ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!
Search for

UniProtKB/Swiss-Prot entry P99999


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

Note: most headings are clickable, even if they don't appear as links. They link to the user manual or other documents.
Entry information
Entry name CYC_HUMAN
Primary accession number P99999
Secondary accession numbers A4D166 P00001 Q6NUR2 Q6NX69 Q96BV4
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on January 23, 2007 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 75)
Name and origin of the protein
Protein name Cytochrome c
Synonyms None
Gene name
Name: CYCS
Synonyms: CYC
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
DOI=10.1073/pnas.85.24.9625; PubMed=2849112 [NCBI, ExPASy, EBI, Israel, Japan]
Evans M.J., Scarpulla R.C.;
"The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution.";
Proc. Natl. Acad. Sci. U.S.A. 85:9625-9629(1988).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Amygdala;
DOI=10.1186/1471-2164-8-399; PubMed=17974005 [NCBI, ExPASy, EBI, Israel, Japan]
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature01782; PubMed=12853948 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1126/science.1083423; PubMed=12690205 [NCBI, ExPASy, EBI, Israel, Japan]
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.;
"Human chromosome 7: DNA sequence and biology.";
Science 300:767-772(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Bone marrow, Brain, Kidney, Lung, Skeletal muscle, Skin, Testis, and Urinary bladder;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
PROTEIN SEQUENCE OF 2-105, AND ACETYLATION AT GLY-2.
TISSUE=Heart;
PubMed=13933734 [NCBI, ExPASy, EBI, Israel, Japan]
Matsubara H., Smith E.L.;
"The amino acid sequence of human heart cytochrome c.";
J. Biol. Chem. 237:3575-3576(1962).
[8]
PROTEIN SEQUENCE OF 2-105.
TISSUE=Heart;
PubMed=14063298 [NCBI, ExPASy, EBI, Israel, Japan]
Matsubara H., Smith E.L.;
"Human heart cytochrome c. Chymotryptic peptides, tryptic peptides, and the complete amino acid sequence.";
J. Biol. Chem. 238:2732-2753(1963).
[9]
REVIEW ON ROLE IN APOPTOSIS.
DOI=10.1016/S0014-5793(98)00061-1; PubMed=9515723 [NCBI, ExPASy, EBI, Israel, Japan]
Skulachev V.P.;
"Cytochrome c in the apoptotic and antioxidant cascades.";
FEBS Lett. 423:275-280(1998).
[10]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[11]
STRUCTURE BY NMR.
Jeng W.-Y., Shiu J.-H., Tsai Y.-H., Chuang W.-J.;
"Solution structure of reduced recombinant human cytochrome c.";
Submitted (FEB-2003) to the PDB data bank.
[12]
VARIANT THC4 SER-42, MASS SPECTROMETRY, CHARACTERIZATION OF VARIANT THC4 SER-42, AND X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF VARIANT THC4 SER-42 AND WILD TYPE.
DOI=10.1038/ng.103; PubMed=18345000 [NCBI, ExPASy, EBI, Israel, Japan]
Morison I.M., Cramer Borde E.M.C., Cheesman E.J., Cheong P.L., Holyoake A.J., Fichelson S., Weeks R.J., Lo A., Davies S.M.K., Wilbanks S.M., Fagerlund R.D., Ludgate M.W., da Silva Tatley F.M., Coker M.S.A., Bockett N.A., Hughes G., Pippig D.A., Smith M.P., Capron C., Ledgerwood E.C.;
"A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia.";
Nat. Genet. 40:387-389(2008).
Comments
  • FUNCTION: Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.
  • FUNCTION: Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.
  • INTERACTION:
    O14727:APAF1; NbExp=2; IntAct=EBI-446479, EBI-446492;
    Q9Y2Q3:GSTK1; NbExp=1; IntAct=EBI-446479, EBI-1053767;
  • SUBCELLULAR LOCATION: Mitochondrion matrix.
  • PTM: Binds 1 heme group per subunit.
  • DISEASE: Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:612004]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.
  • SIMILARITY: Belongs to the cytochrome c family.
  • WEB RESOURCE: Name=Protein Spotlight; Note=Life shuttle - Issue 76 of November 2006; URL="http://www.expasy.org/spotlight/back_issues/sptlt076.shtml";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M22877; AAA35732.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT006946; AAP35592.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL713681; CAD28485.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC007487; AAQ96844.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CH236948; EAL24239.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005299; AAH05299.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008475; AAH08475.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008477; AAH08477.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009578; AAH09578.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009579; AAH09579.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009582; AAH09582.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009587; AAH09587.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009602; AAH09602.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC009607; AAH09607.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC014359; AAH14359.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC014361; AAH14361.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC015130; AAH15130.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC016006; AAH16006.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC021994; AAH21994.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC022330; AAH22330.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067222; AAH67222.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC068464; AAH68464.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC070156; AAH70156.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC070346; AAH70346.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC071761; AAH71761.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00465315; -.
PIR A31764; CCHU.
RefSeq NP_061820.1; -.
UniGene Hs.437060
3D structure databases
PDB
1J3S; NMR; -; A=2-104.[ExPASy / RCSB / EBI]
PDBsum 1J3S; -.
ModBase P99999.
Protein-protein interaction databases
IntAct P99999; 16.
PTM databases
PhosphoSite P99999; -.
Enzyme and pathway databases
Pathway_Interaction_DB caspase_pathway; Caspase cascade in apoptosis.
ceramidepathway; Ceramide signaling pathway.
hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha.
p75ntrpathway; p75(NTR)-mediated signaling.
Reactome REACT_578; Apoptosis.
REACT_6305; Electron Transport Chain.
Organism-specific databases
GeneCards GC07M025124; -.
H-InvDB HIX0006529; -.
HGNC HGNC:19986; CYCS.
GenAtlas CYCS.
HPA CAB005126; -.
CAB018597; -.
MIM 123970; gene. [NCBI / EBI]
612004; phenotype. [NCBI / EBI]
Orphanet 168629; Nonsyndromic thrombocytopenia.
PharmGKB PA134981636; -.
Gene expression databases
ArrayExpress P99999; -.
Bgee P99999; -.
CleanEx HS_CYCS; -.
GermOnline ENSG00000172115; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from mutant phenotype from UniProtKB).
GO:0005758; Cellular component: mitochondrial intermembrane space (traceable author statement from UniProtKB).
GO:0005759; Cellular component: mitochondrial matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005634; Cellular component: nucleus (inferred from direct assay from LIFEdb).
GO:0000159; Cellular component: protein phosphatase type 2A complex (traceable author statement from UniProtKB).
GO:0070469; Cellular component: respiratory chain (inferred from electronic annotation from UniProtKB-KW).
GO:0045155; Molecular function: electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity (inferred from direct assay from UniProtKB).
GO:0020037; Molecular function: heme binding (traceable author statement from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0008635; Biological process: activation of caspase activity by cytochrome c (traceable author statement from UniProtKB).
GO:0045333; Biological process: cellular respiration (traceable author statement from UniProtKB).
GO:0006309; Biological process: DNA fragmentation involved in apoptosis (inferred from mutant phenotype from UniProtKB).
GO:0022900; Biological process: electron transport chain (inferred from electronic annotation from UniProtKB-KW).
GO:0006810; Biological process: transport (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR002327; Cyt_c_1A/1B.
IPR003088; Cyt_c_I.
IPR009056; Cyt_c_monohaem.
Graphical view of domain structure.
Gene3D G3DSA:1.10.760.10; Cytochrome_c_R; 1.
PANTHER PTHR11961; Cyt_CIAB; 1.
Pfam PF00034; Cytochrom_C; 1.
Pfam graphical view of domain structure.
PRINTS PR00604; CYTCHRMECIAB.
ProDom PD000375; Cyt_CIAB; 1.
[Domain structure / List of seq. sharing at least 1 domain]
PROSITE PS51007; CYTC; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PeptideAtlas P99999; -.
PRIDE P99999; -.
Genome annotation databases
Ensembl ENSG00000172115; Homo sapiens. [Contig view]
GeneID 54205; -.
KEGG hsa:54205; -.
Phylogenomic databases
HOGENOM P99999; -.
HOVERGEN P99999; -.
OMA P99999; TMSDYLE.
Other
DrugBank DB01065; Melatonin.
DB01017; Minocycline.
NextBio 56526; -.
SOURCE CYCS; Homo sapiens.
ProtoNet P99999.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Apoptosis; Direct protein sequencing; Disease mutation; Electron transport; Heme; Iron; Metal-binding; Mitochondrion; Polymorphism; Respiratory chain; Transport.
Features
SEVIEWER logo Feature table viewer
KeyFrom  To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   105  104     Cytochrome c. PRO_0000108218
METAL   19    19        Iron (heme axial ligand). 
METAL   81    81        Iron (heme axial ligand). 
BINDING   15    15        Heme (covalent). 
BINDING   18    18        Heme (covalent). 
MOD_RES   2     2        N-acetylglycine. 
VARIANT   42    42  1     G -> S (in THC4; increases the pro-apoptotic function by triggering caspase activation more efficiently than wild-type; does not affect the redox function). VAR_044450 [3D]
VARIANT   56    56  1     K -> R (in dbSNP:rs11548795 [NCBI]). VAR_048850 [3D]
VARIANT   66    66  1     M -> L (in 10% of the molecules). VAR_002204 [3D]
CONFLICT   18    18        C -> Y (in Ref. 6; AAH15130). 
CONFLICT   41    41        T -> I (in Ref. 6; AAH68464). 
HELIX   4    14  11      
TURN   16    18  3      
STRAND   23    25  3      
STRAND   28    30  3      
TURN   36    38  3      
HELIX   51    56  6      
HELIX   62    70  9      
HELIX   72    75  4      
HELIX   89   102  14      
Sequence information
Length: 105 AA [This is the length of the unprocessed precursor] Molecular weight: 11749 Da [This is the MW of the unprocessed precursor] CRC64: 8EE9689E0102506B [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGDVEKGKKI FIMKCSQCHT VEKGGKHKTG PNLHGLFGRK TGQAPGYSYT AANKNKGIIW 

        70         80         90        100 
GEDTLMEYLE NPKKYIPGTK MIFVGIKKKE ERADLIAYLK KATNE 

P99999 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

BLAST logo BLAST submission on ExPASy/SIB
or at NCBI (USA)
Tools Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
PROSITE logo ScanProsite, MotifScan SWISS-MODEL Submit a homology modeling request to SWISS-MODEL
NPSA logo NPSA Sequence analysis tools

ExPASy logo ExPASy Home page Site Map Search ExPASy Contact us Swiss-Prot
 Hosted by ca flag CBR Canada Mirror sites: Australia  Brazil  China  Korea  Switzerland
Notice: This page will be replaced with www.uniprot.org. Please send us your feedback!