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B2MVY4 (CDK4_SHEEP) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 30. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 4

EC=2.7.11.22
Alternative name(s):
Cell division protein kinase 4
OrganismOvis aries (Sheep) [Reference proteome]
Taxonomic identifier9940 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis

Protein attributes

Sequence length303 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

Subunit structure

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.

Subcellular location

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.

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 processCell cycle
Cell division
   Cellular componentCytoplasm
Membrane
Nucleus
   DiseaseProto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell division

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 303302Cyclin-dependent kinase 4
PRO_0000405926

Regions

Domain6 – 295290Protein kinase
Nucleotide binding12 – 209ATP By similarity
Region50 – 567Required for binding D-type cyclins By similarity

Sites

Active site1401Proton acceptor By similarity
Binding site351ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue1721Phosphothreonine; by CAK By similarity

Sequences

Sequence LengthMass (Da)Tools
B2MVY4 [UniParc].

Last modified June 10, 2008. Version 1.
Checksum: 3623FDD0B25EF20A

FASTA30333,647
        10         20         30         40         50         60 
MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGAGGGLP ISTVREVALL 

        70         80         90        100        110        120 
RRLEAFEHPN VVRLMDVCAT ARTDRETKVT LVFEHVDQDL RTYLDKAPPP GLPVETIKDL 

       130        140        150        160        170        180 
MRQFLRGLDF LHANCIVHRD LKPENILVTS GGTVKLADFG LARIYSYQMA LTPVVVTLWY 

       190        200        210        220        230        240 
RAPEVLLQST YATPVDMWSV GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR 

       250        260        270        280        290        300 
DVSLPRGAFS PRGPRPVQSV VPELEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKAEG 


DAE 

« Hide

References

[1]"Molecular clone and sequence analysis of CDK4 from black-boned sheep (Ovis aries)."
Deng W.
Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
[3]Rozance P.J., LoTurco D.G.
Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-281.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EU626223 mRNA. Translation: ACC93618.1.
FJ943997 mRNA. Translation: ACR46652.1.
EU525168 mRNA. Translation: ACB20722.1.
RefSeqNP_001120741.1. NM_001127269.1.
UniGeneOar.4604.

3D structure databases

ProteinModelPortalB2MVY4.
SMRB2MVY4. Positions 2-299.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100144756.

Organism-specific databases

CTD1019.

Phylogenomic databases

HOVERGENHBG014652.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameCDK4_SHEEP
AccessionPrimary (citable) accession number: B2MVY4
Secondary accession number(s): B2CL06
Entry history
Integrated into UniProtKB/Swiss-Prot: March 8, 2011
Last sequence update: June 10, 2008
Last modified: July 9, 2014
This is version 30 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families