TIM10_YEAST
ID TIM10_YEAST Reviewed; 93 AA.
AC P87108; D3DKU9;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Mitochondrial import inner membrane translocase subunit TIM10;
DE AltName: Full=Mitochondrial intermembrane protein MRS11;
GN Name=TIM10; Synonyms=MRS11; OrderedLocusNames=YHR005C-A; ORFNames=YHR005BC;
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.
RC STRAIN=ATCC 44774 / DBY747;
RX PubMed=9236772; DOI=10.1007/s004380050484;
RA Jarosch E., Rodel G., Schweyen R.J.;
RT "A soluble 12-kDa protein of the mitochondrial intermembrane space, Mrs11p,
RT is essential for mitochondrial biogenesis and viability of yeast cells.";
RL Mol. Gen. Genet. 255:157-165(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
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 PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBUNIT.
RX PubMed=9822593; DOI=10.1093/emboj/17.22.6477;
RA Koehler C.M., Merchant S., Oppliger W., Schmid K., Jarosch E., Dolfini L.,
RA Junne T., Schatz G., Tokatlidis K.;
RT "Tim9p, an essential partner subunit of Tim10p for the import of
RT mitochondrial carrier proteins.";
RL EMBO J. 17:6477-6486(1998).
RN [5]
RP PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, ZINC-BINDING WHEN PRESENT IN THE
RP CYTOSOL, AND MUTAGENESIS OF CYS-40; CYS-44; CYS-61 AND CYS-65.
RX PubMed=14973126; DOI=10.1074/jbc.m313046200;
RA Lu H., Golovanov A.P., Alcock F., Grossmann J.G., Allen S., Lian L.-Y.,
RA Tokatlidis K.;
RT "The structural basis of the TIM10 chaperone assembly.";
RL J. Biol. Chem. 279:18959-18966(2004).
RN [6]
RP FUNCTION, ZINC-BINDING, SUBCELLULAR LOCATION, AND INTERACTION WITH TIM12
RP 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, AND INTERACTION WITH TIM12 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 [8]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH TIM9 AND
RP TIM12.
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 [9]
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 [10]
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 [11]
RP FUNCTION.
RX PubMed=11483513; DOI=10.1093/emboj/20.15.4099;
RA Luciano P., Vial S., Vergnolle M.A.S., Dyall S.D., Robinson D.R.,
RA Tokatlidis K.;
RT "Functional reconstitution of the import of the yeast ADP/ATP carrier
RT mediated by the TIM10 complex.";
RL EMBO J. 20:4099-4106(2001).
RN [12]
RP FUNCTION.
RX PubMed=11509656; DOI=10.1128/mcb.21.18.6132-6138.2001;
RA Murphy M.P., Leuenberger D., Curran S.P., Oppliger W., Koehler C.M.;
RT "The essential function of the small Tim proteins in the TIM22 import
RT pathway does not depend on formation of the soluble 70-kilodalton
RT complex.";
RL Mol. Cell. Biol. 21:6132-6138(2001).
RN [13]
RP SUBUNIT, DISULFIDE BONDS, AND LACK OF ZINC-BINDING WHEN PRESENT IN THE
RP MITOCHONDRIAL INTERMEMBRANE SPACE.
RX PubMed=11867522; DOI=10.1093/emboj/21.5.942;
RA Curran S.P., Leuenberger D., Oppliger W., Koehler C.M.;
RT "The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP
RT carrier.";
RL EMBO J. 21:942-953(2002).
RN [14]
RP FUNCTION, AND SUBUNIT.
RX PubMed=12138093; DOI=10.1074/jbc.m202310200;
RA Vial S., Lu H., Allen S., Savory P., Thornton D., Sheehan J.,
RA Tokatlidis K.;
RT "Assembly of Tim9 and Tim10 into a functional chaperone.";
RL J. Biol. Chem. 277:36100-36108(2002).
RN [15]
RP FUNCTION.
RX PubMed=12391147; DOI=10.1128/mcb.22.22.7780-7789.2002;
RA Truscott K.N., Wiedemann N., Rehling P., Mueller H., Meisinger C.,
RA Pfanner N., Guiard B.;
RT "Mitochondrial import of the ADP/ATP carrier: the essential TIM complex of
RT the intermembrane space is required for precursor release from the TOM
RT complex.";
RL Mol. Cell. Biol. 22:7780-7789(2002).
RN [16]
RP FUNCTION, AND IDENTIFICATION IN THE TIM22 COMPLEX WITH TIM12; TIM18; TIM22
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 [17]
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 [18]
RP DISULFIDE BONDS, AND MUTAGENESIS OF CYS-40; CYS-44; CYS-61 AND CYS-65.
RX PubMed=12882976; DOI=10.1074/jbc.m306027200;
RA Allen S., Lu H., Thornton D., Tokatlidis K.;
RT "Juxtaposition of the two distal CX3C motifs via intrachain disulfide
RT bonding is essential for the folding of Tim10.";
RL J. Biol. Chem. 278:38505-38513(2003).
RN [19]
RP FUNCTION IN TRANSFER OF BETA-BARREL PROTEINS.
RX PubMed=14978039; DOI=10.1074/jbc.m400050200;
RA Wiedemann N., Truscott K.N., Pfannschmidt S., Guiard B., Meisinger C.,
RA Pfanner N.;
RT "Biogenesis of the protein import channel Tom40 of the mitochondrial outer
RT membrane: intermembrane space components are involved in an early stage of
RT the assembly pathway.";
RL J. Biol. Chem. 279:18188-18194(2004).
RN [20]
RP DISULFIDE BONDS.
RX PubMed=14973127; DOI=10.1074/jbc.m313045200;
RA Lu H., Allen S., Wardleworth L., Savory P., Tokatlidis K.;
RT "Functional TIM10 chaperone assembly is redox-regulated in vivo.";
RL J. Biol. Chem. 279:18952-18958(2004).
RN [21]
RP FUNCTION.
RX PubMed=16039669; DOI=10.1016/j.jmb.2005.06.010;
RA Vergnolle M.A.S., Baud C., Golovanov A.P., Alcock F., Luciano P.,
RA Lian L.-Y., Tokatlidis K.;
RT "Distinct domains of small Tims involved in subunit interaction and
RT substrate recognition.";
RL J. Mol. Biol. 351:839-849(2005).
RN [22]
RP ZINC-BINDING.
RX PubMed=16199054; DOI=10.1016/j.jmb.2005.09.002;
RA Lu H., Woodburn J.;
RT "Zinc binding stabilizes mitochondrial Tim10 in a reduced and import-
RT competent state kinetically.";
RL J. Mol. Biol. 353:897-910(2005).
RN [23]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=16823961; DOI=10.1021/pr050477f;
RA Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A.;
RT "Toward the complete yeast mitochondrial proteome: multidimensional
RT separation techniques for mitochondrial proteomics.";
RL J. Proteome Res. 5:1543-1554(2006).
RN [24]
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).
CC -!- FUNCTION: Mitochondrial intermembrane chaperone that participates in
CC the import and insertion of multi-pass transmembrane proteins into the
CC mitochondrial inner membrane. Also required for the transfer of beta-
CC barrel precursors from the TOM complex to the sorting and assembly
CC machinery (SAM complex) of the outer membrane. Acts as a chaperone-like
CC protein that protects the hydrophobic precursors from aggregation and
CC guide them through the mitochondrial intermembrane space. Compared to
CC TIM9, it may function as a substrate sensor.
CC {ECO:0000269|PubMed:10369662, ECO:0000269|PubMed:10995434,
CC ECO:0000269|PubMed:11483513, ECO:0000269|PubMed:11509656,
CC ECO:0000269|PubMed:12138093, ECO:0000269|PubMed:12391147,
CC ECO:0000269|PubMed:12637749, ECO:0000269|PubMed:14978039,
CC ECO:0000269|PubMed:16039669, ECO:0000269|PubMed:8955274,
CC ECO:0000269|PubMed:9430585, ECO:0000269|PubMed:9822593,
CC ECO:0000269|PubMed:9889188}.
CC -!- SUBUNIT: Heterohexamer; composed of 3 copies of TIM9 and 3 copies of
CC TIM10, named soluble 70 kDa complex. Associates directly with the TIM12
CC component of the TIM22 complex, whose core is composed of TIM18, TIM22
CC and TIM54. Interacts with the transmembrane regions of multi-pass
CC transmembrane proteins in transit. {ECO:0000269|PubMed:11867522,
CC ECO:0000269|PubMed:12138093, ECO:0000269|PubMed:12637749,
CC ECO:0000269|PubMed:8955274, ECO:0000269|PubMed:9430585,
CC ECO:0000269|PubMed:9822593, ECO:0000269|PubMed:9889188}.
CC -!- INTERACTION:
CC P87108; P32830: TIM12; NbExp=3; IntAct=EBI-9115, EBI-11303;
CC P87108; Q08749: TIM18; NbExp=2; IntAct=EBI-9115, EBI-30499;
CC P87108; O74700: TIM9; NbExp=7; IntAct=EBI-9115, EBI-9108;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:16823961, ECO:0000269|PubMed:8955274,
CC ECO:0000269|PubMed:9236772, ECO:0000269|PubMed:9889188}; Peripheral
CC membrane protein {ECO:0000269|PubMed:16823961,
CC ECO:0000269|PubMed:8955274, ECO:0000269|PubMed:9236772,
CC ECO:0000269|PubMed:9889188}; Intermembrane side
CC {ECO:0000269|PubMed:16823961, ECO:0000269|PubMed:8955274,
CC ECO:0000269|PubMed:9236772, ECO:0000269|PubMed:9889188}. Mitochondrion
CC intermembrane space {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 TIM10 from cytoplasm into mitochondrion, the Cys
CC residues probably coordinate zinc, thereby preventing folding and
CC allowing its transfer across mitochondrial outer membrane.
CC {ECO:0000269|PubMed:12882976}.
CC -!- SIMILARITY: Belongs to the small Tim family. {ECO:0000305}.
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DR EMBL; Z80875; CAB02581.1; -; Genomic_DNA.
DR EMBL; U10555; AAB68435.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06693.1; -; Genomic_DNA.
DR PIR; S72314; S72314.
DR RefSeq; NP_011869.1; NM_001181427.1.
DR PDB; 3DXR; X-ray; 2.50 A; B=1-93.
DR PDB; 6LO8; EM; 3.83 A; H/J=1-93.
DR PDBsum; 3DXR; -.
DR PDBsum; 6LO8; -.
DR AlphaFoldDB; P87108; -.
DR SASBDB; P87108; -.
DR SMR; P87108; -.
DR BioGRID; 36431; 35.
DR ComplexPortal; CPX-1629; TIM22 mitochondrial inner membrane twin-pore carrier translocase complex.
DR ComplexPortal; CPX-2268; TIM9-TIM10 mitochondrial intermembrane space protein transporter complex.
DR ComplexPortal; CPX-2950; TIM9-TIM10-TIM12 mitochondrial intermembrane space protein transporter complex.
DR DIP; DIP-1141N; -.
DR IntAct; P87108; 6.
DR MINT; P87108; -.
DR STRING; 4932.YHR005C-A; -.
DR BindingDB; P87108; -.
DR ChEMBL; CHEMBL1741194; -.
DR TCDB; 3.A.8.1.1; the mitochondrial protein translocase (mpt) family.
DR iPTMnet; P87108; -.
DR MaxQB; P87108; -.
DR PaxDb; P87108; -.
DR PRIDE; P87108; -.
DR EnsemblFungi; YHR005C-A_mRNA; YHR005C-A; YHR005C-A.
DR GeneID; 856395; -.
DR KEGG; sce:YHR005C-A; -.
DR SGD; S000003530; TIM10.
DR VEuPathDB; FungiDB:YHR005C-A; -.
DR eggNOG; KOG3480; Eukaryota.
DR GeneTree; ENSGT00390000003068; -.
DR HOGENOM; CLU_162151_1_0_1; -.
DR InParanoid; P87108; -.
DR OMA; ELEIEMM; -.
DR BioCyc; YEAST:G3O-31244-MON; -.
DR Reactome; R-SCE-1268020; Mitochondrial protein import.
DR EvolutionaryTrace; P87108; -.
DR PRO; PR:P87108; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P87108; protein.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:ComplexPortal.
DR GO; GO:0042719; C:mitochondrial intermembrane space protein transporter complex; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:ComplexPortal.
DR GO; GO:0042721; C:TIM22 mitochondrial import inner membrane insertion complex; IPI:ComplexPortal.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140318; F:protein transporter activity; IDA:SGD.
DR GO; GO:0051082; F:unfolded protein binding; IDA:SGD.
DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:SGD.
DR Gene3D; 1.10.287.810; -; 1.
DR InterPro; IPR027100; Tim10.
DR InterPro; IPR004217; Tim10-like.
DR InterPro; IPR035427; Tim10-like_dom_sf.
DR PANTHER; PTHR11038:SF16; PTHR11038:SF16; 1.
DR Pfam; PF02953; zf-Tim10_DDP; 1.
DR SUPFAM; SSF144122; SSF144122; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Direct protein sequencing; Disulfide bond;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Protein transport; Reference proteome; Translocation; Transport; Zinc.
FT CHAIN 1..93
FT /note="Mitochondrial import inner membrane translocase
FT subunit TIM10"
FT /id="PRO_0000193622"
FT REGION 1..31
FT /note="Interaction with transmembrane regions of
FT transmembrane proteins in transit"
FT REGION 73..93
FT /note="Required for heterohexamerization"
FT MOTIF 40..65
FT /note="Twin CX3C motif"
FT DISULFID 40..65
FT /evidence="ECO:0000269|PubMed:11867522,
FT ECO:0000269|PubMed:12882976, ECO:0000269|PubMed:14973126,
FT ECO:0000269|PubMed:14973127"
FT DISULFID 44..61
FT /evidence="ECO:0000269|PubMed:11867522,
FT ECO:0000269|PubMed:12882976, ECO:0000269|PubMed:14973126,
FT ECO:0000269|PubMed:14973127"
FT MUTAGEN 40
FT /note="C->S: Induces impairment in folding and loss of
FT zinc-binding."
FT /evidence="ECO:0000269|PubMed:12882976,
FT ECO:0000269|PubMed:14973126"
FT MUTAGEN 44
FT /note="C->S: Loss of function due to severely affected
FT folding and the presence of non-native disulfide bonds;
FT loss of zinc-binding."
FT /evidence="ECO:0000269|PubMed:12882976,
FT ECO:0000269|PubMed:14973126"
FT MUTAGEN 61
FT /note="C->S: Loss of function due to severely affected
FT folding and the presence of non-native disulfide bonds;
FT loss of zinc-binding."
FT /evidence="ECO:0000269|PubMed:12882976,
FT ECO:0000269|PubMed:14973126"
FT MUTAGEN 65
FT /note="C->S: Induces impairment in folding and loss of
FT zinc-binding."
FT /evidence="ECO:0000269|PubMed:12882976,
FT ECO:0000269|PubMed:14973126"
FT TURN 16..19
FT /evidence="ECO:0007829|PDB:3DXR"
FT HELIX 20..44
FT /evidence="ECO:0007829|PDB:3DXR"
FT HELIX 56..82
FT /evidence="ECO:0007829|PDB:3DXR"
SQ SEQUENCE 93 AA; 10305 MW; 70DD4764B944FF17 CRC64;
MSFLGFGGGQ PQLSSQQKIQ AAEAELDLVT DMFNKLVNNC YKKCINTSYS EGELNKNESS
CLDRCVAKYF ETNVQVGENM QKMGQSFNAA GKF
