Q5E9Y0 (CDK2_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 2
EC=2.7.11.22

Alternative name(s):
Cell division protein kinase 2

Gene names

Name:	CDK2
Synonyms:	CDKN2

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	298 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 By similarity. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) By similarity.
Subunit structure	Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1 By similarity. Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Found in a complex with both SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta-catenin/CTNNB1 By similarity.
Subcellular location	Cytoplasm › cytoskeleton › centrosome By similarity. Nucleus › Cajal body By similarity. Cytoplasm By similarity. Endosome By similarity. Note: Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic trafficking is mediated during the inhibition by 1,25-(OH)2D3 By similarity.
Post-translational modification	Phosphorylated at Thr-160 by CDK7 in a CAK complex. Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A By similarity. Nitrosylated after treatment with nitric oxide (DETA-NO) 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 DNA damage DNA repair Meiosis Mitosis
Cellular component	Cytoplasm Cytoskeleton Endosome Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Nitration Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: AgBase potassium ion transport Inferred from sequence or structural similarity. Source: AgBase
Cellular component	Cajal body Inferred from electronic annotation. Source: UniProtKB-SubCell cyclin-dependent protein kinase holoenzyme complex Inferred from sequence or structural similarity. Source: AgBase endosome Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell transcription factor complex Inferred from sequence or structural similarity. Source: AgBase
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent protein kinase activity Inferred from sequence or structural similarity. Source: AgBase metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 298	298	Cyclin-dependent kinase 2		PRO_0000085767
Regions
	Domain	4 – 286	283	Protein kinase
	Nucleotide binding	10 – 18	9	ATP By similarity
	Nucleotide binding	81 – 83	3	ATP By similarity
	Nucleotide binding	129 – 132	4	ATP By similarity
Sites
	Active site	127	1	Proton acceptor By similarity
	Metal binding	132	1	Magnesium; catalytic By similarity
	Metal binding	145	1	Magnesium; catalytic By similarity
	Binding site	33	1	ATP By similarity
	Binding site	86	1	ATP By similarity
	Binding site	145	1	ATP By similarity
	Site	9	1	CDK7 binding By similarity
	Site	88 – 89	2	CDK7 binding By similarity
	Site	166	1	CDK7 binding By similarity
Amino acid modifications
	Modified residue	6	1	N6-acetyllysine By similarity
	Modified residue	14	1	Phosphothreonine By similarity
	Modified residue	15	1	Phosphotyrosine; by WEE1 By similarity
	Modified residue	19	1	Phosphotyrosine By similarity
	Modified residue	46	1	Phosphoserine By similarity
	Modified residue	158	1	Phosphothreonine By similarity
	Modified residue	159	1	Phosphotyrosine By similarity
	Modified residue	160	1	Phosphothreonine; by CAK and CCRK By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q5E9Y0 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: EEC785D6A0E87A71	FASTA	298	33,873
	10 20 30 40 50 60 MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH 70 80 90 100 110 120 PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS 130 140 150 160 170 180 HRVLHRDLKP QNLLINADGS IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY 190 200 210 220 230 240 STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF 250 260 270 280 290 PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL

References

[1]	"Characterization of 954 bovine full-CDS cDNA sequences." Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L. BMC Genomics 6:166-166(2005) [PubMed: 16305752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Thymus.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BT020790 mRNA. Translation: AAX08807.1. BC150026 mRNA. Translation: AAI50027.1.
IPI	IPI00712735.
RefSeq	NP_001014934.1. NM_001014934.1.
UniGene	Bt.21444.
3D structure databases
ProteinModelPortal	Q5E9Y0.
SMR	Q5E9Y0. Positions 1-298.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5E9Y0.
Proteomic databases
PRIDE	Q5E9Y0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000005252; ENSBTAP00000005252; ENSBTAG00000004021.
GeneID	519217.
KEGG	bta:519217.
Organism-specific databases
CTD	1017.
Phylogenomic databases
eggNOG	maNOG16767.
GeneTree	ENSGT00600000083998.
HOVERGEN	HBG014652.
InParanoid	Q5E9Y0.
OMA	IFAEMCN.
OrthoDB	EOG4C5CJV.
PhylomeDB	Q5E9Y0.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K02206.
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...

Entry information

Entry name

CDK2_BOVIN

Accession

Primary (citable) accession number: Q5E9Y0
Secondary accession number(s): A6QQX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program