TM175_BOVIN
ID TM175_BOVIN Reviewed; 479 AA.
AC Q32PG7; F1ME05;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Endosomal/lysosomal potassium channel TMEM175 {ECO:0000305};
DE AltName: Full=Transmembrane protein 175 {ECO:0000250|UniProtKB:Q9BSA9};
GN Name=TMEM175 {ECO:0000250|UniProtKB:Q9BSA9};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Organelle-specific potassium channel specifically responsible
CC for potassium conductance in endosomes and lysosomes. Forms a
CC potassium-permeable leak-like channel, which regulates lumenal pH
CC stability and is required for autophagosome-lysosome fusion.
CC Constitutes the major lysosomal potassium channel. Constitutes the
CC pore-forming subunit of the lysoK(GF) complex, a complex activated by
CC extracellular growth factors. The lysoK(GF) complex is composed of
CC TMEM175 and AKT (AKT1, AKT2 or AKT3), a major target of growth factor
CC receptors: in the complex, TMEM175 channel is opened by conformational
CC changes by AKT, leading to its activation. The lysoK(GF) complex is
CC required to protect neurons against stress-induced damage.
CC {ECO:0000250|UniProtKB:Q9BSA9}.
CC -!- ACTIVITY REGULATION: Channel activity is activated following
CC interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes
CC activation from closed to an open state. Activation by AKT is
CC independent of AKT serine/threonine-protein kinase activity.
CC {ECO:0000250|UniProtKB:Q9BSA9}.
CC -!- SUBUNIT: Homodimer. Interacts with AKT (AKT1, AKT2 or AKT3); leading to
CC formation of the lysoK(GF) complex, which activates the channel.
CC {ECO:0000250|UniProtKB:Q9BSA9}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q9BSA9};
CC Multi-pass membrane protein {ECO:0000255}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9BSA9}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: Composed of two modules of six transmembranes, forming a
CC homodimer with a tetrameric architecture. The six transmembrane regions
CC of each module are tightly packed within each subunit without
CC undergoing domain swapping. Forms a central ion-conduction pore lined
CC by the side chains of the pore-lining helices. Conserved isoleucine
CC residues (Ile-46 in the first module and Ile-246 in the second module)
CC in the center of the pore serve as the gate in the closed conformation.
CC In the widened channel in the open conformation, the same residues
CC establish a constriction essential for potassium selectivity.
CC {ECO:0000250|UniProtKB:Q9BSA9}.
CC -!- SIMILARITY: Belongs to the TMEM175 family. {ECO:0000305}.
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DR EMBL; DAAA02018528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02018529; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC108122; AAI08123.1; -; mRNA.
DR RefSeq; NP_001069081.1; NM_001075613.1.
DR AlphaFoldDB; Q32PG7; -.
DR SMR; Q32PG7; -.
DR STRING; 9913.ENSBTAP00000024455; -.
DR PaxDb; Q32PG7; -.
DR PRIDE; Q32PG7; -.
DR GeneID; 513317; -.
DR KEGG; bta:513317; -.
DR CTD; 84286; -.
DR eggNOG; ENOG502QR5C; Eukaryota.
DR InParanoid; Q32PG7; -.
DR OrthoDB; 894975at2759; -.
DR TreeFam; TF328838; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0031303; C:integral component of endosome membrane; ISS:UniProtKB.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; ISS:UniProtKB.
DR GO; GO:0022841; F:potassium ion leak channel activity; ISS:UniProtKB.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; ISS:UniProtKB.
DR InterPro; IPR010617; TMEM175.
DR Pfam; PF06736; TMEM175; 2.
PE 2: Evidence at transcript level;
KW Endosome; Ion channel; Ion transport; Lysosome; Membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..479
FT /note="Endosomal/lysosomal potassium channel TMEM175"
FT /id="PRO_0000282587"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 34..56
FT /note="Helical; Name=TM1-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 57..64
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 65..87
FT /note="Helical; Name=TM2-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 88..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 94..103
FT /note="Helical; Name=TM3-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 104..113
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 114..135
FT /note="Helical; Name=TM4-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 136..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9, ECO:0000305"
FT TRANSMEM 160..180
FT /note="Helical; Name=TM5-1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..185
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 186..205
FT /note="Helical; Name=TM6-1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 233..257
FT /note="Helical; Name=TM1-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 258..284
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 285..307
FT /note="Helical; Name=TM2-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 308..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 314..335
FT /note="Helical; Name=TM3-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 336..350
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 351..371
FT /note="Helical; Name=TM4-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 372..391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 392..415
FT /note="Helical; Name=TM5-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 416..417
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 418..444
FT /note="Helical; Name=TM6-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 445..479
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 52..58
FT /note="Short helix H2-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT REGION 263..271
FT /note="Short helix H1-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT REGION 273..279
FT /note="Short helix H2-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT MOTIF 35..41
FT /note="RxxxFSD motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT MOTIF 235..241
FT /note="RxxxFSD motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 46
FT /note="Hydrophobic filter residue 1-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 50
FT /note="Hydrophobic filter residue 2-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT SITE 246
FT /note="Hydrophobic filter residue 1-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 250
FT /note="Hydrophobic filter residue 2-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT SITE 253
FT /note="Hydrophobic filter residue 3-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
SQ SEQUENCE 479 AA; 51966 MW; 3EF3F63D5BD70231 CRC64;
MSGPQAPEPT LEGQADASAG SPDEDAAEGI QHSHRMLSFS DALLSIIATV MEFDKSVQRL
LATRIAVYLM TFLIVTVAWA AHTRLFQVVG KIDDTLALLN LFSLMVTFPE VPLGIFLFCM
CVIAIGAVQA LIVLYAFHFP HLLSPQIERS AHRGLYRQRV LGIIVRGPAL CLAAAGFSLF
FYPASYLLMA MVIVLPHVSK AAGWCRAQLV GPREPPAHSV EVFTFDLHEP LSKERVEAFS
DGVYAIVATL LILDICEDNV PDAKDVKEKF QGSLVAALGE SGPHFLAYFG SFATVGLLWF
AHHSLFLHIR RATQPMGLLN TLSLAFVGGL PLAYQQTSAF TKQPRDELES VRISCAIIFL
ASIFQFAIWT TALLQEGETL QPSARFGGRE HAFMFAKLAL YPCASLLAFA CTCVLSSFST
AIFHAMQIAV PFAFLLLRLL VRLALAGLRA LRGLVGPVLA RPAPGAADEA QSPLLPAPC
