MDM12_YEAST
ID MDM12_YEAST Reviewed; 271 AA.
AC Q92328; D6W258; Q08064;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Mitochondrial distribution and morphology protein 12 {ECO:0000255|HAMAP-Rule:MF_03104};
DE AltName: Full=Mitochondrial inheritance component MDM12 {ECO:0000255|HAMAP-Rule:MF_03104};
GN Name=MDM12 {ECO:0000255|HAMAP-Rule:MF_03104}; OrderedLocusNames=YOL009C;
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 [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RX PubMed=9024686; DOI=10.1083/jcb.136.3.545;
RA Berger K.H., Sogo L.F., Yaffe M.P.;
RT "Mdm12p, a component required for mitochondrial inheritance that is
RT conserved between budding and fission yeast.";
RL J. Cell Biol. 136:545-553(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(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 IDENTIFICATION IN THE MDM10/MDM12/MMM1 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=13679517; DOI=10.1091/mbc.e03-04-0225;
RA Boldogh I.R., Nowakowski D.W., Yang H.-C., Chung H., Karmon S., Royes P.,
RA Pon L.A.;
RT "A protein complex containing Mdm10p, Mdm12p, and Mmm1p links mitochondrial
RT membranes and DNA to the cytoskeleton-based segregation machinery.";
RL Mol. Biol. Cell 14:4618-4627(2003).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [8]
RP FUNCTION, AND IDENTIFICATION IN MDM12/MMM1 AND MDM10/MDM12/MMM1 COMPLEXES.
RX PubMed=17410204; DOI=10.1038/sj.emboj.7601673;
RA Meisinger C., Pfannschmidt S., Rissler M., Milenkovic D., Becker T.,
RA Stojanovski D., Youngman M.J., Jensen R.E., Chacinska A., Guiard B.,
RA Pfanner N., Wiedemann N.;
RT "The morphology proteins Mdm12/Mmm1 function in the major beta-barrel
RT assembly pathway of mitochondria.";
RL EMBO J. 26:2229-2239(2007).
RN [9]
RP INTERACTION WITH PUF3.
RX PubMed=17210948; DOI=10.1083/jcb.200606054;
RA Garcia-Rodriguez L.J., Gay A.C., Pon L.A.;
RT "Puf3p, a Pumilio family RNA binding protein, localizes to mitochondria and
RT regulates mitochondrial biogenesis and motility in budding yeast.";
RL J. Cell Biol. 176:197-207(2007).
RN [10]
RP FUNCTION, IDENTIFICATION IN ERMES/MDM COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=19556461; DOI=10.1126/science.1175088;
RA Kornmann B., Currie E., Collins S.R., Schuldiner M., Nunnari J.,
RA Weissman J.S., Walter P.;
RT "An ER-mitochondria tethering complex revealed by a synthetic biology
RT screen.";
RL Science 325:477-481(2009).
RN [11]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF GLU-11; SER-12; LEU-16; ASN-17;
RP LEU-19; ILE-20; LYS-22 AND PRO-259.
RX PubMed=22250200; DOI=10.1242/jcs.085118;
RA Toulmay A., Prinz W.A.;
RT "A conserved membrane-binding domain targets proteins to organelle contact
RT sites.";
RL J. Cell Sci. 125:49-58(2012).
RN [12]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-49, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [13]
RP FUNCTION.
RX PubMed=27469264; DOI=10.1038/srep30777;
RA Kojima R., Endo T., Tamura Y.;
RT "A phospholipid transfer function of ER-mitochondria encounter structure
RT revealed in vitro.";
RL Sci. Rep. 6:30777-30777(2016).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.11 ANGSTROMS) IN COMPLEX WITH PHOSPHOLIPID.
RX PubMed=27821511; DOI=10.15252/embr.201642706;
RA Jeong H., Park J., Lee C.;
RT "Crystal structure of Mdm12 reveals the architecture and dynamic
RT organization of the ERMES complex.";
RL EMBO Rep. 17:1857-1871(2016).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (4.10 ANGSTROMS), AND SUBUNIT.
RX PubMed=28479252; DOI=10.1016/j.bbrc.2017.05.021;
RA AhYoung A.P., Lu B., Cascio D., Egea P.F.;
RT "Crystal structure of Mdm12 and combinatorial reconstitution of Mdm12/Mmm1
RT ERMES complexes for structural studies.";
RL Biochem. Biophys. Res. Commun. 488:129-135(2017).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF 212-271.
RX PubMed=29078410; DOI=10.1073/pnas.1715592114;
RA Jeong H., Park J., Jun Y., Lee C.;
RT "Crystal structures of Mmm1 and Mdm12-Mmm1 reveal mechanistic insight into
RT phospholipid trafficking at ER-mitochondria contact sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E9502-E9511(2017).
CC -!- FUNCTION: Component of the ERMES/MDM complex, which serves as a
CC molecular tether to connect the endoplasmic reticulum and mitochondria
CC (PubMed:19556461, PubMed:22250200). Components of this complex are
CC involved in the control of mitochondrial shape and protein biogenesis,
CC and function in nonvesicular lipid trafficking between the ER and
CC mitochondria (PubMed:19556461, PubMed:27469264). MDM12 is required for
CC the interaction of the ER-resident membrane protein MMM1 and the outer
CC mitochondrial membrane-resident beta-barrel protein MDM10. The MDM12-
CC MMM1 subcomplex functions in the major beta-barrel assembly pathway
CC that is responsible for biogenesis of all mitochondrial outer membrane
CC beta-barrel proteins, and acts in a late step after the SAM complex.
CC The MDM10-MDM12-MMM1 subcomplex further acts in the TOM40-specific
CC pathway after the action of the MDM12-MMM1 complex. Essential for
CC establishing and maintaining the structure of mitochondria and
CC maintenance of mtDNA nucleoids (By similarity) (PubMed:17410204).
CC {ECO:0000255|HAMAP-Rule:MF_03104, ECO:0000269|PubMed:17410204,
CC ECO:0000269|PubMed:19556461, ECO:0000269|PubMed:27469264}.
CC -!- SUBUNIT: Component of the ER-mitochondria encounter structure (ERMES)
CC or MDM complex, composed of MMM1, MDM10, MDM12 and MDM34
CC (PubMed:13679517, PubMed:17410204, PubMed:19556461). A MMM1 homodimer
CC associates with one molecule of MDM12 on each side in a pairwise head-
CC to-tail manner, and the SMP-LTD domains of MMM1 and MDM12 generate a
CC continuous hydrophobic tunnel for phospholipid trafficking
CC (PubMed:28479252, PubMed:29078410). Interacts with PUF3 (By similarity)
CC (PubMed:17210948). {ECO:0000255|HAMAP-Rule:MF_03104,
CC ECO:0000269|PubMed:13679517, ECO:0000269|PubMed:17210948,
CC ECO:0000269|PubMed:17410204, ECO:0000269|PubMed:19556461,
CC ECO:0000269|PubMed:28479252, ECO:0000269|PubMed:29078410}.
CC -!- INTERACTION:
CC Q92328; P18409: MDM10; NbExp=4; IntAct=EBI-10584, EBI-10580;
CC Q92328; P41800: MMM1; NbExp=5; IntAct=EBI-10584, EBI-11029;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000255|HAMAP-
CC Rule:MF_03104}; Peripheral membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_03104}; Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_03104}.
CC Endoplasmic reticulum membrane {ECO:0000255|HAMAP-Rule:MF_03104};
CC Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03104};
CC Cytoplasmic side {ECO:0000255|HAMAP-Rule:MF_03104}. Note=The ERMES/MDM
CC complex localizes to a few discrete foci (around 10 per single cell),
CC that represent mitochondria-endoplasmic reticulum junctions. These foci
CC are often found next to mtDNA nucleoids. {ECO:0000255|HAMAP-
CC Rule:MF_03104}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that can bind
CC various types of glycerophospholipids in its interior and mediate their
CC transfer between two adjacent bilayers. {ECO:0000255|HAMAP-
CC Rule:MF_03104, ECO:0000269|PubMed:22250200,
CC ECO:0000269|PubMed:27821511}.
CC -!- MISCELLANEOUS: Present with 1070 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the MDM12 family. {ECO:0000255|HAMAP-
CC Rule:MF_03104}.
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DR EMBL; U62252; AAB17867.1; -; Genomic_DNA.
DR EMBL; Z74751; CAA99008.1; -; Genomic_DNA.
DR EMBL; AY558013; AAS56339.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10774.1; -; Genomic_DNA.
DR PIR; S66691; S66691.
DR RefSeq; NP_014634.1; NM_001183263.1.
DR PDB; 5GYD; X-ray; 3.11 A; A/B/C/D=1-271.
DR PDB; 5GYK; X-ray; 3.60 A; A/B/C/D/E/F=1-73, A/B/C/D/E/F=115-271.
DR PDB; 5VKZ; X-ray; 4.10 A; A/B=1-271.
DR PDB; 5YK7; X-ray; 3.80 A; B/D=1-73, B/D=115-182, B/D=212-271.
DR PDBsum; 5GYD; -.
DR PDBsum; 5GYK; -.
DR PDBsum; 5VKZ; -.
DR PDBsum; 5YK7; -.
DR AlphaFoldDB; Q92328; -.
DR SMR; Q92328; -.
DR BioGRID; 34395; 406.
DR ComplexPortal; CPX-3196; ERMES complex.
DR DIP; DIP-4188N; -.
DR IntAct; Q92328; 4.
DR MINT; Q92328; -.
DR STRING; 4932.YOL009C; -.
DR TCDB; 9.A.58.1.1; the maintenance of mitochondrial morphology (mmm) family.
DR iPTMnet; Q92328; -.
DR MaxQB; Q92328; -.
DR PaxDb; Q92328; -.
DR PRIDE; Q92328; -.
DR EnsemblFungi; YOL009C_mRNA; YOL009C; YOL009C.
DR GeneID; 854153; -.
DR KEGG; sce:YOL009C; -.
DR SGD; S000005369; MDM12.
DR VEuPathDB; FungiDB:YOL009C; -.
DR eggNOG; ENOG502QQS2; Eukaryota.
DR HOGENOM; CLU_026794_2_0_1; -.
DR InParanoid; Q92328; -.
DR OMA; AAWPSWI; -.
DR BioCyc; YEAST:G3O-33426-MON; -.
DR PRO; PR:Q92328; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q92328; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032865; C:ERMES complex; IPI:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0098799; C:outer mitochondrial membrane protein complex; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; HDA:SGD.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:SGD.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; IDA:SGD.
DR GO; GO:1901611; F:phosphatidylglycerol binding; IDA:SGD.
DR GO; GO:0015917; P:aminophospholipid transport; IMP:SGD.
DR GO; GO:0120009; P:intermembrane lipid transfer; IEA:GOC.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IEA:UniProtKB-UniRule.
DR GO; GO:0070096; P:mitochondrial outer membrane translocase complex assembly; IMP:SGD.
DR GO; GO:0000001; P:mitochondrion inheritance; IMP:SGD.
DR GO; GO:0007005; P:mitochondrion organization; IC:ComplexPortal.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IMP:SGD.
DR GO; GO:0055091; P:phospholipid homeostasis; IC:ComplexPortal.
DR GO; GO:0015914; P:phospholipid transport; IGI:SGD.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IEA:UniProtKB-UniRule.
DR HAMAP; MF_03104; Mdm12; 1.
DR InterPro; IPR027532; Mdm12.
DR InterPro; IPR031468; SMP_LBD.
DR PANTHER; PTHR28204; PTHR28204; 1.
DR PROSITE; PS51847; SMP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Isopeptide bond; Lipid transport;
KW Lipid-binding; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Reference proteome; Transport; Ubl conjugation.
FT CHAIN 1..271
FT /note="Mitochondrial distribution and morphology protein
FT 12"
FT /id="PRO_0000096329"
FT DOMAIN 1..267
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03104"
FT CROSSLNK 49
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT MUTAGEN 11
FT /note="E->R: Does not affect function; when associated with
FT A-12; E-17 and D-22."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 12
FT /note="S->A: Does not affect function; when associated with
FT R-11; E-17 and D-22."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 16
FT /note="L->D: Does not affect function; when associated with
FT D-19 and D-20."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 17
FT /note="N->E: Does not affect function; when associated with
FT R-11; A-12 and D-22."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 19
FT /note="L->D: Does not affect function; when associated with
FT D-16 and D-20."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 20
FT /note="I->D: Does not affect function; when associated with
FT D-16 and D-19."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 22
FT /note="K->D: Does not affect function; when associated with
FT R-11; A-12 AND E-17."
FT /evidence="ECO:0000269|PubMed:22250200"
FT MUTAGEN 259
FT /note="P->A: Does not affect function."
FT /evidence="ECO:0000269|PubMed:22250200"
FT CONFLICT 91
FT /note="I -> V (in Ref. 1; AAB17867)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="G -> D (in Ref. 1; AAB17867)"
FT /evidence="ECO:0000305"
FT STRAND 1..6
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 8..11
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 49..60
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 119..128
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 132..141
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 149..171
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 174..182
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 213..222
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:5GYD"
FT HELIX 231..256
FT /evidence="ECO:0007829|PDB:5GYD"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:5GYD"
SQ SEQUENCE 271 AA; 30729 MW; D4A89786CE59CAB4 CRC64;
MSFDINWSTL ESDNRLNDLI RKHLNSYLQN TQLPSYVSNL RVLDFDLGKV GPAITLKEIT
DPLDEFYDSI REEADQETEE NNDNKEDSEH ICPDRTIANH EGPKDDFEAP VVMPSPNDIQ
FLLEVEYKGD LLVTIGADLV LNYPVEKFMT LPVKLSISDI GLHSLCIVAC LSKQLFLSFL
CDVSDPALDD NQTVLDPKGP ILAATKPLER ISIVRSMKIE TEIGEQYQGQ GSVLRSVGEL
EQFLFTIFKD FLRKELAWPS WINLDFNDGD E
