CYC_HUMAN
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 03-AUG-2022, entry version 191.
DE RecName: Full=Cytochrome c;
GN Name=CYCS; Synonyms=CYC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX 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 pseudogenes
RT 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA 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 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., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., 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., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA 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 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., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., 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., Mural R.J.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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, Testis, and
RC 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 project:
RT 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, and the
RT complete amino acid sequence.";
RL J. Biol. Chem. 238:2732-2753(1963).
RN [11]
RP REVIEW ON ROLE IN APOPTOSIS.
RX 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 BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP MUTAGENESIS OF LYS-6; PHE-11; CYS-15; CYS-18 AND HIS-19, AND HEME-BINDING.
RX PubMed=23150584; DOI=10.1073/pnas.1213897109;
RA San Francisco B., Bretsnyder E.C., Kranz R.G.;
RT "Human mitochondrial holocytochrome c synthase's heme binding, maturation
RT determinants, and complex formation with cytochrome c.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E788-E797(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
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 [19]
RP VARIANT THC4 SER-42, IDENTIFICATION BY MASS SPECTROMETRY, CHARACTERIZATION
RP OF VARIANT THC4 SER-42, AND X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF
RP VARIANT 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., Capron C.,
RA Ledgerwood E.C.;
RT "A mutation of human cytochrome c enhances the intrinsic apoptotic pathway
RT but causes only thrombocytopenia.";
RL Nat. Genet. 40:387-389(2008).
CC -!- FUNCTION: Electron carrier protein. The oxidized form of the cytochrome
CC c heme group can accept an electron from the heme group of the
CC cytochrome c1 subunit of cytochrome reductase. Cytochrome c then
CC transfers this electron to the cytochrome oxidase complex, the final
CC protein carrier in the mitochondrial electron-transport chain.
CC -!- FUNCTION: Plays a role in apoptosis. Suppression of the anti-apoptotic
CC members or activation of the pro-apoptotic members of the Bcl-2 family
CC leads to altered mitochondrial membrane permeability resulting in
CC release of cytochrome c into the cytosol. Binding of cytochrome c to
CC Apaf-1 triggers the activation of caspase-9, which then accelerates
CC apoptosis by activating other caspases.
CC -!- INTERACTION:
CC P99999; O14727: APAF1; NbExp=6; IntAct=EBI-446479, EBI-446492;
CC P99999; P05067: APP; NbExp=3; IntAct=EBI-446479, EBI-77613;
CC P99999; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-446479, EBI-10254793;
CC P99999; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-446479, EBI-10693038;
CC P99999; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-446479, EBI-18036948;
CC P99999; Q96BR5: COA7; NbExp=3; IntAct=EBI-446479, EBI-6269632;
CC P99999; Q9UKG9-2: CROT; NbExp=3; IntAct=EBI-446479, EBI-25835363;
CC P99999; O00303: EIF3F; NbExp=3; IntAct=EBI-446479, EBI-711990;
CC P99999; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-446479, EBI-8468186;
CC P99999; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-446479, EBI-6425864;
CC P99999; P06241: FYN; NbExp=3; IntAct=EBI-446479, EBI-515315;
CC P99999; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-446479, EBI-743960;
CC P99999; Q6A162: KRT40; NbExp=6; IntAct=EBI-446479, EBI-10171697;
CC P99999; Q1L5Z9: LONRF2; NbExp=3; IntAct=EBI-446479, EBI-2510853;
CC P99999; Q8IYG6: LRRC56; NbExp=3; IntAct=EBI-446479, EBI-14752528;
CC P99999; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-446479, EBI-16439278;
CC P99999; A0A0A0MR05: MLST8; NbExp=3; IntAct=EBI-446479, EBI-25835557;
CC P99999; Q9BUL5: PHF23; NbExp=3; IntAct=EBI-446479, EBI-722852;
CC P99999; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-446479, EBI-25835994;
CC P99999; Q66K80: RUSC1-AS1; NbExp=3; IntAct=EBI-446479, EBI-10248967;
CC P99999; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-446479, EBI-9089805;
CC P99999; P37840: SNCA; NbExp=3; IntAct=EBI-446479, EBI-985879;
CC P99999; Q13573: SNW1; NbExp=3; IntAct=EBI-446479, EBI-632715;
CC P99999; Q92797-2: SYMPK; NbExp=3; IntAct=EBI-446479, EBI-21560407;
CC P99999; O43829: ZBTB14; NbExp=3; IntAct=EBI-446479, EBI-10176632;
CC P99999; Q9FKS5: CYC1-2; Xeno; NbExp=2; IntAct=EBI-446479, EBI-1777995;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Note=Loosely
CC associated with the inner membrane.
CC -!- PTM: Binds 1 heme c group covalently per subunit.
CC -!- PTM: Phosphorylation at Tyr-49 and Tyr-98 both reduce by half the
CC turnover in the reaction with cytochrome c oxidase, down-regulating
CC mitochondrial respiration. {ECO:0000250}.
CC -!- DISEASE: Thrombocytopenia 4 (THC4) [MIM:612004]: A form of
CC thrombocytopenia, a hematologic disorder defined by a decrease in the
CC number of platelets in circulating blood, resulting in the potential
CC for increased bleeding and decreased ability for clotting.
CC {ECO:0000269|PubMed:18345000}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cytochrome c family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life shuttle - Issue 76 of
CC November 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/076";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=An unexpected place - Issue
CC 88 of November 2007;
CC URL="https://web.expasy.org/spotlight/back_issues/088/";
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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 CCDS; CCDS5393.1; -.
DR PIR; A31764; CCHU.
DR RefSeq; NP_061820.1; NM_018947.5.
DR PDB; 1J3S; NMR; -; A=2-105.
DR PDB; 2N3Y; NMR; -; A=2-105.
DR PDB; 2N9I; NMR; -; A=2-105.
DR PDB; 2N9J; NMR; -; A=2-105.
DR PDB; 3NWV; X-ray; 1.90 A; A/B/C/D=2-105.
DR PDB; 3ZCF; X-ray; 1.65 A; A/B/C/D=2-105.
DR PDB; 3ZOO; X-ray; 1.35 A; A/B/C/D=2-105.
DR PDB; 5EXQ; X-ray; 1.60 A; A/B=2-105.
DR PDB; 5O10; X-ray; 1.36 A; A/B=2-105.
DR PDB; 5TY3; X-ray; 1.25 A; A/B=2-105.
DR PDB; 6DUJ; X-ray; 1.82 A; A/C=2-105.
DR PDB; 6ECJ; X-ray; 2.70 A; A/B/C/D/E/F/G/H=2-105.
DR PDB; 6XNK; X-ray; 2.08 A; A/C/E/G=2-105.
DR PDBsum; 1J3S; -.
DR PDBsum; 2N3Y; -.
DR PDBsum; 2N9I; -.
DR PDBsum; 2N9J; -.
DR PDBsum; 3NWV; -.
DR PDBsum; 3ZCF; -.
DR PDBsum; 3ZOO; -.
DR PDBsum; 5EXQ; -.
DR PDBsum; 5O10; -.
DR PDBsum; 5TY3; -.
DR PDBsum; 6DUJ; -.
DR PDBsum; 6ECJ; -.
DR PDBsum; 6XNK; -.
DR AlphaFoldDB; P99999; -.
DR BMRB; P99999; -.
DR SMR; P99999; -.
DR BioGRID; 119922; 143.
DR ComplexPortal; CPX-3762; Apoptosome.
DR CORUM; P99999; -.
DR DIP; DIP-29683N; -.
DR IntAct; P99999; 67.
DR MINT; P99999; -.
DR STRING; 9606.ENSP00000307786; -.
DR BindingDB; P99999; -.
DR ChEMBL; CHEMBL2189163; -.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB03317; Ferroheme C.
DR DrugBank; DB03366; Imidazole.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB02110; Protoporphyrin Ix Containing Co.
DR DrugBank; DB03977; Trimethyllysine.
DR DrugBank; DB03934; Zinc protoporphyrin.
DR DrugBank; DB04249; Zinc Substituted Heme C.
DR DrugCentral; P99999; -.
DR MoonDB; P99999; Curated.
DR GlyGen; P99999; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P99999; -.
DR PhosphoSitePlus; P99999; -.
DR SwissPalm; P99999; -.
DR BioMuta; CYCS; -.
DR DMDM; 42560196; -.
DR EPD; P99999; -.
DR jPOST; P99999; -.
DR MassIVE; P99999; -.
DR MaxQB; P99999; -.
DR PaxDb; P99999; -.
DR PeptideAtlas; P99999; -.
DR PRIDE; P99999; -.
DR ProteomicsDB; 57831; -.
DR TopDownProteomics; P99999; -.
DR ABCD; P99999; 1 sequenced antibody.
DR Antibodypedia; 3917; 1424 antibodies from 47 providers.
DR DNASU; 54205; -.
DR Ensembl; ENST00000305786.7; ENSP00000307786.2; ENSG00000172115.9.
DR Ensembl; ENST00000409409.5; ENSP00000386270.1; ENSG00000172115.9.
DR Ensembl; ENST00000409764.5; ENSP00000387279.1; ENSG00000172115.9.
DR GeneID; 54205; -.
DR KEGG; hsa:54205; -.
DR MANE-Select; ENST00000305786.7; ENSP00000307786.2; NM_018947.6; NP_061820.1.
DR UCSC; uc003sxl.4; human.
DR CTD; 54205; -.
DR DisGeNET; 54205; -.
DR GeneCards; CYCS; -.
DR HGNC; HGNC:19986; CYCS.
DR HPA; ENSG00000172115; Tissue enhanced (tongue).
DR MalaCards; CYCS; -.
DR MIM; 123970; gene.
DR MIM; 612004; phenotype.
DR neXtProt; NX_P99999; -.
DR OpenTargets; ENSG00000172115; -.
DR Orphanet; 168629; Autosomal thrombocytopenia with normal platelets.
DR PharmGKB; PA134981636; -.
DR VEuPathDB; HostDB:ENSG00000172115; -.
DR eggNOG; KOG3453; Eukaryota.
DR GeneTree; ENSGT00390000009405; -.
DR InParanoid; P99999; -.
DR OMA; AQCHTIN; -.
DR OrthoDB; 1533604at2759; -.
DR PhylomeDB; P99999; -.
DR TreeFam; TF300226; -.
DR BioCyc; MetaCyc:ENSG00000172115-MON; -.
DR PathwayCommons; P99999; -.
DR Reactome; R-HSA-111457; Release of apoptotic factors from the mitochondria.
DR Reactome; R-HSA-111458; Formation of apoptosome.
DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs.
DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SignaLink; P99999; -.
DR SIGNOR; P99999; -.
DR BioGRID-ORCS; 54205; 515 hits in 1007 CRISPR screens.
DR ChiTaRS; CYCS; human.
DR EvolutionaryTrace; P99999; -.
DR GeneWiki; Cytochrome_c; -.
DR GenomeRNAi; 54205; -.
DR Pharos; P99999; Tchem.
DR PRO; PR:P99999; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P99999; protein.
DR Bgee; ENSG00000172115; Expressed in mucosa of transverse colon and 179 other tissues.
DR ExpressionAtlas; P99999; baseline and differential.
DR Genevisible; P99999; HS.
DR GO; GO:0043293; C:apoptosome; IPI:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:CAFA.
DR GO; GO:0005739; C:mitochondrion; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0070469; C:respirasome; IEA:UniProtKB-KW.
DR GO; GO:0009055; F:electron transfer activity; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IDA:ComplexPortal.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; IDA:ComplexPortal.
DR GO; GO:0045333; P:cellular respiration; TAS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IC:ComplexPortal.
DR GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IBA:GO_Central.
DR GO; GO:0006122; P:mitochondrial electron transport, ubiquinol to cytochrome c; IBA:GO_Central.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR Gene3D; 1.10.760.10; -; 1.
DR InterPro; IPR009056; Cyt_c-like_dom.
DR InterPro; IPR036909; Cyt_c-like_dom_sf.
DR InterPro; IPR002327; Cyt_c_1A/1B.
DR PANTHER; PTHR11961; PTHR11961; 1.
DR Pfam; PF00034; Cytochrom_C; 1.
DR PRINTS; PR00604; CYTCHRMECIAB.
DR SUPFAM; SSF46626; SSF46626; 1.
DR PROSITE; PS51007; CYTC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Direct protein sequencing;
KW Disease variant; Electron transport; Heme; Iron; Metal-binding;
KW Mitochondrion; Phosphoprotein; Reference proteome; Respiratory chain;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:13933734,
FT ECO:0000269|PubMed:14063298"
FT CHAIN 2..105
FT /note="Cytochrome c"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00433"
FT /id="PRO_0000108218"
FT BINDING 15
FT /ligand="heme c"
FT /ligand_id="ChEBI:CHEBI:61717"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00433,
FT ECO:0000269|PubMed:23150584"
FT BINDING 18
FT /ligand="heme c"
FT /ligand_id="ChEBI:CHEBI:61717"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00433,
FT ECO:0000269|PubMed:23150584"
FT BINDING 19
FT /ligand="heme c"
FT /ligand_id="ChEBI:CHEBI:61717"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00433,
FT ECO:0000269|PubMed:23150584"
FT BINDING 81
FT /ligand="heme c"
FT /ligand_id="ChEBI:CHEBI:61717"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0000269|PubMed:13933734"
FT MOD_RES 49
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P62894"
FT MOD_RES 56
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62897"
FT MOD_RES 73
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62897"
FT MOD_RES 73
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62897"
FT MOD_RES 98
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P62894"
FT MOD_RES 100
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62897"
FT VARIANT 42
FT /note="G -> S (in THC4; increases the pro-apoptotic
FT function by triggering caspase activation more efficiently
FT than wild-type; does not affect the redox function;
FT dbSNP:rs121918552)"
FT /evidence="ECO:0000269|PubMed:18345000"
FT /id="VAR_044450"
FT VARIANT 56
FT /note="K -> R (in dbSNP:rs11548795)"
FT /id="VAR_048850"
FT VARIANT 66
FT /note="M -> L"
FT /id="VAR_002204"
FT MUTAGEN 6
FT /note="K->A,D,R: No effect on covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 11
FT /note="F->A: Decreased covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 11
FT /note="F->Y: No effect on covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 15
FT /note="C->S: Decreased covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 18
FT /note="C->A: Decreased covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT MUTAGEN 19
FT /note="H->A: Loss of covalent heme attachment."
FT /evidence="ECO:0000269|PubMed:23150584"
FT CONFLICT 18
FT /note="C -> Y (in Ref. 8; AAH15130)"
FT /evidence="ECO:0000305"
FT CONFLICT 41
FT /note="T -> I (in Ref. 8; AAH68464)"
FT /evidence="ECO:0000305"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:5TY3"
FT TURN 15..18
FT /evidence="ECO:0007829|PDB:5TY3"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1J3S"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1J3S"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:1J3S"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:2N9I"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:5TY3"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2N3Y"
FT HELIX 62..70
FT /evidence="ECO:0007829|PDB:5TY3"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:5TY3"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:2N3Y"
FT HELIX 89..102
FT /evidence="ECO:0007829|PDB:5TY3"
SQ SEQUENCE 105 AA; 11749 MW; 8EE9689E0102506B CRC64;
MGDVEKGKKI FIMKCSQCHT VEKGGKHKTG PNLHGLFGRK TGQAPGYSYT AANKNKGIIW
GEDTLMEYLE NPKKYIPGTK MIFVGIKKKE ERADLIAYLK KATNE
