CYC1/YJR048W Summary Help

Standard Name CYC1
Systematic Name YJR048W
Feature Type ORF, Verified
Description Cytochrome c, isoform 1; electron carrier of the mitochondrial intermembrane space that transfers electrons from ubiquinone-cytochrome c oxidoreductase to cytochrome c oxidase during cellular respiration; mutations in human homolog cause insulin-responsive hyperglycemia; CYC1 has a paralog, CYC7, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description CYtochrome C
Gene Product Alias iso-1-cytochrome c 4
Chromosomal Location
ChrX:526335 to 526664 | ORF Map | GBrowse
Gbrowse
Genetic position: 34 cM
Gene Ontology Annotations All CYC1 GO evidence and references
  View Computational GO annotations for CYC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 10 genes
Resources
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
overexpression
Resources
87 total interaction(s) for 72 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 2
  • Biochemical Activity: 4
  • Co-crystal Structure: 4
  • Co-purification: 2
  • Reconstituted Complex: 3
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Rescue: 9
  • Negative Genetic: 36
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 2
  • Positive Genetic: 7
  • Synthetic Growth Defect: 1
  • Synthetic Rescue: 6

Resources
Expression Summary
histogram
Resources
Length (a.a.) 109
Molecular Weight (Da) 12,182
Isoelectric Point (pI) 10.2
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrX:526335 to 526664 | ORF Map | GBrowse
SGD ORF map
Genetic position: 34 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..330 526335..526664 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003809
SUMMARY PARAGRAPH for CYC1

CYC1 encodes the iso-1 form of the electron carrier protein cytochrome c (4). Iso-1-cytochrome c facilitates the penultimate and last steps of the mitochondrial respiratory chain via its covalently attached heme group: electron transfer from respiratory complex III to respiratory complex IV, and the final transfer of electrons to oxygen catalyzed by complex IV, cytochrome c oxidase. Cyc1p functions at the outer surface of the inner mitochondrial membrane and comprises 95% of the total cytochrome c in aerobically grown cells (5, 6, and reviewed in 7). cyc1 null mutants are viable but exhibit decreased growth on non-fermentable carbon sources such as lactate (5, 8). In vertebrates, it has been shown that mitochondrial release of cytochrome c initiates apoptosis by triggering caspase activation (9 and references therein).

CYC1 transcription is induced by oxygen, heme and lactate, and repressed by glucose (10, 11, 12, 13). Induction by oxygen occurs through binding of the transcription factor Hap1p to one of two upstream activation sequences (UAS1) in the CYC1 promoter (14). A second upstream activation sequence, UAS2, mediates CYC1 repression by glucose via binding by Mig1p and the CCAAT-binding activator complex subunits Hap2p and Hap3p (15, 16). In addition, chromatin structure has been postulated to contribute to transcriptional regulation (17 and references contained therein).

Newly-translated Cyc1p without an attached heme moiety, known as apocytochrome c, is prone to degradation by the ubiquitin-dependent degradation pathway (18). However, apocytochrome c can be protected from degradation, and its transport into the mitochondria enhanced, through tri-methylation of lysine-77 by the specific methyltransferase Ctm1p (19, 20, 21). Apocytochrome c is imported into mitochondria by insertion into the outer face of the outer membrane followed by interaction with the translocase of outer membrane (TOM) complex (22, 23). Once in the mitochondrial intermembrane space, apocytochrome c binds to the cytochrome c heme lyase Cyc3p, which covalently attaches a heme group to Cyc1p (24). Heme attachment also results in Cyc1p conformational change, trapping the mature protein, holocytochrome c, in the intermembrane space (6).

Due to the ease of Cyc1p mutant identification and protein purification as well as early knowledge of the peptide sequence, the cytochrome c system has been used to study many general biological processes including mRNA 3'-end formation, post-translational modification, chromosomal translocation, and evolutionary divergence of duplicated regions (comprehensive reviews can be found in 7 and 25).

Last updated: 2008-03-21 Contact SGD

References cited on this page View Complete Literature Guide for CYC1
1) Berg J M, et al.  (2002) Biochemistry (5th edition)
2) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
3) Gaignard P, et al.  (2013) Mutations in CYC1, Encoding Cytochrome c1 Subunit of Respiratory Chain Complex III, Cause Insulin-Responsive Hyperglycemia. Am J Hum Genet 93(2):384-9
4) Sherman F, et al.  (1966) The structural gene for yeast cytochrome C. Proc Natl Acad Sci U S A 55(6):1498-504
5) Sherman F, et al.  (1965) Genetic determination of iso-cytochromes c in yeast. J Mol Biol 13(1):21-39
6) Dumont ME, et al.  (1991) Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. Mol Cell Biol 11(11):5487-96
7) Sherman F  (2005) The importance of mutation, then and now: studies with yeast cytochrome c. Mutat Res 589(1):1-16
8) Sherman F, et al.  (1974) Mutants of yeast defective in iso-1-cytochrome c. Genetics 77(2):255-84
9) Sharonov GV, et al.  (2005) Comparative analysis of proapoptotic activity of cytochrome c mutants in living cells. Apoptosis 10(4):797-808
10) Hortner H, et al.  (1982) Regulation of synthesis of catalases and iso-1-cytochrome c in Saccharomyces cerevisiae by glucose, oxygen and heme. Eur J Biochem 128(1):179-84
11) Guarente L and Mason T  (1983) Heme regulates transcription of the CYC1 gene of S. cerevisiae via an upstream activation site. Cell 32(4):1279-86
12) Boss JM, et al.  (1980) Characterization of yeast iso-1-cytochrome c mRNA. J Biol Chem 255(18):8623-8
13) Guarente L, et al.  (1984) Distinctly regulated tandem upstream activation sites mediate catabolite repression of the CYC1 gene of S. cerevisiae. Cell 36(2):503-11
14) Pfeifer K, et al.  (1987) Yeast HAP1 activator competes with the factor RC2 for binding to the upstream activation site UAS1 of the CYC1 gene. Cell 49(1):9-18
15) Treitel MA and Carlson M  (1995) Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A 92(8):3132-6
16) Olesen J, et al.  (1987) Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner. Cell 51(6):953-61
17) Martens C, et al.  (2001) RNA polymerase II and TBP occupy the repressed CYC1 promoter. Mol Microbiol 40(4):1009-19
18) Pearce DA and Sherman F  (1997) Differential ubiquitin-dependent degradation of the yeast apo-cytochrome c isozymes. J Biol Chem 272(50):31829-36
19) Paik WK, et al.  (1980) Protein methylation: cytochrome c methylation as a model system. Adv Enzyme Regul 19():471-86
20) Park KS, et al.  (1987) Enzymatic methylation of in vitro synthesized apocytochrome c enhances its transport into mitochondria. J Biol Chem 262(30):14702-8
21) Polevoda B, et al.  (2000) Cytochrome c methyltransferase, Ctm1p, of yeast. J Biol Chem 275(27):20508-13
22) Diekert K, et al.  (2001) Apocytochrome c requires the TOM complex for translocation across the mitochondrial outer membrane. EMBO J 20(20):5626-35
23) Wiedemann N, et al.  (2003) Biogenesis of yeast mitochondrial cytochrome c: a unique relationship to the TOM machinery. J Mol Biol 327(2):465-74
24) Dumont ME, et al.  (1987) Identification and sequence of the gene encoding cytochrome c heme lyase in the yeast Saccharomyces cerevisiae. EMBO J 6(1):235-41
25) Sherman F  (1990) Studies of yeast cytochrome c: how and why they started and why they continued. Genetics 125(1):9-12