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 27-MAR-2024, entry version 189. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7VBY; EM; 2.54 A; B/I=1-361. DR PDB; 7VC4; EM; 3.74 A; B/I=1-361. DR PDB; 7VD2; EM; 2.53 A; B/I=1-361. DR PDB; 7VDD; EM; 3.74 A; B/I=1-361. DR PDBsum; 7CK6; -. DR PDBsum; 7CP9; -. DR PDBsum; 7VBY; -. DR PDBsum; 7VC4; -. DR PDBsum; 7VD2; -. DR PDBsum; 7VDD; -. DR AlphaFoldDB; O96008; -. DR EMDB; EMD-30382; -. DR EMDB; EMD-30421; -. DR EMDB; EMD-31888; -. DR EMDB; EMD-31904; -. DR EMDB; EMD-31914; -. DR SMR; O96008; -. DR BioGRID; 115716; 330. DR ComplexPortal; CPX-6121; TOM40 mitochondrial outer membrane translocase complex. DR CORUM; O96008; -. DR IntAct; O96008; 57. 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; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000410339; -. DR PeptideAtlas; O96008; -. DR ProteomicsDB; 51187; -. [O96008-1] DR ProteomicsDB; 51188; -. [O96008-2] DR Pumba; O96008; -. DR TopDownProteomics; O96008-1; -. [O96008-1] DR Antibodypedia; 3972; 194 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 AGR; HGNC:18001; -. 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; TRFNYRW; -. DR OrthoDB; 5489886at2759; -. 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; 780 hits in 1166 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 210 other cell types or tissues. DR ExpressionAtlas; O96008; baseline and differential. DR Genevisible; O96008; HS. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA: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; ISS:BHF-UCL. 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:0140596; C:TOM complex; NAS:ComplexPortal. 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:monoatomic 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; NAS:ComplexPortal. DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:UniProtKB. DR CDD; cd07305; Porin3_Tom40; 1. DR Gene3D; 2.40.160.10; Porin; 1. DR InterPro; IPR023614; Porin_dom_sf. DR InterPro; IPR027246; Porin_Euk/Tom40. DR InterPro; IPR037930; Tom40. DR PANTHER; PTHR10802; MITOCHONDRIAL IMPORT RECEPTOR SUBUNIT TOM40; 1. DR PANTHER; PTHR10802:SF1; MITOCHONDRIAL IMPORT RECEPTOR SUBUNIT TOM40 HOMOLOG; 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 83..85 FT /evidence="ECO:0007829|PDB:7VD2" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 100..121 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 128..139 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 141..144 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 147..155 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:7CP9" FT STRAND 160..169 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 172..183 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 185..195 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 197..209 FT /evidence="ECO:0007829|PDB:7VD2" FT TURN 210..213 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 214..240 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 243..255 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 257..277 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 279..291 FT /evidence="ECO:0007829|PDB:7VD2" FT TURN 292..295 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 296..307 FT /evidence="ECO:0007829|PDB:7VD2" FT HELIX 308..310 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 312..319 FT /evidence="ECO:0007829|PDB:7VD2" FT TURN 320..322 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 323..331 FT /evidence="ECO:0007829|PDB:7VD2" FT TURN 333..336 FT /evidence="ECO:0007829|PDB:7VBY" FT STRAND 338..346 FT /evidence="ECO:0007829|PDB:7VD2" FT TURN 347..350 FT /evidence="ECO:0007829|PDB:7VD2" FT STRAND 351..359 FT /evidence="ECO:0007829|PDB:7VD2" 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 //