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P79432

- CDK4_PIG

UniProt

P79432 - CDK4_PIG

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Protein

Cyclin-dependent kinase 4

Gene
CDK4
Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5 - Protein inferred from homologyi

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 phosphorylates SMAD3 in a cell-cycle-dependent manner and represses 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

GO - Biological processi

  1. cell division Source: UniProtKB-KW
  2. G1/S transition of mitotic cell cycle Source: Ensembl
  3. negative regulation of cell cycle arrest Source: UniProtKB
  4. positive regulation of fibroblast proliferation Source: Ensembl
  5. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  6. regulation of gene expression Source: Ensembl
  7. response to drug Source: Ensembl
  8. signal transduction Source: Ensembl
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

Enzyme and pathway databases

ReactomeiREACT_191907. Oncogene Induced Senescence.
REACT_191909. Senescence-Associated Secretory Phenotype (SASP).
REACT_193624. Oxidative Stress Induced Senescence.
REACT_205748. Cyclin D associated events in G1.
REACT_207430. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 4 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 4
Gene namesi
Name:CDK4
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: 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. chromatin Source: Ensembl
  2. cyclin-dependent protein kinase holoenzyme complex Source: Ensembl
  3. cytosol Source: Ensembl
  4. nuclear membrane Source: Ensembl
  5. nucleolus Source: Ensembl
  6. tight junction Source: Ensembl
  7. transcription factor complex Source: Ensembl
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 4PRO_0000085780Add
BLAST

Amino acid modifications

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

Post-translational modificationi

Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B 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. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression By similarity.

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000000473.

Structurei

3D structure databases

ProteinModelPortaliP79432.
SMRiP79432. Positions 2-299.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00720000108415.
HOVERGENiHBG014652.
KOiK02089.
OMAiIDQDLRT.
OrthoDBiEOG73JKVV.
TreeFamiTF101022.

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.

P79432-1 [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 VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKAEG 300
NPE 303
Length:303
Mass (Da):33,690
Last modified:May 1, 1997 - v1
Checksum:iD77C5630B25EF20B
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68478 Genomic DNA. Translation: AAB39636.1.
U68479 Genomic DNA. Translation: AAB39637.1.
RefSeqiNP_001116569.1. NM_001123097.1.
UniGeneiSsc.11051.

Genome annotation databases

EnsembliENSSSCT00000028348; ENSSSCP00000022407; ENSSSCG00000025092.
GeneIDi100144492.
KEGGissc:100144492.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U68478 Genomic DNA. Translation: AAB39636.1 .
U68479 Genomic DNA. Translation: AAB39637.1 .
RefSeqi NP_001116569.1. NM_001123097.1.
UniGenei Ssc.11051.

3D structure databases

ProteinModelPortali P79432.
SMRi P79432. Positions 2-299.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9823.ENSSSCP00000000473.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSSSCT00000028348 ; ENSSSCP00000022407 ; ENSSSCG00000025092 .
GeneIDi 100144492.
KEGGi ssc:100144492.

Organism-specific databases

CTDi 1019.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00720000108415.
HOVERGENi HBG014652.
KOi K02089.
OMAi IDQDLRT.
OrthoDBi EOG73JKVV.
TreeFami TF101022.

Enzyme and pathway databases

Reactomei REACT_191907. Oncogene Induced Senescence.
REACT_191909. Senescence-Associated Secretory Phenotype (SASP).
REACT_193624. Oxidative Stress Induced Senescence.
REACT_205748. Cyclin D associated events in G1.
REACT_207430. Meiotic recombination.

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. "Sequence and intron/exon organization of porcine CDK4 gene."
    Shibuya H., Renshaw F.G., Bouchard G.F., Nonneman D., Johnson G.S.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Entry informationi

Entry nameiCDK4_PIG
AccessioniPrimary (citable) accession number: P79432
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: September 3, 2014
This is version 89 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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