TMM70_HUMAN
ID TMM70_HUMAN Reviewed; 260 AA.
AC Q9BUB7; E9PDY9; Q9NWY5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Transmembrane protein 70, mitochondrial {ECO:0000305};
DE Flags: Precursor;
GN Name=TMEM70 {ECO:0000312|HGNC:HGNC:26050};
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 [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS ALA-250
RP AND GLU-259.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [4]
RP FUNCTION, AND INVOLVEMENT IN MC5DN2.
RX PubMed=18953340; DOI=10.1038/ng.246;
RA Cizkova A., Stranecky V., Mayr J.A., Tesarova M., Havlickova V., Paul J.,
RA Ivanek R., Kuss A.W., Hansikova H., Kaplanova V., Vrbacky M.,
RA Hartmannova H., Noskova L., Honzik T., Drahota Z., Magner M.,
RA Hejzlarova K., Sperl W., Zeman J., Houstek J., Kmoch S.;
RT "TMEM70 mutations cause isolated ATP synthase deficiency and neonatal
RT mitochondrial encephalocardiomyopathy.";
RL Nat. Genet. 40:1288-1290(2008).
RN [5]
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20937241; DOI=10.1016/j.bbabio.2010.10.005;
RA Hejzlarova K., Tesarova M., Vrbacka-Cizkova A., Vrbacky M., Hartmannova H.,
RA Kaplanova V., Noskova L., Kratochvilova H., Buzkova J., Havlickova V.,
RA Zeman J., Kmoch S., Houstek J.;
RT "Expression and processing of the TMEM70 protein.";
RL Biochim. Biophys. Acta 1807:144-149(2011).
RN [7]
RP TOPOLOGY, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=24576557; DOI=10.1016/j.mito.2014.02.010;
RA Kratochvilova H., Hejzlarova K., Vrbacky M., Mracek T., Karbanova V.,
RA Tesarova M., Gombitova A., Cmarko D., Wittig I., Zeman J., Houstek J.;
RT "Mitochondrial membrane assembly of TMEM70 protein.";
RL Mitochondrion 15:1-9(2014).
RN [8]
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 [9]
RP TISSUE SPECIFICITY, INTERACTION WITH ATP5MC1, AND FUNCTION.
RX PubMed=31652072; DOI=10.1096/fj.201900685rr;
RA Kovalcikova J., Vrbacky M., Pecina P., Tauchmannova K., Nuskova H.,
RA Kaplanova V., Brazdova A., Alan L., Elias J., Cunatova K., Korinek V.,
RA Sedlacek R., Mracek T., Houstek J.;
RT "TMEM70 facilitates biogenesis of mammalian ATP synthase by promoting
RT subunit c incorporation into the rotor structure of the enzyme.";
RL FASEB J. 33:14103-14117(2019).
RN [10]
RP FUNCTION.
RX PubMed=32275929; DOI=10.1016/j.bbabio.2020.148202;
RA Sanchez-Caballero L., Elurbe D.M., Baertling F., Guerrero-Castillo S.,
RA van den Brand M., van Strien J., van Dam T.J.P., Rodenburg R., Brandt U.,
RA Huynen M.A., Nijtmans L.G.J.;
RT "TMEM70 functions in the assembly of complexes I and V.";
RL Biochim. Biophys. Acta 1861:148202-148202(2020).
RN [11]
RP SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, AND INTERACTION WITH ATP5MC1.
RX PubMed=33359711; DOI=10.1016/j.bbamcr.2020.118942;
RA Bahri H., Buratto J., Rojo M., Dompierre J.P., Salin B., Blancard C.,
RA Cuvellier S., Rose M., Ben Ammar Elgaaied A., Tetaud E., di Rago J.P.,
RA Devin A., Duvezin-Caubet S.;
RT "TMEM70 forms oligomeric scaffolds within mitochondrial cristae promoting
RT in situ assembly of mammalian ATP synthase proton channel.";
RL Biochim. Biophys. Acta 1868:118942-118942(2021).
RN [12]
RP INTERACTION WITH ATP5MC3; TMEM242; ACAD9; ECSIT; NDUFAF1; TMEM126B AND
RP TIMMDC1, AND FUNCTION.
RX PubMed=33753518; DOI=10.1073/pnas.2100558118;
RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.;
RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase
RT and interact with assembly factors for complex I.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [13]
RP VARIANT MC5DN2 PRO-210.
RX PubMed=22986587; DOI=10.1007/s10048-012-0343-8;
RA Torraco A., Verrigni D., Rizza T., Meschini M.C., Vazquez-Memije M.E.,
RA Martinelli D., Bianchi M., Piemonte F., Dionisi-Vici C., Santorelli F.M.,
RA Bertini E., Carrozzo R.;
RT "TMEM70: a mutational hot spot in nuclear ATP synthase deficiency with a
RT pivotal role in complex V biogenesis.";
RL Neurogenetics 13:375-386(2012).
CC -!- FUNCTION: Scaffold protein that participates in the c-ring assembly of
CC mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by
CC facilitating the membrane insertion and oligomer formation of the
CC subunit c/ATP5MC1 through its interaction (PubMed:31652072,
CC PubMed:33753518, PubMed:33359711, PubMed:32275929). Therefore,
CC participates in the early stage of mitochondrial ATP synthase
CC biogenesis and also protects subunit c/ATP5MC1 against
CC intramitochondrial proteolysis (PubMed:33359711, PubMed:18953340,
CC PubMed:20937241, PubMed:31652072). In addition, binds the mitochondrial
CC proton-transporting ATP synthase complexes I and may play a role in the
CC stability of its membrane-bound subassemblies (PubMed:32275929).
CC {ECO:0000269|PubMed:18953340, ECO:0000269|PubMed:20937241,
CC ECO:0000269|PubMed:31652072, ECO:0000269|PubMed:32275929,
CC ECO:0000269|PubMed:33359711, ECO:0000269|PubMed:33753518}.
CC -!- SUBUNIT: Homooligomer (PubMed:24576557, PubMed:33359711). Interacts
CC (homooligomer form) with ATP5MC1; this interaction facilitates the
CC oligomer formation of subunit c/ATP5MC1 (c-ring) and the c-ring
CC membrane insertion and also protects ATP5MC1 against intramitochondrial
CC proteolysis (PubMed:31652072, PubMed:33359711). Interacts with the core
CC subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 of the MCIA complex
CC (PubMed:33753518). Interacts with ATP5MC3, TMEM242 AND TIMMDC1
CC (PubMed:33753518). {ECO:0000269|PubMed:24576557,
CC ECO:0000269|PubMed:31652072, ECO:0000269|PubMed:33359711,
CC ECO:0000269|PubMed:33753518}.
CC -!- INTERACTION:
CC Q9BUB7; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-726363, EBI-12033434;
CC Q9BUB7; P61019: RAB2A; NbExp=3; IntAct=EBI-726363, EBI-752037;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20937241, ECO:0000269|PubMed:24576557,
CC ECO:0000269|PubMed:33359711}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20937241, ECO:0000269|PubMed:24576557}. Note=Mostly
CC located within the inner cristae membrane.
CC {ECO:0000269|PubMed:33359711}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9BUB7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BUB7-2; Sequence=VSP_020759;
CC Name=3;
CC IsoId=Q9BUB7-3; Sequence=VSP_054227, VSP_054228;
CC -!- TISSUE SPECIFICITY: Lower expressed in the heart than in the liver (at
CC protein level). {ECO:0000269|PubMed:31652072}.
CC -!- DISEASE: Mitochondrial complex V deficiency, nuclear type 2 (MC5DN2)
CC [MIM:614052]: A mitochondrial disorder with heterogeneous clinical
CC manifestations including dysmorphic features, psychomotor retardation,
CC hypotonia, growth retardation, cardiomyopathy, enlarged liver,
CC hypoplastic kidneys and elevated lactate levels in urine, plasma and
CC cerebrospinal fluid. {ECO:0000269|PubMed:18953340,
CC ECO:0000269|PubMed:22986587}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TMEM70 family. {ECO:0000305}.
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DR EMBL; AK000540; BAA91240.1; -; mRNA.
DR EMBL; AC022868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002748; AAH02748.2; -; mRNA.
DR CCDS; CCDS47876.1; -. [Q9BUB7-3]
DR CCDS; CCDS6215.1; -. [Q9BUB7-1]
DR RefSeq; NP_001035703.1; NM_001040613.2. [Q9BUB7-3]
DR RefSeq; NP_060336.3; NM_017866.5. [Q9BUB7-1]
DR AlphaFoldDB; Q9BUB7; -.
DR BioGRID; 120305; 258.
DR IntAct; Q9BUB7; 35.
DR MINT; Q9BUB7; -.
DR STRING; 9606.ENSP00000312599; -.
DR TCDB; 8.A.96.1.1; the tmem70 (tmem70) family.
DR iPTMnet; Q9BUB7; -.
DR PhosphoSitePlus; Q9BUB7; -.
DR SwissPalm; Q9BUB7; -.
DR BioMuta; TMEM70; -.
DR DMDM; 74733203; -.
DR EPD; Q9BUB7; -.
DR jPOST; Q9BUB7; -.
DR MassIVE; Q9BUB7; -.
DR MaxQB; Q9BUB7; -.
DR PaxDb; Q9BUB7; -.
DR PeptideAtlas; Q9BUB7; -.
DR PRIDE; Q9BUB7; -.
DR ProteomicsDB; 19777; -.
DR ProteomicsDB; 79075; -. [Q9BUB7-1]
DR ProteomicsDB; 79076; -. [Q9BUB7-2]
DR TopDownProteomics; Q9BUB7-1; -. [Q9BUB7-1]
DR TopDownProteomics; Q9BUB7-2; -. [Q9BUB7-2]
DR Antibodypedia; 42550; 145 antibodies from 29 providers.
DR DNASU; 54968; -.
DR Ensembl; ENST00000312184.6; ENSP00000312599.5; ENSG00000175606.11. [Q9BUB7-1]
DR Ensembl; ENST00000517439.1; ENSP00000429467.1; ENSG00000175606.11. [Q9BUB7-3]
DR GeneID; 54968; -.
DR KEGG; hsa:54968; -.
DR MANE-Select; ENST00000312184.6; ENSP00000312599.5; NM_017866.6; NP_060336.3.
DR UCSC; uc003yab.4; human. [Q9BUB7-1]
DR CTD; 54968; -.
DR DisGeNET; 54968; -.
DR GeneCards; TMEM70; -.
DR HGNC; HGNC:26050; TMEM70.
DR HPA; ENSG00000175606; Tissue enriched (skeletal).
DR MalaCards; TMEM70; -.
DR MIM; 612418; gene.
DR MIM; 614052; phenotype.
DR neXtProt; NX_Q9BUB7; -.
DR OpenTargets; ENSG00000175606; -.
DR Orphanet; 1194; TMEM70-related mitochondrial encephalo-cardio-myopathy.
DR PharmGKB; PA142670783; -.
DR VEuPathDB; HostDB:ENSG00000175606; -.
DR eggNOG; KOG4478; Eukaryota.
DR GeneTree; ENSGT00390000018710; -.
DR HOGENOM; CLU_096509_1_0_1; -.
DR InParanoid; Q9BUB7; -.
DR OMA; YKDTHTH; -.
DR OrthoDB; 1513532at2759; -.
DR PhylomeDB; Q9BUB7; -.
DR TreeFam; TF314656; -.
DR PathwayCommons; Q9BUB7; -.
DR SignaLink; Q9BUB7; -.
DR BioGRID-ORCS; 54968; 18 hits in 1083 CRISPR screens.
DR GenomeRNAi; 54968; -.
DR Pharos; Q9BUB7; Tbio.
DR PRO; PR:Q9BUB7; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9BUB7; protein.
DR Bgee; ENSG00000175606; Expressed in vastus lateralis and 202 other tissues.
DR ExpressionAtlas; Q9BUB7; baseline and differential.
DR Genevisible; Q9BUB7; HS.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0030061; C:mitochondrial crista; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0140260; F:mitochondrial proton-transporting ATP synthase complex binding; IDA:UniProtKB.
DR GO; GO:0033615; P:mitochondrial proton-transporting ATP synthase complex assembly; IMP:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR InterPro; IPR009724; TMEM70.
DR InterPro; IPR045325; TMEM70/TMEM186/TMEM223.
DR PANTHER; PTHR13281; PTHR13281; 1.
DR Pfam; PF06979; TMEM70; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..81
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 82..260
FT /note="Transmembrane protein 70, mitochondrial"
FT /id="PRO_0000251472"
FT TOPO_DOM 82..102
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:24576557"
FT TRANSMEM 103..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..141
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:33359711"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..260
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:24576557"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020759"
FT VAR_SEQ 107
FT /note="V -> K (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054227"
FT VAR_SEQ 108..260
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054228"
FT VARIANT 34
FT /note="A -> P (in dbSNP:rs8075)"
FT /id="VAR_027686"
FT VARIANT 210
FT /note="T -> P (in MC5DN2)"
FT /evidence="ECO:0000269|PubMed:22986587"
FT /id="VAR_068847"
FT VARIANT 228
FT /note="N -> K (in dbSNP:rs35564486)"
FT /id="VAR_034565"
FT VARIANT 250
FT /note="T -> A (in dbSNP:rs1053079)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_027687"
FT VARIANT 259
FT /note="D -> E (in dbSNP:rs1053077)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_027688"
SQ SEQUENCE 260 AA; 28969 MW; 6206F853D18F12DC CRC64;
MLFLALGSPW AVELPLCGRR TALCAAAALR GPRASVSRAS SSSGPSGPVA GWSTGPSGAA
RLLRRPGRAQ IPVYWEGYVR FLNTPSDKSE DGRLIYTGNM ARAVFGVKCF SYSTSLIGLT
FLPYIFTQNN AISESVPLPI QIIFYGIMGS FTVITPVLLH FITKGYVIRL YHEATTDTYK
AITYNAMLAE TSTVFHQNDV KIPDAKHVFT TFYAKTKSLL VNPVLFPNRE DYIHLMGYDK
EEFILYMEET SEEKRHKDDK
