TM175_RAT
ID TM175_RAT Reviewed; 499 AA.
AC Q6AY05;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Endosomal/lysosomal potassium channel TMEM175 {ECO:0000305};
DE AltName: Full=Transmembrane protein 175 {ECO:0000250|UniProtKB:Q9BSA9};
GN Name=Tmem175 {ECO:0000312|RGD:1309712};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23436907; DOI=10.1074/mcp.m112.021980;
RA Chapel A., Kieffer-Jaquinod S., Sagne C., Verdon Q., Ivaldi C., Mellal M.,
RA Thirion J., Jadot M., Bruley C., Garin J., Gasnier B., Journet A.;
RT "An extended proteome map of the lysosomal membrane reveals novel potential
RT transporters.";
RL Mol. Cell. Proteomics 12:1572-1588(2013).
RN [3]
RP FUNCTION.
RX PubMed=32799888; DOI=10.1186/s13041-020-00651-z;
RA Zhang M., Lu H., Xie X., Shen H., Li X., Zhang Y., Wu J., Ni J., Li H.,
RA Chen G.;
RT "TMEM175 mediates lysosomal function and participates in neuronal injury
RT induced by cerebral ischemia-reperfusion.";
RL Mol. Brain 13:113-113(2020).
CC -!- FUNCTION: Organelle-specific potassium channel specifically responsible
CC for potassium conductance in endosomes and lysosomes (By similarity).
CC Forms a potassium-permeable leak-like channel, which regulates lumenal
CC pH stability and is required for autophagosome-lysosome fusion (By
CC similarity). Constitutes the major lysosomal potassium channel (By
CC similarity). Constitutes the pore-forming subunit of the lysoK(GF)
CC complex, a complex activated by extracellular growth factors (By
CC similarity). The lysoK(GF) complex is composed of TMEM175 and AKT
CC (AKT1, AKT2 or AKT3), a major target of growth factor receptors: in the
CC complex, TMEM175 channel is opened by conformational changes by AKT,
CC leading to its activation (By similarity). The lysoK(GF) complex is
CC required to protect neurons against stress-induced damage
CC (PubMed:32799888) (Probable). {ECO:0000250|UniProtKB:Q9BSA9,
CC ECO:0000305|PubMed:32799888}.
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:0000269|PubMed:23436907}; 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-43 in the first module and Ile-268 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; BC079245; AAH79245.1; -; mRNA.
DR RefSeq; NP_001014013.1; NM_001013991.1.
DR RefSeq; XP_006250620.1; XM_006250558.3.
DR RefSeq; XP_017454749.1; XM_017599260.1.
DR AlphaFoldDB; Q6AY05; -.
DR SMR; Q6AY05; -.
DR STRING; 10116.ENSRNOP00000000050; -.
DR PhosphoSitePlus; Q6AY05; -.
DR PaxDb; Q6AY05; -.
DR PRIDE; Q6AY05; -.
DR Ensembl; ENSRNOT00000000050; ENSRNOP00000000050; ENSRNOG00000000044.
DR GeneID; 305623; -.
DR KEGG; rno:305623; -.
DR UCSC; RGD:1309712; rat.
DR CTD; 84286; -.
DR RGD; 1309712; Tmem175.
DR eggNOG; ENOG502QR5C; Eukaryota.
DR GeneTree; ENSGT00390000015667; -.
DR HOGENOM; CLU_052593_0_0_1; -.
DR InParanoid; Q6AY05; -.
DR OMA; FFFPVSY; -.
DR OrthoDB; 894975at2759; -.
DR PhylomeDB; Q6AY05; -.
DR TreeFam; TF328838; -.
DR PRO; PR:Q6AY05; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000000044; Expressed in testis and 18 other tissues.
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 1: Evidence at protein 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..499
FT /note="Endosomal/lysosomal potassium channel TMEM175"
FT /id="PRO_0000282590"
FT TOPO_DOM 1..30
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 31..53
FT /note="Helical; Name=TM1-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 54..74
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 75..97
FT /note="Helical; Name=TM2-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 98..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 104..125
FT /note="Helical; Name=TM3-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 126..135
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 136..157
FT /note="Helical; Name=TM4-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 158..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 182..202
FT /note="Helical; Name=TM5-1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..207
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 208..227
FT /note="Helical; Name=TM6-1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 255..279
FT /note="Helical; Name=TM1-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 280..306
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 307..329
FT /note="Helical; Name=TM2-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 330..335
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 336..357
FT /note="Helical; Name=TM3-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 358..372
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 373..393
FT /note="Helical; Name=TM4-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 394..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 414..437
FT /note="Helical; Name=TM5-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 438..439
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TRANSMEM 440..466
FT /note="Helical; Name=TM6-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT TOPO_DOM 467..499
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 55..60
FT /note="Short helix H1-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT REGION 62..68
FT /note="Short helix H2-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT REGION 285..293
FT /note="Short helix H1-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT REGION 295..301
FT /note="Short helix H2-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT MOTIF 32..38
FT /note="RxxxFSD motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT MOTIF 257..263
FT /note="RxxxFSD motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 43
FT /note="Hydrophobic filter residue 1-1"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 47
FT /note="Hydrophobic filter residue 2-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT SITE 50
FT /note="Hydrophobic filter residue 3-1"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT SITE 268
FT /note="Hydrophobic filter residue 1-2"
FT /evidence="ECO:0000250|UniProtKB:Q9BSA9"
FT SITE 272
FT /note="Hydrophobic filter residue 2-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
FT SITE 275
FT /note="Hydrophobic filter residue 3-2"
FT /evidence="ECO:0000250|UniProtKB:K9UJK2"
SQ SEQUENCE 499 AA; 55706 MW; 416114F28FEF3AEA CRC64;
MSRLQVQEQA VDSEGDSSLY RRDEEGTQSS HRMLGFSDAL LSIIATVMIL PVTHTEISPE
QQFDKSIQKL LATRIAVYLM TFLIVTVAWA AHTRLFQVVG KIDDTLALLN LACMMTITLL
PYTFSLMVTF PDVPLGIFLF CMCVIAIGSV QAMIVGYAFH FPHLLNPQIQ CSTHRALSRR
HILHLVLRGP ALCFVAAVFS LFFFPLSYLL MVTVIFLPHI SKATTWCKDK FMGHRESPAH
NVEPFSIDLH APLSKERVEA FSDGVYAIVA TLLILDICED NVPDPKDVQQ KFSGSLVAAL
GAYGPQFLAY FGSFATVGLL WFAHHSLFLH VRKATQTMGL FNILSLAFVG GLPLAYQQTS
AFARQPRDEL ERVRVSCAII FFASIFQFAI WTTALLHQRE TLQPAVQFGG QEHAFMFAKL
ALYPCASLLA FAATCLLSRF STAIFHLMQI AVPFAFLLLR LLVRLALAGL QVLWDLWPER
PQQDQGEPET QSQLLPASC
