UniProtKB - P30279 (CCND2_HUMAN)
G1/S-specific cyclin-D2
CCND2
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 (PubMed:8114739, PubMed:18827403).
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 (PubMed:8114739, PubMed:18827403).
Hypophosphorylates RB1 in early G1 phase (PubMed:8114739, PubMed:18827403).
Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:8114739, PubMed:18827403).
2 PublicationsGO - Molecular functioni
- cyclin-dependent protein serine/threonine kinase regulator activity Source: GO_Central
- protein kinase binding Source: BHF-UCL
GO - Biological processi
- cell division Source: UniProtKB-KW
- mitotic cell cycle phase transition Source: GO_Central
- negative regulation of apoptotic process Source: BHF-UCL
- positive regulation of cell population 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
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
Keywordsi
Molecular function | Cyclin |
Biological process | Cell cycle, Cell division |
Enzyme and pathway databases
PathwayCommonsi | P30279 |
Reactomei | R-HSA-69231, Cyclin D associated events in G1 R-HSA-8934593, Regulation of RUNX1 Expression and Activity R-HSA-9661069, Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) |
SignaLinki | P30279 |
SIGNORi | P30279 |
Names & Taxonomyi
Protein namesi | Recommended name: G1/S-specific cyclin-D21 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1583, CCND2 |
MIMi | 123833, gene |
neXtProti | NX_P30279 |
VEuPathDBi | HostDB:ENSG00000118971 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Nucleus
- Nucleus 1 Publication
- Nucleus membrane 1 Publication
Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated into the nucleus through interaction with KIP/CIP family members.1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: UniProtKB
Nucleus
- nuclear membrane Source: UniProtKB
- nucleolus Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- chromatin Source: UniProtKB
- cyclin D2-CDK4 complex Source: ComplexPortal
- cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072370 | 280 | T → A in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777618EnsemblClinVar. | 1 | |
Natural variantiVAR_072371 | 280 | T → N in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777620EnsemblClinVar. | 1 | |
Natural variantiVAR_072372 | 281 | P → L in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar. | 1 | |
Natural variantiVAR_072373 | 281 | P → R in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar. | 1 | |
Natural variantiVAR_072374 | 284 | V → G in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs777786993EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 894 |
GeneReviewsi | CCND2 |
MalaCardsi | CCND2 |
MIMi | 615938, phenotype |
OpenTargetsi | ENSG00000118971 |
Orphaneti | 83473, Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome |
PharmGKBi | PA26150 |
Miscellaneous databases
Pharosi | P30279, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2095942 CHEMBL3301385 CHEMBL3301386 |
Genetic variation databases
BioMutai | CCND2 |
DMDMi | 231741 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080437 | 1 – 289 | G1/S-specific cyclin-D2Add BLAST | 289 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 271 | PhosphoserineCombined sources | 1 | |
Modified residuei | 280 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P30279 |
jPOSTi | P30279 |
MassIVEi | P30279 |
MaxQBi | P30279 |
PaxDbi | P30279 |
PeptideAtlasi | P30279 |
PRIDEi | P30279 |
ProteomicsDBi | 54647 [P30279-1] |
PTM databases
iPTMneti | P30279 |
PhosphoSitePlusi | P30279 |
Expressioni
Gene expression databases
Bgeei | ENSG00000118971, Expressed in amniotic fluid and 254 other tissues |
ExpressionAtlasi | P30279, baseline and differential |
Genevisiblei | P30279, HS |
Organism-specific databases
HPAi | ENSG00000118971, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
P30279
With | #Exp. | IntAct |
---|---|---|
CDK4 [P11802] | 15 | EBI-748789,EBI-295644 |
CDK5 [Q00535] | 15 | EBI-748789,EBI-1041567 |
CDKN1A [P38936] | 17 | EBI-748789,EBI-375077 |
CDKN1B [P46527] | 6 | EBI-748789,EBI-519280 |
GO - Molecular functioni
- protein kinase binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 107334, 144 interactors |
ComplexPortali | CPX-2011, Cyclin D2-CDK4 complex |
CORUMi | P30279 |
DIPi | DIP-178N |
IntActi | P30279, 11 interactors |
MINTi | P30279 |
STRINGi | 9606.ENSP00000261254 |
Chemistry databases
BindingDBi | P30279 |
Miscellaneous databases
RNActi | P30279, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 151 | Cyclin N-terminalAdd BLAST | 126 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 264 – 289 | DisorderedSequence analysisAdd BLAST | 26 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 265 – 289 | Basic and acidic residuesSequence analysisAdd BLAST | 25 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0656, Eukaryota |
GeneTreei | ENSGT00940000155180 |
HOGENOMi | CLU_052190_0_0_1 |
InParanoidi | P30279 |
OMAi | CLEMDTN |
OrthoDBi | 1234739at2759 |
PhylomeDBi | P30279 |
TreeFami | TF101004 |
Family and domain databases
CDDi | cd00043, CYCLIN, 1 hit |
InterProi | View protein in InterPro IPR039361, Cyclin IPR013763, Cyclin-like IPR036915, Cyclin-like_sf IPR004367, Cyclin_C-dom IPR015451, Cyclin_D IPR006671, Cyclin_N |
PANTHERi | PTHR10177, PTHR10177, 1 hit PTHR10177:SF66, PTHR10177:SF66, 1 hit |
Pfami | View protein in Pfam PF02984, Cyclin_C, 1 hit PF00134, Cyclin_N, 1 hit |
SMARTi | View protein in SMART SM00385, CYCLIN, 1 hit SM01332, Cyclin_C, 1 hit |
SUPFAMi | SSF47954, SSF47954, 2 hits |
PROSITEi | View protein in PROSITE PS00292, CYCLINS, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
138-209: EWELVVLGKL...SMIATGSVGA → VMTGPFLPSF...YYVPRLRAQH
210-289: Missing.
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A6Q8PGZ3 | A0A6Q8PGZ3_HUMAN | G1/S-specific cyclin-D2 | CCND2 | 303 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 166 – 167 | KL → NV in AAA51928 (PubMed:1386335).Curated | 2 | |
Sequence conflicti | 224 | T → H in AAA51928 (PubMed:1386335).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018820 | 268 | G → R1 PublicationCorresponds to variant dbSNP:rs3217921Ensembl. | 1 | |
Natural variantiVAR_072370 | 280 | T → A in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777618EnsemblClinVar. | 1 | |
Natural variantiVAR_072371 | 280 | T → N in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777620EnsemblClinVar. | 1 | |
Natural variantiVAR_072372 | 281 | P → L in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar. | 1 | |
Natural variantiVAR_072373 | 281 | P → R in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs587777622EnsemblClinVar. | 1 | |
Natural variantiVAR_072374 | 284 | V → G in MPPH3. 1 PublicationCorresponds to variant dbSNP:rs777786993EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057295 | 138 – 209 | EWELV…GSVGA → VMTGPFLPSFLRFPLSPGQQ YAFYHHCQSKFLGSRMTPPI EFTHLWAIAHLIGNHCLFFV CSYYVPRLRAQH in isoform 2. 1 PublicationAdd BLAST | 72 | |
Alternative sequenceiVSP_057296 | 210 – 289 | Missing in isoform 2. 1 PublicationAdd BLAST | 80 |
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. |
CCDSi | CCDS8524.1 [P30279-1] |
PIRi | A42822 |
RefSeqi | NP_001750.1, NM_001759.3 [P30279-1] |
Genome annotation databases
Ensembli | ENST00000261254; ENSP00000261254; ENSG00000118971 ENST00000676279; ENSP00000502597; ENSG00000118971 ENST00000676411; ENSP00000502654; ENSG00000118971 |
GeneIDi | 894 |
KEGGi | hsa:894 |
MANE-Selecti | ENST00000261254.8; ENSP00000261254.3; NM_001759.4; NP_001750.1 |
UCSCi | uc001qmo.4, human [P30279-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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. |
CCDSi | CCDS8524.1 [P30279-1] |
PIRi | A42822 |
RefSeqi | NP_001750.1, NM_001759.3 [P30279-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6EI2 | X-ray | 1.61 | C | 114-123 | [»] | |
SMRi | P30279 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107334, 144 interactors |
ComplexPortali | CPX-2011, Cyclin D2-CDK4 complex |
CORUMi | P30279 |
DIPi | DIP-178N |
IntActi | P30279, 11 interactors |
MINTi | P30279 |
STRINGi | 9606.ENSP00000261254 |
Chemistry databases
BindingDBi | P30279 |
ChEMBLi | CHEMBL2095942 CHEMBL3301385 CHEMBL3301386 |
PTM databases
iPTMneti | P30279 |
PhosphoSitePlusi | P30279 |
Genetic variation databases
BioMutai | CCND2 |
DMDMi | 231741 |
Proteomic databases
EPDi | P30279 |
jPOSTi | P30279 |
MassIVEi | P30279 |
MaxQBi | P30279 |
PaxDbi | P30279 |
PeptideAtlasi | P30279 |
PRIDEi | P30279 |
ProteomicsDBi | 54647 [P30279-1] |
Protocols and materials databases
Antibodypediai | 10540, 820 antibodies from 38 providers |
DNASUi | 894 |
Genome annotation databases
Ensembli | ENST00000261254; ENSP00000261254; ENSG00000118971 ENST00000676279; ENSP00000502597; ENSG00000118971 ENST00000676411; ENSP00000502654; ENSG00000118971 |
GeneIDi | 894 |
KEGGi | hsa:894 |
MANE-Selecti | ENST00000261254.8; ENSP00000261254.3; NM_001759.4; NP_001750.1 |
UCSCi | uc001qmo.4, human [P30279-1] |
Organism-specific databases
CTDi | 894 |
DisGeNETi | 894 |
GeneCardsi | CCND2 |
GeneReviewsi | CCND2 |
HGNCi | HGNC:1583, CCND2 |
HPAi | ENSG00000118971, Low tissue specificity |
MalaCardsi | CCND2 |
MIMi | 123833, gene 615938, phenotype |
neXtProti | NX_P30279 |
OpenTargetsi | ENSG00000118971 |
Orphaneti | 83473, Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome |
PharmGKBi | PA26150 |
VEuPathDBi | HostDB:ENSG00000118971 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0656, Eukaryota |
GeneTreei | ENSGT00940000155180 |
HOGENOMi | CLU_052190_0_0_1 |
InParanoidi | P30279 |
OMAi | CLEMDTN |
OrthoDBi | 1234739at2759 |
PhylomeDBi | P30279 |
TreeFami | TF101004 |
Enzyme and pathway databases
PathwayCommonsi | P30279 |
Reactomei | R-HSA-69231, Cyclin D associated events in G1 R-HSA-8934593, Regulation of RUNX1 Expression and Activity R-HSA-9661069, Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) |
SignaLinki | P30279 |
SIGNORi | P30279 |
Miscellaneous databases
BioGRID-ORCSi | 894, 46 hits in 1064 CRISPR screens |
ChiTaRSi | CCND2, human |
GeneWikii | Cyclin_D2 |
GenomeRNAii | 894 |
Pharosi | P30279, Tbio |
PROi | PR:P30279 |
RNActi | P30279, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000118971, Expressed in amniotic fluid and 254 other tissues |
ExpressionAtlasi | P30279, baseline and differential |
Genevisiblei | P30279, HS |
Family and domain databases
CDDi | cd00043, CYCLIN, 1 hit |
InterProi | View protein in InterPro IPR039361, Cyclin IPR013763, Cyclin-like IPR036915, Cyclin-like_sf IPR004367, Cyclin_C-dom IPR015451, Cyclin_D IPR006671, Cyclin_N |
PANTHERi | PTHR10177, PTHR10177, 1 hit PTHR10177:SF66, PTHR10177:SF66, 1 hit |
Pfami | View protein in Pfam PF02984, Cyclin_C, 1 hit PF00134, Cyclin_N, 1 hit |
SMARTi | View protein in SMART SM00385, CYCLIN, 1 hit SM01332, Cyclin_C, 1 hit |
SUPFAMi | SSF47954, SSF47954, 2 hits |
PROSITEi | View protein in PROSITE PS00292, CYCLINS, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CCND2_HUMAN | |
Accessioni | P30279Primary (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: | February 23, 2022 | |
This is version 206 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families