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Protein

G1/S-specific cyclin-D3

Gene

CCND3

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

Functioni

Regulatory component of the cyclin D3-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 D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.1 Publication

GO - Molecular functioni

  • cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  • 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-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
SignaLinkiP30281
SIGNORiP30281

Names & Taxonomyi

Protein namesi
Recommended name:
G1/S-specific cyclin-D3
Gene namesi
Name:CCND3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112576.12
HGNCiHGNC:1585 CCND3
MIMi123834 gene
neXtProtiNX_P30281

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

Organism-specific databases

DisGeNETi896
OpenTargetsiENSG00000112576
PharmGKBiPA26152

Chemistry databases

ChEMBLiCHEMBL2422

Polymorphism and mutation databases

BioMutaiCCND3
DMDMi20981685

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000804421 – 292G1/S-specific cyclin-D3Add BLAST292

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei264PhosphoserineBy similarity1
Modified residuei279PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30281
MaxQBiP30281
PaxDbiP30281
PeptideAtlasiP30281
PRIDEiP30281
ProteomicsDBi54648
54649 [P30281-2]

PTM databases

iPTMnetiP30281
PhosphoSitePlusiP30281

Expressioni

Gene expression databases

BgeeiENSG00000112576 Expressed in 225 organ(s), highest expression level in blood
CleanExiHS_CCND3
ExpressionAtlasiP30281 baseline and differential
GenevisibleiP30281 HS

Organism-specific databases

HPAiCAB000116

Interactioni

Subunit structurei

Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Interacts with ATF5. Interacts with EIF3K. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Can form similar complexes with either CDKN1A or CDKN2A.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107336, 52 interactors
ComplexPortaliCPX-2012 Cyclin D3-CDK4 complex
CPX-2013 Cyclin D3-CDK6 complex
CORUMiP30281
DIPiDIP-31734N
IntActiP30281, 36 interactors
MINTiP30281
STRINGi9606.ENSP00000362082

Chemistry databases

BindingDBiP30281

Structurei

Secondary structure

1292
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP30281
SMRiP30281
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30281

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 152Cyclin N-terminalAdd BLAST126

Sequence similaritiesi

Belongs to the cyclin family. Cyclin D subfamily.Curated

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00930000150931
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP30281
KOiK10152
OMAiWMHEVCE
OrthoDBiEOG091G0URX
PhylomeDBiP30281
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:SF65 PTHR10177:SF65, 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 (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P30281-1) [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
MELLCCEGTR HAPRAGPDPR LLGDQRVLQS LLRLEERYVP RASYFQCVQR
60 70 80 90 100
EIKPHMRKML AYWMLEVCEE QRCEEEVFPL AMNYLDRYLS CVPTRKAQLQ
110 120 130 140 150
LLGAVCMLLA SKLRETTPLT IEKLCIYTDH AVSPRQLRDW EVLVLGKLKW
160 170 180 190 200
DLAAVIAHDF LAFILHRLSL PRDRQALVKK HAQTFLALCA TDYTFAMYPP
210 220 230 240 250
SMIATGSIGA AVQGLGACSM SGDELTELLA GITGTEVDCL RACQEQIEAA
260 270 280 290
LRESLREASQ TSSSPAPKAP RGSSSQGPSQ TSTPTDVTAI HL
Length:292
Mass (Da):32,520
Last modified:May 15, 2002 - v2
Checksum:i16E7B1604FEB0029
GO
Isoform 2 (identifier: P30281-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-81: Missing.

Note: No experimental confirmation available.
Show »
Length:211
Mass (Da):22,887
Checksum:iF88EA393BA1B96DB
GO
Isoform 3 (identifier: P30281-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-138: Missing.

Note: No experimental confirmation available.
Show »
Length:220
Mass (Da):24,238
Checksum:i15BC01266FE6BF4B
GO
Isoform 4 (identifier: P30281-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-196: Missing.

Note: No experimental confirmation available.
Show »
Length:96
Mass (Da):9,736
Checksum:i83F7CF9D0B743ED7
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T8J1Q5T8J1_HUMAN
G1/S-specific cyclin-D3
CCND3
242Annotation score:
H0Y8M4H0Y8M4_HUMAN
G1/S-specific cyclin-D3
CCND3
175Annotation score:
D6RI00D6RI00_HUMAN
G1/S-specific cyclin-D3
CCND3
195Annotation score:
D6RIX2D6RIX2_HUMAN
G1/S-specific cyclin-D3
CCND3
118Annotation score:
D6RDL3D6RDL3_HUMAN
G1/S-specific cyclin-D3
CCND3
43Annotation score:
D6RDF8D6RDF8_HUMAN
G1/S-specific cyclin-D3
CCND3
46Annotation score:
A0A1D5RMS0A0A1D5RMS0_HUMAN
G1/S-specific cyclin-D3
CCND3
10Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020412134P → S. Corresponds to variant dbSNP:rs3218089Ensembl.1
Natural variantiVAR_033726253E → D. Corresponds to variant dbSNP:rs33966734Ensembl.1
Natural variantiVAR_014205259S → A6 PublicationsCorresponds to variant dbSNP:rs1051130Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0462661 – 196Missing in isoform 4. 1 PublicationAdd BLAST196
Alternative sequenceiVSP_0426491 – 81Missing in isoform 2. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_04626767 – 138Missing in isoform 3. 1 PublicationAdd BLAST72

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90814 mRNA Translation: AAA51927.1
M92287 mRNA Translation: AAA52137.1
AF517525 Genomic DNA Translation: AAM51826.1
BX400719 mRNA No translation available.
AK057206 mRNA Translation: BAG51884.1
AK097856 mRNA No translation available.
AK315421 mRNA Translation: BAG37810.1
CR542246 mRNA Translation: CAG47042.1
AL160163 Genomic DNA No translation available.
AL513008 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04071.1
BC011616 mRNA Translation: AAH11616.1
M88087
, M88084, M88085, M88086 Genomic DNA Translation: AAA51929.1
CCDSiCCDS47425.1 [P30281-3]
CCDS47426.1 [P30281-2]
CCDS47427.1 [P30281-4]
CCDS4863.1 [P30281-1]
PIRiB42822
RefSeqiNP_001129489.1, NM_001136017.3 [P30281-2]
NP_001129597.1, NM_001136125.2 [P30281-3]
NP_001129598.1, NM_001136126.2 [P30281-4]
NP_001274356.1, NM_001287427.1
NP_001274363.1, NM_001287434.1 [P30281-4]
NP_001751.1, NM_001760.4 [P30281-1]
UniGeneiHs.534307

Genome annotation databases

EnsembliENST00000372988; ENSP00000362079; ENSG00000112576 [P30281-2]
ENST00000372991; ENSP00000362082; ENSG00000112576 [P30281-1]
ENST00000414200; ENSP00000397545; ENSG00000112576 [P30281-3]
ENST00000415497; ENSP00000401595; ENSG00000112576 [P30281-4]
ENST00000511642; ENSP00000426212; ENSG00000112576 [P30281-2]
ENST00000616010; ENSP00000484424; ENSG00000112576 [P30281-4]
GeneIDi896
KEGGihsa:896
UCSCiuc003orn.4 human [P30281-1]

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
M90814 mRNA Translation: AAA51927.1
M92287 mRNA Translation: AAA52137.1
AF517525 Genomic DNA Translation: AAM51826.1
BX400719 mRNA No translation available.
AK057206 mRNA Translation: BAG51884.1
AK097856 mRNA No translation available.
AK315421 mRNA Translation: BAG37810.1
CR542246 mRNA Translation: CAG47042.1
AL160163 Genomic DNA No translation available.
AL513008 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04071.1
BC011616 mRNA Translation: AAH11616.1
M88087
, M88084, M88085, M88086 Genomic DNA Translation: AAA51929.1
CCDSiCCDS47425.1 [P30281-3]
CCDS47426.1 [P30281-2]
CCDS47427.1 [P30281-4]
CCDS4863.1 [P30281-1]
PIRiB42822
RefSeqiNP_001129489.1, NM_001136017.3 [P30281-2]
NP_001129597.1, NM_001136125.2 [P30281-3]
NP_001129598.1, NM_001136126.2 [P30281-4]
NP_001274356.1, NM_001287427.1
NP_001274363.1, NM_001287434.1 [P30281-4]
NP_001751.1, NM_001760.4 [P30281-1]
UniGeneiHs.534307

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3G33X-ray3.00B/D1-292[»]
ProteinModelPortaliP30281
SMRiP30281
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107336, 52 interactors
ComplexPortaliCPX-2012 Cyclin D3-CDK4 complex
CPX-2013 Cyclin D3-CDK6 complex
CORUMiP30281
DIPiDIP-31734N
IntActiP30281, 36 interactors
MINTiP30281
STRINGi9606.ENSP00000362082

Chemistry databases

BindingDBiP30281
ChEMBLiCHEMBL2422

PTM databases

iPTMnetiP30281
PhosphoSitePlusiP30281

Polymorphism and mutation databases

BioMutaiCCND3
DMDMi20981685

Proteomic databases

EPDiP30281
MaxQBiP30281
PaxDbiP30281
PeptideAtlasiP30281
PRIDEiP30281
ProteomicsDBi54648
54649 [P30281-2]

Protocols and materials databases

DNASUi896
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372988; ENSP00000362079; ENSG00000112576 [P30281-2]
ENST00000372991; ENSP00000362082; ENSG00000112576 [P30281-1]
ENST00000414200; ENSP00000397545; ENSG00000112576 [P30281-3]
ENST00000415497; ENSP00000401595; ENSG00000112576 [P30281-4]
ENST00000511642; ENSP00000426212; ENSG00000112576 [P30281-2]
ENST00000616010; ENSP00000484424; ENSG00000112576 [P30281-4]
GeneIDi896
KEGGihsa:896
UCSCiuc003orn.4 human [P30281-1]

Organism-specific databases

CTDi896
DisGeNETi896
EuPathDBiHostDB:ENSG00000112576.12
GeneCardsiCCND3
HGNCiHGNC:1585 CCND3
HPAiCAB000116
MIMi123834 gene
neXtProtiNX_P30281
OpenTargetsiENSG00000112576
PharmGKBiPA26152
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0656 Eukaryota
ENOG410XRKC LUCA
GeneTreeiENSGT00930000150931
HOGENOMiHOG000008182
HOVERGENiHBG050837
InParanoidiP30281
KOiK10152
OMAiWMHEVCE
OrthoDBiEOG091G0URX
PhylomeDBiP30281
TreeFamiTF101004

Enzyme and pathway databases

ReactomeiR-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-69231 Cyclin D associated events in G1
R-HSA-8934593 Regulation of RUNX1 Expression and Activity
SignaLinkiP30281
SIGNORiP30281

Miscellaneous databases

ChiTaRSiCCND3 human
EvolutionaryTraceiP30281
GeneWikiiCyclin_D3
GenomeRNAii896
PROiPR:P30281
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112576 Expressed in 225 organ(s), highest expression level in blood
CleanExiHS_CCND3
ExpressionAtlasiP30281 baseline and differential
GenevisibleiP30281 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:SF65 PTHR10177:SF65, 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 nameiCCND3_HUMAN
AccessioniPrimary (citable) accession number: P30281
Secondary accession number(s): B2RD63
, B3KQ22, E9PAS4, E9PB36, Q5T8J0, Q6FG62, Q96F49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: May 15, 2002
Last modified: November 7, 2018
This is version 190 of the entry and version 2 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 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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