CCND3 cyclin D3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCND3provided by HGNC
Official Full Name: cyclin D3provided by HGNC
Primary source: HGNC:HGNC:1585
See related: Ensembl:ENSG00000112576 MIM:123834; AllianceGenome:HGNC:1585
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
Expression: Broad expression in bone marrow (RPKM 45.2), lymph node (RPKM 40.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (41934933..42050035, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (41763493..41878294, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (41902671..42016632, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeting diacylglycerol kinase alpha impairs lung tumorigenesis by inhibiting cyclin D3.
Title: Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3.
Cyclin D3 restricts SARS-CoV-2 envelope incorporation into virions and interferes with viral spread.
Title: Cyclin D3 restricts SARS-CoV-2 envelope incorporation into virions and interferes with viral spread.
Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.
Title: Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.
CircMYLK promotes the growth, migration, invasion, and survival of bladder cancer cells by upregulating CCND3 level via competitively binding to miR-34a.
Title: CircMYLK promotes the growth, migration, invasion, and survival of bladder cancer cells by upregulating CCND3 level via competitively binding to miR-34a.
Keratin 19 interacts with GSK3beta to regulate its nuclear accumulation and degradation of cyclin D3.
Title: Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3.
CCND2 played an oncogenic role in gastric cancer, whereas it could also be a tumor suppressor in NSCLC.
Title: Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta-analysis.
miR-195 targets cyclin D3 to cause cell cycle arrest at the G1 phase and that miR-195 targets survivin to induce apoptosis and senescence in NSCLC cells. Overexpression of cyclin D3 or survivin reverses the effects of miR-195 in NSCLC cells.
Title: miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer.
virtually all cyclin D1(-) mantle cell lymphoma carry CCND2/CCND3 rearrangements with immunoglobulin genes, including a novel IGK/L enhancer hijacking mechanism
Title: CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1(-) mantle cell lymphoma.
Cyclin D3 expression is regulated by Hes3 in lung cancer cells.
Title: Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression.
The novel tumor suppressor miR-4779 inhibits cancer cell growth via cell cycle arrest and apoptosis by directly targeting PAK2 and CCND3.
Title: MicroRNA miR-4779 suppresses tumor growth by inducing apoptosis and cell cycle arrest through direct targeting of PAK2 and CCND3.

Submit: New GeneRIF Correction See all GeneRIFs (99)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	When expressed in astrocytes, neurons, and non-glial 293T cells, HIV-1 Tat interacts with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA	PubMed
matrix	gag	HIV-1 MA natural variant S75X upregulates the expression of two cyclins D2 and D3, and induces significant release of cytokine IL-6, which leads to enhance proliferation of both Epstein-Barr virus (EBV)-infected primary and fully transformed B-lymphocytes	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D6S2062 (e-PCR)
- UniSTS:13316

RH16378 (e-PCR)
- UniSTS:15120

D6S1441 (e-PCR)
- UniSTS:25633

STS-N70302 (e-PCR)
- UniSTS:23931

G34997 (e-PCR)
- UniSTS:56460

D6S1552 (e-PCR)
- UniSTS:13468

CCND3_93 (e-PCR)
- UniSTS:276170

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cyclin-dependent protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables cyclin-dependent protein serine/threonine kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables cyclin-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables cyclin-dependent protein serine/threonine kinase regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in G1/S transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in G1/S transition of mitotic cell cycle	NAS Non-traceable Author Statement more info	PubMed
involved_in G1/S transition of mitotic cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in centrosome	IBA Inferred from Biological aspect of Ancestor more info
part_of cyclin D3-CDK4 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of cyclin D3-CDK6 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of cyclin-dependent protein kinase holoenzyme complex	IBA Inferred from Biological aspect of Ancestor more info
part_of cyclin-dependent protein kinase holoenzyme complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: G1/S-specific cyclin-D3

Names: D3-type cyclin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_041939.1 RefSeqGene

Range

5001..118962

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_998

mRNA and Protein(s)

NM_001136017.3 → NP_001129489.1 G1/S-specific cyclin-D3 isoform 1

See identical proteins and their annotated locations for NP_001129489.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence, and represents use of an alternate promoter, compared to variant 2. The resulting isoform (1) is shorter at the N-terminus compared to isoform 2. Variants 1, 8, and 9 all encode the same isoform (1).

Source sequence(s)

AK057206, AL160163, BC011616, DA999482, DB001987

Consensus CDS

CCDS47426.1

UniProtKB/TrEMBL

B3KTY3

Related

ENSP00000362079.4, ENST00000372988.8

Conserved Domains (2) summary

pfam00134
Location:1 → 72

Cyclin_N; Cyclin, N-terminal domain

pfam02984
Location:74 → 170

Cyclin_C; Cyclin, C-terminal domain
NM_001136125.3 → NP_001129597.1 G1/S-specific cyclin-D3 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 2. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 2.

Source sequence(s)

AK057206, AL160163, BC011616, DC360231, M92287

Consensus CDS

CCDS47425.1

UniProtKB/Swiss-Prot

P30281

Related

ENSP00000397545.2, ENST00000414200.6

Conserved Domains (2) summary

pfam02984
Location:83 → 179

Cyclin_C; Cyclin, C-terminal domain

cl00050
Location:27 → 66

CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...
NM_001136126.3 → NP_001129598.1 G1/S-specific cyclin-D3 isoform 4

See identical proteins and their annotated locations for NP_001129598.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 2. The resulting isoform (4) is shorter at the N-terminus compared to isoform 2. Variants 4, 5, 10, and 11 all encode the same protein.

Source sequence(s)

AK057206, AL160163, BC011616, DA069566, DB001987

Consensus CDS

CCDS47427.1

UniProtKB/Swiss-Prot

P30281

Related

ENSP00000401595.2, ENST00000415497.6

Conserved Domains (1) summary

pfam02984
Location:1 → 55

Cyclin_C; Cyclin, C-terminal domain
NM_001287427.2 → NP_001274356.1 G1/S-specific cyclin-D3 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate in-frame splice site in the 5' coding region and uses a downstream start codon compared to variant 2. It encodes isoform 5 which has a shorter N-terminus compared to isoform 2.

Source sequence(s)

AK055519, AL160163, BC011616, BE247367, DA411470, M92287

Consensus CDS

CCDS75452.1

UniProtKB/TrEMBL

B3KP19, Q5T8J1

Related

ENSP00000362078.4, ENST00000372987.8

Conserved Domains (2) summary

pfam00134
Location:16 → 103

Cyclin_N; Cyclin, N-terminal domain

pfam02984
Location:105 → 201

Cyclin_C; Cyclin, C-terminal domain
NM_001287434.2 → NP_001274363.1 G1/S-specific cyclin-D3 isoform 4

See identical proteins and their annotated locations for NP_001274363.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence, and represents use of an alternate promoter, compared to variant 2. The resulting isoform (4) is shorter at the N-terminus compared to isoform 2. Variants 4, 5, 10, and 11 all encode the same protein.

Source sequence(s)

AL513008, BX117734, CA424172, DB104254, DB110132, DB544217, DR761231

Consensus CDS

CCDS47427.1

UniProtKB/Swiss-Prot

P30281

Related

ENSP00000484424.1, ENST00000616010.4

Conserved Domains (1) summary

pfam02984
Location:1 → 55

Cyclin_C; Cyclin, C-terminal domain
NM_001424052.1 → NP_001410981.1 G1/S-specific cyclin-D3 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (7) encodes the longest isoform (6).

Source sequence(s)

AL160163
NM_001424053.1 → NP_001410982.1 G1/S-specific cyclin-D3 isoform 1

Status: REVIEWED

Source sequence(s)

AL160163, AL513008

UniProtKB/TrEMBL

B3KTY3

Related

ENSP00000426212.1, ENST00000511642.5
NM_001424055.1 → NP_001410984.1 G1/S-specific cyclin-D3 isoform 1

Status: REVIEWED

Source sequence(s)

AL160163, AL513008

UniProtKB/TrEMBL

B3KTY3
NM_001424056.1 → NP_001410985.1 G1/S-specific cyclin-D3 isoform 4

Status: REVIEWED

Source sequence(s)

AL160163
NM_001424057.1 → NP_001410986.1 G1/S-specific cyclin-D3 isoform 4

Status: REVIEWED

Source sequence(s)

AL160163, AL513008
NM_001424058.1 → NP_001410987.1 G1/S-specific cyclin-D3 isoform 7

Status: REVIEWED

Source sequence(s)

AL160163, AL513008
NM_001424059.1 → NP_001410988.1 G1/S-specific cyclin-D3 isoform 7

Status: REVIEWED

Source sequence(s)

AL160163
NM_001424060.1 → NP_001410989.1 G1/S-specific cyclin-D3 isoform 7

Status: REVIEWED

Source sequence(s)

AL160163
NM_001424061.1 → NP_001410990.1 G1/S-specific cyclin-D3 isoform 7

Status: REVIEWED

Source sequence(s)

AL160163, AL513008
NM_001760.5 → NP_001751.1 G1/S-specific cyclin-D3 isoform 2

See identical proteins and their annotated locations for NP_001751.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes isoform 2.

Source sequence(s)

AK057206, AL160163, BC011616, M92287

Consensus CDS

CCDS4863.1

UniProtKB/Swiss-Prot

B2RD63, B3KQ22, E9PAS4, E9PB36, P30281, Q5T8J0, Q6FG62, Q96F49

Related

ENSP00000362082.5, ENST00000372991.9

Conserved Domains (2) summary

pfam00134
Location:27 → 153

Cyclin_N; Cyclin, N-terminal domain

pfam02984
Location:155 → 251

Cyclin_C; Cyclin, C-terminal domain

RNA

NR_187571.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL513008

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

41934933..42050035 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419491.1 → XP_047275447.1 G1/S-specific cyclin-D3 isoform X2
XM_011514971.3 → XP_011513273.1 G1/S-specific cyclin-D3 isoform X1

Conserved Domains (1) summary

pfam00134
Location:27 → 153

Cyclin_N; Cyclin, N-terminal domain