CCNH cyclin H [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCNHprovided by HGNC
Official Full Name: cyclin Hprovided by HGNC
Primary source: HGNC:HGNC:1594
See related: Ensembl:ENSG00000134480 MIM:601953; AllianceGenome:HGNC:1594
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
Also known as: CAK; p34; p37; CycH
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 CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. A pseudogene of this gene is found on chromosome 4. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Nov 2010]
Expression: Ubiquitous expression in placenta (RPKM 15.0), testis (RPKM 11.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q14.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (87311471..87412930, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (87789500..87894036, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (86607288..86708747, complement)

Chromosome 5 - NC_000005.10 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?

Cytomegalovirus cyclin-dependent kinase ortholog vCDK/pUL97 undergoes regulatory interaction with human cyclin H and CDK7 to codetermine viral replication efficiency.
Title: Cytomegalovirus cyclin-dependent kinase ortholog vCDK/pUL97 undergoes regulatory interaction with human cyclin H and CDK7 to codetermine viral replication efficiency.
Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer.
Title: Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer.
Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97
Title: Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97.
Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients.
Title: Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients.
Expressions of components of the CAK complex, CDK7, MAT1, and Cyclin H are elevated in breast cancer.
Title: Expression of CDK7, Cyclin H, and MAT1 Is Elevated in Breast Cancer and Is Prognostic in Estrogen Receptor-Positive Breast Cancer.
Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of esophageal squamous cell carcinoma .
Title: Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression.
SNPs in CCNH and ABCG2 can modulate the development of severe oxaliplatin-induced peripheral neuropathy.
Title: Pharmacogenetic predictors of severe peripheral neuropathy in colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy: a GEMCAD group study.
Hemodynamic forces modulate EC proliferative phenotype through the miR-23b/CAK/cyclin H pathway.
Title: MicroRNA-23b regulates cyclin-dependent kinase-activating kinase complex through cyclin H repression to modulate endothelial transcription and growth under flow.
When considering all thyroid cancer (DTC) cases, only rs2230641 (CCNH) was associated with DTC risk.
Title: The role of CCNH Val270Ala (rs2230641) and other nucleotide excision repair polymorphisms in individual susceptibility to well-differentiated thyroid cancer.
CCNH and CDK7 may play an important role in the tumorigenesis and development of esophageal squamous cell carcinoma.
Title: Low expression of cyclinH and cyclin-dependent kinase 7 can decrease the proliferation of human esophageal squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (26)

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
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. 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	Interaction of HIV-1 Tat with TFIIH stimulates phosphorylation of Ser-5 of the RNA polymerase II C-terminal domain (CTD), which in turn also stimulates co-transcriptional capping of HIV-1 mRNA	PubMed
	tat	TFIIH subunits CDK7 and cyclin H have been identified as two components associated with the Tat-associated CTD kinase (TTK) that binds to HIV-1 Tat	PubMed
	tat	TFIIH interacts with HIV-1 Tat as a component of the HIV-1 transcription preinitiation complex, but is released from the elongation complex which includes P-TEFb	PubMed
	tat	CAK/TFIIH is required for HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter	PubMed
	tat	Amino acids 1-48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3	PubMed
	tat	TFIIH synergizes with HIV-1 Tat to induce transcription elongation from the HIV-1 LTR promoter	PubMed
	tat	HIV-1 Tat interacts with the RNA polymerase II holoenzyme and transcription preinitiation complexes, which include TFIIH, during Tat-mediated transactivation of the HIV-1 LTR	PubMed
Vpr	vpr	As a component of the TFIIH transcription complex, cyclin H inhibits HIV-1 Vpr cell cycle-arresting function	PubMed
	vpr	As a component of the TFIIH transcription complex, cyclin H enhances the synergistic activation of glucocorticoid receptor by HIV-1 Vpr and p300	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

RH17996 (e-PCR)
- UniSTS:51972

RH69527 (e-PCR)
- UniSTS:18467

G67291 (e-PCR)
- UniSTS:186421

G67292 (e-PCR)
- UniSTS:186422

SGC30189 (e-PCR)
- UniSTS:64329

STS-M23379 (e-PCR)
- UniSTS:79697

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to RNA polymerase II general transcription initiation factor activity	IDA Inferred from Direct Assay more info	PubMed
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

Process	Evidence Code	Pubs
involved_in cell cycle	IEA Inferred from Electronic Annotation more info
involved_in protein stabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of G1/S transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in transcription initiation at RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of CAK-ERCC2 complex	IDA Inferred from Direct Assay more info	PubMed
part_of cyclin-dependent protein kinase activating kinase holoenzyme complex	IDA Inferred from Direct Assay more info	PubMed
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
part_of transcription factor TFIIH core complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIIH holo complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIIK complex	IBA Inferred from Biological aspect of Ancestor more info
part_of transcription factor TFIIK complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIIK complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: cyclin-H

Names: CAK complex subunit; CDK-activating kinase complex subunit; MO15-associated protein; cyclin-dependent kinase-activating kinase complex subunit

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.

mRNA and Protein(s)

NM_001199189.2 → NP_001186118.1 cyclin-H isoform 2

See identical proteins and their annotated locations for NP_001186118.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and the 3' UTR and coding sequence, and initiates translation at a downstream start codon, compared to variant 3. The encoded isoform (2) is shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform 3.

Source sequence(s)

AC018754, BX537673

UniProtKB/TrEMBL

D6RHI7

Related

ENSP00000426075.1, ENST00000504878.1

Conserved Domains (3) summary

TIGR00569
Location:1 → 255

ccl1; cyclin ccl1

smart00385
Location:9 → 99

CYCLIN; domain present in cyclins, TFIIB and Retinoblastoma

pfam16899
Location:109 → 209

Cyclin_C_2; Cyclin C-terminal domain
NM_001239.4 → NP_001230.1 cyclin-H isoform 1

See identical proteins and their annotated locations for NP_001230.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 3' UTR and coding sequence compared to variant 3. The resulting isoform (1) has a shorter and distinct C-terminus compared to isoform 3.

Source sequence(s)

BC005280, BC016705, BP244381

Consensus CDS

CCDS4064.1

UniProtKB/Swiss-Prot

P51946, Q53X72, Q8TBL9

UniProtKB/TrEMBL

A8K6Q5

Related

ENSP00000256897.4, ENST00000256897.9

Conserved Domains (1) summary

TIGR00569
Location:2 → 308

ccl1; cyclin ccl1
NM_001363539.2 → NP_001350468.1 cyclin-H isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (3).

Source sequence(s)

AC018754

Consensus CDS

CCDS87309.1

UniProtKB/TrEMBL

A0A2R8YEM2, A8K6Q5

Related

ENSP00000494460.1, ENST00000645953.1

Conserved Domains (1) summary

TIGR00569
Location:2 → 308

ccl1; cyclin ccl1
NM_001364075.2 → NP_001351004.1 cyclin-H isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 3' UTR and coding sequence compared to variant 3. The resulting isoform (4) is the same length as isoform 3 but has a distinct C-terminus.

Source sequence(s)

AC018754, AC035142

UniProtKB/TrEMBL

A8K6Q5

Conserved Domains (1) summary

TIGR00569
Location:2 → 308

ccl1; cyclin ccl1
NM_001364076.2 → NP_001351005.1 cyclin-H isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 3. The resulting isoform (5) is shorter at the N-terminus compared to isoform 3.

Source sequence(s)

AC018754

UniProtKB/TrEMBL

Q59FW7

Conserved Domains (1) summary

TIGR00569
Location:1 → 255

ccl1; cyclin ccl1

RNA

NR_157068.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018754, AC035142
NR_157069.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018754, AC035142
NR_157070.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018754, AC035142
NR_157071.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC018754