TMM65_DANRE
ID TMM65_DANRE Reviewed; 212 AA.
AC B3DHU2;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Transmembrane protein 65;
GN Name=tmem65;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
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).
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 (PubMed:26403541). Regulates mitochondrial
CC respiration and mitochondrial DNA copy number maintenance (By
CC similarity). {ECO:0000250|UniProtKB:Q6PI78,
CC ECO:0000269|PubMed:26403541}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with GJA1.
CC {ECO:0000250|UniProtKB:Q4VAE3}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q4VAE3};
CC Multi-pass membrane protein {ECO:0000255}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q6PI78}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes at the intercalated disk in ventricular
CC tissue and cardiomyocytes. {ECO:0000250|UniProtKB:Q4VAE3}.
CC -!- TISSUE SPECIFICITY: Expression is restricted to the heart (at protein
CC level). {ECO:0000269|PubMed:26403541}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC pericardial edema and altered cardiac morphology in 4 days post-
CC fertilization (dpf) embryos and severity increases as embryos age.
CC Morrphants are not viable by 7 dpf. Hearts showed abnormal cardiac
CC looping in the morphants and a significant decline in heart beat rates
CC seen in after 4.5 dpf and continue decreasing at 5 and 6 dpf.
CC Ventricles show a significant reduction in amplitude of Ca(2+)
CC transients in morphants between 4 and 6 dpf.
CC {ECO:0000269|PubMed:26403541}.
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DR EMBL; CABZ01067086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC162888; AAI62888.1; -; mRNA.
DR RefSeq; NP_001122284.1; NM_001128812.1.
DR AlphaFoldDB; B3DHU2; -.
DR STRING; 7955.ENSDARP00000100142; -.
DR PaxDb; B3DHU2; -.
DR PeptideAtlas; B3DHU2; -.
DR Ensembl; ENSDART00000111580; ENSDARP00000100142; ENSDARG00000076393.
DR GeneID; 100005403; -.
DR KEGG; dre:100005403; -.
DR CTD; 157378; -.
DR ZFIN; ZDB-GENE-081022-99; tmem65.
DR eggNOG; KOG4619; Eukaryota.
DR GeneTree; ENSGT00390000017802; -.
DR HOGENOM; CLU_075402_1_0_1; -.
DR InParanoid; B3DHU2; -.
DR OMA; CCWMGTH; -.
DR OrthoDB; 936872at2759; -.
DR PhylomeDB; B3DHU2; -.
DR TreeFam; TF105823; -.
DR PRO; PR:B3DHU2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000076393; Expressed in retina and 21 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003231; P:cardiac ventricle development; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:1903779; P:regulation of cardiac conduction; IMP: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; Transmembrane; Transmembrane helix.
FT CHAIN 1..212
FT /note="Transmembrane protein 65"
FT /id="PRO_0000435274"
FT TOPO_DOM 1..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q6PI78"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..116
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q6PI78"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q6PI78"
FT TRANSMEM 140..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..178
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q6PI78"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q6PI78"
SQ SEQUENCE 212 AA; 23070 MW; 8243D898FECE5D11 CRC64;
MIRSVLLRAL AARPPSAPVP GHLHRCLLGT HRRKIKPEQL ELPNQTREFV YSLSPETRSR
LLKELQTFES KTEDSGEASR LTAAQLRYIL LHNAIPFIGF GFLDNAIMIA AGTQIELSIG
LTLGISTMAA AALGNLVSDL AGLGLAGYVE ALAVRLGMQI PDLSPRQVDM WQTRVSSHMG
KAIGVAIGCI LGMFPLLFLS DEEDKKPKKD SN
