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Protein

G1/S-specific cyclin-D2

Gene

CCND2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • cyclin-dependent protein serine/threonine kinase regulator activity Source: GO_Central
  • protein kinase binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionCyclin
Biological processCell cycle, Cell division

Enzyme and pathway databases

ReactomeiR-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
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

EuPathDBiHostDB:ENSG00000118971.7
HGNCiHGNC:1583 CCND2
MIMi123833 gene
neXtProtiNX_P30279

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

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 dbSNP:rs587777618EnsemblClinVar.1
Natural variantiVAR_072371280T → N in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777620EnsemblClinVar.1
Natural variantiVAR_072372281P → L in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar.1
Natural variantiVAR_072373281P → R in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar.1
Natural variantiVAR_072374284V → G in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs777786993EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

ChEMBLiCHEMBL3301386

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
ProteomicsDBi54647

PTM databases

iPTMnetiP30279
PhosphoSitePlusiP30279

Expressioni

Gene expression databases

BgeeiENSG00000118971 Expressed in 240 organ(s), highest expression level in amniotic fluid
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107334, 91 interactors
ComplexPortaliCPX-2011 Cyclin D2-CDK4 complex
CORUMiP30279
DIPiDIP-178N
IntActiP30279, 8 interactors
MINTiP30279
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

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00930000150931
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP30279
KOiK10151
OMAiVVPTKKC
OrthoDBiEOG091G0URX
PhylomeDBiP30279
TreeFamiTF101004

Family and domain databases

CDDicd00043 CYCLIN, 1 hit
InterProiView protein in InterPro
IPR039361 Cyclin
IPR013763 Cyclin-like
IPR036915 Cyclin-like_sf
IPR004367 Cyclin_C-dom
IPR015451 Cyclin_D
IPR006671 Cyclin_N
PANTHERiPTHR10177 PTHR10177, 1 hit
PTHR10177:SF66 PTHR10177:SF66, 1 hit
PfamiView protein in Pfam
PF02984 Cyclin_C, 1 hit
PF00134 Cyclin_N, 1 hit
PIRSFiPIRSF001771 Cyclin_A_B_D_E, 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YGD4H0YGD4_HUMAN
G1/S-specific cyclin-D2
CCND2
170Annotation score:

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 → R1 PublicationCorresponds to variant dbSNP:rs3217921Ensembl.1
Natural variantiVAR_072370280T → A in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777618EnsemblClinVar.1
Natural variantiVAR_072371280T → N in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777620EnsemblClinVar.1
Natural variantiVAR_072372281P → L in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar.1
Natural variantiVAR_072373281P → R in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar.1
Natural variantiVAR_072374284V → G in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs777786993EnsemblClinVar.1

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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6EI2X-ray1.61C114-123[»]
ProteinModelPortaliP30279
SMRiP30279
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107334, 91 interactors
ComplexPortaliCPX-2011 Cyclin D2-CDK4 complex
CORUMiP30279
DIPiDIP-178N
IntActiP30279, 8 interactors
MINTiP30279
STRINGi9606.ENSP00000261254

Chemistry databases

ChEMBLiCHEMBL3301386

PTM databases

iPTMnetiP30279
PhosphoSitePlusiP30279

Polymorphism and mutation databases

BioMutaiCCND2
DMDMi231741

Proteomic databases

EPDiP30279
MaxQBiP30279
PaxDbiP30279
PeptideAtlasiP30279
PRIDEiP30279
ProteomicsDBi54647

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
EuPathDBiHostDB:ENSG00000118971.7
GeneCardsiCCND2
HGNCiHGNC:1583 CCND2
HPAiHPA049138
HPA054196
MalaCardsiCCND2
MIMi123833 gene
615938 phenotype
neXtProtiNX_P30279
OpenTargetsiENSG00000118971
Orphaneti83473 Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
PharmGKBiPA26150
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00930000150931
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP30279
KOiK10151
OMAiVVPTKKC
OrthoDBiEOG091G0URX
PhylomeDBiP30279
TreeFamiTF101004

Enzyme and pathway databases

ReactomeiR-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
SignaLinkiP30279
SIGNORiP30279

Miscellaneous databases

ChiTaRSiCCND2 human
GeneWikiiCyclin_D2
GenomeRNAii894
PROiPR:P30279
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118971 Expressed in 240 organ(s), highest expression level in amniotic fluid
CleanExiHS_CCND2
ExpressionAtlasiP30279 baseline and differential
GenevisibleiP30279 HS

Family and domain databases

CDDicd00043 CYCLIN, 1 hit
InterProiView protein in InterPro
IPR039361 Cyclin
IPR013763 Cyclin-like
IPR036915 Cyclin-like_sf
IPR004367 Cyclin_C-dom
IPR015451 Cyclin_D
IPR006671 Cyclin_N
PANTHERiPTHR10177 PTHR10177, 1 hit
PTHR10177:SF66 PTHR10177:SF66, 1 hit
PfamiView protein in Pfam
PF02984 Cyclin_C, 1 hit
PF00134 Cyclin_N, 1 hit
PIRSFiPIRSF001771 Cyclin_A_B_D_E, 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
ProtoNetiSearch...

Entry informationi

Entry nameiCCND2_HUMAN
AccessioniPrimary (citable) accession number: P30279
Secondary accession number(s): A8K531, Q13955, Q5U035
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 7, 2018
This is version 186 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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