ID   TIM22_YEAST             Reviewed;         207 AA.
AC   Q12328; D6VRD7;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=Mitochondrial import inner membrane translocase subunit TIM22;
GN   Name=TIM22; OrderedLocusNames=YDL217C; ORFNames=D0884;
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].
RC   STRAIN=ATCC 96604 / S288c / FY1679;
RX   PubMed=9046097;
RX   DOI=10.1002/(sici)1097-0061(199702)13:2<163::aid-yea54>3.0.co;2-4;
RA   Bahr A., Moeller-Rieker S., Hankeln T., Kraemer C., Protin U.,
RA   Schmidt E.R.;
RT   "The nucleotide sequence of a 39 kb segment of yeast chromosome IV: 12 new
RT   open reading frames, nine known genes and one gene for Gly-tRNA.";
RL   Yeast 13:163-169(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169867;
RA   Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA   Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA   Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA   Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA   Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA   Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA   Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA   Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA   Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA   Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA   Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA   Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA   Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA   Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA   Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA   Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA   Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA   Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA   Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA   Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA   Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA   Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA   Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA   Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA   Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA   Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA   Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA   Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA   Mewes H.-W., Zollner A., Zaccaria P.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL   Nature 387:75-78(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, SUBCELLULAR LOCATION, AND INTERACTION WITH TIM10 AND TIM12.
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   [6]
RP   INTERACTION WITH TIM10 AND TIM12.
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   [7]
RP   INTERACTION WITH TIM10 AND TIM12.
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   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=10397776; DOI=10.1091/mbc.10.7.2461;
RA   Kurz M., Martin H., Rassow J., Pfanner N., Ryan M.T.;
RT   "Biogenesis of Tim proteins of the mitochondrial carrier import pathway:
RT   differential targeting mechanisms and crossing over with the main import
RT   pathway.";
RL   Mol. Biol. Cell 10:2461-2474(1999).
RN   [9]
RP   IDENTIFICATION IN A THE TIM22 COMPLEX WITH TIM12; TIM18 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   [10]
RP   FUNCTION.
RX   PubMed=11864609; DOI=10.1016/s1097-2765(02)00446-x;
RA   Kovermann P., Truscott K.N., Guiard B., Rehling P., Sepuri N.B.,
RA   Mueller H., Jensen R.E., Wagner R., Pfanner N.;
RT   "Tim22, the essential core of the mitochondrial protein insertion complex,
RT   forms a voltage-activated and signal-gated channel.";
RL   Mol. Cell 9:363-373(2002).
RN   [11]
RP   FUNCTION, AND IDENTIFICATION IN THE TIM22 COMPLEX WITH TIM10; TIM12; TIM18
RP   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   [12]
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   [13]
RP   DISULFIDE BOND, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX   PubMed=27265872; DOI=10.1038/srep27484;
RA   Wrobel L., Sokol A.M., Chojnacka M., Chacinska A.;
RT   "The presence of disulfide bonds reveals an evolutionarily conserved
RT   mechanism involved in mitochondrial protein translocase assembly.";
RL   Sci. Rep. 6:27484-27484(2016).
CC   -!- FUNCTION: Essential core component of the TIM22 complex, a complex that
CC       mediates the import and insertion of multi-pass transmembrane proteins,
CC       such as mitochondrial carrier family members, into the mitochondrial
CC       inner membrane. In the TIM22 complex, it constitutes the voltage-
CC       activated and signal-gated channel. Forms a twin-pore translocase that
CC       uses the membrane potential as external driving force in 2 voltage-
CC       dependent steps. Mediates the insertion of precursor proteins in a 3
CC       step process. After the precursor is tethered to the translocase
CC       without losing energy from the Delta(psi), 2 energy-requiring steps are
CC       needed. First, Delta(psi) acts on the precursor protein and promotes
CC       its docking in the translocase complex. Then, Delta(psi) and an
CC       internal signal peptide together induce rapid gating transitions in one
CC       pore and closing of the other pore and drive membrane insertion to
CC       completion. {ECO:0000269|PubMed:11864609, ECO:0000269|PubMed:12637749,
CC       ECO:0000269|PubMed:8955274}.
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). {ECO:0000269|PubMed:10648604,
CC       ECO:0000269|PubMed:12637749}.
CC   -!- INTERACTION:
CC       Q12328; P53220: TIM21; NbExp=2; IntAct=EBI-9132, EBI-23128;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000269|PubMed:10397776, ECO:0000269|PubMed:8955274,
CC       ECO:0000305|PubMed:27265872}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:10397776, ECO:0000269|PubMed:8955274}. Note=Import
CC       into inner membrane protein requires TOM20 function.
CC   -!- SIMILARITY: Belongs to the Tim17/Tim22/Tim23 family. {ECO:0000305}.
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DR   EMBL; X99000; CAA67473.1; -; Genomic_DNA.
DR   EMBL; Z74265; CAA98795.1; -; Genomic_DNA.
DR   EMBL; AY558171; AAS56497.1; -; Genomic_DNA.
DR   EMBL; BK006938; DAA11647.1; -; Genomic_DNA.
DR   PIR; S67776; S67776.
DR   RefSeq; NP_010064.1; NM_001180277.1.
DR   PDB; 6LO8; EM; 3.83 A; A=1-206.
DR   PDBsum; 6LO8; -.
DR   AlphaFoldDB; Q12328; -.
DR   EMDB; EMD-0935; -.
DR   SMR; Q12328; -.
DR   BioGRID; 31828; 581.
DR   ComplexPortal; CPX-1629; TIM22 mitochondrial inner membrane twin-pore carrier translocase complex.
DR   DIP; DIP-1142N; -.
DR   IntAct; Q12328; 6.
DR   MINT; Q12328; -.
DR   STRING; 4932.YDL217C; -.
DR   TCDB; 3.A.8.1.1; the mitochondrial protein translocase (mpt) family.
DR   MaxQB; Q12328; -.
DR   PaxDb; 4932-YDL217C; -.
DR   PeptideAtlas; Q12328; -.
DR   EnsemblFungi; YDL217C_mRNA; YDL217C; YDL217C.
DR   GeneID; 851309; -.
DR   KEGG; sce:YDL217C; -.
DR   AGR; SGD:S000002376; -.
DR   SGD; S000002376; TIM22.
DR   VEuPathDB; FungiDB:YDL217C; -.
DR   eggNOG; KOG3225; Eukaryota.
DR   GeneTree; ENSGT00390000016067; -.
DR   HOGENOM; CLU_091077_1_0_1; -.
DR   InParanoid; Q12328; -.
DR   OMA; HSYAKNF; -.
DR   OrthoDB; 47656at2759; -.
DR   BioCyc; YEAST:G3O-29598-MONOMER; -.
DR   Reactome; R-SCE-1268020; Mitochondrial protein import.
DR   BioGRID-ORCS; 851309; 5 hits in 10 CRISPR screens.
DR   PRO; PR:Q12328; -.
DR   Proteomes; UP000002311; Chromosome IV.
DR   RNAct; Q12328; Protein.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0042721; C:TIM22 mitochondrial import inner membrane insertion complex; IDA:SGD.
DR   GO; GO:0030943; F:mitochondrion targeting sequence binding; IDA:SGD.
DR   GO; GO:0008320; F:protein transmembrane transporter activity; IDA:SGD.
DR   GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:ComplexPortal.
DR   InterPro; IPR039175; TIM22.
DR   PANTHER; PTHR14110; MITOCHONDRIAL IMPORT INNER MEMBRANE TRANSLOCASE SUBUNIT TIM22; 1.
DR   PANTHER; PTHR14110:SF0; MITOCHONDRIAL IMPORT INNER MEMBRANE TRANSLOCASE SUBUNIT TIM22; 1.
DR   Pfam; PF02466; Tim17; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Protein transport; Reference proteome;
KW   Translocation; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..207
FT                   /note="Mitochondrial import inner membrane translocase
FT                   subunit TIM22"
FT                   /id="PRO_0000210301"
FT   TOPO_DOM        1..46
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000305|PubMed:27265872"
FT   TRANSMEM        47..67
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        152..172
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        173..193
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        194..207
FT                   /note="Mitochondrial intermembrane"
FT                   /evidence="ECO:0000305|PubMed:27265872"
FT   DISULFID        42..141
FT                   /evidence="ECO:0000305|PubMed:27265872"
SQ   SEQUENCE   207 AA;  21864 MW;  3C94DBF31F413968 CRC64;
     MVYTGFGLEQ ISPAQKKPYN ELTPEEQGER GAEMIMNFMT SCPGKSVVSG VTGFALGGVL
     GLFMASMAYD TPLHTPTPAN TAATATAGNI GVGGISRTVQ QISDLPFRQQ MKLQFTDMGK
     KSYSSAKNFG YIGMIYAGVE CVIESLRAKN DIYNGVTAGF FTGAGLAYKA GPQAALMGGA
     GFAAFSAAID LYMKSEDGRP PQNDFKE
//