Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

G1/S-specific cyclin-D2

Gene

CCND2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulatory component of the cyclin D2-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 D2/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (By similarity).By similarity

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • positive regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cyclin

Keywords - Biological processi

Cell cycle, Cell division

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118971-MONOMER.
ReactomeiR-HSA-69231. Cyclin D associated events in G1.
SignaLinkiP30279.
SIGNORiP30279.

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D2
Gene namesi
Name:CCND2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:1583. CCND2.

Subcellular locationi

Isoform 2 :

GO - Cellular componenti

  • chromatin Source: UniProtKB
  • cyclin D2-CDK4 complex Source: Ensembl
  • cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  • cytosol Source: UniProtKB
  • nuclear membrane Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by megalencephaly, ventriculomegaly that may lead to hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
See also OMIM:615938
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072370280T → A in MPPH3. 1 PublicationCorresponds to variant rs587777618dbSNPEnsembl.1
Natural variantiVAR_072371280T → N in MPPH3. 1 PublicationCorresponds to variant rs587777620dbSNPEnsembl.1
Natural variantiVAR_072372281P → L in MPPH3. 1 PublicationCorresponds to variant rs587777622dbSNPEnsembl.1
Natural variantiVAR_072373281P → R in MPPH3. 1 PublicationCorresponds to variant rs587777622dbSNPEnsembl.1
Natural variantiVAR_072374284V → G in MPPH3. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi894.
MalaCardsiCCND2.
MIMi615938. phenotype.
OpenTargetsiENSG00000118971.
Orphaneti83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBiPA26150.

Chemistry databases

ChEMBLiCHEMBL3301385.

Polymorphism and mutation databases

BioMutaiCCND2.
DMDMi231741.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000804371 – 289G1/S-specific cyclin-D2Add BLAST289

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei271PhosphoserineCombined sources1
Modified residuei280PhosphothreonineBy similarity1

Post-translational modificationi

Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30279.
MaxQBiP30279.
PaxDbiP30279.
PeptideAtlasiP30279.
PRIDEiP30279.

PTM databases

iPTMnetiP30279.
PhosphoSitePlusiP30279.

Expressioni

Gene expression databases

BgeeiENSG00000118971.
CleanExiHS_CCND2.
ExpressionAtlasiP30279. baseline and differential.
GenevisibleiP30279. HS.

Organism-specific databases

HPAiHPA049138.
HPA054196.

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK4P118028EBI-748789,EBI-295644
CDK5Q0053510EBI-748789,EBI-1041567
CDKN1AP3893614EBI-748789,EBI-375077

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107334. 23 interactors.
DIPiDIP-178N.
IntActiP30279. 7 interactors.
MINTiMINT-1433179.
STRINGi9606.ENSP00000261254.

Structurei

3D structure databases

ProteinModelPortaliP30279.
SMRiP30279.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 151Cyclin N-terminalAdd BLAST126

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.
InParanoidiP30279.
KOiK10151.
OMAiNLLHDDR.
OrthoDBiEOG091G0URX.
PhylomeDBiP30279.
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:SF66. PTHR10177:SF66. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30279-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELLCHEVDP VRRAVRDRNL LRDDRVLQNL LTIEERYLPQ CSYFKCVQKD
60 70 80 90 100
IQPYMRRMVA TWMLEVCEEQ KCEEEVFPLA MNYLDRFLAG VPTPKSHLQL
110 120 130 140 150
LGAVCMFLAS KLKETSPLTA EKLCIYTDNS IKPQELLEWE LVVLGKLKWN
160 170 180 190 200
LAAVTPHDFI EHILRKLPQQ REKLSLIRKH AQTFIALCAT DFKFAMYPPS
210 220 230 240 250
MIATGSVGAA ICGLQQDEEV SSLTCDALTE LLAKITNTDV DCLKACQEQI
260 270 280
EAVLLNSLQQ YRQDQRDGSK SEDELDQAST PTDVRDIDL
Length:289
Mass (Da):33,067
Last modified:April 1, 1993 - v1
Checksum:iE4E5FEF476D76D90
GO
Isoform 2 (identifier: P30279-2) [UniParc]FASTAAdd to basket
Also known as: Truncated

The sequence of this isoform differs from the canonical sequence as follows:
     138-209: EWELVVLGKL...SMIATGSVGA → VMTGPFLPSF...YYVPRLRAQH
     210-289: Missing.

Note: Acts as proto-oncogene. Retains ability to bind CDK4, but unable to catalyze efficiently RB phosphorylation and inactivation.1 Publication
Show »
Length:209
Mass (Da):24,461
Checksum:i35CABC2E9A5BF46E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti166 – 167KL → NV in AAA51928 (PubMed:1386335).Curated2
Sequence conflicti224T → H in AAA51928 (PubMed:1386335).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018820268G → R.1 PublicationCorresponds to variant rs3217921dbSNPEnsembl.1
Natural variantiVAR_072370280T → A in MPPH3. 1 PublicationCorresponds to variant rs587777618dbSNPEnsembl.1
Natural variantiVAR_072371280T → N in MPPH3. 1 PublicationCorresponds to variant rs587777620dbSNPEnsembl.1
Natural variantiVAR_072372281P → L in MPPH3. 1 PublicationCorresponds to variant rs587777622dbSNPEnsembl.1
Natural variantiVAR_072373281P → R in MPPH3. 1 PublicationCorresponds to variant rs587777622dbSNPEnsembl.1
Natural variantiVAR_072374284V → G in MPPH3. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_057295138 – 209EWELV…GSVGA → VMTGPFLPSFLRFPLSPGQQ YAFYHHCQSKFLGSRMTPPI EFTHLWAIAHLIGNHCLFFV CSYYVPRLRAQH in isoform 2. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_057296210 – 289Missing in isoform 2. 1 PublicationAdd BLAST80

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90813 mRNA. Translation: AAA51926.1.
X68452 mRNA. Translation: CAA48493.1.
D13639 mRNA. Translation: BAA02802.1.
BT019847 mRNA. Translation: AAV38650.1.
AF518005 Genomic DNA. Translation: AAM54041.1.
AK291146 mRNA. Translation: BAF83835.1.
AC006122 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88851.1.
BC010958 mRNA. Translation: AAH10958.1.
BC089384 mRNA. Translation: AAH89384.1.
M88083
, M88080, M88081, M88082 Genomic DNA. Translation: AAA51928.1.
AI146555 mRNA. No translation available.
CCDSiCCDS8524.1. [P30279-1]
PIRiA42822.
RefSeqiNP_001750.1. NM_001759.3. [P30279-1]
UniGeneiHs.376071.

Genome annotation databases

EnsembliENST00000261254; ENSP00000261254; ENSG00000118971. [P30279-1]
GeneIDi894.
KEGGihsa:894.
UCSCiuc001qmo.4. human. [P30279-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90813 mRNA. Translation: AAA51926.1.
X68452 mRNA. Translation: CAA48493.1.
D13639 mRNA. Translation: BAA02802.1.
BT019847 mRNA. Translation: AAV38650.1.
AF518005 Genomic DNA. Translation: AAM54041.1.
AK291146 mRNA. Translation: BAF83835.1.
AC006122 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88851.1.
BC010958 mRNA. Translation: AAH10958.1.
BC089384 mRNA. Translation: AAH89384.1.
M88083
, M88080, M88081, M88082 Genomic DNA. Translation: AAA51928.1.
AI146555 mRNA. No translation available.
CCDSiCCDS8524.1. [P30279-1]
PIRiA42822.
RefSeqiNP_001750.1. NM_001759.3. [P30279-1]
UniGeneiHs.376071.

3D structure databases

ProteinModelPortaliP30279.
SMRiP30279.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107334. 23 interactors.
DIPiDIP-178N.
IntActiP30279. 7 interactors.
MINTiMINT-1433179.
STRINGi9606.ENSP00000261254.

Chemistry databases

ChEMBLiCHEMBL3301385.

PTM databases

iPTMnetiP30279.
PhosphoSitePlusiP30279.

Polymorphism and mutation databases

BioMutaiCCND2.
DMDMi231741.

Proteomic databases

EPDiP30279.
MaxQBiP30279.
PaxDbiP30279.
PeptideAtlasiP30279.
PRIDEiP30279.

Protocols and materials databases

DNASUi894.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261254; ENSP00000261254; ENSG00000118971. [P30279-1]
GeneIDi894.
KEGGihsa:894.
UCSCiuc001qmo.4. human. [P30279-1]

Organism-specific databases

CTDi894.
DisGeNETi894.
GeneCardsiCCND2.
HGNCiHGNC:1583. CCND2.
HPAiHPA049138.
HPA054196.
MalaCardsiCCND2.
MIMi123833. gene.
615938. phenotype.
neXtProtiNX_P30279.
OpenTargetsiENSG00000118971.
Orphaneti83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
PharmGKBiPA26150.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0656. Eukaryota.
ENOG410XRKC. LUCA.
GeneTreeiENSGT00760000118939.
HOGENOMiHOG000008182.
HOVERGENiHBG050837.
InParanoidiP30279.
KOiK10151.
OMAiNLLHDDR.
OrthoDBiEOG091G0URX.
PhylomeDBiP30279.
TreeFamiTF101004.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118971-MONOMER.
ReactomeiR-HSA-69231. Cyclin D associated events in G1.
SignaLinkiP30279.
SIGNORiP30279.

Miscellaneous databases

ChiTaRSiCCND2. human.
GeneWikiiCyclin_D2.
GenomeRNAii894.
PROiP30279.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118971.
CleanExiHS_CCND2.
ExpressionAtlasiP30279. baseline and differential.
GenevisibleiP30279. HS.

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:SF66. PTHR10177:SF66. 1 hit.
PfamiPF02984. Cyclin_C. 1 hit.
PF00134. Cyclin_N. 1 hit.
[Graphical view]
SMARTiSM00385. CYCLIN. 1 hit.
SM01332. Cyclin_C. 1 hit.
[Graphical view]
SUPFAMiSSF47954. SSF47954. 2 hits.
PROSITEiPS00292. CYCLINS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCND2_HUMAN
AccessioniPrimary (citable) accession number: P30279
Secondary accession number(s): A8K531, Q13955, Q5U035
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 30, 2016
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.