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Protein

G1/S-specific cyclin-D1

Gene

CCND1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex 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 D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCyclin, Repressor
Biological processCell cycle, Cell division, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-BTA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-BTA-3214858 RMTs methylate histone arginines
R-BTA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-BTA-69231 Cyclin D associated events in G1
R-BTA-8849470 PTK6 Regulates Cell Cycle
R-BTA-8878166 Transcriptional regulation by RUNX2
R-BTA-8934593 Regulation of RUNX1 Expression and Activity
R-BTA-8951936 RUNX3 regulates p14-ARF

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D1
Gene namesi
Name:CCND1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 29

Organism-specific databases

VGNCiVGNC:26962 CCND1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002444611 – 295G1/S-specific cyclin-D1Add BLAST295

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei286PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex (By similarity).By similarity
Ubiquitinated, primarily as 'Lys-48'-linked polyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation. Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ2KI22
PRIDEiQ2KI22

Expressioni

Gene expression databases

BgeeiENSBTAG00000017514

Interactioni

Subunit structurei

Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Interacts directly with CDKN1B. Can form similar complexes with either CDKN1A or CDKN2A. Interacts with USP2 and FBXO4. Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation. Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity. Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000023277

Structurei

3D structure databases

ProteinModelPortaliQ2KI22
SMRiQ2KI22
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 152Cyclin N-terminalAdd BLAST125

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi273 – 280Poly-Glu8

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00910000144111
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiQ2KI22
KOiK04503
OMAiLGSPNNF
OrthoDBiEOG091G0URX
TreeFamiTF101004

Family and domain databases

CDDicd00043 CYCLIN, 1 hit
InterProiView protein in InterPro
IPR013763 Cyclin-like
IPR036915 Cyclin-like_sf
IPR004367 Cyclin_C-dom
IPR015451 Cyclin_D
IPR006671 Cyclin_N
PANTHERiPTHR10177:SF67 PTHR10177:SF67, 1 hit
PfamiView protein in Pfam
PF02984 Cyclin_C, 1 hit
PF00134 Cyclin_N, 1 hit
SMARTiView protein in SMART
SM00385 CYCLIN, 1 hit
SM01332 Cyclin_C, 1 hit
SUPFAMiSSF47954 SSF47954, 2 hits
PROSITEiView protein in PROSITE
PS00292 CYCLINS, 1 hit

Sequencei

Sequence statusi: Complete.

Q2KI22-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHQLLCCEM ETIRRAYPDA NLLNDRVLRA MLKAEETCAP SVSYFKCVQK
60 70 80 90 100
EILPSMRKIV ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPVKKSRLQ
110 120 130 140 150
LLGATCMFVA SKMKETIPLT AEKLCIYTDN SIRPDELLHM ELVLVNKLKW
160 170 180 190 200
NLAAMTPHDF IEHFLSKMPV AEENKQIIRK HAQTFVALCA TDVKFISNPP
210 220 230 240 250
SMVAAGSVAA AAQGLHLGSA NGFLSYHRLT RFLSKVIRCD PDCLRACQEQ
260 270 280 290
IEALLESSLR QAQQQNLDPK AAEEEEEEEE VDLACTPTDV RDVNI
Length:295
Mass (Da):33,407
Last modified:March 7, 2006 - v1
Checksum:i4D9E5E0121C3314C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC112798 mRNA Translation: AAI12799.1
RefSeqiNP_001039738.1, NM_001046273.2
UniGeneiBt.88783

Genome annotation databases

EnsembliENSBTAT00000023277; ENSBTAP00000023277; ENSBTAG00000017514
GeneIDi524530
KEGGibta:524530

Similar proteinsi

Entry informationi

Entry nameiCCND1_BOVIN
AccessioniPrimary (citable) accession number: Q2KI22
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: March 7, 2006
Last modified: March 28, 2018
This is version 92 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health