Tmem175
entrez
72392
canonical
uniprot
Q9CXY1
canonical
ensembl
ENSMUSG00000013495
resolver
ensp
ENSMUSP00000068607
resolver
ensp
ENSMUSP00000077437
resolver
ensp
ENSMUSP00000112780
resolver
ensp
ENSMUSP00000278981
resolver
ensp
ENSMUSP00000278982
resolver
ensp
ENSMUSP00000278984
resolver
ensp
ENSMUSP00000278994
resolver
ensp
ENSMUSP00000279008
resolver
ensp
ENSMUSP00000279023
resolver
enst
ENSMUST00000063272
resolver
enst
ENSMUST00000078323
resolver
enst
ENSMUST00000120327
resolver
genesymbol
Tmem175
resolver
uniprot
Q3TDC4
resolver
uniprot
Q8BM80
resolver
uniprot
Q99K00
resolver
uniprot_entry
Q8BM80_MOUSE
resolver
uniprot_entry
TM175_MOUSE
resolver
uniprot_sec
Q3TDC4
resolver
uniprot_sec
Q99K00
resolver
activity_regulation
ACTIVITY REGULATION: Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons (By similarity). Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity (By similarity). Proton channel activity is directly inhibited by LAMP1 or LAMP2, facilitating lysosomal acidification (By similarity). Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state (PubMed:33505021). Activation by AKT is independent of AKT serine/threonine-protein kinase activity (PubMed:33505021). {ECO:0000250|UniProtKB:Q9BSA9, ECO:0000269|PubMed:33505021}.
uniprot
proteins
amino_acid_sequence
MSRLQTEEQAVDSEGDSSLHRRNEEGTQSSHRMLGFSDALLSIIATVMILPVTHTEISPEQQFDKSIQKLLATRIAVYLMTFLIVTVAWTAHTRLFQVVGKIDDTLALLNLACMMTITLLPYTFSLMVTFPDVPLGIFLFCVCVIAIGSVQAMIVGYAFHFPHLLNPQIQCSTHRDLSRRHILHLVLRGPALCFVAAVFSLFFFPLSYLLMVTVIFLPHISKATTWCKDKLMGQRESPAHDMEPFSIDLHAPLSKERVEAFSDGVYAIVATLLILDICEDNVPDPKDVQEKFSGSLVAALGAYGPQFLAYFGSFATVGLLWFAHHSLFLHVRKATQTMGLLNILSLAFVGGLPLAYQQTSAFARQPHDELERVRVSCAIIFFASIFQFAIWTTALLHQTETLQPAVQFGGQEHAFMFAKLALYPCASLLAFAATCLLSRFSTAIFHLMQISVPFAFLLLRLLVRLALAGLQVLRGLWPHHPQQDQSEPEAQSQLLPDPC
uniprot
proteins
function
FUNCTION: Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH (PubMed:35750034). Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis (By similarity). Regulation of lumenal pH stability is required for autophagosome-lysosome fusion (PubMed:26317472). Also acts as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes (PubMed:26317472, PubMed:33505021). Constitutes the pore-forming subunit of the lysoK(GF) complex, a complex activated by extracellular growth factors (PubMed:33505021). The lysoK(GF) complex is composed of TMEM175 and AKT (AKT1, AKT2 or AKT3), a major target of growth factor receptors: in the complex, TMEM175 channel is opened by conformational changes by AKT, leading to its activation (PubMed:33505021). The lysoK(GF) complex is required to protect neurons against stress-induced damage (PubMed:33505021). {ECO:0000250|UniProtKB:Q9BSA9, ECO:0000269|PubMed:26317472, ECO:0000269|PubMed:33505021, ECO:0000269|PubMed:35750034}.
uniprot
proteins
mass_dalton
55578
uniprot
proteins
mutagenesis
MUTAGEN 62; /note="Q->P: Gain-of-function mutant; increased potassium channel activity in knockin mice."; /evidence="ECO:0000269|PubMed:33505021"; MUTAGEN 390; /note="I->T: Reduced potassium channel activity in knockin mice."; /evidence="ECO:0000269|PubMed:33505021
uniprot
proteins
protein_family
TMEM175 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
26317472
uniprot
proteins
pubmed
33505021
uniprot
proteins
pubmed
35750034
uniprot
proteins
sequence_length
499
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q9BSA9}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q9BSA9}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 31..53; /note="Helical; Name=TM1-1"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 75..97; /note="Helical; Name=TM2-1"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 104..125; /note="Helical; Name=TM3-1"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 136..157; /note="Helical; Name=TM4-1"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 182..202; /note="Helical; Name=TM5-1"; /evidence="ECO:0000255"; TRANSMEM 208..227; /note="Helical; Name=TM6-1"; /evidence="ECO:0000255"; TRANSMEM 255..279; /note="Helical; Name=TM1-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 307..329; /note="Helical; Name=TM2-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 336..357; /note="Helical; Name=TM3-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 373..393; /note="Helical; Name=TM4-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 414..437; /note="Helical; Name=TM5-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9"; TRANSMEM 440..466; /note="Helical; Name=TM6-2"; /evidence="ECO:0000250|UniProtKB:Q9BSA9
uniprot
proteins