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B2MVY4

- CDK4_SHEEP

UniProt

B2MVY4 - CDK4_SHEEP

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Protein
Cyclin-dependent kinase 4
Gene
N/A
Organism
Ovis aries (Sheep)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at transcript leveli

Functioni

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 activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei35 – 351ATP By similarity
Active sitei140 – 1401Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi12 – 209ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB-EC
Complete GO annotation...

GO - Biological processi

  1. cell division Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 4 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 4
OrganismiOvis aries (Sheep)
Taxonomic identifieri9940 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
ProteomesiUP000002356: Unplaced

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. membrane Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 303302Cyclin-dependent kinase 4
PRO_0000405926Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei172 – 1721Phosphothreonine; by CAK By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliB2MVY4.
SMRiB2MVY4. Positions 2-299.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 295290Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni50 – 567Required for binding D-type cyclins By similarity

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG014652.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

B2MVY4-1 [UniParc]FASTAAdd to Basket

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MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGAGGGLP    50
ISTVREVALL RRLEAFEHPN VVRLMDVCAT ARTDRETKVT LVFEHVDQDL 100
RTYLDKAPPP GLPVETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS 150
GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV 200
GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFS 250
PRGPRPVQSV VPELEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKAEG 300
DAE 303
Length:303
Mass (Da):33,647
Last modified:June 10, 2008 - v1
Checksum:i3623FDD0B25EF20A
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
EU626223 mRNA. Translation: ACC93618.1.
FJ943997 mRNA. Translation: ACR46652.1.
EU525168 mRNA. Translation: ACB20722.1.
RefSeqiNP_001120741.1. NM_001127269.1.
UniGeneiOar.4604.

Genome annotation databases

GeneIDi100144756.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
EU626223 mRNA. Translation: ACC93618.1 .
FJ943997 mRNA. Translation: ACR46652.1 .
EU525168 mRNA. Translation: ACB20722.1 .
RefSeqi NP_001120741.1. NM_001127269.1.
UniGenei Oar.4604.

3D structure databases

ProteinModelPortali B2MVY4.
SMRi B2MVY4. Positions 2-299.
ModBasei Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100144756.

Organism-specific databases

CTDi 1019.

Phylogenomic databases

HOVERGENi HBG014652.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiCDK4_SHEEP
AccessioniPrimary (citable) accession number: B2MVY4
Secondary accession number(s): B2CL06
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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