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Protein

Cytochrome c

Gene

CYCS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei15Heme (covalent)1
Binding sitei18Heme (covalent)1
Metal bindingi19Iron (heme axial ligand)1
Metal bindingi81Iron (heme axial ligand)1

GO - Molecular functioni

  • electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity Source: UniProtKB
  • heme binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Electron transport, Respiratory chain, Transport

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000172115-MONOMER.
ReactomeiR-HSA-111457. Release of apoptotic factors from the mitochondria.
R-HSA-111458. Formation of apoptosome.
R-HSA-111459. Activation of caspases through apoptosome-mediated cleavage.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-3299685. Detoxification of Reactive Oxygen Species.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-611105. Respiratory electron transport.
SIGNORiP99999.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome c
Gene namesi
Name:CYCS
Synonyms:CYC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:19986. CYCS.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • mitochondrial inner membrane Source: Reactome
  • mitochondrial intermembrane space Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
  • protein phosphatase type 2A complex Source: UniProtKB
  • respiratory chain Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Thrombocytopenia 4 (THC4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
See also OMIM:612004
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04445042G → S in THC4; increases the pro-apoptotic function by triggering caspase activation more efficiently than wild-type; does not affect the redox function. 1 PublicationCorresponds to variant rs121918552dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi54205.
MalaCardsiCYCS.
MIMi612004. phenotype.
OpenTargetsiENSG00000172115.
Orphaneti168629. Autosomal thrombocytopenia with normal platelets.
PharmGKBiPA134981636.

Chemistry databases

DrugBankiDB01017. Minocycline.

Polymorphism and mutation databases

BioMutaiCYCS.
DMDMi42560196.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001082182 – 105Cytochrome cAdd BLAST104

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylglycine1 Publication1
Modified residuei49PhosphotyrosineBy similarity1
Modified residuei56N6-succinyllysineBy similarity1
Modified residuei73N6-acetyllysine; alternateBy similarity1
Modified residuei73N6-succinyllysine; alternateBy similarity1
Modified residuei98PhosphotyrosineBy similarity1
Modified residuei100N6-acetyllysineBy similarity1

Post-translational modificationi

Binds 1 heme group per subunit.
Phosphorylation at Tyr-49 and Tyr-98 both reduce by half the turnover in the reaction with cytochrome c oxidase, down-regulating mitochondrial respiration.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP99999.
MaxQBiP99999.
PaxDbiP99999.
PeptideAtlasiP99999.
PRIDEiP99999.
TopDownProteomicsiP99999.

PTM databases

iPTMnetiP99999.
PhosphoSitePlusiP99999.
SwissPalmiP99999.

Expressioni

Gene expression databases

BgeeiENSG00000172115.
CleanExiHS_CYCS.
ExpressionAtlasiP99999. baseline and differential.
GenevisibleiP99999. HS.

Organism-specific databases

HPAiCAB004222.
CAB005126.
CAB018597.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
APAF1O147276EBI-446479,EBI-446492
BCL2L1Q078172EBI-446479,EBI-78035
CYC12Q9FKS52EBI-446479,EBI-1777995From a different organism.
KRT40Q6A1623EBI-446479,EBI-10171697

Protein-protein interaction databases

BioGridi119922. 48 interactors.
DIPiDIP-29683N.
IntActiP99999. 16 interactors.
MINTiMINT-3023956.
STRINGi9606.ENSP00000307786.

Structurei

Secondary structure

1105
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 14Combined sources11
Turni15 – 18Combined sources4
Beta strandi23 – 25Combined sources3
Beta strandi28 – 30Combined sources3
Turni36 – 38Combined sources3
Beta strandi39 – 42Combined sources4
Helixi51 – 55Combined sources5
Helixi62 – 70Combined sources9
Helixi72 – 75Combined sources4
Helixi89 – 102Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J3SNMR-A2-105[»]
2N9INMR-A2-105[»]
2N9JNMR-A2-105[»]
3NWVX-ray1.90A/B/C/D2-105[»]
3ZCFX-ray1.65A/B/C/D2-105[»]
3ZOOX-ray1.35A/B/C/D2-105[»]
ProteinModelPortaliP99999.
SMRiP99999.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP99999.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome c family.Curated

Phylogenomic databases

eggNOGiKOG3453. Eukaryota.
COG3474. LUCA.
GeneTreeiENSGT00390000009405.
HOGENOMiHOG000009762.
HOVERGENiHBG003023.
InParanoidiP99999.
KOiK08738.
OMAiWNEETLM.
OrthoDBiEOG091G0UQY.
PhylomeDBiP99999.
TreeFamiTF300226.

Family and domain databases

Gene3Di1.10.760.10. 1 hit.
InterProiIPR009056. Cyt_c-like_dom.
IPR002327. Cyt_c_1A/1B.
[Graphical view]
PANTHERiPTHR11961. PTHR11961. 1 hit.
PfamiPF00034. Cytochrom_C. 1 hit.
[Graphical view]
PRINTSiPR00604. CYTCHRMECIAB.
SUPFAMiSSF46626. SSF46626. 1 hit.
PROSITEiPS51007. CYTC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P99999-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDVEKGKKI FIMKCSQCHT VEKGGKHKTG PNLHGLFGRK TGQAPGYSYT
60 70 80 90 100
AANKNKGIIW GEDTLMEYLE NPKKYIPGTK MIFVGIKKKE ERADLIAYLK

KATNE
Length:105
Mass (Da):11,749
Last modified:January 23, 2007 - v2
Checksum:i8EE9689E0102506B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18C → Y in AAH15130 (PubMed:15489334).Curated1
Sequence conflicti41T → I in AAH68464 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04445042G → S in THC4; increases the pro-apoptotic function by triggering caspase activation more efficiently than wild-type; does not affect the redox function. 1 PublicationCorresponds to variant rs121918552dbSNPEnsembl.1
Natural variantiVAR_04885056K → R.Corresponds to variant rs11548795dbSNPEnsembl.1
Natural variantiVAR_00220466M → L.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5393.1.
PIRiA31764. CCHU.
RefSeqiNP_061820.1. NM_018947.5.
UniGeneiHs.437060.
Hs.617193.

Genome annotation databases

EnsembliENST00000305786; ENSP00000307786; ENSG00000172115.
ENST00000409409; ENSP00000386270; ENSG00000172115.
ENST00000409764; ENSP00000387279; ENSG00000172115.
GeneIDi54205.
KEGGihsa:54205.
UCSCiuc003sxl.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Life shuttle - Issue 76 of November 2006

Protein Spotlight

An unexpected place - Issue 88 of November 2007

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5393.1.
PIRiA31764. CCHU.
RefSeqiNP_061820.1. NM_018947.5.
UniGeneiHs.437060.
Hs.617193.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J3SNMR-A2-105[»]
2N9INMR-A2-105[»]
2N9JNMR-A2-105[»]
3NWVX-ray1.90A/B/C/D2-105[»]
3ZCFX-ray1.65A/B/C/D2-105[»]
3ZOOX-ray1.35A/B/C/D2-105[»]
ProteinModelPortaliP99999.
SMRiP99999.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119922. 48 interactors.
DIPiDIP-29683N.
IntActiP99999. 16 interactors.
MINTiMINT-3023956.
STRINGi9606.ENSP00000307786.

Chemistry databases

DrugBankiDB01017. Minocycline.

PTM databases

iPTMnetiP99999.
PhosphoSitePlusiP99999.
SwissPalmiP99999.

Polymorphism and mutation databases

BioMutaiCYCS.
DMDMi42560196.

Proteomic databases

EPDiP99999.
MaxQBiP99999.
PaxDbiP99999.
PeptideAtlasiP99999.
PRIDEiP99999.
TopDownProteomicsiP99999.

Protocols and materials databases

DNASUi54205.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305786; ENSP00000307786; ENSG00000172115.
ENST00000409409; ENSP00000386270; ENSG00000172115.
ENST00000409764; ENSP00000387279; ENSG00000172115.
GeneIDi54205.
KEGGihsa:54205.
UCSCiuc003sxl.4. human.

Organism-specific databases

CTDi54205.
DisGeNETi54205.
GeneCardsiCYCS.
HGNCiHGNC:19986. CYCS.
HPAiCAB004222.
CAB005126.
CAB018597.
MalaCardsiCYCS.
MIMi123970. gene.
612004. phenotype.
neXtProtiNX_P99999.
OpenTargetsiENSG00000172115.
Orphaneti168629. Autosomal thrombocytopenia with normal platelets.
PharmGKBiPA134981636.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3453. Eukaryota.
COG3474. LUCA.
GeneTreeiENSGT00390000009405.
HOGENOMiHOG000009762.
HOVERGENiHBG003023.
InParanoidiP99999.
KOiK08738.
OMAiWNEETLM.
OrthoDBiEOG091G0UQY.
PhylomeDBiP99999.
TreeFamiTF300226.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000172115-MONOMER.
ReactomeiR-HSA-111457. Release of apoptotic factors from the mitochondria.
R-HSA-111458. Formation of apoptosome.
R-HSA-111459. Activation of caspases through apoptosome-mediated cleavage.
R-HSA-2151201. Transcriptional activation of mitochondrial biogenesis.
R-HSA-3299685. Detoxification of Reactive Oxygen Species.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-611105. Respiratory electron transport.
SIGNORiP99999.

Miscellaneous databases

ChiTaRSiCYCS. human.
EvolutionaryTraceiP99999.
GeneWikiiCytochrome_c.
GenomeRNAii54205.
PROiP99999.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172115.
CleanExiHS_CYCS.
ExpressionAtlasiP99999. baseline and differential.
GenevisibleiP99999. HS.

Family and domain databases

Gene3Di1.10.760.10. 1 hit.
InterProiIPR009056. Cyt_c-like_dom.
IPR002327. Cyt_c_1A/1B.
[Graphical view]
PANTHERiPTHR11961. PTHR11961. 1 hit.
PfamiPF00034. Cytochrom_C. 1 hit.
[Graphical view]
PRINTSiPR00604. CYTCHRMECIAB.
SUPFAMiSSF46626. SSF46626. 1 hit.
PROSITEiPS51007. CYTC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCYC_HUMAN
AccessioniPrimary (citable) accession number: P99999
Secondary accession number(s): A4D166
, B2R4I1, P00001, Q6NUR2, Q6NX69, Q96BV4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.