Cyclin-dependent kinase 2 - Cricetulus griseus (Chinese hamster)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Preferred order of sections

Molecule processing

Regions

Sites

Amino acid modifications

Sequence databases

3D structure databases

Proteomic databases

Protocols and materials databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

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O55076 (CDK2_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 90. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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:	CDKN7

Organism

Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)

Taxonomic identifier

10029 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Cricetulus

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

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. Interacts with CACUL1 By similarity. May interact with CEP63 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.

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Meiosis Mitosis
Cellular component	Cytoplasm Cytoskeleton Endosome Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
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
Cellular_component	Cajal body Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell midbody Inferred from direct assay PubMed 15166316. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cyclin-dependent protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 298

298

Cyclin-dependent kinase 2

PRO_0000085768

Domain

4 – 286

283

Protein kinase

Nucleotide binding

10 – 18

ATP By similarity

Nucleotide binding

81 – 83

ATP By similarity

Nucleotide binding

129 – 132

ATP By similarity

Active site

127

Proton acceptor By similarity

Metal binding

132

Magnesium; catalytic By similarity

Metal binding

145

Magnesium; catalytic By similarity

Binding site

ATP By similarity

Binding site

ATP By similarity

Binding site

145

ATP By similarity

Site

CDK7 binding By similarity

Site

88 – 89

CDK7 binding By similarity

Site

166

CDK7 binding By similarity

Modified residue

N-acetylmethionine By similarity

Modified residue

N6-acetyllysine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphotyrosine; by WEE1 By similarity

Modified residue

Phosphotyrosine By similarity

Modified residue

160

Phosphothreonine; by CAK and CCRK By similarity

Sequence

Length

Mass (Da)

Tools

Isoform CDK2-alpha [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 3B580D8C2460CD8E
Show »

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 MDASAVTGIP LPLIKSYLFQ LLQGLAFCHS 

       130        140        150        160        170        180 
HRVLHRDLKP QNLLINAEGS 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

« Hide

Isoform CDK2-beta (Sequence not available).

–

[1]

"The long form of CDK2 arises via alternative splicing and forms an active protein kinase with cyclins A and E."
Ellenrieder C., Bartosch B., Lee G.Y., Murphy M., Sweeney C., Hergersberg M., Carrington M., Jaussi R., Hunt T.
DNA Cell Biol. 20:413-423(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Sequence databases
EMBL GenBank DDBJ	AJ223949 mRNA. Translation: CAA11680.1.
3D structure databases
ProteinModelPortal	O55076.
SMR	O55076. Positions 1-298.
ModBase	Search...
Proteomic databases
PRIDE	O55076.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG014652.
Enzyme and pathway databases
BRENDA	2.7.11.22. 1309.
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...

Entry name

CDK2_CRIGR

Accession

Primary (citable) accession number: O55076

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

This entry describes 2 isoforms produced by alternative splicing. [Select]

Isoform CDK2-alpha (identifier: O55076-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform CDK2-beta (identifier: O55076-2)

The sequence of this isoform is not available.