Overview
| Uniprot ID | Q6PI78 |
| Protein Name | Transmembrane protein 65 |
| Gene Name | TMEM65 |
| Organism | Homo 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.