TMEM65
entrez
157378
canonical
uniprot
Q6PI78
canonical
ensembl
ENSG00000164983
resolver
ensp
ENSP00000297632
resolver
enst
ENST00000297632
resolver
genesymbol
TMEM65
resolver
hgnc
HGNC:25203
resolver
uniprot
Q8N5G8
resolver
uniprot
Q8WVK5
resolver
uniprot_entry
TMM65_HUMAN
resolver
uniprot_sec
Q8N5G8
resolver
uniprot_sec
Q8WVK5
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by CGP-37157, the mitochondrial sodium/calcium exchange inhibitor. {ECO:0000269|PubMed:40691517}.
uniprot
proteins
amino_acid_sequence
MSRLLPLLRSRTARSLRPGPAAAAAPRPPSWCCCGRGLLALAPPGGLPGGPRRLGTHPKKEPMEALNTAQGARDFIYSLHSTERSCLLKELHRFESIAIAQEKLEAPPPTPGQLRYVFIHNAIPFIGFGFLDNAIMIVAGTHIEMSIGIILGISTMAAAALGNLVSDLAGLGLAGYVEALASRLGLSIPDLTPKQVDMWQTRLSTHLGKAVGVTIGCILGMFPLIFFGGGEEDEKLETKS
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in TMEM65 may cause a mitochondrial disorder characterized by a complex encephalomyopathic phenotype. Clinical features includ microcephaly, dysmorphic features, psychomotor regression, hypotonia, growth retardation, lactic acidosis, intractable seizures, dyskenetics movements, without cardiomyopathy (PubMed:28295037). {ECO:0000269|PubMed:28295037}.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q4VAE3, ECO:0000269|PubMed:40200126, ECO:0000269|PubMed:40691517}.
uniprot
proteins
mass_dalton
25498
uniprot
proteins
mutagenesis
MUTAGEN 125; /note="F->A,Q: Reduced sensitivity to CGP-37157 inhibitor."; /evidence="ECO:0000269|PubMed:40691517"; MUTAGEN 128; /note="F->L,A: Abolished ability to promote calcium efflux from mitochondrion."; /evidence="ECO:0000269|PubMed:40691517"; MUTAGEN 163..167; /note="NLVSD->ALVSA: Abolished ability to promote calcium efflux from mitochondrion."; /evidence="ECO:0000269|PubMed:40200126"; MUTAGEN 167; /note="D->N: Abolished ability to promote calcium efflux from mitochondrion."; /evidence="ECO:0000269|PubMed:40691517"; MUTAGEN 171; /note="L->A: Does not affect sensitivity to CGP-37157 inhibitor."; /evidence="ECO:0000269|PubMed:40691517"; MUTAGEN 174; /note="A->S,L: Reduced ability to promote calcium efflux from mitochondrion."; /evidence="ECO:0000269|PubMed:40691517"; MUTAGEN 174; /note="A->W: Abolished ability to promote calcium efflux from mitochondrion."; /evidence="ECO:0000269|PubMed:40691517
uniprot
proteins
protein_family
TMEM65 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
24765583
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26403541
uniprot
proteins
pubmed
28295037
uniprot
proteins
pubmed
40200126
uniprot
proteins
pubmed
40691517
uniprot
proteins
sequence_length
240
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:24765583, ECO:0000269|PubMed:28295037, ECO:0000269|PubMed:40200126, ECO:0000269|PubMed:40691517}; Multi-pass membrane protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:26403541}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes at the intercalated disk in the ventricular tissue (PubMed:26403541). {ECO:0000269|PubMed:26403541}.
uniprot
proteins
transmembrane_region
TRANSMEM 111..131; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 143..165; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 210..230; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins