ID CYC_HUMAN Reviewed; 105 AA. AC P99999; A4D166; B2R4I1; P00001; Q6NUR2; Q6NX69; Q96BV4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 24-NOV-2009, entry version 81. DE RecName: Full=Cytochrome c; GN Name=CYCS; Synonyms=CYC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=89071748; PubMed=2849112; DOI=10.1073/pnas.85.24.9625; RA Evans M.J., Scarpulla R.C.; RT "The human somatic cytochrome c gene: two classes of processed RT pseudogenes demarcate a period of rapid molecular evolution."; RL Proc. Natl. Acad. Sci. U.S.A. 85:9625-9629(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22616434; PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone marrow, Brain, Kidney, Lung, Skeletal muscle, Skin, RC Testis, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-105, AND ACETYLATION AT GLY-2. RC TISSUE=Heart; RX PubMed=13933734; RA Matsubara H., Smith E.L.; RT "The amino acid sequence of human heart cytochrome c."; RL J. Biol. Chem. 237:3575-3576(1962). RN [10] RP PROTEIN SEQUENCE OF 2-105. RC TISSUE=Heart; RX PubMed=14063298; RA Matsubara H., Smith E.L.; RT "Human heart cytochrome c. Chymotryptic peptides, tryptic peptides, RT and the complete amino acid sequence."; RL J. Biol. Chem. 238:2732-2753(1963). RN [11] RP REVIEW ON ROLE IN APOPTOSIS. RX MEDLINE=98175474; PubMed=9515723; DOI=10.1016/S0014-5793(98)00061-1; RA Skulachev V.P.; RT "Cytochrome c in the apoptotic and antioxidant cascades."; RL FEBS Lett. 423:275-280(1998). RN [12] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [13] RP STRUCTURE BY NMR. RA Jeng W.-Y., Shiu J.-H., Tsai Y.-H., Chuang W.-J.; RT "Solution structure of reduced recombinant human cytochrome c."; RL Submitted (FEB-2003) to the PDB data bank. RN [14] RP VARIANT THC4 SER-42, MASS SPECTROMETRY, CHARACTERIZATION OF VARIANT RP THC4 SER-42, AND X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF VARIANT RP THC4 SER-42 AND WILD TYPE. RX PubMed=18345000; DOI=10.1038/ng.103; RA Morison I.M., Cramer Borde E.M.C., Cheesman E.J., Cheong P.L., RA Holyoake A.J., Fichelson S., Weeks R.J., Lo A., Davies S.M.K., RA Wilbanks S.M., Fagerlund R.D., Ludgate M.W., da Silva Tatley F.M., RA Coker M.S.A., Bockett N.A., Hughes G., Pippig D.A., Smith M.P., RA Capron C., Ledgerwood E.C.; RT "A mutation of human cytochrome c enhances the intrinsic apoptotic RT pathway but causes only thrombocytopenia."; RL Nat. Genet. 40:387-389(2008). CC -!- FUNCTION: Electron carrier protein. The oxidized form of the CC cytochrome c heme group can accept an electron from the heme group CC of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c CC then transfers this electron to the cytochrome oxidase complex, CC the final protein carrier in the mitochondrial electron-transport CC chain. CC -!- FUNCTION: Plays a role in apoptosis. Suppression of the anti- CC apoptotic members or activation of the pro-apoptotic members of CC the Bcl-2 family leads to altered mitochondrial membrane CC permeability resulting in release of cytochrome c into the CC cytosol. Binding of cytochrome c to Apaf-1 triggers the activation CC of caspase-9, which then accelerates apoptosis by activating other CC caspases. CC -!- INTERACTION: CC O14727:APAF1; NbExp=2; IntAct=EBI-446479, EBI-446492; CC Q9Y2Q3:GSTK1; NbExp=1; IntAct=EBI-446479, EBI-1053767; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. CC -!- PTM: Binds 1 heme group per subunit. CC -!- DISEASE: Defects in CYCS are the cause of thrombocytopenia type 4 CC (THC4) [MIM:612004]; also known as autosomal dominant CC thrombocytopenia type 4. Thrombocytopenia is the presence of CC relatively few platelets in blood. THC4 is a non-syndromic form of CC thrombocytopenia. Clinical manifestations of thrombocytopenia are CC absent or mild. THC4 may be caused by dysregulated platelet CC formation. CC -!- SIMILARITY: Belongs to the cytochrome c family. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life shuttle - Issue 76 CC of November 2006; CC URL="http://www.expasy.org/spotlight/back_issues/sptlt076.shtml"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M22877; AAA35732.1; -; Genomic_DNA. DR EMBL; BT006946; AAP35592.1; -; mRNA. DR EMBL; AK311836; BAG34778.1; -; mRNA. DR EMBL; AL713681; CAD28485.1; -; mRNA. DR EMBL; AC007487; AAQ96844.1; -; Genomic_DNA. DR EMBL; CH236948; EAL24239.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93822.1; -; Genomic_DNA. DR EMBL; BC005299; AAH05299.1; -; mRNA. DR EMBL; BC008475; AAH08475.1; -; mRNA. DR EMBL; BC008477; AAH08477.1; -; mRNA. DR EMBL; BC009578; AAH09578.1; -; mRNA. DR EMBL; BC009579; AAH09579.1; -; mRNA. DR EMBL; BC009582; AAH09582.1; -; mRNA. DR EMBL; BC009587; AAH09587.1; -; mRNA. DR EMBL; BC009602; AAH09602.1; -; mRNA. DR EMBL; BC009607; AAH09607.1; -; mRNA. DR EMBL; BC014359; AAH14359.1; -; mRNA. DR EMBL; BC014361; AAH14361.1; -; mRNA. DR EMBL; BC015130; AAH15130.1; -; mRNA. DR EMBL; BC016006; AAH16006.1; -; mRNA. DR EMBL; BC021994; AAH21994.1; -; mRNA. DR EMBL; BC022330; AAH22330.1; -; mRNA. DR EMBL; BC067222; AAH67222.1; -; mRNA. DR EMBL; BC068464; AAH68464.1; -; mRNA. DR EMBL; BC070156; AAH70156.1; -; mRNA. DR EMBL; BC070346; AAH70346.1; -; mRNA. DR EMBL; BC071761; AAH71761.1; -; mRNA. DR IPI; IPI00465315; -. DR PIR; A31764; CCHU. DR RefSeq; NP_061820.1; -. DR UniGene; Hs.437060; -. DR UniGene; Hs.617193; -. DR PDB; 1J3S; NMR; -; A=2-104. DR PDBsum; 1J3S; -. DR IntAct; P99999; 16. DR STRING; P99999; -. DR PhosphoSite; P99999; -. DR PeptideAtlas; P99999; -. DR PRIDE; P99999; -. DR Ensembl; ENST00000305786; ENSP00000307786; ENSG00000172115; Homo sapiens. DR Ensembl; ENST00000409409; ENSP00000386270; ENSG00000172115; Homo sapiens. DR Ensembl; ENST00000409764; ENSP00000387279; ENSG00000172115; Homo sapiens. DR GeneID; 54205; -. DR KEGG; hsa:54205; -. DR UCSC; uc003sxl.1; human. DR CTD; 54205; -. DR GeneCards; GC07M025124; -. DR H-InvDB; HIX0006529; -. DR HGNC; HGNC:19986; CYCS. DR HPA; CAB004222; -. DR HPA; CAB005126; -. DR HPA; CAB018597; -. DR MIM; 123970; gene. DR MIM; 612004; phenotype. DR Orphanet; 168629; Nonsyndromic thrombocytopenia. DR PharmGKB; PA134981636; -. DR HOGENOM; P99999; -. DR HOVERGEN; P99999; -. DR OMA; ANLKEWL; -. DR OrthoDB; EOG9TF34R; -. DR Pathway_Interaction_DB; caspase_pathway; Caspase cascade in apoptosis. DR Pathway_Interaction_DB; ceramidepathway; Ceramide signaling pathway. DR Pathway_Interaction_DB; hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha. DR Pathway_Interaction_DB; p75ntrpathway; p75(NTR)-mediated signaling. DR Reactome; REACT_1505; Integration of energy metabolism. DR Reactome; REACT_15380; Diabetes pathways. DR Reactome; REACT_578; Apoptosis. DR DrugBank; DB01065; Melatonin. DR DrugBank; DB01017; Minocycline. DR NextBio; 56526; -. DR ArrayExpress; P99999; -. DR Bgee; P99999; -. DR CleanEx; HS_CYCS; -. DR Genevestigator; P99999; -. DR GermOnline; ENSG00000172115; Homo sapiens. DR GO; GO:0005829; C:cytosol; IMP:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; TAS:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:LIFEdb. DR GO; GO:0000159; C:protein phosphatase type 2A complex; TAS:UniProtKB. DR GO; GO:0070469; C:respiratory chain; IEA:UniProtKB-KW. DR GO; GO:0045155; F:electron transporter, transferring electron...; IDA:UniProtKB. DR GO; GO:0020037; F:heme binding; TAS:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0008635; P:activation of caspase activity by cytochrome c; TAS:UniProtKB. DR GO; GO:0045333; P:cellular respiration; TAS:UniProtKB. DR GO; GO:0006309; P:DNA fragmentation involved in apoptosis; IMP:UniProtKB. DR GO; GO:0022900; P:electron transport chain; IEA:UniProtKB-KW. DR GO; GO:0006810; P:transport; IEA:UniProtKB-KW. DR InterPro; IPR002327; Cyt_c_1A/1B. DR InterPro; IPR003088; Cyt_c_I. DR InterPro; IPR009056; Cyt_c_monohaem. DR Gene3D; G3DSA:1.10.760.10; Cytochrome_c_R; 1. DR PANTHER; PTHR11961; Cyt_CIAB; 1. DR Pfam; PF00034; Cytochrom_C; 1. DR PRINTS; PR00604; CYTCHRMECIAB. DR PROSITE; PS51007; CYTC; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Complete proteome; KW Direct protein sequencing; Disease mutation; Electron transport; Heme; KW Iron; Metal-binding; Mitochondrion; Polymorphism; Respiratory chain; KW Transport. FT INIT_MET 1 1 Removed. FT CHAIN 2 105 Cytochrome c. FT /FTId=PRO_0000108218. FT METAL 19 19 Iron (heme axial ligand). FT METAL 81 81 Iron (heme axial ligand). FT BINDING 15 15 Heme (covalent). FT BINDING 18 18 Heme (covalent). FT MOD_RES 2 2 N-acetylglycine. FT VARIANT 42 42 G -> S (in THC4; increases the pro- FT apoptotic function by triggering caspase FT activation more efficiently than wild- FT type; does not affect the redox FT function). FT /FTId=VAR_044450. FT VARIANT 56 56 K -> R (in dbSNP:rs11548795). FT /FTId=VAR_048850. FT VARIANT 66 66 M -> L (in 10% of the molecules). FT /FTId=VAR_002204. FT CONFLICT 18 18 C -> Y (in Ref. 8; AAH15130). FT CONFLICT 41 41 T -> I (in Ref. 8; AAH68464). FT HELIX 4 14 FT TURN 16 18 FT STRAND 23 25 FT STRAND 28 30 FT TURN 36 38 FT HELIX 51 56 FT HELIX 62 70 FT HELIX 72 75 FT HELIX 89 102 SQ SEQUENCE 105 AA; 11749 MW; 8EE9689E0102506B CRC64; MGDVEKGKKI FIMKCSQCHT VEKGGKHKTG PNLHGLFGRK TGQAPGYSYT AANKNKGIIW GEDTLMEYLE NPKKYIPGTK MIFVGIKKKE ERADLIAYLK KATNE //