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P24863 (CCNC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-C
Alternative name(s):
SRB11 homolog
Short name=hSRB11
Gene names
Name:CCNC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length283 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDK8P493366EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 283283Cyclin-C
PRO_0000080420

Regions

Domain46 – 14499Cyclin N-terminal

Amino acid modifications

Modified residue2751Phosphoserine Ref.12

Natural variations

Alternative sequence1 – 8585Missing in isoform 2.
VSP_043075

Secondary structure

...................................... 283
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: CF8AC5E94E621F4C

FASTA28333,243
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 1A22C22167A775E7
Show »

FASTA19822,945

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 expand/collapse EMBL AC list , 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.
PIRA40268.
RefSeqNP_001013417.1. NM_001013399.1.
NP_005181.2. NM_005190.3.
UniGeneHs.430646.
Hs.633351.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3RGFX-ray2.20B1-283[»]
4F6SX-ray2.60B1-283[»]
4F6UX-ray2.10B1-283[»]
4F6WX-ray2.39B1-283[»]
4F70X-ray3.00B1-283[»]
4F7JX-ray2.60B1-283[»]
4F7LX-ray2.90B1-283[»]
4F7NX-ray2.65B1-283[»]
4F7SX-ray2.20B1-283[»]
4G6LX-ray2.70B1-283[»]
ProteinModelPortalP24863.
SMRP24863. Positions 1-257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107333. 30 interactions.
DIPDIP-32920N.
IntActP24863. 14 interactions.
STRING9606.ENSP00000358222.

PTM databases

PhosphoSiteP24863.

Polymorphism databases

DMDM166214910.

Proteomic databases

PaxDbP24863.
PRIDEP24863.

Protocols and materials databases

DNASU892.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000520429; ENSP00000428982; ENSG00000112237. [P24863-1]
ENST00000523799; ENSP00000430014; ENSG00000112237. [P24863-2]
ENST00000523985; ENSP00000430119; ENSG00000112237. [P24863-2]
GeneID892.
KEGGhsa:892.
UCSCuc003pqd.3. human. [P24863-1]

Organism-specific databases

CTD892.
GeneCardsGC06M100037.
HGNCHGNC:1581. CCNC.
HPACAB010499.
MIM123838. gene.
neXtProtNX_P24863.
PharmGKBPA26149.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5333.
HOGENOMHOG000008007.
HOVERGENHBG050836.
InParanoidP24863.
KOK15161.
OMAFFANVIQ.
OrthoDBEOG7WX08X.
PhylomeDBP24863.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_71. Gene Expression.
SignaLinkP24863.

Gene expression databases

ArrayExpressP24863.
BgeeP24863.
CleanExHS_CCNC.
GenevestigatorP24863.

Family and domain databases

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

Other

GeneWikiCCNC_(gene).
GenomeRNAi892.
NextBio3690.
PROP24863.
SOURCESearch...

Entry information

Entry nameCCNC_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 141 of the entry and version 2 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 chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM