CYC1

Cytochrome c1, heme protein, mitochondrial (CYC1), also known as UQCR4, MC3DN6, Complex III subunit 4, Cytochrome b-c1 complex subunit 4, or Ubiquinol-cytochrome-c reductase complex cytochrome c1 subunit is a protein that in humans is encoded by the CYC1 gene. CYC1 is a respiratory subunit of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear, type 6.[5][6][7]

CYC1
Identifiers
AliasesCYC1, MC3DN6, UQCR4, cytochrome c1
External IDsOMIM: 123980 MGI: 1913695 HomoloGene: 55617 GeneCards: CYC1
Orthologs
SpeciesHumanMouse
Entrez

1537

66445

Ensembl

ENSG00000179091

ENSMUSG00000022551

UniProt

P08574

Q9D0M3

RefSeq (mRNA)

NM_001916

NM_025567

RefSeq (protein)

NP_001907

NP_079843

Location (UCSC)Chr 8: 144.1 – 144.1 MbChr 15: 76.23 – 76.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

CYC1 is located on the q arm of chromosome 8 in position 24.3 and has 8 exons.[5] The CYC1 gene produces a 13.5 kDa protein composed of 130 amino acids.[8][9] CYC1 belongs to the cytochrome c family. CYC1 is a phosphoprotein and subunit of Ubiquinol Cytochrome c Reductase that binds heme groups. It has helix, transit peptide, and transmembrane domains and contains 9 alpha helixes, 5 beta strands, and 3 turns. The transmembrane protein passes through the inner mitochondrial membrane once and the majority of the protein is found on the intermembrane side. CYC1 contains covalent heme bindings sites at positions 121 and 124 and heme axial ligand iron-metal binding sites at positions 125 and 244.[6][7]

Function

CYC1 encodes a protein that is located in the inner mitochondrial membrane and is part of Ubiquinol Cytochrome c Reductase (complex III). The encoded protein, CYC1, is a respiratory subunit of the cytochrome bc1 complex, which plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c.[5][6][7]

Species

CYC1 is a human gene that is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C. elegans, S. cerevisiae, K. lactis, E. gossypii, S. pombe, N. crassa, A. thaliana, rice, and frog.[10] There are orthologs of CYC1 in 137 known organisms.[11]

Clinical Significance

Variants of CYC1 have been associated with mitochondrial complex III deficiency, nuclear, type 6. Mitochondrial complex III deficiency, nuclear, type 6 is an autosomal recessive disorder of the mitochondrial respiratory chain resulting from a defect in Ubiquinol Cytochrome c Reductase (complex III) that leads to reduced complex III activity. Clinical features tend to emerge in early childhood and include episodic acute lactic acidosis, ketoacidosis, insulin-responsive hyperglycemia, liver dysfunction, encephalopathy, and associated infection, although psychomotor development may remain normal. Pathogenic mutations have included c.288G>T, p.Trp96Cys and c.643C>T p. Leu215Phe.[6][7][12]

Interactions

CYC1 has 78 protein-protein interactions with 72 of them being co-complex interactions.[13] CYC1 is one of 11 subunits of Ubiquinol Cytochrome c Reductase (b1-c complex) that includes the respiratory subunits cytochrome b, cytochrome c1 (CYC1), UQCRFS1, the core proteins UQCRC1 and UQCRC2, and the low-molecular weight proteins UQCRH, UQCRB, UQCRQ, UQCR10, UQCR11, as well as an additional cleavage product of UQCRFS1.[6][7] Additionally, CCP1, CDKA-1, and CDKB1-1 have also been found to interact with CYC1.[13]

References
  1. GRCh38: Ensembl release 89: ENSG00000179091 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022551 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: CYC1 cytochrome c-1".
  6. "CYC1 - Cytochrome c1, heme protein, mitochondrial precursor - Homo sapiens (Human) - CYC1 gene & protein". www.uniprot.org. Retrieved 2018-07-31.
  7. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  8. Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Archived from the original on 2018-08-01. Retrieved 2018-07-31.
  9. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. "CYC1 cytochrome c1 [Homo sapiens (human)]". National Center for Biotechnology Information. U.S. National Library of Medicine. Retrieved 2016-07-29.
  11. "ortholog_gene_1537[group]". National Center for Biotechnology Information. U.S. National Library of Medicine. Retrieved 2016-07-29.
  12. Gaignard P, Menezes M, Schiff M, Bayot A, Rak M, Ogier de Baulny H, Su CH, Gilleron M, Lombes A, Abida H, Tzagoloff A, Riley L, Cooper ST, Mina K, Sivadorai P, Davis MR, Allcock RJ, Kresoje N, Laing NG, Thorburn DR, Slama A, Christodoulou J, Rustin P (August 2013). "Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia". American Journal of Human Genetics. 93 (2): 384–9. doi:10.1016/j.ajhg.2013.06.015. PMC 3738829. PMID 23910460.
  13. "81 binary interactions found for search term CYC1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

Further reading

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