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Protein

Cytochrome c

Gene

CYCS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processApoptosis, Electron transport, Respiratory chain, Transport
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000172115.8
HGNCiHGNC:19986 CYCS
MIMi123970 gene
neXtProtiNX_P99999

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs121918552Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

DrugBankiDB03317 Heme C
DB01017 Minocycline
DB03977 N-Trimethyllysine
DB02110 Protoporphyrin Ix Containing Co
DB03934 Protoporphyrin Ix Containing Zn
DB04249 Zinc Substituted Heme C

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

Show more details

Protein-protein interaction databases

BioGridi119922, 50 interactors
CORUMiP99999
DIPiDIP-29683N
IntActiP99999, 30 interactors
MINTiP99999
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
Beta strandi56 – 58Combined sources3
Helixi62 – 70Combined sources9
Helixi72 – 75Combined sources4
Beta strandi76 – 78Combined sources3
Helixi89 – 102Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J3SNMR-A2-105[»]
2N3YNMR-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[»]
5EXQX-ray1.60A/B2-105[»]
5TY3X-ray1.25A/B2-105[»]
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
OMAiGLFKTRC
OrthoDBiEOG091G0UQY
PhylomeDBiP99999
TreeFamiTF300226

Family and domain databases

Gene3Di1.10.760.10, 1 hit
InterProiView protein in InterPro
IPR009056 Cyt_c-like_dom
IPR036909 Cyt_c-like_dom_sf
IPR002327 Cyt_c_1A/1B
PANTHERiPTHR11961 PTHR11961, 1 hit
PfamiView protein in Pfam
PF00034 Cytochrom_C, 1 hit
PRINTSiPR00604 CYTCHRMECIAB
SUPFAMiSSF46626 SSF46626, 1 hit
PROSITEiView protein in PROSITE
PS51007 CYTC, 1 hit

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 dbSNP:rs121918552Ensembl.1
Natural variantiVAR_04885056K → R. Corresponds to variant dbSNP:rs11548795Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCYC_HUMAN
AccessioniPrimary (citable) accession number: P99999
Secondary accession number(s): A4D166
, B2R4I1, P00001, Q6NUR2, Q6NX69, Q96BV4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 164 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health