B2MVY4 (CDK4_SHEEP) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 25. History...
Names and origin
|Protein names||Recommended name:|
Cyclin-dependent kinase 4
Cell division protein kinase 4
|Organism||Ovis aries (Sheep)|
|Taxonomic identifier||9940 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Ovis|
|Sequence length||303 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex By similarity.
ATP + a protein = ADP + a phosphoprotein.
Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation.
Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4 By similarity.
Cytoplasm By similarity. Nucleus By similarity. Membrane By similarity. Note: Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G1 phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G1 to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus By similarity.
Contains 1 protein kinase domain.
|Biological process||Cell cycle|
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: UniProtKB-KW
Inferred from electronic annotation. Source: UniProtKB-SubCellmembrane
Inferred from electronic annotation. Source: UniProtKB-SubCellnucleus
Inferred from electronic annotation. Source: UniProtKB-SubCell
Inferred from electronic annotation. Source: UniProtKB-KWcyclin-dependent protein serine/threonine kinase activity
Inferred from electronic annotation. Source: EC
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 303||303||Cyclin-dependent kinase 4||PRO_0000405926|
|Domain||6 – 295||290||Protein kinase|
|Nucleotide binding||12 – 20||9||ATP By similarity|
|Region||50 – 56||7||Required for binding D-type cyclins By similarity|
|Active site||140||1||Proton acceptor By similarity|
|Binding site||35||1||ATP By similarity|
Amino acid modifications
|Modified residue||172||1||Phosphothreonine; by CAK By similarity|
|||"Molecular clone and sequence analysis of CDK4 from black-boned sheep (Ovis aries)."|
Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"CDK4 cyclin-dependent kinase 4."|
Liu G.Y., Ge C.R.
Submitted (APR-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||Rozance P.J., LoTurco D.G.|
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-281.
|EU626223 mRNA. Translation: ACC93618.1.|
FJ943997 mRNA. Translation: ACR46652.1.
EU525168 mRNA. Translation: ACB20722.1.
|RefSeq||NP_001120741.1. NM_001127269.1. |
3D structure databases
|SMR||B2MVY4. Positions 2-299. |
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|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.
|Accession||Primary (citable) accession number: B2MVY4|
Secondary accession number(s): B2CL06
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families