EBI-1041567,EBI-2008436
AATK	Q6ZMQ8-2	1	EBI-1041567,EBI-2008441
CDKN1A	P38936	1	EBI-1041567,EBI-375077
CDKN1B	P46527	2	EBI-1041567,EBI-519280

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 292

292

Cell division protein kinase 5

PRO_0000085784

Regions

Domain

4 – 286

283

Protein kinase

Nucleotide binding

10 – 18

9

ATP By similarity

Sites

Active site

126

1

Proton acceptor By similarity

Binding site

33

1

ATP By similarity

Amino acid modifications

Modified residue

14

1

Phosphothreonine By similarity

Modified residue

15

1

Phosphotyrosine; by ABL1

Modified residue

159

1

Phosphoserine By similarity

Natural variations

Natural variant

225

1

E → D

VAR_041977

Secondary structure

1

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292

Helix Strand Turn

Details...

Beta strand

4 – 9

6

Beta strand

17 – 23

7

Turn

24 – 26

3

Beta strand

29 – 38

10

Beta strand

40 – 42

3

Helix

45 – 55

11

Beta strand

66 – 72

7

Beta strand

75 – 81

7

Beta strand

84 – 86

3

Helix

87 – 93

7

Turn

94 – 96

3

Helix

100 – 119

20

Helix

129 – 131

3

Beta strand

132 – 134

3

Beta strand

140 – 142

3

Helix

145 – 147

3

Helix

165 – 167

3

Helix

170 – 173

4

Helix

182 – 195

14

Turn

196 – 198

3

Helix

208 – 219

12

Turn

224 – 226

3

Helix

230 – 232

3

Turn

249 – 251

3

Helix

257 – 266

10

Helix

271 – 273

3

Helix

277 – 280

4

Helix

284 – 286

3

Sequences

	Sequence		Length	Mass (Da)
	Q00535-1 [UniParc]. Last modified December 15, 1998. Version 3. Checksum: 54D10495F017D527	FASTA	292	33,304
	10 20 30 40 50 60 MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR EICLLKELKH 70 80 90 100 110 120 KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP EIVKSFLFQL LKGLGFCHSR 130 140 150 160 170 180 NVLHRDLKPQ NLLINRNGEL KLADFGLARA FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS 190 200 210 220 230 240 TSIDMWSAGC IFAELANAGR PLFPGNDVDD QLKRIFRLLG TPTEEQWPSM TKLPDYKPYP 250 260 270 280 290 MYPATTSLVN VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A family of human cdc2-related protein kinases." Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., Harlow E., Tsai L.-H. EMBO J. 11:2909-2917(1992) [PubMed: 1639063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	Meyerson M. Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	Hu X., Xu Y., Zhang B., Peng X., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[6]	"Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein." Honma N., Asada A., Takeshita S., Enomoto M., Yamakawa E., Tsutsumi K., Saito T., Satoh T., Itoh H., Kaziro Y., Kishimoto T., Hisanaga S. Biochem. Biophys. Res. Commun. 310:398-404(2003) [PubMed: 14521924] [Abstract] Cited for: INTERACTION WITH AATK.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-15, MASS SPECTROMETRY.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-225.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X66364 mRNA. Translation: CAA47007.1.
AY049778 mRNA. Translation: AAL15435.1.
BT006680 mRNA. Translation: AAP35326.1.
BC005115 mRNA. Translation: AAH05115.1.

PIR

S23386.

RefSeq

NP_004926.1.

UniGene

Hs.647078

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H4L	X-ray	2.65	A/B	1-292	[»]
1LFR	model	-	A	1-292	[»]
1UNG	X-ray	2.30	A/B	1-292	[»]
1UNH	X-ray	2.35	A/B	1-292	[»]
1UNL	X-ray	2.20	A/B	1-292	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24221N.

IntAct

Q00535.

PTM databases

PhosphoSite

Q00535.

Genome annotation databases

Ensembl

ENSG00000164885. Homo sapiens. [Contig view]

GeneID

1020.

KEGG

hsa:1020.

Organism-specific databases

H-InvDB

HIX0019667.

HGNC

HGNC:1774. CDK5.

HPA

CAB008909.

MIM

123831. gene.

PharmGKB

PA26310.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q00535.

HOVERGEN

Q00535.

Gene expression databases

ArrayExpress

Q00535.

CleanEx

HS_CDK5.

GermOnline

ENSG00000164885. Homo sapiens.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

Q00535.

LinkHub

Q00535.

NextBio

4287.

SOURCE

Search...

Entry information

Entry name

CDK5_HUMAN

Accession

Primary (citable) accession number: Q00535

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	December 15, 1998
Last modified:	November 25, 2008
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)