P51946 (CCNH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-H

Alternative name(s):
MO15-associated protein
p34
p37

Gene names

Name:

CCNH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Protein existence	Evidence 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-terminus 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 process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Cyclin
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	7-methylguanosine mRNA capping Traceable author statement. Source: Reactome G1 phase of mitotic cell cycle 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 S phase of mitotic cell cycle 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 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 reproduction Traceable author statement. Source: Reactome
Cellular_component	TFIIK 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
Molecular_function	cyclin-dependent protein serine/threonine kinase regulator activity Inferred from electronic annotation. Source: InterPro kinase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	2	EBI-741406,EBI-375096
CTBP2	P56545	5	EBI-741406,EBI-741533

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

Cyclin-H

PRO_0000080471

Regions

Compositional bias

310 – 313

4

Poly-Glu

Amino acid modifications

Modified residue

5

1

Phosphoserine; by CDK8 Ref.9

Modified residue

132

1

Phosphoserine Ref.11

Modified residue

304

1

Phosphoserine; by CDK8 Ref.9

Modified residue

315

1

Phosphothreonine Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17

Modified residue

322

1

Phosphoserine Ref.11 Ref.15

Natural variations

Natural variant

28

1

R → L. Ref.4
Corresponds to variant rs2234942 [ dbSNP | Ensembl ].

VAR_013067

Natural variant

54

1

M → V. Ref.4
Corresponds to variant rs3093785 [ dbSNP | Ensembl ].

VAR_013068

Natural variant

138

1

K → R. Ref.4
Corresponds to variant rs2266691 [ dbSNP | Ensembl ].

VAR_013069

Natural variant

270

1

V → A. Ref.3 Ref.4 Ref.5
Corresponds to variant rs2230641 [ dbSNP | Ensembl ].

VAR_013070

Experimental info

Mutagenesis

5

1

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

Mutagenesis

304

1

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

Secondary structure

1

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323

Helix Strand Turn

Details...

Helix

16 – 36

21

Beta strand

38 – 40

3

Helix

50 – 70

21

Turn

72 – 74

3

Helix

77 – 90

14

Helix

91 – 93

3

Turn

96 – 98

3

Helix

101 – 115

15

Helix

122 – 125

4

Helix

126 – 128

3

Beta strand

129 – 131

3

Helix

133 – 153

21

Turn

154 – 156

3

Helix

164 – 177

14

Helix

179 – 182

4

Helix

184 – 198

15

Turn

200 – 202

3

Helix

203 – 206

4

Helix

209 – 224

16

Helix

231 – 235

5

Beta strand

240 – 242

3

Helix

246 – 260

15

Helix

267 – 282

16

Sequences

	Sequence		Length	Mass (Da)
	P51946 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: BB48D55DA397A0E4	FASTA	323	37,643
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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

NIEHS-SNPs

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.

IPI

IPI00021305.

PIR

I38731.

RefSeq

NP_001230.1. NM_001239.3.

UniGene

Hs.292524.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JKW	X-ray	2.60	A	1-323	[»]
1KXU	X-ray	2.60	A	1-323	[»]

DisProt

DP00307.

ProteinModelPortal

P51946.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5996N.

IntAct

P51946. 16 interactions.

MINT

MINT-1434271.

STRING

9606.ENSP00000256897.

PTM databases

PhosphoSite

P51946.

Polymorphism databases

DMDM

1706232.

Proteomic databases

PaxDb

P51946.

PeptideAtlas

P51946.

PRIDE

P51946.

Protocols and materials databases

DNASU

902.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256897; ENSP00000256897; ENSG00000134480.

GeneID

902.

KEGG

hsa:902.

UCSC

uc003kja.3. human.

Organism-specific databases

CTD

902.

GeneCards

GC05M086690.

HGNC

HGNC:1594. CCNH.

HPA

CAB019416.

MIM

601953. gene.

neXtProt

NX_P51946.

PharmGKB

PA26159.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5333.

HOGENOM

HOG000232149.

HOVERGEN

HBG050840.

InParanoid

P51946.

KO

K06634.

OMA

EILATCV.

OrthoDB

EOG47SSF4.

PhylomeDB

P51946.

Enzyme and pathway databases

Pathway_Interaction_DB

retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.

Reactome

REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_1675. mRNA Processing.
REACT_1788. Transcription.
REACT_216. DNA Repair.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P51946.

Bgee

P51946.

CleanEx

HS_CCNH.

Genevestigator

P51946.

GermOnline

ENSG00000134480. Homo sapiens.

Family and domain databases

Gene3D

1.10.472.10. 2 hits.

InterPro

IPR013763. Cyclin-like.
IPR015429. Cyclin_C/H/T/L.
IPR006671. Cyclin_N.
IPR023598. CyclinC.
IPR027081. CyclinH/Ccl1.
[Graphical view]

PANTHER

PTHR10026. PTHR10026. 1 hit.
PTHR10026:SF8. PTHR10026:SF8. 1 hit.

Pfam

PF00134. Cyclin_N. 1 hit.
[Graphical view]

PIRSF

PIRSF028758. PIRSF028758. 1 hit.

SMART

SM00385. CYCLIN. 1 hit.
[Graphical view]

SUPFAM

SSF47954. Cyclin_like. 2 hits.

TIGRFAMs

TIGR00569. ccl1. 1 hit.

PROSITE

PS00292. CYCLINS. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P51946.

ChEMBL

CHEMBL2165.

ChiTaRS

CCNH. human.

EvolutionaryTrace

P51946.

GenomeRNAi

902.

NextBio

3728.

SOURCE

Search...

Entry information

Entry name

CCNH_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.