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Protein

G1/S-specific cyclin-D1

Gene

Ccnd1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • canonical Wnt signaling pathway Source: Ensembl
  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: Ensembl
  • fat cell differentiation Source: Ensembl
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • lactation Source: Ensembl
  • Leydig cell differentiation Source: RGD
  • liver development Source: RGD
  • liver regeneration Source: Ensembl
  • mammary gland alveolus development Source: Ensembl
  • mammary gland epithelial cell proliferation Source: Ensembl
  • mitotic G1 DNA damage checkpoint Source: UniProtKB
  • negative regulation of cell cycle arrest Source: UniProtKB
  • negative regulation of epithelial cell differentiation Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: Ensembl
  • organ regeneration Source: RGD
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of mammary gland epithelial cell proliferation Source: Ensembl
  • positive regulation of protein phosphorylation Source: UniProtKB
  • re-entry into mitotic cell cycle Source: Ensembl
  • regulation of cell cycle Source: RGD
  • response to calcium ion Source: RGD
  • response to corticosterone Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to estrogen Source: RGD
  • response to ethanol Source: RGD
  • response to glucocorticoid Source: RGD
  • response to iron ion Source: RGD
  • response to leptin Source: Ensembl
  • response to magnesium ion Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to steroid hormone Source: RGD
  • response to UV-A Source: UniProtKB
  • response to vitamin E Source: RGD
  • response to X-ray Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Cyclin, Repressor

Keywords - Biological processi

Cell cycle, Cell division, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-RNO-3214858. RMTs methylate histone arginines.
R-RNO-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-RNO-69231. Cyclin D associated events in G1.
R-RNO-8849470. PTK6 Regulates Cell Cycle.

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D1
Gene namesi
Name:Ccnd1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi68384. Ccnd1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity
  • Membrane By similarity

  • Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members.By similarity

GO - Cellular componenti

  • bicellular tight junction Source: Ensembl
  • cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  • cytoplasm Source: RGD
  • membrane Source: UniProtKB-SubCell
  • nucleoplasm Source: Ensembl
  • nucleus Source: RGD
  • transcriptional repressor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 295295G1/S-specific cyclin-D1PRO_0000080433Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki269 – 269Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei286 – 2861PhosphothreonineBy similarity

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

PaxDbiP39948.

PTM databases

iPTMnetiP39948.
PhosphoSiteiP39948.

Expressioni

Gene expression databases

BgeeiENSRNOG00000020918.
ExpressionAtlasiP39948. baseline and differential.
GenevisibleiP39948. RN.

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 complex binding Source: RGD
  • protein kinase binding Source: RGD

Protein-protein interaction databases

IntActiP39948. 1 interaction.
STRINGi10116.ENSRNOP00000028411.

Structurei

3D structure databases

ProteinModelPortaliP39948.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 152125Cyclin N-terminalAdd
BLAST

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated
Contains 1 cyclin N-terminal domain.Curated

Phylogenomic databases

eggNOGiKOG0656. Eukaryota.
ENOG410XRKC. LUCA.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000008182.
HOVERGENiHBG050837.
InParanoidiP39948.
KOiK04503.
OMAiMKETVPL.
OrthoDBiEOG091G0URX.
PhylomeDBiP39948.
TreeFamiTF101004.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR015451. Cyclin_D.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERiPTHR10177:SF67. PTHR10177:SF67. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 2 hits.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P39948-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEHQLLCCEV ETIRRAYPDT NLLNDRVLRA MLKTEETCAP SVSYFKCVQR
60 70 80 90 100
EIVPSMRKIV ATWMLEVCEE QKCEEEVFPL AMNYLDRFLS LEPLKKSRLQ
110 120 130 140 150
LLGATCMFVA SKMKETIPLT AEKLCIYTDN SIRPEELLQM ELLLVNKLKW
160 170 180 190 200
NLAAMTPHDF IEHFLSKMPE ADENKQIIRK HAQTFVALCA TDVKFISNPP
210 220 230 240 250
SMVAAGSVVA AMQGLNLGSP NNFLSCYRTT HFLSRVIKCD PDCLRACQEQ
260 270 280 290
IEALLESSLR QAQQNIDPKA TEEEGEVEEE AGLACTPTDV RDVDI
Length:295
Mass (Da):33,483
Last modified:February 1, 1995 - v1
Checksum:iC777436B5C79635E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 273DRV → RPG in BAA03115 (PubMed:8336937).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14014 mRNA. Translation: BAA03115.1.
X75207 mRNA. Translation: CAA53020.1.
PIRiJC2342.
RefSeqiNP_741989.3. NM_171992.4.
UniGeneiRn.22279.

Genome annotation databases

EnsembliENSRNOT00000028411; ENSRNOP00000028411; ENSRNOG00000020918.
GeneIDi58919.
KEGGirno:58919.
UCSCiRGD:68384. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14014 mRNA. Translation: BAA03115.1.
X75207 mRNA. Translation: CAA53020.1.
PIRiJC2342.
RefSeqiNP_741989.3. NM_171992.4.
UniGeneiRn.22279.

3D structure databases

ProteinModelPortaliP39948.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP39948. 1 interaction.
STRINGi10116.ENSRNOP00000028411.

PTM databases

iPTMnetiP39948.
PhosphoSiteiP39948.

Proteomic databases

PaxDbiP39948.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000028411; ENSRNOP00000028411; ENSRNOG00000020918.
GeneIDi58919.
KEGGirno:58919.
UCSCiRGD:68384. rat.

Organism-specific databases

CTDi595.
RGDi68384. Ccnd1.

Phylogenomic databases

eggNOGiKOG0656. Eukaryota.
ENOG410XRKC. LUCA.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000008182.
HOVERGENiHBG050837.
InParanoidiP39948.
KOiK04503.
OMAiMKETVPL.
OrthoDBiEOG091G0URX.
PhylomeDBiP39948.
TreeFamiTF101004.

Enzyme and pathway databases

ReactomeiR-RNO-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-RNO-3214858. RMTs methylate histone arginines.
R-RNO-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-RNO-69231. Cyclin D associated events in G1.
R-RNO-8849470. PTK6 Regulates Cell Cycle.

Miscellaneous databases

PROiP39948.

Gene expression databases

BgeeiENSRNOG00000020918.
ExpressionAtlasiP39948. baseline and differential.
GenevisibleiP39948. RN.

Family and domain databases

Gene3Di1.10.472.10. 2 hits.
InterProiIPR013763. Cyclin-like.
IPR004367. Cyclin_C-dom.
IPR015451. Cyclin_D.
IPR006671. Cyclin_N.
[Graphical view]
PANTHERiPTHR10177:SF67. PTHR10177:SF67. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 2 hits.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCND1_RAT
AccessioniPrimary (citable) accession number: P39948
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: September 7, 2016
This is version 124 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.