CYTOCHROME C (Homo sapiens)
Description [+]
- Synonyms: CYTOCHROME C, HCS, CYCS
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Cytochrome c [Source:UniProtKB/Swiss-Prot;Acc:P99999]
- Family: Other
- Process: apoptosis,
- Pathways: intrinsic pathway, post-mitochondrial caspase activation,
- Criteria: manually curated
- Curator comment: Cytochrome c is a nuclear encoded gene that upon import into the mitochondria obtains a heme moiety forming the holoenzyme. In healthy cells, cytochrome c resides in the mitochondrial intermembrane space where it is required for oxidative phosphorylation by transferring electrons between complexes III and IV of the respiratory chain. During apoptosis, cytochrome c is released from mitochondria following mitochondrial outer membrane permeabilisation where it drives caspase activation [8689682] . Once in the cytosol, cytochrome c binds Apaf-1 leading to formation of the heptameric Apaf-1 caspase activating platform termed the apoptosome. Cytochrome c is absolutely required for caspase activation in the majority of intrinsic apoptosis pathways 1590747
- WIKI: CYTOCHROME C-H_sapiens
References [+]
- Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c.
- Liu X, Kim CN, Yang J, Jemmerson R, Wang X
- A cell-free system based on cytosols of normally growing cells is established that reproduces aspects of the apoptotic program in vitro. The apoptotic program is initiated by addition of dATP. Fractionation of cytosol yielded a 15 kDa protein that is required for in vitro apoptosis. The absorption spectrum and protein sequence revealed that this protein is cytochrome c. Elimination of cytochrome c from cytosol by immunodepletion, or inclusion of sucrose to stabilize mitochondria during cytosol preparation, diminished the apoptotic activity. Adding back cytochrome c to the cytochrome c-depleted extracts restored their apoptotic activity. Cells undergoing apoptosis in vivo showed increased release of cytochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c. Cell. 1996 Jul 12;86(1):147-57.
- Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis.
- Hao Z, Duncan GS, Chang CC, Elia A, Fang M, Wakeham A, Okada H, Calzascia T, Jang Y, You-Ten A, Yeh WC, Ohashi P, Wang X, Mak TW
- As components of the apoptosome, a caspase-activating complex, cytochrome c (Cyt c) and Apaf-1 are thought to play critical roles during apoptosis. Due to the obligate function of Cyt c in electron transport, its requirement for apoptosis in animals has been difficult to establish. We generated knockin mice expressing a mutant Cyt c (KA allele), which retains normal electron transfer function but fails to activate Apaf-1. Most KA/KA mice displayed embryonic or perinatal lethality caused by defects in the central nervous system, and surviving mice exhibited impaired lymphocyte homeostasis. Although fibroblasts from the KA/KA mice were resistant to apoptosis, their thymocytes were markedly more sensitive to death stimuli than Apaf-1(-/-) thymocytes. Upon treatment with gamma irradiation, procaspases were efficiently activated in apoptotic KA/KA thymocytes, but Apaf-1 oligomerization was not observed. These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation. Cell. 2005 May 20;121(4):579-91.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Cytochrom_C | 4 | 103 |
Protein sequence [+]
Cytochrome c | Homo sapiens | 9606 | length:105
MGDVEKGKKIFIMKCSQCHTVEKGGKHKTGPNLHGLFGRKTGQAPGYSYTAANKNKGIIW
GEDTLMEYLENPKKYIPGTKMIFVGIKKKEERADLIAYLKKATNE
GEDTLMEYLENPKKYIPGTKMIFVGIKKKEERADLIAYLKKATNE
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0006810 | transport | biological_proccess | IEA |
| GO:0022900 | electron transport chain | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IDA |
| GO:0006309 | DNA fragmentation during apoptosis | biological_proccess | IMP |
| GO:0008635 | activation of caspase activity by cytochrome c | biological_proccess | TAS |
| GO:0045333 | cellular respiration | biological_proccess | TAS |
| GO:0046872 | metal ion binding | mollecular_function | IEA |
| GO:0020037 | heme binding | mollecular_function | TAS |
| GO:0045155 | electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity | mollecular_function | IDA |
| GO:0004722 | protein serine/threonine phosphatase activity | mollecular_function | TAS |
| GO:0005515 | protein binding | mollecular_function | IPI |
| GO:0005506 | iron ion binding | mollecular_function | IEA |
| GO:0009055 | electron carrier activity | mollecular_function | IEA |
| GO:0020037 | heme binding | mollecular_function | IEA |
| GO:0005634 | nucleus | cell_component | IDA |
| GO:0005829 | cytosol | cell_component | EXP |
| GO:0005759 | mitochondrial matrix | cell_component | IEA |
| GO:0005739 | mitochondrion | cell_component | IEA |
| GO:0070469 | respiratory chain | cell_component | IEA |
| GO:0005758 | mitochondrial intermembrane space | cell_component | TAS |
| GO:0000159 | protein phosphatase type 2A complex | cell_component | TAS |
Check GO Evidence Codes here
KEGG Pathways [+]
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000326934 | OTTHUMP00000202043 |
| OTTHUMT00000326935 | OTTHUMP00000202044 |
| OTTHUMT00000326936 | OTTHUMP00000202045 |
| OTTHUMT00000250299 * | OTTHUMP00000158609 * |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :19986
- Gene related info from GeneCards [?] : Cytochrome c
- Ensembl genome browser [?] : ENSG00000172115
- Expression info from Arrayexpress [?] : ENSG00000172115
- Protein expression from Protein Atlas: [?] ENSG00000172115
- Community gene edition from Wikigenes: [?] 54205
Click on [?] for more information.
