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    CCNH cyclin H [ Homo sapiens (human) ]

    Gene ID: 902, updated on 2-Nov-2024

    Summary

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    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

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    See CCNH in Genome Data Viewer
    Location:
    5q14.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (87311471..87412930, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (87789500..87894036, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (86607288..86708747, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene RAS p21 protein activator 1 Neighboring gene uncharacterized LOC124901022 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:86595594-86596094 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:86596095-86596595 Neighboring gene RNA, 7SL, cytoplasmic 629, pseudogene Neighboring gene RNA, U6 small nuclear 606, pseudogene Neighboring gene uncharacterized LOC644285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22753 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22754 Neighboring gene uncharacterized LOC105379066 Neighboring gene RNA, U6 small nuclear 727, pseudogene Neighboring gene uncharacterized LOC124901222

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. The structure of cyclin H: common mode of kinase activation and specific features. Andersen G, et al. EMBO J, 1997 Mar 3. PMID 9118957, Free PMC Article
    2. Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma. Bavi P, et al. Hum Pathol, 2008 Jun. PMID 18400256
    3. Cyclin H expression is increased in GIST with very-high risk of malignancy. Dorn J, et al. BMC Cancer, 2010 Jul 2. PMID 20598140, Free PMC Article
    4. The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies. Jordan P, et al. Mol Biol Cell, 1997 Jul. PMID 9243502, Free PMC Article
    5. Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer. Mao L, et al. Comput Math Methods Med, 2021. PMID 33777168, Free PMC Article

    See all (166) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer.
      Title: Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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

    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

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    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 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 transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in transcription initiation at RNA polymerase II promoter IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 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)

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    1. NR_157068.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018754, AC035142

    2. NR_157069.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018754, AC035142

    3. NR_157070.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018754, AC035142

    4. NR_157071.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC018754

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      87311471..87412930 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047417863.1 → XP_047273819.1  cyclin-H isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      87789500..87894036 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353747.1 → XP_054209722.1  cyclin-H isoform X1

    RNA

    1. XR_008487193.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51946.1 GenPept UniProtKB/Swiss-Prot:P51946

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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