P99999 (CYC_HUMAN)
Reviewed,
UniProtKB/Swiss-Prot
Last modified
August 10, 2010.
Version 88.
History...
Names and origin
| Protein names | Recommended name: Cytochrome c | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 105 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (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. 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. |
| Subcellular location | |
| Post-translational modification | Binds 1 heme group per subunit. |
| Involvement in 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. Ref.14 |
| Sequence similarities | Belongs to the cytochrome c family. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| APAF1 | O14727 | 2 | EBI-446479,EBI-446492 | |
| GSTK1 | Q9Y2Q3 | 1 | EBI-446479,EBI-1053767 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed Ref.9 Ref.10 | ||||||||||||||||||||||||
| Chain | 2 – 105 | 104 | Cytochrome c | PRO_0000108218 | |||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||
| Metal binding | 19 | 1 | Iron (heme axial ligand) | ||||||||||||||||||||||||
| Metal binding | 81 | 1 | Iron (heme axial ligand) | ||||||||||||||||||||||||
| Binding site | 15 | 1 | Heme (covalent) | ||||||||||||||||||||||||
| Binding site | 18 | 1 | Heme (covalent) | ||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||
| Modified residue | 2 | 1 | N-acetylglycine Ref.9 | ||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||
| Natural variant | 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. Ref.14 | VAR_044450 | |||||||||||||||||||||||
| Natural variant | 56 | 1 | K → R. [dbSNP:rs11548795] | VAR_048850 | |||||||||||||||||||||||
| Natural variant | 66 | 1 | M → L in 10% of the molecules. | VAR_002204 | |||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||
| Sequence conflict | 18 | 1 | C → Y in AAH15130. Ref.8 | ||||||||||||||||||||||||
| Sequence conflict | 41 | 1 | T → I in AAH68464. Ref.8 | ||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||
| Helix | 4 – 14 | 11 | |||||||||||||||||||||||||
| Turn | 16 – 18 | 3 | |||||||||||||||||||||||||
| Beta strand | 23 – 25 | 3 | |||||||||||||||||||||||||
| Beta strand | 28 – 30 | 3 | |||||||||||||||||||||||||
| Turn | 36 – 38 | 3 | |||||||||||||||||||||||||
| Helix | 51 – 56 | 6 | |||||||||||||||||||||||||
| Helix | 62 – 70 | 9 | |||||||||||||||||||||||||
| Helix | 72 – 75 | 4 | |||||||||||||||||||||||||
| Helix | 89 – 102 | 14 | |||||||||||||||||||||||||
Sequences
References
| « Hide 'large scale' references | |
| [1] | "The human somatic cytochrome c gene: two classes of processed pseudogenes demarcate a period of rapid molecular evolution." Evans M.J., Scarpulla R.C. Proc. Natl. Acad. Sci. U.S.A. 85:9625-9629(1988) [PubMed: 2849112] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." 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. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum. |
| [4] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala. |
| [5] | "The DNA sequence of human chromosome 7." 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. Wilson R.K.Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "Human chromosome 7: DNA sequence and biology." 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. Tsui L.-C.Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow, Brain, Kidney, Lung, Skeletal muscle, Skin, Testis and Urinary bladder. |
| [9] | "The amino acid sequence of human heart cytochrome c." Matsubara H., Smith E.L. J. Biol. Chem. 237:3575-3576(1962) [PubMed: 13933734] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-105, ACETYLATION AT GLY-2. Tissue: Heart. |
| [10] | "Human heart cytochrome c. Chymotryptic peptides, tryptic peptides, and the complete amino acid sequence." Matsubara H., Smith E.L. J. Biol. Chem. 238:2732-2753(1963) [PubMed: 14063298] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-105. Tissue: Heart. |
| [11] | "Cytochrome c in the apoptotic and antioxidant cascades." Skulachev V.P. FEBS Lett. 423:275-280(1998) [PubMed: 9515723] [Abstract] Cited for: REVIEW ON ROLE IN APOPTOSIS. |
| [12] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [13] | "Solution structure of reduced recombinant human cytochrome c." Jeng W.-Y., Shiu J.-H., Tsai Y.-H., Chuang W.-J. Submitted (FEB-2003) to the PDB data bank Cited for: STRUCTURE BY NMR. |
| [14] | "A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia." 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. Nat. Genet. 40:387-389(2008) [PubMed: 18345000] [Abstract] Cited for: VARIANT THC4 SER-42, MASS SPECTROMETRY, CHARACTERIZATION OF VARIANT THC4 SER-42, X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF VARIANT THC4 SER-42 AND WILD TYPE. |
| + | Additional computationally mapped references. |
Web resources
| Protein Spotlight Life shuttle - Issue 76 of November 2006 |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | M22877 Genomic DNA. Translation: AAA35732.1. BT006946 mRNA. Translation: AAP35592.1. AK311836 mRNA. Translation: BAG34778.1. AL713681 mRNA. Translation: CAD28485.1. AC007487 Genomic DNA. Translation: AAQ96844.1. CH236948 Genomic DNA. Translation: EAL24239.1. CH471073 Genomic DNA. Translation: EAW93822.1. BC005299 mRNA. Translation: AAH05299.1. BC008475 mRNA. Translation: AAH08475.1. BC008477 mRNA. Translation: AAH08477.1. BC009578 mRNA. Translation: AAH09578.1. BC009579 mRNA. Translation: AAH09579.1. BC009582 mRNA. Translation: AAH09582.1. BC009587 mRNA. Translation: AAH09587.1. BC009602 mRNA. Translation: AAH09602.1. BC009607 mRNA. Translation: AAH09607.1. BC014359 mRNA. Translation: AAH14359.1. BC014361 mRNA. Translation: AAH14361.1. BC015130 mRNA. Translation: AAH15130.1. BC016006 mRNA. Translation: AAH16006.1. BC021994 mRNA. Translation: AAH21994.1. BC022330 mRNA. Translation: AAH22330.1. BC067222 mRNA. Translation: AAH67222.1. BC068464 mRNA. Translation: AAH68464.1. BC070156 mRNA. Translation: AAH70156.1. BC070346 mRNA. Translation: AAH70346.1. BC071761 mRNA. Translation: AAH71761.1. | ||||||||||||
| IPI | IPI00465315. | ||||||||||||
| PIR | CCHU. A31764. | ||||||||||||
| RefSeq | NP_061820.1. | ||||||||||||
| UniGene | Hs.437060. Hs.617193. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | P99999. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-29683N. | ||||||||||||
| IntAct | P99999. 21 interactions. | ||||||||||||
| STRING | P99999. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P99999. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | P99999. | ||||||||||||
| PRIDE | P99999. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000305786; ENSP00000307786; ENSG00000172115; Homo sapiens. [Genome view] ENST00000409409; ENSP00000386270; ENSG00000172115; Homo sapiens. [Genome view] ENST00000409764; ENSP00000387279; ENSG00000172115; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 54205. | ||||||||||||
| KEGG | hsa:54205. | ||||||||||||
| UCSC | uc003sxl.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 54205. | ||||||||||||
| GeneCards | GC07M025124. | ||||||||||||
| H-InvDB | HIX0006529. | ||||||||||||
| HGNC | HGNC:19986. CYCS. | ||||||||||||
| HPA | CAB004222. CAB005126. CAB018597. | ||||||||||||
| MIM | 123970. gene. 612004. phenotype. | ||||||||||||
| Orphanet | 168629. Nonsyndromic thrombocytopenia. | ||||||||||||
| PharmGKB | PA134981636. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG20206. | ||||||||||||
| HOGENOM | HBG692582. | ||||||||||||
| HOVERGEN | HBG003023. | ||||||||||||
| InParanoid | P99999. | ||||||||||||
| OMA | ANLKEWL. | ||||||||||||
| OrthoDB | EOG9TF34R. | ||||||||||||
| PhylomeDB | 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. Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P99999. | ||||||||||||
| Bgee | P99999. | ||||||||||||
| CleanEx | HS_CYCS. | ||||||||||||
| Genevestigator | P99999. | ||||||||||||
| GermOnline | ENSG00000172115. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR002327. Cyt_c_1A/1B. IPR009056. Cyt_c_dom. IPR003088. Cyt_c_I. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:1.10.760.10. Cytochrome_c_R. 1 hit. | ||||||||||||
| PANTHER | PTHR11961. Cyt_CIAB. 1 hit. | ||||||||||||
| Pfam | PF00034. Cytochrom_C. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00604. CYTCHRMECIAB. | ||||||||||||
| SUPFAM | SSF46626. Cytochrome_c. 1 hit. | ||||||||||||
| PROSITE | PS51007. CYTC. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| DrugBank | DB01065. Melatonin. DB01017. Minocycline. | ||||||||||||
| NextBio | 56526. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | CYC_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P99999 Secondary accession number(s): A4D166 Q96BV4 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 7 Human chromosome 7: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Protein Spotlight Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


