P24863 (CCNC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-C

Alternative name(s):
SRB11 homolog
Short name=hSRB11

Gene names

Name:

CCNC

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	283 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Ref.5 Ref.11
Subunit structure	Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Ref.6 Ref.7 Ref.10
Subcellular location	Nucleus Probable.
Tissue specificity	Highest levels in pancreas. High levels in heart, liver, skeletal muscle and kidney. Low levels in brain.
Sequence similarities	Belongs to the cyclin family. Cyclin C subfamily. Contains 1 cyclin N-terminal domain.
Sequence caution	The sequence AAC50825.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Activator Cyclin Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome positive regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	DNA-directed RNA polymerase II, holoenzyme Inferred from electronic annotation. Source: InterPro mediator complex Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK8	P49336	3	EBI-395261,EBI-394377

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P24863-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P24863-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 283

283

Cyclin-C

PRO_0000080420

Regions

Domain

46 – 144

99

Cyclin N-terminal

Amino acid modifications

Modified residue

275

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

1 – 85

85

Missing in isoform 2.

VSP_043075

Secondary structure

1

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283

Helix Strand Turn

Details...

Turn

1 – 3

3

Helix

5 – 7

3

Helix

9 – 14

6

Helix

18 – 25

8

Helix

26 – 30

5

Helix

34 – 54

21

Helix

59 – 75

17

Helix

83 – 97

15

Helix

105 – 119

15

Turn

121 – 123

3

Helix

132 – 145

14

Turn

146 – 148

3

Helix

156 – 166

11

Helix

169 – 183

15

Helix

188 – 191

4

Helix

194 – 208

15

Helix

214 – 218

5

Helix

224 – 243

20

Helix

246 – 256

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: CF8AC5E94E621F4C	FASTA	283	33,243
	10 20 30 40 50 60 MAGNFWQSSH YLQWILDKQD LLKERQKDLK FLSEEEYWKL QIFFTNVIQA LGEHLKLRQQ 70 80 90 100 110 120 VIATATVYFK RFYARYSLKS IDPVLMAPTC VFLASKVEEF GVVSNTRLIA AATSVLKTRF 130 140 150 160 170 180 SYAFPKEFPY RMNHILECEF YLLELMDCCL IVYHPYRPLL QYVQDMGQED MLLPLAWRIV 190 200 210 220 230 240 NDTYRTDLCL LYPPFMIALA CLHVACVVQQ KDARQWFAEL SVDMEKILEI IRVILKLYEQ 250 260 270 280 WKNFDERKEM ATILSKMPKP KPPPNSEGEQ GPNGSQNSSY SQS
	Isoform 2 [UniParc]. Checksum: 1A22C22167A775E7	FASTA	198	22,945
	10 20 30 40 50 60 MAPTCVFLAS KVEEFGVVSN TRLIAAATSV LKTRFSYAFP KEFPYRMNHI LECEFYLLEL 70 80 90 100 110 120 MDCCLIVYHP YRPLLQYVQD MGQEDMLLPL AWRIVNDTYR TDLCLLYPPF MIALACLHVA 130 140 150 160 170 180 CVVQQKDARQ WFAELSVDME KILEIIRVIL KLYEQWKNFD ERKEMATILS KMPKPKPPPN 190 SEGEQGPNGS QNSSYSQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast." Lew D.J., Dulic V., Reed S.I. Cell 66:1197-1206(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors." Li H., Lahti J.M., Valentine M., Saito M., Reed S.I., Look A.T., Kidd V.J. Genomics 32:253-259(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II." Rickert P., Seghezzi W., Shanahan F., Cho H., Lees E. Oncogene 12:2631-2640(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription." Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D. Mol. Cell 2:213-222(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A FORM OF THE MEDIATOR COMPLEX.
[7]	"A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation." Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., Qin J., Roeder R.G. Mol. Cell 3:97-108(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE SMCC COMPLEX.
[8]	Erratum Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., Qin J., Roeder R.G. Mol. Cell 3:541-541(1999)
[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: INTERACTION WITH MED6.
[10]	"A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology." Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., Conaway R.C. Mol. Cell 14:685-691(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX.
[11]	"Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly." Baek H.J., Kang Y.K., Roeder R.G. J. Biol. Chem. 281:15172-15181(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MED1 AND MED10.
[12]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder." Schneider E.V., Bottcher J., Blaesse M., Neumann L., Huber R., Maskos K. J. Mol. Biol. 412:251-266(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH CDK8 AND INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M74091 mRNA. No translation available.
U40739 , U40728, U40729, U40730, U40731, U40732, U40733, U40734, U40735, U40736, U40737, U40738 Genomic DNA. Translation: AAC50825.1. Different initiation.
AK298558 mRNA. Translation: BAG60753.1.
AL137784 Genomic DNA. Translation: CAC14563.1.

IPI

IPI00031076.
IPI00554688.

PIR

A40268.

RefSeq

NP_001013417.1. NM_001013399.1.
NP_005181.2. NM_005190.3.

UniGene

Hs.430646.
Hs.633351.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RGF	X-ray	2.20	B	1-283	[»]

ProteinModelPortal

P24863.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32920N.

IntAct

P24863. 11 interactions.

STRING

9606.ENSP00000358222.

PTM databases

PhosphoSite

P24863.

Polymorphism databases

DMDM

166214910.

Proteomic databases

PaxDb

P24863.

PRIDE

P24863.

Protocols and materials databases

DNASU

892.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000520429; ENSP00000428982; ENSG00000112237.
ENST00000523799; ENSP00000430014; ENSG00000112237.
ENST00000523985; ENSP00000430119; ENSG00000112237.

GeneID

892.

KEGG

hsa:892.

UCSC

uc003pqd.3. human.

Organism-specific databases

CTD

892.

GeneCards

GC06M100037.

HGNC

HGNC:1581. CCNC.

HPA

CAB010499.

MIM

123838. gene.

neXtProt

NX_P24863.

PharmGKB

PA26149.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5333.

HOGENOM

HOG000008007.

HOVERGEN

HBG050836.

InParanoid

P24863.

KO

K15161.

OMA

FFANVIQ.

OrthoDB

EOG4G1MGX.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P24863.

Bgee

P24863.

CleanEx

HS_CCNC.

Genevestigator

P24863.

GermOnline

ENSG00000112237. Homo sapiens.

Family and domain databases

Gene3D

1.10.472.10. 1 hit.

InterPro

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

PANTHER

PTHR10026. PTHR10026. 1 hit.

Pfam

PF00134. Cyclin_N. 1 hit.
[Graphical view]

PIRSF

PIRSF028758. PIRSF028758. 1 hit.

SMART

SM00385. CYCLIN. 2 hits.
[Graphical view]

SUPFAM

SSF47954. Cyclin_like. 2 hits.

PROSITE

PS00292. CYCLINS. False negative.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

892.

NextBio

3690.

SOURCE

Search...

Entry information

Entry name

CCNC_HUMAN

Accession

Primary (citable) accession number: P24863
Secondary accession number(s): B4DPZ1, Q9H543

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 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.