Overview
| Uniprot ID | Q4VAE3 |
| Protein Name | Transmembrane protein 65 |
| Gene Name | Tmem65 |
| Organism | Mus 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.