TOM40_HUMAN
ID TOM40_HUMAN Reviewed; 361 AA.
AC O96008; A0A024R0P9; Q86VW4; Q8WY09; Q8WY10; Q8WY11; Q9BR95;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Mitochondrial import receptor subunit TOM40 homolog;
DE AltName: Full=Protein Haymaker;
DE AltName: Full=Translocase of outer membrane 40 kDa subunit homolog;
DE AltName: Full=p38.5;
GN Name=TOMM40; Synonyms=C19orf1, PEREC1, TOM40;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10520737; DOI=10.3109/10425179809086433;
RA Freitas E.M., Zhang W.J., Lalonde J.P., Tay G.K., Gaudieri S.,
RA Ashworth L.K., Van Bockxmeer F.M., Dawkins R.L.;
RT "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene:
RT PEREC1.";
RL DNA Seq. 9:89-100(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RA Yoshiura K., Murray J.C.;
RT "A transcriptional map in the region of 19q13 derived using direct
RT sequencing and exon trapping.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lymphocyte;
RX PubMed=11745481; DOI=10.1002/ijc.1555;
RA Das B., Tao S.-Z., Mushnitsky R., Norin A.J.;
RT "Genetic identity and differential expression of p38.5 (Haymaker) in human
RT malignant and non-malignant cells.";
RL Int. J. Cancer 94:800-806(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, Lung, Skin, Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 185-195 AND 332-348, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP IDENTIFICATION IN THE TOM COMPLEX WITH TOMM7; TOMM20 AND TOMM22.
RX PubMed=12198123; DOI=10.1074/jbc.m205613200;
RA Johnston A.J., Hoogenraad J., Dougan D.A., Truscott K.N., Yano M., Mori M.,
RA Hoogenraad N.J., Ryan M.T.;
RT "Insertion and assembly of human tom7 into the preprotein translocase
RT complex of the outer mitochondrial membrane.";
RL J. Biol. Chem. 277:42197-42204(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE TOM COMPLEX WITH
RP TOMM20; TOMM22 AND TOMM70.
RX PubMed=15644312; DOI=10.1074/jbc.m413816200;
RA Humphries A.D., Streimann I.C., Stojanovski D., Johnston A.J., Yano M.,
RA Hoogenraad N.J., Ryan M.T.;
RT "Dissection of the mitochondrial import and assembly pathway for human
RT Tom40.";
RL J. Biol. Chem. 280:11535-11543(2005).
RN [9]
RP IDENTIFICATION IN THE TOM COMPLEX.
RX PubMed=18331822; DOI=10.1016/j.bbrc.2008.02.150;
RA Kato H., Mihara K.;
RT "Identification of Tom5 and Tom6 in the preprotein translocase complex of
RT human mitochondrial outer membrane.";
RL Biochem. Biophys. Res. Commun. 369:958-963(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP INTERACTION WITH TIMM29.
RX PubMed=27554484; DOI=10.7554/elife.17463;
RA Kang Y., Baker M.J., Liem M., Louber J., McKenzie M., Atukorala I.,
RA Ang C.S., Keerthikumar S., Mathivanan S., Stojanovski D.;
RT "Tim29 is a novel subunit of the human TIM22 translocase and is involved in
RT complex assembly and stability.";
RL Elife 5:0-0(2016).
RN [14]
RP FUNCTION, INTERACTION WITH BCAP31 AND NDUFS4, AND SUBCELLULAR LOCATION.
RX PubMed=31206022; DOI=10.1126/sciadv.aaw1386;
RA Namba T.;
RT "BAP31 regulates mitochondrial function via interaction with Tom40 within
RT ER-mitochondria contact sites.";
RL Sci. Adv. 5:eaaw1386-eaaw1386(2019).
CC -!- FUNCTION: Channel-forming protein essential for import of protein
CC precursors into mitochondria (PubMed:15644312, PubMed:31206022). Plays
CC a role in the assembly of the mitochondrial membrane respiratory chain
CC NADH dehydrogenase (Complex I) by forming a complex with BCAP31 and
CC mediating the translocation of Complex I components from the cytosol to
CC the mitochondria (PubMed:31206022). {ECO:0000269|PubMed:15644312,
CC ECO:0000269|PubMed:31206022}.
CC -!- SUBUNIT: Forms part of the preprotein translocase complex of the outer
CC mitochondrial membrane (TOM complex) which consists of at least 7
CC different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and
CC TOMM70). Interacts with mitochondrial targeting sequences
CC (PubMed:12198123, PubMed:15644312, PubMed:18331822). Interacts with
CC TIMM29; linking the TIM22 complex to the TOM complex (PubMed:27554484).
CC Forms a complex with BCAP31 (via C-terminus) which mediates the
CC translocation of components of the mitochondrial membrane respiratory
CC chain NADH dehydrogenase (Complex I) from the cytosol to the
CC mitochondria (PubMed:31206022). Interacts (via N-terminus) with CYP1A1
CC (via mitochondrial targeting signal); this interaction is required for
CC CYP1A1 translocation across the mitochondrial outer membrane (By
CC similarity). {ECO:0000250|UniProtKB:Q75Q40,
CC ECO:0000269|PubMed:12198123, ECO:0000269|PubMed:15644312,
CC ECO:0000269|PubMed:18331822, ECO:0000269|PubMed:27554484,
CC ECO:0000269|PubMed:31206022}.
CC -!- INTERACTION:
CC O96008; Q2TAZ0: ATG2A; NbExp=7; IntAct=EBI-1057581, EBI-2514077;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:15644312, ECO:0000269|PubMed:31206022}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Associates with the mitochondria-
CC associated ER membrane via interaction with BCAP31.
CC {ECO:0000269|PubMed:31206022}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O96008-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O96008-2; Sequence=VSP_008589, VSP_008590;
CC -!- SIMILARITY: Belongs to the Tom40 family. {ECO:0000305}.
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DR EMBL; AF050154; AAD02504.1; -; Genomic_DNA.
DR EMBL; AF043250; AAC82342.1; -; mRNA.
DR EMBL; AF043253; AAC82343.1; -; Genomic_DNA.
DR EMBL; AF043251; AAC82343.1; JOINED; Genomic_DNA.
DR EMBL; AF043252; AAC82343.1; JOINED; Genomic_DNA.
DR EMBL; AF316398; AAL46624.1; -; mRNA.
DR EMBL; AF316399; AAL46625.1; -; mRNA.
DR EMBL; AF316401; AAL46626.1; -; mRNA.
DR EMBL; AF316402; AAL46627.1; -; mRNA.
DR EMBL; CH471126; EAW57302.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57304.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57305.1; -; Genomic_DNA.
DR EMBL; BC001779; AAH01779.1; -; mRNA.
DR EMBL; BC006413; AAH06413.1; -; mRNA.
DR EMBL; BC012134; AAH12134.1; -; mRNA.
DR EMBL; BC017224; AAH17224.1; -; mRNA.
DR EMBL; BC047528; AAH47528.1; -; mRNA.
DR CCDS; CCDS12646.1; -. [O96008-1]
DR RefSeq; NP_001122388.1; NM_001128916.1. [O96008-1]
DR RefSeq; NP_001122389.1; NM_001128917.1. [O96008-1]
DR RefSeq; NP_006105.1; NM_006114.2. [O96008-1]
DR PDB; 7CK6; EM; 3.40 A; A/B=1-361.
DR PDB; 7CP9; EM; 3.00 A; I/J=1-361.
DR PDBsum; 7CK6; -.
DR PDBsum; 7CP9; -.
DR AlphaFoldDB; O96008; -.
DR SMR; O96008; -.
DR BioGRID; 115716; 311.
DR ComplexPortal; CPX-6121; TOM40 mitochondrial outer membrane translocase complex.
DR CORUM; O96008; -.
DR IntAct; O96008; 54.
DR MINT; O96008; -.
DR STRING; 9606.ENSP00000410339; -.
DR ChEMBL; CHEMBL4523158; -.
DR TCDB; 1.B.8.2.5; the mitochondrial and plastid porin (mpp) family.
DR GlyGen; O96008; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O96008; -.
DR MetOSite; O96008; -.
DR PhosphoSitePlus; O96008; -.
DR SwissPalm; O96008; -.
DR BioMuta; TOMM40; -.
DR REPRODUCTION-2DPAGE; IPI00014053; -.
DR EPD; O96008; -.
DR jPOST; O96008; -.
DR MassIVE; O96008; -.
DR MaxQB; O96008; -.
DR PaxDb; O96008; -.
DR PeptideAtlas; O96008; -.
DR PRIDE; O96008; -.
DR ProteomicsDB; 51187; -. [O96008-1]
DR ProteomicsDB; 51188; -. [O96008-2]
DR TopDownProteomics; O96008-1; -. [O96008-1]
DR Antibodypedia; 3972; 160 antibodies from 35 providers.
DR DNASU; 10452; -.
DR Ensembl; ENST00000252487.9; ENSP00000252487.4; ENSG00000130204.13. [O96008-1]
DR Ensembl; ENST00000405636.6; ENSP00000385184.2; ENSG00000130204.13. [O96008-1]
DR Ensembl; ENST00000426677.7; ENSP00000410339.1; ENSG00000130204.13. [O96008-1]
DR Ensembl; ENST00000592434.5; ENSP00000466084.1; ENSG00000130204.13. [O96008-2]
DR GeneID; 10452; -.
DR KEGG; hsa:10452; -.
DR MANE-Select; ENST00000426677.7; ENSP00000410339.1; NM_001128917.2; NP_001122389.1.
DR UCSC; uc002ozx.4; human. [O96008-1]
DR CTD; 10452; -.
DR DisGeNET; 10452; -.
DR GeneCards; TOMM40; -.
DR HGNC; HGNC:18001; TOMM40.
DR HPA; ENSG00000130204; Low tissue specificity.
DR MalaCards; TOMM40; -.
DR MIM; 608061; gene.
DR neXtProt; NX_O96008; -.
DR OpenTargets; ENSG00000130204; -.
DR Orphanet; 1020; Early-onset autosomal dominant Alzheimer disease.
DR PharmGKB; PA38274; -.
DR VEuPathDB; HostDB:ENSG00000130204; -.
DR eggNOG; KOG3296; Eukaryota.
DR GeneTree; ENSGT00390000003308; -.
DR HOGENOM; CLU_054399_0_0_1; -.
DR InParanoid; O96008; -.
DR OMA; SHQFAMG; -.
DR OrthoDB; 1346842at2759; -.
DR PhylomeDB; O96008; -.
DR TreeFam; TF106204; -.
DR PathwayCommons; O96008; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR SignaLink; O96008; -.
DR SIGNOR; O96008; -.
DR BioGRID-ORCS; 10452; 749 hits in 1087 CRISPR screens.
DR ChiTaRS; TOMM40; human.
DR GeneWiki; TOMM40; -.
DR GenomeRNAi; 10452; -.
DR Pharos; O96008; Tbio.
DR PRO; PR:O96008; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O96008; protein.
DR Bgee; ENSG00000130204; Expressed in olfactory bulb and 208 other tissues.
DR ExpressionAtlas; O96008; baseline and differential.
DR Genevisible; O96008; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISS:BHF-UCL.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:CAFA.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005742; C:mitochondrial outer membrane translocase complex; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0008320; F:protein transmembrane transporter activity; ISS:BHF-UCL.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0030150; P:protein import into mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IC:ComplexPortal.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:UniProtKB.
DR CDD; cd07305; Porin3_Tom40; 1.
DR Gene3D; 2.40.160.10; -; 1.
DR InterPro; IPR023614; Porin_dom_sf.
DR InterPro; IPR027246; Porin_Euk/Tom40.
DR InterPro; IPR037930; Tom40.
DR PANTHER; PTHR10802; PTHR10802; 1.
DR Pfam; PF01459; Porin_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Ion transport; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Porin; Protein transport; Reference proteome; Transmembrane;
KW Transmembrane beta strand; Transport.
FT CHAIN 1..361
FT /note="Mitochondrial import receptor subunit TOM40 homolog"
FT /id="PRO_0000051523"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..37
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 317..329
FT /note="SVDSNWIVGATLE -> KGLGSPTRETGRR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008589"
FT VAR_SEQ 330..361
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008590"
FT CONFLICT 49
FT /note="S -> R (in Ref. 5; AAH06413)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="A -> S (in Ref. 3; AAL46625)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="H -> R (in Ref. 3; AAL46624)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="N -> S (in Ref. 3; AAL46626)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="T -> A (in Ref. 3; AAL46626)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="L -> F (in Ref. 3; AAL46624)"
FT /evidence="ECO:0000305"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 114..121
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 128..136
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:7CK6"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 169..181
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 184..196
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 199..207
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 215..224
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 229..240
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 243..255
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 282..291
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 296..307
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 308..311
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 312..319
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 322..332
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 337..346
FT /evidence="ECO:0007829|PDB:7CP9"
FT TURN 347..350
FT /evidence="ECO:0007829|PDB:7CP9"
FT STRAND 351..359
FT /evidence="ECO:0007829|PDB:7CP9"
SQ SEQUENCE 361 AA; 37893 MW; CFE55E01F8003D32 CRC64;
MGNVLAASSP PAGPPPPPAP ALVGLPPPPP SPPGFTLPPL GGSLGAGTST SRSSERTPGA
ATASASGAAE DGACGCLPNP GTFEECHRKC KELFPIQMEG VKLTVNKGLS NHFQVNHTVA
LSTIGESNYH FGVTYVGTKQ LSPTEAFPVL VGDMDNSGSL NAQVIHQLGP GLRSKMAIQT
QQSKFVNWQV DGEYRGSDFT AAVTLGNPDV LVGSGILVAH YLQSITPCLA LGGELVYHRR
PGEEGTVMSL AGKYTLNNWL ATVTLGQAGM HATYYHKASD QLQVGVEFEA STRMQDTSVS
FGYQLDLPKA NLLFKGSVDS NWIVGATLEK KLPPLPLTLA LGAFLNHRKN KFQCGFGLTI
G
