TIM12_YEAST
ID TIM12_YEAST Reviewed; 109 AA.
AC P32830; D6VQ92;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM12;
DE AltName: Full=Mitochondrial regulator of splicing 5;
GN Name=TIM12; Synonyms=MRS5; OrderedLocusNames=YBR091C; ORFNames=YBR0812;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8663351; DOI=10.1074/jbc.271.29.17219;
RA Jarosch E., Tuller G., Daum G., Waldherr M., Voskova A., Schweyen R.J.;
RT "Mrs5p, an essential protein of the mitochondrial intermembrane space,
RT affects protein import into yeast mitochondria.";
RL J. Biol. Chem. 271:17219-17225(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7900426; DOI=10.1002/yea.320101014;
RA Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.;
RT "Analysis of a 70 kb region on the right arm of yeast chromosome II.";
RL Yeast 10:1363-1381(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [4]
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 [5]
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 [6]
RP INTERACTION WITH TIM10 AND TIM22.
RX PubMed=8955274; DOI=10.1038/384582a0;
RA Sirrenberg C., Bauer M.D., Guiard B., Neupert W., Brunner M.;
RT "Import of carrier proteins into the mitochondrial inner membrane mediated
RT by Tim22.";
RL Nature 384:582-585(1996).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, PROBABLE ZINC-BINDING, AND INTERACTION WITH
RP TIM10 AND TIM22.
RX PubMed=9495346; DOI=10.1038/36136;
RA Sirrenberg C., Endres M., Foelsch H., Stuart R.A., Neupert W., Brunner M.;
RT "Carrier protein import into mitochondria mediated by the intermembrane
RT proteins Tim10/Mrs11 and Tim12/Mrs5.";
RL Nature 391:912-915(1998).
RN [8]
RP FUNCTION, AND INTERACTION WITH TIM10 AND TIM22.
RX PubMed=9430585; DOI=10.1126/science.279.5349.369;
RA Koehler C.M., Jarosch E., Tokatlidis K., Schmid K., Schweyen R.J.,
RA Schatz G.;
RT "Import of mitochondrial carriers mediated by essential proteins of the
RT intermembrane space.";
RL Science 279:369-373(1998).
RN [9]
RP FUNCTION.
RX PubMed=10995434; DOI=10.1083/jcb.150.6.1271;
RA Davis A.J., Sepuri N.B., Holder J., Johnson A.E., Jensen R.E.;
RT "Two intermembrane space TIM complexes interact with different domains of
RT Tim23p during its import into mitochondria.";
RL J. Cell Biol. 150:1271-1282(2000).
RN [10]
RP INTERACTION WITH TIM9 AND TIM10.
RX PubMed=9889188; DOI=10.1093/emboj/18.2.313;
RA Adam A., Endres M., Sirrenberg C., Lottspeich F., Neupert W., Brunner M.;
RT "Tim9, a new component of the TIM22.54 translocase in mitochondria.";
RL EMBO J. 18:313-319(1999).
RN [11]
RP FUNCTION.
RX PubMed=10369662; DOI=10.1093/emboj/18.12.3214;
RA Endres M., Neupert W., Brunner M.;
RT "Transport of the ADP/ATP carrier of mitochondria from the TOM complex to
RT the TIM22.54 complex.";
RL EMBO J. 18:3214-3221(1999).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A THE TIM22
RP COMPLEX WITH TIM18; TIM22 AND TIM54.
RX PubMed=10648604; DOI=10.1128/mcb.20.4.1187-1193.2000;
RA Koehler C.M., Murphy M.P., Bally N.A., Leuenberger D., Oppliger W.,
RA Dolfini L., Junne T., Schatz G., Or E.;
RT "Tim18p, a new subunit of the TIM22 complex that mediates insertion of
RT imported proteins into the yeast mitochondrial inner membrane.";
RL Mol. Cell. Biol. 20:1187-1193(2000).
RN [13]
RP IDENTIFICATION IN THE TIM22 COMPLEX WITH TIM10; TIM18; TIM22 AND TIM54.
RX PubMed=12637749; DOI=10.1126/science.1080945;
RA Rehling P., Model K., Brandner K., Kovermann P., Sickmann A., Meyer H.E.,
RA Kuehlbrandt W., Wagner R., Truscott K.N., Pfanner N.;
RT "Protein insertion into the mitochondrial inner membrane by a twin-pore
RT translocase.";
RL Science 299:1747-1751(2003).
RN [14]
RP ERRATUM OF PUBMED:12637749.
RA Rehling P., Model K., Brandner K., Kovermann P., Sickmann A., Meyer H.E.,
RA Kuehlbrandt W., Wagner R., Truscott K.N., Pfanner N.;
RL Science 300:251-251(2003).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RX PubMed=22984289; DOI=10.1074/mcp.m112.021105;
RA Voegtle F.N., Burkhart J.M., Rao S., Gerbeth C., Hinrichs J.,
RA Martinou J.C., Chacinska A., Sickmann A., Zahedi R.P., Meisinger C.;
RT "Intermembrane space proteome of yeast mitochondria.";
RL Mol. Cell. Proteomics 11:1840-1852(2012).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Essential component of the TIM22 complex, a complex that
CC mediates the import and insertion of multi-pass transmembrane proteins
CC into the mitochondrial inner membrane. The TIM22 complex forms a twin-
CC pore translocase that uses the membrane potential as external driving
CC force. In the TIM22 complex, it acts as a docking point for the soluble
CC TIM9-TIM10 heterohexamer that guides the target proteins in transit
CC through the aqueous mitochondrial intermembrane space.
CC {ECO:0000269|PubMed:10369662, ECO:0000269|PubMed:10995434,
CC ECO:0000269|PubMed:8663351, ECO:0000269|PubMed:9430585,
CC ECO:0000269|PubMed:9495346}.
CC -!- SUBUNIT: Component of the TIM22 complex, whose core is composed of
CC TIM18, TIM22 and TIM54, associated with the peripheral proteins
CC MRS5/TIM12 and the 70 kDa heterohexamer composed of TIM9 and TIM10 (or
CC TIM8 and TIM13). Interacts directly with both the TIM22 protein and the
CC TIM9-TIM10 heterohexamer. Interacts with multi-pass transmembrane
CC proteins in transit. {ECO:0000269|PubMed:10648604,
CC ECO:0000269|PubMed:12637749, ECO:0000269|PubMed:8955274,
CC ECO:0000269|PubMed:9430585, ECO:0000269|PubMed:9495346,
CC ECO:0000269|PubMed:9889188}.
CC -!- INTERACTION:
CC P32830; P16892: FUS3; NbExp=2; IntAct=EBI-11303, EBI-7193;
CC P32830; P87108: TIM10; NbExp=3; IntAct=EBI-11303, EBI-9115;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:8663351, ECO:0000269|PubMed:9495346}; Peripheral
CC membrane protein {ECO:0000269|PubMed:8663351,
CC ECO:0000269|PubMed:9495346}. Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:22984289}.
CC -!- DOMAIN: The twin CX3C motif contains 4 conserved Cys residues that form
CC 2 disulfide bonds in the mitochondrial intermembrane space. However,
CC during the transit of TIM12 from cytoplasm into mitochondrion, the Cys
CC residues probably coordinate zinc, thereby preventing folding and
CC allowing its transfer across mitochondrial outer membrane (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the small Tim family. {ECO:0000305}.
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DR EMBL; M90689; AAC37483.1; -; Genomic_DNA.
DR EMBL; X78993; CAA55596.1; -; Genomic_DNA.
DR EMBL; Z35960; CAA85044.1; -; Genomic_DNA.
DR EMBL; AY558529; AAS56855.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07212.1; -; Genomic_DNA.
DR PIR; S30793; S30793.
DR RefSeq; NP_009649.1; NM_001178439.1.
DR PDB; 6LO8; EM; 3.83 A; F=1-109.
DR PDBsum; 6LO8; -.
DR AlphaFoldDB; P32830; -.
DR SASBDB; P32830; -.
DR SMR; P32830; -.
DR BioGRID; 32797; 26.
DR ComplexPortal; CPX-1629; TIM22 mitochondrial inner membrane twin-pore carrier translocase complex.
DR ComplexPortal; CPX-2950; TIM9-TIM10-TIM12 mitochondrial intermembrane space protein transporter complex.
DR DIP; DIP-1140N; -.
DR IntAct; P32830; 5.
DR STRING; 4932.YBR091C; -.
DR iPTMnet; P32830; -.
DR MaxQB; P32830; -.
DR PaxDb; P32830; -.
DR PRIDE; P32830; -.
DR EnsemblFungi; YBR091C_mRNA; YBR091C; YBR091C.
DR GeneID; 852388; -.
DR KEGG; sce:YBR091C; -.
DR SGD; S000000295; TIM12.
DR VEuPathDB; FungiDB:YBR091C; -.
DR eggNOG; KOG3480; Eukaryota.
DR GeneTree; ENSGT00390000003068; -.
DR HOGENOM; CLU_162151_0_0_1; -.
DR InParanoid; P32830; -.
DR OMA; EKCIPHE; -.
DR BioCyc; YEAST:G3O-29057-MON; -.
DR PRO; PR:P32830; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P32830; protein.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0042719; C:mitochondrial intermembrane space protein transporter complex; IPI:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IDA:ComplexPortal.
DR GO; GO:0042721; C:TIM22 mitochondrial import inner membrane insertion complex; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IDA:SGD.
DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:SGD.
DR GO; GO:0071806; P:protein transmembrane transport; IEA:GOC.
DR Gene3D; 1.10.287.810; -; 1.
DR InterPro; IPR004217; Tim10-like.
DR InterPro; IPR035427; Tim10-like_dom_sf.
DR InterPro; IPR027102; Tim12.
DR PANTHER; PTHR11038:SF18; PTHR11038:SF18; 1.
DR Pfam; PF02953; zf-Tim10_DDP; 1.
DR SUPFAM; SSF144122; SSF144122; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Disulfide bond; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Protein transport;
KW Reference proteome; Translocation; Transport; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..109
FT /note="Mitochondrial import inner membrane translocase
FT subunit TIM12"
FT /id="PRO_0000096581"
FT MOTIF 40..66
FT /note="Twin CX3C motif"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT DISULFID 40..66
FT /evidence="ECO:0000250"
FT DISULFID 44..62
FT /evidence="ECO:0000250"
SQ SEQUENCE 109 AA; 12284 MW; 2C4B7DEE9695866D CRC64;
MSFFLNSLRG NQEVSQEKLD VAGVQFDAMC STFNNILSTC LEKCIPHEGF GEPDLTKGEQ
CCIDRCVAKM HYSNRLIGGF VQTRGFGPEN QLRHYSRFVA KEIADDSKK
