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Overview

Uniprot IDQ6PI78
Protein NameTransmembrane protein 65
Gene NameTMEM65
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
103 SIAIAQEKLEAPPPT

Function

Mitochondrial protein that plays a critical role in the sodium-dependent calcium efflux from mitochondrion (PubMed:40200126, PubMed:40691517). The precise role of TMEM65 in mitochondrial sodium/calcium exchange is however unclear: TMEM65 associates with the SLC8B1/NCLX antiporter and probably promotes the sodium/calcium exchange mediated by SLC8B1/NCLX (PubMed:40200126). According to another report, TMEM65 functions as the mitochondrial sodium/calcium antiporter itself: homodimerization drives formation of a pocket capable of binding calcium (PubMed:40691517). Essential for maintaining proper cardiac intercalated disk (ICD) structure and function as well as cardiac conduction velocity in the heart (By similarity). Its association with SCN1B is required for stabilizing the perinexus in the ICD and for localization of GJA1 and SCN5A to the ICD (By similarity)

Protein Sequence

10 MSRLLPLLRS 20 RTARSLRPGP 30 AAAAAPRPPS 40 WCCCGRGLLA 50 LAPPGGLPGG 60 PRRLGTHPKK 70 EPMEALNTAQ 80 GARDFIYSLH 90 STERSCLLKE 100 LHRFESIAIA 110 QEKLEAPPPT 120 PGQLRYVFIH 130 NAIPFIGFGF 140 LDNAIMIVAG 150 THIEMSIGII 160 LGISTMAAAA 170 LGNLVSDLAG 180 LGLAGYVEAL 190 ASRLGLSIPD 200 LTPKQVDMWQ 210 TRLSTHLGKA 220 VGVTIGCILG 230 MFPLIFFGGG 240 EEDEKLETKS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0014704 intercalated disc
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005886 plasma membrane
Molecular Function GO:0005432 calcium:sodium antiporter activity
Biological Process GO:0099093 calcium export from the mitochondrion
Biological Process GO:0061337 cardiac conduction
Biological Process GO:0003231 cardiac ventricle development
Biological Process GO:1903779 regulation of cardiac conduction

Reference

[1] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.