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Protein

Endosomal/lysosomal potassium channel TMEM175

Gene

TMEM175

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Organelle-specific potassium channel specifically responsible for potassium conductance in endosomes and lysosomes. Forms a potassium-permeable leak-like channel, which regulates lumenal pH stability and is required for autophagosome-lysosome fusion. Constitutes the major lysosomal potassium channel.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei46Hydrophobic filter residue 1-11 Publication1
Sitei50Hydrophobic filter residue 2-1By similarity1
Sitei53Hydrophobic filter residue 3-1By similarity1
Sitei271Hydrophobic filter residue 1-21 Publication1
Sitei275Hydrophobic filter residue 2-2By similarity1
Sitei278Hydrophobic filter residue 3-2By similarity1

GO - Molecular functioni

  • potassium channel activity Source: UniProtKB
  • potassium ion leak channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel, Potassium channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Protein family/group databases

TCDBi1.A.78.1.1. the k+-selective channel in endosomes and lysosomes (kel) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Endosomal/lysosomal potassium channel TMEM175Curated
Alternative name(s):
Transmembrane protein 175Imported
Short name:
hTMEM1752 Publications
Gene namesi
Name:TMEM175Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000127419.16.
HGNCiHGNC:28709. TMEM175.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 35Cytoplasmic1 PublicationAdd BLAST35
Transmembranei36 – 56Helical; Name=TM1-1Sequence analysisAdd BLAST21
Topological domaini57 – 72LumenalCuratedAdd BLAST16
Transmembranei73 – 93Helical; Name=TM2-1Sequence analysisAdd BLAST21
Topological domaini94 – 110CytoplasmicCuratedAdd BLAST17
Transmembranei111 – 131Helical; Name=TM3-1Sequence analysisAdd BLAST21
Topological domaini132 – 137LumenalCurated6
Transmembranei138 – 158Helical; Name=TM4-1Sequence analysisAdd BLAST21
Topological domaini159 – 184CytoplasmicCuratedAdd BLAST26
Transmembranei185 – 205Helical; Name=TM5-1Sequence analysisAdd BLAST21
Topological domaini206 – 210LumenalCurated5
Transmembranei211 – 230Helical; Name=TM6-1Sequence analysisAdd BLAST20
Topological domaini231 – 260CytoplasmicCuratedAdd BLAST30
Transmembranei261 – 281Helical; Name=TM1-2Sequence analysisAdd BLAST21
Topological domaini282 – 309LumenalCuratedAdd BLAST28
Transmembranei310 – 330Helical; Name=TM2-2Sequence analysisAdd BLAST21
Topological domaini331 – 339CytoplasmicCurated9
Transmembranei340 – 360Helical; Name=TM3-2Sequence analysisAdd BLAST21
Topological domaini361 – 377LumenalCuratedAdd BLAST17
Transmembranei378 – 398Helical; Name=TM4-2Sequence analysisAdd BLAST21
Topological domaini399 – 416CytoplasmicCuratedAdd BLAST18
Transmembranei417 – 437Helical; Name=TM5-2Sequence analysisAdd BLAST21
Topological domaini438 – 452LumenalCuratedAdd BLAST15
Transmembranei453 – 473Helical; Name=TM6-2Sequence analysisAdd BLAST21
Topological domaini474 – 504Cytoplasmic1 PublicationAdd BLAST31

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Parkinson disease (PARK)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry. TMEM175 defects result in unstable lysosomal pH, leading to decreased lysosomal catalytic activity, decreased glucocerebrosidase activity, impaired autophagosome clearance by the lysosome and decreased mitochondrial respiration (PubMed:28193887).1 Publication
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
See also OMIM:168600

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35R → A: Impaired potassium channel activity. Curated1
Mutagenesisi39F → V: Impaired potassium channel activity. Curated1
Mutagenesisi40S → A: Impaired potassium channel activity. Curated1
Mutagenesisi41D → A, E or N: Impaired potassium channel activity. Curated1
Mutagenesisi46I → N: Impaired selectivity; can conduct both K(+) and Na(+); when associated with N-271. 1 Publication1
Mutagenesisi50V → A: Does not affect selectivity; when associated with A-275. 1 Publication1
Mutagenesisi53L → A: Does not affect selectivity; when associated with A-278. 1 Publication1
Mutagenesisi271I → N: Impaired selectivity; can conduct both K(+) and Na(+); when associated with N-46. 1 Publication1
Mutagenesisi275L → A: Does not affect selectivity; when associated with A-50. 1 Publication1
Mutagenesisi278L → A: Does not affect selectivity; when associated with A-53. 1 Publication1

Keywords - Diseasei

Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi84286.
MIMi168600. phenotype.
OpenTargetsiENSG00000127419.
PharmGKBiPA162405946.

Polymorphism and mutation databases

BioMutaiTMEM175.
DMDMi74732981.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002825881 – 504Endosomal/lysosomal potassium channel TMEM175Add BLAST504

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9BSA9.
PaxDbiQ9BSA9.
PeptideAtlasiQ9BSA9.
PRIDEiQ9BSA9.

PTM databases

iPTMnetiQ9BSA9.
PhosphoSitePlusiQ9BSA9.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000127419.
CleanExiHS_TMEM175.
ExpressionAtlasiQ9BSA9. baseline and differential.
GenevisibleiQ9BSA9. HS.

Organism-specific databases

HPAiHPA057160.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi124013. 3 interactors.
IntActiQ9BSA9. 4 interactors.

Structurei

3D structure databases

ProteinModelPortaliQ9BSA9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 63Short helix H1-1By similarity6
Regioni65 – 71Short helix H2-1By similarity7
Regioni288 – 296Short helix H1-2By similarity9
Regioni298 – 304Short helix H2-2By similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi35 – 41RxxxFSD motif 11 Publication7
Motifi260 – 266RxxxFSD motif 21 Publication7

Domaini

Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture (PubMed:28723891). The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping (By similarity). Transmembranes TM1-TM3 of each module are positioned on the inner circle of the channel tetramer and participate in inter-subunit interactions that are central to the assembly of the ion conduction pore (By similarity). The RxxxFSD motifs within transmembranes TM1 coordinate a network of specific inter- and intra-subunit interactions with other conserved residues on TM2 and TM3 and play a key role in the tetrameric assembly of the channel (By similarity). Transmembranes TM4-TM6 are positioned on the periphery of the channel and do not contribute contacts with neighboring subunits (By similarity). Transmembranes TM1 and TM2 are linked by an extended strand-like tail and two short helices (H1 and H2) which protrude outwards from the main body of the transmembrane domain and enclose the external open entrance of the ion conduction pore in the channel tetramer (By similarity). Transmembranes TM1 form the pore-lining inner helix at the center of the channel, creating an hourglass-shaped ion permeation pathway in the channel tetramer (By similarity). Three hydrophobic residues on the C-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel (By similarity). Ile-46 (and Ile-271) are probably responsible for channel selectivity (PubMed:28723891).By similarity1 Publication

Sequence similaritiesi

Belongs to the TMEM175 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIWE. Eukaryota.
ENOG410ZP3B. LUCA.
GeneTreeiENSGT00390000015667.
HOGENOMiHOG000154616.
HOVERGENiHBG059914.
InParanoidiQ9BSA9.
OMAiACMMLIT.
OrthoDBiEOG091G05QO.
PhylomeDBiQ9BSA9.
TreeFamiTF328838.

Family and domain databases

InterProiView protein in InterPro
IPR010617. TMEM175.
PfamiView protein in Pfam
PF06736. DUF1211. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BSA9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSQPRTPEQA LDTPGDCPPG RRDEDAGEGI QCSQRMLSFS DALLSIIATV
60 70 80 90 100
MILPVTHTEI SPEQQFDRSV QRLLATRIAV YLMTFLIVTV AWAAHTRLFQ
110 120 130 140 150
VVGKTDDTLA LLNLACMMTI TFLPYTFSLM VTFPDVPLGI FLFCVCVIAI
160 170 180 190 200
GVVQALIVGY AFHFPHLLSP QIQRSAHRAL YRRHVLGIVL QGPALCFAAA
210 220 230 240 250
IFSLFFVPLS YLLMVTVILL PYVSKVTGWC RDRLLGHREP SAHPVEVFSF
260 270 280 290 300
DLHEPLSKER VEAFSDGVYA IVATLLILDI CEDNVPDPKD VKERFSGSLV
310 320 330 340 350
AALSATGPRF LAYFGSFATV GLLWFAHHSL FLHVRKATRA MGLLNTLSLA
360 370 380 390 400
FVGGLPLAYQ QTSAFARQPR DELERVRVSC TIIFLASIFQ LAMWTTALLH
410 420 430 440 450
QAETLQPSVW FGGREHVLMF AKLALYPCAS LLAFASTCLL SRFSVGIFHL
460 470 480 490 500
MQIAVPCAFL LLRLLVGLAL ATLRVLRGLA RPEHPPPAPT GQDDPQSQLL

PAPC
Length:504
Mass (Da):55,615
Last modified:June 1, 2001 - v1
Checksum:i7FEE4C22CA248094
GO
Isoform 2 (identifier: Q9BSA9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.

Show »
Length:388
Mass (Da):42,847
Checksum:i179ED37576BCB367
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05387365Q → P. Corresponds to variant dbSNP:rs34884217Ensembl.1
Natural variantiVAR_053874393M → T. Corresponds to variant dbSNP:rs34311866Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0242131 – 116Missing in isoform 2. 1 PublicationAdd BLAST116

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL834199 mRNA. Translation: CAD38888.1.
CH471131 Genomic DNA. Translation: EAW82633.1.
CH471131 Genomic DNA. Translation: EAW82638.1.
BC005158 mRNA. Translation: AAH05158.1.
CCDSiCCDS3341.1. [Q9BSA9-1]
CCDS75088.1. [Q9BSA9-2]
RefSeqiNP_001284355.1. NM_001297426.1. [Q9BSA9-2]
NP_001284356.1. NM_001297427.1. [Q9BSA9-2]
NP_001284357.1. NM_001297428.1. [Q9BSA9-2]
NP_115702.1. NM_032326.3. [Q9BSA9-1]
XP_005272361.1. XM_005272304.1. [Q9BSA9-2]
XP_016864190.1. XM_017008701.1. [Q9BSA9-1]
XP_016864194.1. XM_017008705.1. [Q9BSA9-2]
UniGeneiHs.478936.

Genome annotation databases

EnsembliENST00000264771; ENSP00000264771; ENSG00000127419. [Q9BSA9-1]
ENST00000515740; ENSP00000427039; ENSG00000127419. [Q9BSA9-2]
ENST00000622959; ENSP00000485461; ENSG00000127419. [Q9BSA9-2]
GeneIDi84286.
KEGGihsa:84286.
UCSCiuc003gbq.4. human. [Q9BSA9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTM175_HUMAN
AccessioniPrimary (citable) accession number: Q9BSA9
Secondary accession number(s): D3DVN4, Q8ND13
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: June 1, 2001
Last modified: October 25, 2017
This is version 106 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families