CCC1_YEAST
ID CCC1_YEAST Reviewed; 322 AA.
AC P47818; D6VYM0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Protein CCC1;
DE AltName: Full=Cross-complementer of CSG1 protein 1;
GN Name=CCC1; OrderedLocusNames=YLR220W; ORFNames=L8083.6;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7941738; DOI=10.1002/yea.320100411;
RA Fu D., Beeler T.J., Dunn T.M.;
RT "Sequence, mapping and disruption of CCC1, a gene that cross-complements
RT the Ca(2+)-sensitive phenotype of csg1 mutants.";
RL Yeast 10:515-521(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP FUNCTION.
RC STRAIN=S288c / YPH1;
RX PubMed=8668190; DOI=10.1128/mcb.16.7.3730;
RA Pozos T.C., Sekler I., Cyert M.S.;
RT "The product of HUM1, a novel yeast gene, is required for vacuolar Ca2+/H+
RT exchange and is related to mammalian Na+/Ca2+ exchangers.";
RL Mol. Cell. Biol. 16:3730-3741(1996).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=8866476; DOI=10.1111/j.1365-2958.1996.tb02561.x;
RA Lapinskas P.J., Lin S.-J., Culotta V.C.;
RT "The role of the Saccharomyces cerevisiae CCC1 gene in the homeostasis of
RT manganese ions.";
RL Mol. Microbiol. 21:519-528(1996).
RN [7]
RP OVEREXPRESSION PHENOTYPE.
RX PubMed=10713071; DOI=10.1074/jbc.275.11.7626;
RA Chen O.S., Kaplan J.;
RT "CCC1 suppresses mitochondrial damage in the yeast model of Friedreich's
RT ataxia by limiting mitochondrial iron accumulation.";
RL J. Biol. Chem. 275:7626-7632(2000).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF DELETION MUTANT.
RX PubMed=11390404; DOI=10.1074/jbc.m103944200;
RA Li L., Chen O.S., McVey Ward D., Kaplan J.;
RT "CCC1 is a transporter that mediates vacuolar iron storage in yeast.";
RL J. Biol. Chem. 276:29515-29519(2001).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [10]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [11]
RP CHARACTERIZATION OF DELETION MUTANT.
RX PubMed=15161905; DOI=10.1074/jbc.m403146200;
RA Li L., Kaplan J.;
RT "A mitochondrial-vacuolar signaling pathway in yeast that affects iron and
RT copper metabolism.";
RL J. Biol. Chem. 279:33653-33661(2004).
RN [12]
RP INDUCTION.
RX PubMed=15652485; DOI=10.1016/j.cell.2004.11.032;
RA Puig S., Askeland E., Thiele D.J.;
RT "Coordinated remodeling of cellular metabolism during iron deficiency
RT through targeted mRNA degradation.";
RL Cell 120:99-110(2005).
RN [13]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [14]
RP EFFECT OF OVEREXPRESSION.
RX PubMed=17603109; DOI=10.1534/genetics.107.073577;
RA Devasahayam G., Burke D.J., Sturgill T.W.;
RT "Golgi manganese transport is required for rapamycin signaling in
RT Saccharomyces cerevisiae.";
RL Genetics 177:231-238(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [16]
RP INDUCTION.
RX PubMed=18070921; DOI=10.1128/mcb.01219-07;
RA Li L., Bagley D., Ward D.M., Kaplan J.;
RT "Yap5 is an iron-responsive transcriptional activator that regulates
RT vacuolar iron storage in yeast.";
RL Mol. Cell. Biol. 28:1326-1337(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29; SER-68; SER-71 AND
RP SER-83, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53; SER-68; SER-71 AND
RP SER-83, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Has a role in both calcium and manganese homeostasis.
CC Involved in the transfer of iron and Mn(2+) from the cytosol to the
CC vacuole for storage of these metals. {ECO:0000269|PubMed:11390404,
CC ECO:0000269|PubMed:8668190, ECO:0000269|PubMed:8866476}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:11390404, ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:8866476}. Vacuole membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- INDUCTION: Down-regulated under iron starvation by TIS11.
CC Transcriptionally up-regulated by YAP5 in response to increased
CC cytosolic iron. {ECO:0000269|PubMed:15652485,
CC ECO:0000269|PubMed:18070921}.
CC -!- DISRUPTION PHENOTYPE: Deletion causes an increase in metal sensitivity
CC at 15 mM manganese, but does not affect invertase glycosylation.
CC Deletion shows increased sensitivity to external iron, which is
CC suppressed by MRS3 or MRS4 overexpression requiring oxygen but not
CC respiration, and exacerbated by ectopic expression of the iron
CC transporter FET4. Deletion also results in decreased vacuolar iron
CC content and decreased iron stores, which affect cytosolic iron levels
CC and cell growth. Deletion together with MRS3 and MRS4 restores cellular
CC and mitochondrial iron homeostasis to near normal level, corrects the
CC MRS3 and MRS4 double deletion phenotype (which shows increased
CC resistance to cobalt but decreased resistance to copper and cadmium),
CC and has near normal levels of aconitase activity. When overexpressed,
CC maintains respiratory function in a YFH1 deletion mutant regardless of
CC extracellular iron concentration, activates the iron-dependent
CC transcription factor AFT1 resulting in an increase in iron uptake,
CC cytosolic iron accumulation and a change in copper metabolism.
CC Overexpression prevents excessive mitochondrial iron accumulation by
CC limiting mitochondrial iron uptake and results in increased expression
CC of the high affinity iron transport system composed of FET3 and FTR1.
CC Overexpression also suppresses the rapamycin-resistant phenotype of
CC PMR1 deletion mutant. {ECO:0000269|PubMed:8866476}.
CC -!- MISCELLANEOUS: Present with 2840 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the CCC1 family. {ECO:0000305}.
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DR EMBL; L24112; AAA62622.1; -; mRNA.
DR EMBL; U14913; AAB67452.1; -; Genomic_DNA.
DR EMBL; U19027; AAB67409.1; -; Genomic_DNA.
DR EMBL; AY557952; AAS56278.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09536.1; -; Genomic_DNA.
DR PIR; S43453; S43453.
DR RefSeq; NP_013321.1; NM_001182107.1.
DR AlphaFoldDB; P47818; -.
DR SMR; P47818; -.
DR BioGRID; 31487; 132.
DR DIP; DIP-782N; -.
DR IntAct; P47818; 1.
DR MINT; P47818; -.
DR STRING; 4932.YLR220W; -.
DR TCDB; 2.A.89.1.1; the vacuolar iron transporter (vit) family.
DR iPTMnet; P47818; -.
DR MaxQB; P47818; -.
DR PaxDb; P47818; -.
DR PRIDE; P47818; -.
DR EnsemblFungi; YLR220W_mRNA; YLR220W; YLR220W.
DR GeneID; 850917; -.
DR KEGG; sce:YLR220W; -.
DR SGD; S000004210; CCC1.
DR VEuPathDB; FungiDB:YLR220W; -.
DR eggNOG; KOG4473; Eukaryota.
DR HOGENOM; CLU_038957_0_0_1; -.
DR InParanoid; P47818; -.
DR OMA; MNFHHTL; -.
DR BioCyc; YEAST:G3O-32334-MON; -.
DR PRO; PR:P47818; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P47818; protein.
DR GO; GO:0000324; C:fungal-type vacuole; IDA:SGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IDA:SGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IMP:SGD.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IMP:SGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:SGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:SGD.
DR GO; GO:0030026; P:cellular manganese ion homeostasis; IMP:SGD.
DR GO; GO:0006880; P:intracellular sequestering of iron ion; IBA:GO_Central.
DR GO; GO:0006826; P:iron ion transport; IMP:SGD.
DR GO; GO:0006828; P:manganese ion transport; IMP:SGD.
DR InterPro; IPR008217; Ccc1_fam.
DR PANTHER; PTHR31851; PTHR31851; 1.
DR Pfam; PF01988; VIT1; 1.
PE 1: Evidence at protein level;
KW Golgi apparatus; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..322
FT /note="Protein CCC1"
FT /id="PRO_0000089394"
FT TOPO_DOM 1..99
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 121..129
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..259
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322
FT /note="Vacuolar"
FT /evidence="ECO:0000255"
FT REGION 19..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
SQ SEQUENCE 322 AA; 34250 MW; 374081A49F0C43D1 CRC64;
MSIVALKNAV VTLIQKAKGS GGTSELGGSE STPLLRGSNS NSSRHDNLSS SSSDIIYGRN
SAQDLENSPM SVGKDNRNGD NGSDNEKANL GFFQSVDPRV ISDLIIGLSD GLTVPFALTA
GLSSLGDAKL VITGGFAELI SGAISMGLGG YLGAKSESDY YHAEVKKEKR KFYDNSNLIN
REIEDILLEI NPNFSDETIV SFIKDLQRTP ELMVDFIIRY GRGLDEPAEN RELISAVTIG
GGYLLGGLVP LVPYFFVSDV GTGLIYSIIV MVVTLFWFGY VKTKLSMGSG SSTSKKVTEG
VEMVVVGGVA AGAAWFFVKL LG
