UPS1_YEAST
ID UPS1_YEAST Reviewed; 175 AA.
AC Q05776; D6VYJ6;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein UPS1, mitochondrial;
DE AltName: Full=Unprocessed MGM1 protein 1;
GN Name=UPS1; OrderedLocusNames=YLR193C;
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] {ECO:0000312|EMBL:AAB67434.1}
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 [2]
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 [3] {ECO:0000305}
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 [4] {ECO:0000305}
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 [5] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16754953; DOI=10.1083/jcb.200603092;
RA Sesaki H., Dunn C.D., Iijima M., Shepard K.A., Yaffe M.P., Machamer C.E.,
RA Jensen R.E.;
RT "Ups1p, a conserved intermembrane space protein, regulates mitochondrial
RT shape and alternative topogenesis of Mgm1p.";
RL J. Cell Biol. 173:651-658(2006).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19221197; DOI=10.1083/jcb.200810189;
RA Osman C., Haag M., Potting C., Rodenfels J., Dip P.V., Wieland F.T.,
RA Brugger B., Westermann B., Langer T.;
RT "The genetic interactome of prohibitins: coordinated control of cardiolipin
RT and phosphatidylethanolamine by conserved regulators in mitochondria.";
RL J. Cell Biol. 184:583-596(2009).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19506038; DOI=10.1083/jcb.200812018;
RA Tamura Y., Endo T., Iijima M., Sesaki H.;
RT "Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in
RT mitochondria.";
RL J. Cell Biol. 185:1029-1045(2009).
RN [8]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION MDM35.
RX PubMed=20622808; DOI=10.1038/emboj.2010.149;
RA Tamura Y., Iijima M., Sesaki H.;
RT "Mdm35p imports Ups proteins into the mitochondrial intermembrane space by
RT functional complex formation.";
RL EMBO J. 29:2875-2887(2010).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MDM35.
RX PubMed=20657548; DOI=10.1038/emboj.2010.169;
RA Potting C., Wilmes C., Engmann T., Osman C., Langer T.;
RT "Regulation of mitochondrial phospholipids by Ups1/PRELI-like proteins
RT depends on proteolysis and Mdm35.";
RL EMBO J. 29:2888-2898(2010).
RN [10]
RP FUNCTION, INTERACTION WITH MDM35, AND MUTAGENESIS OF ARG-54.
RX PubMed=26071602; DOI=10.15252/embr.201540229;
RA Miliara X., Garnett J.A., Tatsuta T., Abid Ali F., Baldie H.,
RA Perez-Dorado I., Simpson P., Yague E., Langer T., Matthews S.;
RT "Structural insight into the TRIAP1/PRELI-like domain family of
RT mitochondrial phospholipid transfer complexes.";
RL EMBO Rep. 16:824-835(2015).
RN [11] {ECO:0007744|PDB:4XHR, ECO:0007744|PDB:4XIZ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-170 IN COMPLEX WITH
RP PHOSPHATIDIC ACID AND MDM35, INTERACTION WITH MDM35, FUNCTION, AND
RP MUTAGENESIS OF PHE-23; HIS-33; ARG-42; LEU-50; LYS-58; LYS-61; TRP-77;
RP ILE-78; VAL-84; ARG-96; ASN-97; MET-104; VAL-106; TRP-144; LYS-148 AND
RP LYS-155.
RX PubMed=26071601; DOI=10.15252/embr.201540137;
RA Yu F., He F., Yao H., Wang C., Wang J., Li J., Qi X., Xue H., Ding J.,
RA Zhang P.;
RT "Structural basis of intramitochondrial phosphatidic acid transport
RT mediated by Ups1-Mdm35 complex.";
RL EMBO Rep. 16:813-823(2015).
RN [12] {ECO:0007744|PDB:4YTW, ECO:0007744|PDB:4YTX}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 1-170 IN COMPLEX WITH
RP PHOSPHATIDIC ACID AND MDM35, INTERACTION WITH MDM35, FUNCTION, MUTAGENESIS
RP OF ARG-25; LYS-61 AND LYS-155, AND SUBCELLULAR LOCATION.
RX PubMed=26235513; DOI=10.1038/ncomms8922;
RA Watanabe Y., Tamura Y., Kawano S., Endo T.;
RT "Structural and mechanistic insights into phospholipid transfer by Ups1-
RT Mdm35 in mitochondria.";
RL Nat. Commun. 6:7922-7922(2015).
CC -!- FUNCTION: Required for maintenance of normal mitochondrial morphology
CC (PubMed:16754953, PubMed:26071601). Required for PCP1-dependent
CC processing of MGM1 (PubMed:16754953). The UPS1:MDM35 complex mediates
CC the transfer of phosphatidic acid (PA) between liposomes and probably
CC functions as a PA transporter across the mitochondrion intermembrane
CC space (PubMed:26071602, PubMed:26071601, PubMed:26235513). Phosphatidic
CC acid release requires dissociation of the UPS1:MDM35 complex
CC (PubMed:26235513). Phosphatidic acid import is required for cardiolipin
CC (CL) synthesis in the mitochondrial inner membrane (PubMed:26071602).
CC With UPS2, controls the level of cardiolipin in mitochondria
CC (PubMed:19506038). Cardiolipin is a unique phospholipid with four fatty
CC acid chains and is present mainly in the mitochondrial inner membrane
CC where it stabilizes the electron transport chain supercomplex between
CC complexes III and IV through direct interaction of their subunits.
CC {ECO:0000269|PubMed:16754953, ECO:0000269|PubMed:19221197,
CC ECO:0000269|PubMed:19506038, ECO:0000269|PubMed:20622808,
CC ECO:0000269|PubMed:26071602, ECO:0000269|PubMed:26235513}.
CC -!- SUBUNIT: Interacts with MDM35 (PubMed:20622808, PubMed:20657548,
CC PubMed:26071602, PubMed:26071601, PubMed:26235513). Found associated
CC with a 170 kDa complex. {ECO:0000269|PubMed:16754953,
CC ECO:0000269|PubMed:20622808, ECO:0000269|PubMed:20657548,
CC ECO:0000269|PubMed:26071601, ECO:0000269|PubMed:26071602,
CC ECO:0000269|PubMed:26235513}.
CC -!- INTERACTION:
CC Q05776; O60200: MDM35; NbExp=5; IntAct=EBI-30337, EBI-2080774;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:26235513}; Peripheral membrane protein
CC {ECO:0000269|PubMed:26235513}; Intermembrane side {ECO:0000305}.
CC Mitochondrion intermembrane space {ECO:0000269|PubMed:26235513}.
CC Note=Lacks the two major intermembrane space-targeting signals,
CC bipartite presequences and cysteine motifs, and import is mediated by
CC another IMS protein, MDM35. {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Cells show slow growth, fragmented mitochondria
CC and have a 50-fold reduced level of s-MGM1. These defects can be
CC complemented by human PRELI or bypassed by growth on a nonfermentable
CC carbon source. {ECO:0000269|PubMed:16754953}.
CC -!- MISCELLANEOUS: Present with 704 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the slowmo family. {ECO:0000305}.
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DR EMBL; U14913; AAB67434.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09512.1; -; Genomic_DNA.
DR PIR; S48546; S48546.
DR RefSeq; NP_013294.1; NM_001182080.1.
DR PDB; 4XHR; X-ray; 2.55 A; A/B=1-175.
DR PDB; 4XIZ; X-ray; 2.00 A; A/B=1-170.
DR PDB; 4YTW; X-ray; 1.40 A; B/D=1-170.
DR PDB; 4YTX; X-ray; 3.20 A; B/D/F/H/J/L/N/P=1-170.
DR PDB; 5JQL; X-ray; 2.90 A; A/C/E/G/I/K=1-175.
DR PDB; 5JQM; X-ray; 1.50 A; A/B/C=1-175.
DR PDB; 6KYL; X-ray; 3.55 A; B/D=1-175.
DR PDBsum; 4XHR; -.
DR PDBsum; 4XIZ; -.
DR PDBsum; 4YTW; -.
DR PDBsum; 4YTX; -.
DR PDBsum; 5JQL; -.
DR PDBsum; 5JQM; -.
DR PDBsum; 6KYL; -.
DR AlphaFoldDB; Q05776; -.
DR SMR; Q05776; -.
DR BioGRID; 31463; 578.
DR DIP; DIP-4798N; -.
DR IntAct; Q05776; 1.
DR MINT; Q05776; -.
DR STRING; 4932.YLR193C; -.
DR MaxQB; Q05776; -.
DR PaxDb; Q05776; -.
DR PRIDE; Q05776; -.
DR DNASU; 850890; -.
DR EnsemblFungi; YLR193C_mRNA; YLR193C; YLR193C.
DR GeneID; 850890; -.
DR KEGG; sce:YLR193C; -.
DR SGD; S000004183; UPS1.
DR VEuPathDB; FungiDB:YLR193C; -.
DR eggNOG; KOG3337; Eukaryota.
DR GeneTree; ENSGT00950000182810; -.
DR HOGENOM; CLU_067902_3_1_1; -.
DR InParanoid; Q05776; -.
DR OMA; LAFFNRY; -.
DR BioCyc; YEAST:G3O-32315-MON; -.
DR Reactome; R-SCE-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR PRO; PR:Q05776; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q05776; protein.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IDA:SGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:SGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:1990050; F:phosphatidic acid transfer activity; IDA:SGD.
DR GO; GO:0032048; P:cardiolipin metabolic process; IMP:SGD.
DR GO; GO:0045332; P:phospholipid translocation; IDA:SGD.
DR GO; GO:0015914; P:phospholipid transport; IDA:SGD.
DR GO; GO:2001247; P:positive regulation of phosphatidylcholine biosynthetic process; IMP:SGD.
DR DisProt; DP02326; -.
DR InterPro; IPR006797; PRELI/MSF1_dom.
DR InterPro; IPR037365; Slowmo/Ups.
DR PANTHER; PTHR11158; PTHR11158; 1.
DR Pfam; PF04707; PRELI; 1.
DR PROSITE; PS50904; PRELI_MSF1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Lipid transport; Lipid-binding; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transport.
FT CHAIN 1..175
FT /note="Protein UPS1, mitochondrial"
FT /id="PRO_0000271269"
FT DOMAIN 2..172
FT /note="PRELI/MSF1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00158"
FT REGION 1..80
FT /note="Required for mitochondrial targeting"
FT /evidence="ECO:0000269|PubMed:16754953"
FT BINDING 26
FT /ligand="a 1,2-diacyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58608"
FT /evidence="ECO:0000269|PubMed:26235513"
FT BINDING 58
FT /ligand="a 1,2-diacyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58608"
FT /evidence="ECO:0000269|PubMed:26235513"
FT BINDING 148
FT /ligand="a 1,2-diacyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58608"
FT /evidence="ECO:0000269|PubMed:26071601"
FT BINDING 152
FT /ligand="a 1,2-diacyl-sn-glycero-3-phosphate"
FT /ligand_id="ChEBI:CHEBI:58608"
FT /evidence="ECO:0000269|PubMed:26071601,
FT ECO:0000269|PubMed:26235513"
FT MUTAGEN 23
FT /note="F->D: Strongly impairs interaction with MDM35.
FT Failure to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 25
FT /note="R->E: Nearly abolishes phosphatidic acid transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:26235513"
FT MUTAGEN 25
FT /note="R->K: No effect on phosphatidic acid transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:26235513"
FT MUTAGEN 33
FT /note="H->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-58;
FT E-61; E-148 and E-155."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 42
FT /note="R->D: Impairs interaction with MDM35. Reduces
FT ability to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 50
FT /note="L->D: Strongly impairs interaction with MDM35.
FT Failure to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 54
FT /note="R->E: Decreases phosphatidic acid transfer activity
FT and impairs cardiolipin biosynthesis."
FT /evidence="ECO:0000269|PubMed:26071602"
FT MUTAGEN 58
FT /note="K->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-33;
FT E-61; E-148 and E-155."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 61
FT /note="K->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-33;
FT E-58; E-148 and E-155."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 61
FT /note="K->E: Nearly abolishes phosphatidic acid transfer
FT activity; when associated with E-155."
FT /evidence="ECO:0000269|PubMed:26235513"
FT MUTAGEN 62
FT /note="L->A: Decreases phosphatidic acid binding and
FT impairs cardiolipin biosynthesis; when associated with A-
FT 65."
FT /evidence="ECO:0000269|PubMed:26071602"
FT MUTAGEN 65
FT /note="W->A: Decreases phosphatidic acid binding and
FT impairs cardiolipin biosynthesis; when associated with A-
FT 62."
FT /evidence="ECO:0000269|PubMed:26071602"
FT MUTAGEN 77
FT /note="W->D: Impairs interaction with MDM35. Reduces
FT ability to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 78
FT /note="I->D: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 84
FT /note="V->E: Strongly impairs interaction with MDM35.
FT Failure to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 96
FT /note="R->D: Strongly impairs interaction with MDM35.
FT Failure to complement the mitochondrial defects of UPS1-
FT deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 97
FT /note="N->A: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 104
FT /note="M->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-
FT 144."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 106
FT /note="V->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 144
FT /note="W->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-
FT 104."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 148
FT /note="K->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-33;
FT E-58; E-61 and E-155."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 155
FT /note="K->E: Failure to complement the mitochondrial
FT defects of UPS1-deficient cells; when associated with E-33;
FT E-58; E-61 and E-148."
FT /evidence="ECO:0000269|PubMed:26071601"
FT MUTAGEN 155
FT /note="K->E: Nearly abolishes phosphatidic acid transfer
FT activity; when associated with E-61."
FT /evidence="ECO:0000269|PubMed:26235513"
FT STRAND 2..13
FT /evidence="ECO:0007829|PDB:4YTW"
FT HELIX 15..23
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 34..44
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 50..59
FT /evidence="ECO:0007829|PDB:4YTW"
FT TURN 64..69
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 75..85
FT /evidence="ECO:0007829|PDB:4YTW"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 90..100
FT /evidence="ECO:0007829|PDB:4YTW"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 105..115
FT /evidence="ECO:0007829|PDB:4YTW"
FT TURN 116..119
FT /evidence="ECO:0007829|PDB:4YTW"
FT STRAND 120..130
FT /evidence="ECO:0007829|PDB:4YTW"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:4YTW"
FT HELIX 137..167
FT /evidence="ECO:0007829|PDB:4YTW"
SQ SEQUENCE 175 AA; 20108 MW; 5B9003B6A2323109 CRC64;
MVLLHKSTHI FPTDFASVSR AFFNRYPNPY SPHVLSIDTI SRNVDQEGNL RTTRLLKKSG
KLPTWVKPFL RGITETWIIE VSVVNPANST MKTYTRNLDH TGIMKVEEYT TYQFDSATSS
TIADSRVKFS SGFNMGIKSK VEDWSRTKFD ENVKKSRMGM AFVIQKLEEA RNPQF
