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Overview

Uniprot IDQ4VAE3
Protein NameTransmembrane protein 65
Gene NameTmem65
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
54 LLGTHPKKEPMEALN
83 TERSCLLKELHRFES

Function

Mitochondrial protein that plays a critical role in the sodium-dependent calcium efflux from mitochondrion (PubMed:40200126). 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 (By similarity). According to another report, TMEM65 functions as the mitochondrial sodium/calcium antiporter itself: homodimerization drives formation of a pocket capable of binding calcium (By similarity). Essential for maintaining proper cardiac intercalated disk (ICD) structure and function as well as cardiac conduction velocity in the heart (PubMed:36257954). Its association with SCN1B is required for stabilizing the perinexus in the ICD and for localization of GJA1 and SCN5A to the ICD (PubMed:26403541, PubMed:36257954)

Protein Sequence

10 MSRLLPLLGS 20 RTARSLRPGP 30 AAAPRLPSWC 40 CCGRGLLALG 50 VPGGPRLLGT 60 HPKKEPMEAL 70 NTAQGARDFI 80 YSLHSTERSC 90 LLKELHRFES 100 IAIAQEKLEA 110 LPPTPGQLRY 120 VFFHNAIPFV 130 GFGFLDNAIM 140 IVAGTQIELS 150 IGIILGISTM 160 AAAALGNLVS 170 DLAGLGLAGY 180 VEALASRLGL 190 SIPDLTPKQV 200 DMWQTRVSTH 210 LGKAVGVTIG 220 CILGMFPLIF 230 FGGSEEDEKL ETTN

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:0005730 nucleolus
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] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.