Q00526 (CDK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 3
EC=2.7.11.22

Alternative name(s):
Cell division protein kinase 3

Gene names

Name:	CDK3
Synonyms:	CDKN3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner. Ref.3 Ref.4 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with CABLES1 and CABLES2 By similarity. Interacts with ATF1. Binding to CCNC/cyclin-C promotes RB1 phosphorylation. Ref.4 Ref.5
Tissue specificity	Expressed in cancer cell lines and glioblastoma tissue. Ref.5
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 Mitosis
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G0 to G1 transition Traceable author statement Ref.4. Source: UniProtKB G1/S transition of mitotic cell cycle Traceable author statement Ref.3. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement Ref.5. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent protein serine/threonine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 305

305

Cyclin-dependent kinase 3

PRO_0000085776

Regions

Domain

4 – 286

283

Protein kinase

Nucleotide binding

10 – 18

9

ATP By similarity

Sites

Active site

127

1

Proton acceptor By similarity

Binding site

33

1

ATP By similarity

Amino acid modifications

Modified residue

15

1

Phosphotyrosine By similarity

Natural variations

Natural variant

106

1

S → N in a glioblastoma multiforme sample; somatic mutation. Ref.7

VAR_041973

Natural variant

124

1

I → T. Ref.7
Corresponds to variant rs34918446 [ dbSNP | Ensembl ].

VAR_041974

Natural variant

214

1

R → H. Ref.7
Corresponds to variant rs34670267 [ dbSNP | Ensembl ].

VAR_041975

Natural variant

226

1

T → I. Ref.2
Corresponds to variant rs2069532 [ dbSNP | Ensembl ].

VAR_021101

Natural variant

264

1

M → T. Ref.2 Ref.7
Corresponds to variant rs17884251 [ dbSNP | Ensembl ].

VAR_021102

Secondary structure

1

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305

Helix Strand Turn

Details...

Beta strand

4 – 12

9

Beta strand

14 – 23

10

Turn

24 – 26

3

Beta strand

29 – 36

8

Beta strand

39 – 42

4

Helix

46 – 57

12

Beta strand

66 – 71

6

Beta strand

73 – 81

9

Beta strand

84 – 86

3

Helix

87 – 93

7

Turn

95 – 97

3

Helix

101 – 120

20

Helix

130 – 132

3

Beta strand

133 – 135

3

Beta strand

141 – 143

3

Beta strand

154 – 157

4

Turn

159 – 161

3

Helix

171 – 175

5

Helix

183 – 198

16

Helix

208 – 219

12

Turn

224 – 226

3

Helix

230 – 232

3

Helix

248 – 251

4

Helix

257 – 266

10

Turn

271 – 273

3

Helix

277 – 282

6

Helix

284 – 286

3

Sequences

	Sequence		Length	Mass (Da)
	Q00526 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 1128BE0096EA262A	FASTA	305	35,046
	10 20 30 40 50 60 MDMFQKVEKI GEGTYGVVYK AKNRETGQLV ALKKIRLDLE MEGVPSTAIR EISLLKELKH 70 80 90 100 110 120 PNIVRLLDVV HNERKLYLVF EFLSQDLKKY MDSTPGSELP LHLIKSYLFQ LLQGVSFCHS 130 140 150 160 170 180 HRVIHRDLKP QNLLINELGA IKLADFGLAR AFGVPLRTYT HEVVTLWYRA PEILLGSKFY 190 200 210 220 230 240 TTAVDIWSIG CIFAEMVTRK ALFPGDSEID QLFRIFRMLG TPSEDTWPGV TQLPDYKGSF 250 260 270 280 290 300 PKWTRKGLEE IVPNLEPEGR DLLMQLLQYD PSQRITAKTA LAHPYFSSPE PSPAARQYVL QRFRH

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-226 AND THR-264.
[3]	"Differential effects of cdk2 and cdk3 on the control of pRb and E2F function during G1 exit." Hofmann F., Livingston D.M. Genes Dev. 10:851-861(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN G1-S TRANSITION.
[4]	"Cyclin C/cdk3 promotes Rb-dependent G0 exit." Ren S., Rollins B.J. Cell 117:239-251(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RB1 KINASE, FUNCTION IN G0-G1 TRANSITION, INTERACTION WITH CCNC.
[5]	"Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation." Zheng D., Cho Y.-Y., Lau A.T.Y., Zhang J., Ma W.-Y., Bode A.M., Dong Z. Cancer Res. 68:7650-7660(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS ATF1 KINASE, TISSUE SPECIFICITY, INTERACTION WITH ATF1.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-106; THR-124; HIS-214 AND THR-264.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66357 mRNA. Translation: CAA47001.1.
AY789470 Genomic DNA. Translation: AAV40830.1.

IPI

IPI00023503.

PIR

S23382.

RefSeq

NP_001249.1. NM_001258.2.

UniGene

Hs.706766.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LFN	model	-	A	1-305	[»]

ProteinModelPortal

Q00526.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-686N.

IntAct

Q00526. 9 interactions.

STRING

9606.ENSP00000400088.

PTM databases

PhosphoSite

Q00526.

Polymorphism databases

DMDM

231726.

Proteomic databases

PaxDb

Q00526.

PRIDE

Q00526.

Protocols and materials databases

DNASU

1018.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000425876; ENSP00000410561; ENSG00000250506.
ENST00000448471; ENSP00000400088; ENSG00000250506.

GeneID

1018.

KEGG

hsa:1018.

UCSC

uc002jqg.4. human.

Organism-specific databases

CTD

1018.

GeneCards

GC17P073996.

HGNC

HGNC:1772. CDK3.

HPA

HPA007420.

MIM

123828. gene.

neXtProt

NX_Q00526.

PharmGKB

PA26309.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233024.

HOVERGEN

HBG014652.

InParanoid

Q00526.

KO

K02088.

OMA

PYFSSTE.

OrthoDB

EOG4C5CJV.

PhylomeDB

Q00526.

Enzyme and pathway databases

BRENDA

2.7.11.22. 2681.

Gene expression databases

Bgee

Q00526.

CleanEx

HS_CDK3.

Genevestigator

Q00526.

GermOnline

ENSG00000108504. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

Q00526.

ChEMBL

CHEMBL4442.

GenomeRNAi

1018.

NextBio

4279.

SOURCE

Search...

Entry information

Entry name

CDK3_HUMAN

Accession

Primary (citable) accession number: Q00526

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.