Reviewed, UniProtKB/Swiss-Prot Q00534 (CDK6_HUMAN)

Names and origin

Protein names

Recommended name:
    Cell division protein kinase 6
    EC=2.7.11.22
Alternative name(s):
    Serine/threonine-protein kinase PLSTIRE

Gene names

Name:

CDK6

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	326 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 D-type G1 cyclins.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
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
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	G1 phase of mitotic cell cycle Inferred from expression pattern. Source: UniProtKB cell dedifferentiation Inferred from mutant phenotype. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW gliogenesis Inferred from mutant phenotype. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from mutant phenotype. Source: UniProtKB negative regulation of osteoblast differentiation Inferred from direct assay. Source: UniProtKB positive regulation of cell-matrix adhesion Inferred from direct assay. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro regulation of erythrocyte differentiation Inferred from mutant phenotype. Source: UniProtKB regulation of gene expression Inferred from direct assay. Source: UniProtKB
Cellular component	cyclin-dependent protein kinase holoenzyme complex Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA ruffle Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.6 Inferred from electronic annotation. Source: InterPro cyclin binding Inferred from physical interaction. Source: UniProtKB cyclin-dependent protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCND1	P24385	1	EBI-295663,EBI-375001
CCND3	P30281	1	EBI-295663,EBI-375013
CDC37	Q16543	1	EBI-295663,EBI-295634
CDKN1A	P38936	1	EBI-295663,EBI-375077
CDKN2A	O77617-1	1	EBI-295663,EBI-1542248	From a different organism.
CDKN2A	P42771	5	EBI-295663,EBI-375053
CDKN2C	P42773	2	EBI-295663,EBI-711290
Cdkn2d	Q60773	1	EBI-295663,EBI-1027163	From a different organism.
MCM10	Q7L590	1	EBI-295663,EBI-374912
MCM2	P49736	1	EBI-295663,EBI-374819

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 326

326

Cell division protein kinase 6

PRO_0000085789

Regions

Domain

13 – 300

288

Protein kinase

Nucleotide binding

19 – 27

9

ATP By similarity

Sites

Active site

145

1

Proton acceptor

Binding site

43

1

ATP By similarity

Amino acid modifications

Modified residue

13

1

Phosphotyrosine

Modified residue

24

1

Phosphotyrosine

Natural variations

Natural variant

110

1

D → N

VAR_041978

Natural variant

199

1

P → L in a metastatic melanoma sample; somatic mutation.

VAR_041979

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

326

Helix Strand Turn

Details...

Helix

9 – 11

3

Beta strand

13 – 22

10

Beta strand

25 – 32

8

Turn

33 – 37

5

Beta strand

39 – 49

11

Helix

58 – 70

13

Beta strand

79 – 87

9

Beta strand

89 – 99

11

Helix

105 – 111

7

Helix

119 – 138

20

Helix

148 – 150

3

Beta strand

151 – 153

3

Beta strand

159 – 161

3

Helix

172 – 176

5

Helix

188 – 191

4

Helix

199 – 214

16

Helix

224 – 235

12

Helix

240 – 242

3

Helix

251 – 253

3

Helix

262 – 264

3

Helix

271 – 280

10

Turn

285 – 287

3

Helix

291 – 295

5

Helix

298 – 300

3

Sequences

	Sequence		Length	Mass (Da)
	Q00534-1 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 571733EE6BE7FD4A	FASTA	326	36,938
	10 20 30 40 50 60 MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG EEGMPLSTIR 70 80 90 100 110 120 EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH VDQDLTTYLD KVPEPGVPTE 130 140 150 160 170 180 TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN ILVTSSGQIK LADFGLARIY SFQMALTSVV 190 200 210 220 230 240 VTLWYRAPEV LLQSSYATPV DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE 250 260 270 280 290 300 EDWPRDVALP RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF 310 320 QDLERCKENL DSHLPPSQNT SELNTA

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].
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Brain.
[5]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13 AND TYR-24, MASS SPECTROMETRY.
[6]	"Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a." Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P. Nature 395:237-243(1998) [PubMed: 9751050] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEXES WITH INK4A AND INK4D.
[7]	"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: VARIANTS [LARGE SCALE ANALYSIS] ASN-110 AND LEU-199.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X66365 mRNA. Translation: CAA47008.1.
AY128534 Genomic DNA. Translation: AAM76970.1.
AC000065 Genomic DNA. No translation available.
AC004128 Genomic DNA. No translation available.
AC004011 Genomic DNA. No translation available.
BC052264 mRNA. Translation: AAH52264.1.

PIR

S23387.

RefSeq

NP_001250.1.

UniGene

Hs.119882

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BI7	X-ray	3.40	A	1-326	[»]
1BI8	X-ray	2.80	A/C	1-326	[»]
1BLX	X-ray	1.90	A	1-326	[»]
1G3N	X-ray	2.90	A/E	1-326	[»]
1JOW	X-ray	3.10	B	1-308	[»]
1XO2	X-ray	2.90	B	1-308	[»]
2EUF	X-ray	3.00	B	1-308	[»]
2F2C	X-ray	2.80	B	1-308	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:687N.

IntAct

Q00534.

PTM databases

PhosphoSite

Q00534.

Polymorphism databases

NIEHS-SNPs

Search...

Proteomic databases

PeptideAtlas

Q00534.

Genome annotation databases

Ensembl

ENSG00000105810. Homo sapiens. [Contig view]

GeneID

1021.

KEGG

hsa:1021.

Organism-specific databases

H-InvDB

HIX0006844.

HGNC

HGNC:1777. CDK6.

HPA

CAB004363.
HPA002637.

MIM

603368. gene.

PharmGKB

PA103.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q00534.

HOVERGEN

Q00534.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

Q00534.

CleanEx

HS_CDK6.

GermOnline

ENSG00000105810. 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

Q00534.

LinkHub

Q00534.

NextBio

4291.

SOURCE

Search...

Entry information

Entry name

CDK6_HUMAN

Accession

Primary (citable) accession number: Q00534

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	November 25, 2008
This is version 96 of the entry and version 1 of the sequence.