TMM65_HUMAN
ID TMM65_HUMAN Reviewed; 240 AA.
AC Q6PI78; Q8N5G8; Q8WVK5;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Transmembrane protein 65;
DE Flags: Precursor;
GN Name=TMEM65;
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-97.
RC TISSUE=Brain;
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 [3]
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 [4]
RP SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND TISSUE SPECIFICITY.
RX PubMed=26403541; DOI=10.1038/ncomms9391;
RA Sharma P., Abbasi C., Lazic S., Teng A.C., Wang D., Dubois N.,
RA Ignatchenko V., Wong V., Liu J., Araki T., Tiburcy M., Ackerley C.,
RA Zimmermann W.H., Hamilton R., Sun Y., Liu P.P., Keller G., Stagljar I.,
RA Scott I.C., Kislinger T., Gramolini A.O.;
RT "Evolutionarily conserved intercalated disc protein Tmem65 regulates
RT cardiac conduction and connexin 43 function.";
RL Nat. Commun. 6:8391-8391(2015).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=24765583; DOI=10.7717/peerj.349;
RA Nishimura N., Gotoh T., Oike Y., Yano M.;
RT "TMEM65 is a mitochondrial inner-membrane protein.";
RL PeerJ 2:E349-E349(2014).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION, FUNCTION, AND INVOLVEMENT IN MITOCHONDRIAL MYOPATHY.
RX PubMed=28295037; DOI=10.1038/ejhg.2017.20;
RA Nazli A., Safdar A., Saleem A., Akhtar M., Brady L.I., Schwartzentruber J.,
RA Tarnopolsky M.A.;
RT "A mutation in the TMEM65 gene results in mitochondrial myopathy with
RT severe neurological manifestations.";
RL Eur. J. Hum. Genet. 25:744-751(2017).
CC -!- FUNCTION: May play an important role in cardiac development and
CC function. May regulate cardiac conduction and the function of the gap
CC junction protein GJA1. May contribute to the stability and proper
CC localization of GJA1 to cardiac intercalated disk thereby regulating
CC gap junction communication (By similarity). May also play a role in the
CC regulation of mitochondrial respiration and mitochondrial DNA copy
CC number maintenance (PubMed:28295037). {ECO:0000250|UniProtKB:Q4VAE3,
CC ECO:0000269|PubMed:28295037}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (PubMed:26403541).
CC Interacts with GJA1 (By similarity). Interacts weakly with DSP (By
CC similarity). {ECO:0000250|UniProtKB:Q4VAE3,
CC ECO:0000269|PubMed:26403541}.
CC -!- INTERACTION:
CC Q6PI78; O95870: ABHD16A; NbExp=3; IntAct=EBI-6656213, EBI-348517;
CC Q6PI78; Q13520: AQP6; NbExp=3; IntAct=EBI-6656213, EBI-13059134;
CC Q6PI78; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-6656213, EBI-11343438;
CC Q6PI78; P49447: CYB561; NbExp=3; IntAct=EBI-6656213, EBI-8646596;
CC Q6PI78; Q53TN4: CYBRD1; NbExp=3; IntAct=EBI-6656213, EBI-8637742;
CC Q6PI78; Q15125: EBP; NbExp=3; IntAct=EBI-6656213, EBI-3915253;
CC Q6PI78; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-6656213, EBI-781551;
CC Q6PI78; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-6656213, EBI-18636064;
CC Q6PI78; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-6656213, EBI-18304435;
CC Q6PI78; P48165: GJA8; NbExp=3; IntAct=EBI-6656213, EBI-17458373;
CC Q6PI78; O15529: GPR42; NbExp=3; IntAct=EBI-6656213, EBI-18076404;
CC Q6PI78; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-6656213, EBI-1052304;
CC Q6PI78; Q9P2J2-2: IGSF9; NbExp=3; IntAct=EBI-6656213, EBI-17451184;
CC Q6PI78; P26951: IL3RA; NbExp=3; IntAct=EBI-6656213, EBI-1757512;
CC Q6PI78; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-6656213, EBI-10266796;
CC Q6PI78; Q9HDC5: JPH1; NbExp=3; IntAct=EBI-6656213, EBI-465137;
CC Q6PI78; Q15800: MSMO1; NbExp=3; IntAct=EBI-6656213, EBI-949102;
CC Q6PI78; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-6656213, EBI-716063;
CC Q6PI78; O14684: PTGES; NbExp=3; IntAct=EBI-6656213, EBI-11161398;
CC Q6PI78; P15151: PVR; NbExp=3; IntAct=EBI-6656213, EBI-3919694;
CC Q6PI78; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-6656213, EBI-7545592;
CC Q6PI78; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-6656213, EBI-10192441;
CC Q6PI78; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-6656213, EBI-17247926;
CC Q6PI78; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-6656213, EBI-18159983;
CC Q6PI78; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-6656213, EBI-17595455;
CC Q6PI78; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-6656213, EBI-17295964;
CC Q6PI78; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-6656213, EBI-13292283;
CC Q6PI78; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-6656213, EBI-6268651;
CC Q6PI78; Q96IK0: TMEM101; NbExp=3; IntAct=EBI-6656213, EBI-3922699;
CC Q6PI78; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-6656213, EBI-11742770;
CC Q6PI78; Q9Y320: TMX2; NbExp=3; IntAct=EBI-6656213, EBI-6447886;
CC Q6PI78; Q5T4F4: ZFYVE27; NbExp=3; IntAct=EBI-6656213, EBI-3892947;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26403541};
CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:24765583, ECO:0000269|PubMed:28295037}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Localizes at the intercalated disk
CC in the ventricular tissue (PubMed:26403541).
CC {ECO:0000269|PubMed:26403541}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed the ventricular tissue (at
CC protein level). {ECO:0000269|PubMed:26403541}.
CC -!- DISEASE: Note=Defects in TMEM65 may cause a mitochondrial disorder
CC characterized by a complex encephalomyopathic phenotype. Clinical
CC features includ microcephaly, dysmorphic features, psychomotor
CC regression, hypotonia, growth retardation, lactic acidosis, intractable
CC seizures, dyskenetics movements, without cardiomyopathy
CC (PubMed:28295037). {ECO:0000269|PubMed:28295037}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32396.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC090192; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017881; AAH17881.1; -; mRNA.
DR EMBL; BC032396; AAH32396.1; ALT_INIT; mRNA.
DR EMBL; BC041379; AAH41379.1; -; mRNA.
DR CCDS; CCDS6348.1; -.
DR RefSeq; NP_919267.2; NM_194291.2.
DR AlphaFoldDB; Q6PI78; -.
DR BioGRID; 127596; 50.
DR IntAct; Q6PI78; 37.
DR MINT; Q6PI78; -.
DR STRING; 9606.ENSP00000297632; -.
DR iPTMnet; Q6PI78; -.
DR SwissPalm; Q6PI78; -.
DR BioMuta; TMEM65; -.
DR DMDM; 296452844; -.
DR EPD; Q6PI78; -.
DR jPOST; Q6PI78; -.
DR MassIVE; Q6PI78; -.
DR MaxQB; Q6PI78; -.
DR PaxDb; Q6PI78; -.
DR PeptideAtlas; Q6PI78; -.
DR PRIDE; Q6PI78; -.
DR ProteomicsDB; 67144; -.
DR TopDownProteomics; Q6PI78; -.
DR Antibodypedia; 13901; 100 antibodies from 17 providers.
DR DNASU; 157378; -.
DR Ensembl; ENST00000297632.8; ENSP00000297632.6; ENSG00000164983.8.
DR GeneID; 157378; -.
DR KEGG; hsa:157378; -.
DR MANE-Select; ENST00000297632.8; ENSP00000297632.6; NM_194291.3; NP_919267.2.
DR UCSC; uc010mdl.4; human.
DR CTD; 157378; -.
DR DisGeNET; 157378; -.
DR GeneCards; TMEM65; -.
DR HGNC; HGNC:25203; TMEM65.
DR HPA; ENSG00000164983; Low tissue specificity.
DR MIM; 616609; gene.
DR neXtProt; NX_Q6PI78; -.
DR OpenTargets; ENSG00000164983; -.
DR PharmGKB; PA142670778; -.
DR VEuPathDB; HostDB:ENSG00000164983; -.
DR eggNOG; KOG4619; Eukaryota.
DR GeneTree; ENSGT00390000017802; -.
DR HOGENOM; CLU_075402_1_0_1; -.
DR InParanoid; Q6PI78; -.
DR OMA; QRCNLGT; -.
DR OrthoDB; 936872at2759; -.
DR PhylomeDB; Q6PI78; -.
DR TreeFam; TF105823; -.
DR PathwayCommons; Q6PI78; -.
DR SignaLink; Q6PI78; -.
DR BioGRID-ORCS; 157378; 16 hits in 1086 CRISPR screens.
DR ChiTaRS; TMEM65; human.
DR GenomeRNAi; 157378; -.
DR Pharos; Q6PI78; Tdark.
DR PRO; PR:Q6PI78; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6PI78; protein.
DR Bgee; ENSG00000164983; Expressed in left ventricle myocardium and 185 other tissues.
DR Genevisible; Q6PI78; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014704; C:intercalated disc; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0003231; P:cardiac ventricle development; ISS:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; ISS:UniProtKB.
DR InterPro; IPR019537; TMEM65.
DR PANTHER; PTHR21706; PTHR21706; 1.
DR Pfam; PF10507; TMEM65; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..61
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 62..240
FT /note="Transmembrane protein 65"
FT /id="PRO_0000251404"
FT TOPO_DOM 62..110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26403541"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..142
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26403541"
FT TRANSMEM 143..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:26403541"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..240
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26403541"
FT VARIANT 97
FT /note="I -> V (in dbSNP:rs17854113)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060384"
FT CONFLICT 6
FT /note="P -> R (in Ref. 2; AAH41379)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 240 AA; 25498 MW; D24964048FF24DF2 CRC64;
MSRLLPLLRS RTARSLRPGP AAAAAPRPPS WCCCGRGLLA LAPPGGLPGG PRRLGTHPKK
EPMEALNTAQ GARDFIYSLH STERSCLLKE LHRFESIAIA QEKLEAPPPT PGQLRYVFIH
NAIPFIGFGF LDNAIMIVAG THIEMSIGII LGISTMAAAA LGNLVSDLAG LGLAGYVEAL
ASRLGLSIPD LTPKQVDMWQ TRLSTHLGKA VGVTIGCILG MFPLIFFGGG EEDEKLETKS
