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P51946 (CCNH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-H
Alternative name(s):
MO15-associated protein
p34
p37
Gene names
Name:CCNH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length323 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. Ref.6 Ref.8

Subunit structure

Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor. Ref.7

Subcellular location

Nucleus.

Sequence similarities

Belongs to the cyclin family. Cyclin C subfamily.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   Molecular functionCyclin
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process7-methylguanosine mRNA capping

Traceable author statement. Source: Reactome

ATP catabolic process

Inferred from direct assay Ref.7. Source: GOC

DNA repair

Traceable author statement. Source: Reactome

G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

G2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

mitotic cell cycle

Traceable author statement. Source: Reactome

nucleotide-excision repair

Traceable author statement. Source: Reactome

nucleotide-excision repair, DNA damage removal

Traceable author statement. Source: Reactome

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 8692841. Source: UniProtKB

positive regulation of viral transcription

Traceable author statement. Source: Reactome

protein phosphorylation

Inferred from direct assay Ref.7. Source: GOC

regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: InterPro

termination of RNA polymerase I transcription

Traceable author statement. Source: Reactome

transcription elongation from RNA polymerase I promoter

Traceable author statement. Source: Reactome

transcription elongation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription from RNA polymerase I promoter

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Inferred from direct assay Ref.7. Source: UniProtKB

transcription initiation from RNA polymerase I promoter

Traceable author statement. Source: Reactome

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription-coupled nucleotide-excision repair

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

   Cellular_componentTFIIK complex

Inferred from electronic annotation. Source: InterPro

cyclin-dependent protein kinase activating kinase holoenzyme complex

Inferred from direct assay PubMed 8692842. Source: UniProtKB

holo TFIIH complex

Inferred from direct assay Ref.7. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functioncyclin-dependent protein serine/threonine kinase regulator activity

Inferred from electronic annotation. Source: InterPro

kinase activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 21988832PubMed 8521818PubMed 9840943. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDK2P249412EBI-741406,EBI-375096
CTBP2P565455EBI-741406,EBI-741533

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 323323Cyclin-H
PRO_0000080471

Regions

Compositional bias310 – 3134Poly-Glu

Amino acid modifications

Modified residue51Phosphoserine; by CDK8 Ref.9
Modified residue1321Phosphoserine Ref.11
Modified residue3041Phosphoserine; by CDK8 Ref.9
Modified residue3151Phosphothreonine Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17
Modified residue3221Phosphoserine Ref.11 Ref.15

Natural variations

Natural variant281R → L. Ref.4
Corresponds to variant rs2234942 [ dbSNP | Ensembl ].
VAR_013067
Natural variant541M → V. Ref.4
Corresponds to variant rs3093785 [ dbSNP | Ensembl ].
VAR_013068
Natural variant1381K → R. Ref.4
Corresponds to variant rs2266691 [ dbSNP | Ensembl ].
VAR_013069
Natural variant2701V → A. Ref.3 Ref.4 Ref.5
Corresponds to variant rs2230641 [ dbSNP | Ensembl ].
VAR_013070

Experimental info

Mutagenesis51S → A: No effect on the transcriptional activity of the reconstituted TFIIH complex. Ref.9
Mutagenesis3041S → A: No effect on the transcriptional activity of the reconstituted TFIIH complex. Ref.9

Secondary structure

.......................................... 323
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51946 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: BB48D55DA397A0E4

FASTA32337,643
        10         20         30         40         50         60 
MYHNSSQKRH WTFSSEEQLA RLRADANRKF RCKAVANGKV LPNDPVFLEP HEEMTLCKYY 

        70         80         90        100        110        120 
EKRLLEFCSV FKPAMPRSVV GTACMYFKRF YLNNSVMEYH PRIIMLTCAF LACKVDEFNV 

       130        140        150        160        170        180 
SSPQFVGNLR ESPLGQEKAL EQILEYELLL IQQLNFHLIV HNPYRPFEGF LIDLKTRYPI 

       190        200        210        220        230        240 
LENPEILRKT ADDFLNRIAL TDAYLLYTPS QIALTAILSS ASRAGITMES YLSESLMLKE 

       250        260        270        280        290        300 
NRTCLSQLLD IMKSMRNLVK KYEPPRSEEV AVLKQKLERC HSAELALNVI TKKRKGYEDD 

       310        320 
DYVSKKSKHE EEEWTDDDLV ESL 

« Hide

References

« Hide 'large scale' references
[1]"A cyclin associated with the CDK-activating kinase MO15."
Maekelae T.P., Tassan J.-P., Nigg E.A., Frutiger S., Hughes G.J., Weinberg R.A.
Nature 371:254-257(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-20; 106-133 AND 256-279.
Tissue: Liver.
[2]"A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase."
Fisher R.P., Morgan D.O.
Cell 78:713-724(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 10-21; 90-102 AND 190-197.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-270.
[4]NIEHS SNPs program
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-28; VAL-54; ARG-138 AND ALA-270.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-270.
Tissue: Bone marrow, Brain, Embryonic brain and Urinary bladder.
[6]"Cdk-activating kinase complex is a component of human transcription factor TFIIH."
Shiekhattar R., Mermelstein F., Fisher R.P., Drapkin R., Dynlacht B., Wessling H.C., Morgan D.O., Reinberg D.
Nature 374:283-287(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes."
Kershnar E., Wu S.-Y., Chiang C.-M.
J. Biol. Chem. 273:34444-34453(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR.
[8]"Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7."
Tirode F., Busso D., Coin F., Egly J.-M.
Mol. Cell 3:87-95(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"TFIIH is negatively regulated by cdk8-containing mediator complexes."
Akoulitchev S., Chuikov S., Reinberg D.
Nature 407:102-106(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-5 AND SER-304, MUTAGENESIS OF SER-5 AND SER-304.
[10]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; THR-315 AND SER-322, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315 AND SER-322, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase."
Kim K.K., Chamberlin H.M., Morgan D.O., Kim S.-H.
Nat. Struct. Biol. 3:849-855(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[19]"The structure of cyclin H: common mode of kinase activation and specific features."
Andersen G., Busso D., Poterszman A., Hwang J.R., Wurtz J.-M., Ripp R., Thierry J.-C., Egly J.-M., Moras D.
EMBO J. 16:958-967(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 11-287.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U11791 mRNA. Translation: AAA21361.1.
U12685 mRNA. Translation: AAA57006.1.
CR407658 mRNA. Translation: CAG28586.1.
AF477979 Genomic DNA. Translation: AAL74271.1.
BC005280 mRNA. Translation: AAH05280.1.
BC016705 mRNA. Translation: AAH16705.1.
BC016823 mRNA. Translation: AAH16823.1.
BC022351 mRNA. Translation: AAH22351.1.
CCDSCCDS4064.1.
PIRI38731.
RefSeqNP_001230.1. NM_001239.3.
UniGeneHs.292524.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JKWX-ray2.60A1-323[»]
1KXUX-ray2.60A1-323[»]
DisProtDP00307.
ProteinModelPortalP51946.
SMRP51946. Positions 11-286.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107342. 41 interactions.
DIPDIP-5996N.
IntActP51946. 16 interactions.
MINTMINT-1434271.
STRING9606.ENSP00000256897.

Chemistry

BindingDBP51946.
ChEMBLCHEMBL3038473.

PTM databases

PhosphoSiteP51946.

Polymorphism databases

DMDM1706232.

Proteomic databases

MaxQBP51946.
PaxDbP51946.
PeptideAtlasP51946.
PRIDEP51946.

Protocols and materials databases

DNASU902.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256897; ENSP00000256897; ENSG00000134480.
GeneID902.
KEGGhsa:902.
UCSCuc003kja.3. human.

Organism-specific databases

CTD902.
GeneCardsGC05M086690.
HGNCHGNC:1594. CCNH.
HPACAB019416.
HPA044138.
MIM601953. gene.
neXtProtNX_P51946.
PharmGKBPA26159.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5333.
HOGENOMHOG000232149.
HOVERGENHBG050840.
InParanoidP51946.
KOK06634.
OMAAFHYFKR.
PhylomeDBP51946.
TreeFamTF101008.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_1788. Transcription.
REACT_216. DNA Repair.
REACT_71. Gene Expression.
SignaLinkP51946.

Gene expression databases

ArrayExpressP51946.
BgeeP51946.
CleanExHS_CCNH.
GenevestigatorP51946.

Family and domain databases

Gene3D1.10.472.10. 2 hits.
InterProIPR013763. Cyclin-like.
IPR015429. Cyclin_C/H/T/L.
IPR006671. Cyclin_N.
IPR023598. CyclinC.
IPR027081. CyclinH/Ccl1.
[Graphical view]
PANTHERPTHR10026. PTHR10026. 1 hit.
PfamPF00134. Cyclin_N. 1 hit.
[Graphical view]
PIRSFPIRSF028758. PIRSF028758. 1 hit.
SMARTSM00385. CYCLIN. 1 hit.
[Graphical view]
SUPFAMSSF47954. SSF47954. 2 hits.
TIGRFAMsTIGR00569. ccl1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCCNH. human.
EvolutionaryTraceP51946.
GeneWikiCyclin_H.
GenomeRNAi902.
NextBio3728.
PROP51946.
SOURCESearch...

Entry information

Entry nameCCNH_HUMAN
AccessionPrimary (citable) accession number: P51946
Secondary accession number(s): Q53X72, Q8TBL9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM