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Protein

Endosomal/lysomomal 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.1 Publication

GO - Molecular functioni

  • potassium ion leak channel activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

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/lysomomal potassium channel TMEM175Curated
Alternative name(s):
Transmembrane protein 175Imported
Short name:
hTMEM1751 Publication
Gene namesi
Name:TMEM175Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:28709. TMEM175.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535Cytoplasmic1 PublicationAdd
BLAST
Transmembranei36 – 5621Helical; Name=IS1Sequence analysisAdd
BLAST
Topological domaini57 – 7216LumenalCuratedAdd
BLAST
Transmembranei73 – 9321Helical; Name=IS2Sequence analysisAdd
BLAST
Topological domaini94 – 11017CytoplasmicCuratedAdd
BLAST
Transmembranei111 – 13121Helical; Name=IS3Sequence analysisAdd
BLAST
Topological domaini132 – 1376LumenalCurated
Transmembranei138 – 15821Helical; Name=IS4Sequence analysisAdd
BLAST
Topological domaini159 – 18426CytoplasmicCuratedAdd
BLAST
Transmembranei185 – 20521Helical; Name=IS5Sequence analysisAdd
BLAST
Topological domaini206 – 2105LumenalCurated
Transmembranei211 – 23020Helical; Name=IS6Sequence analysisAdd
BLAST
Topological domaini231 – 26030CytoplasmicCuratedAdd
BLAST
Transmembranei261 – 28121Helical; Name=IIS1Sequence analysisAdd
BLAST
Topological domaini282 – 30928LumenalCuratedAdd
BLAST
Transmembranei310 – 33021Helical; Name=IIS2Sequence analysisAdd
BLAST
Topological domaini331 – 3399CytoplasmicCurated
Transmembranei340 – 36021Helical; Name=IIS3Sequence analysisAdd
BLAST
Topological domaini361 – 37717LumenalCuratedAdd
BLAST
Transmembranei378 – 39821Helical; Name=IIS4Sequence analysisAdd
BLAST
Topological domaini399 – 41618CytoplasmicCuratedAdd
BLAST
Transmembranei417 – 43721Helical; Name=IIS5Sequence analysisAdd
BLAST
Topological domaini438 – 45215LumenalCuratedAdd
BLAST
Transmembranei453 – 47321Helical; Name=IIS6Sequence analysisAdd
BLAST
Topological domaini474 – 50431Cytoplasmic1 PublicationAdd
BLAST

GO - Cellular componenti

  • endosome Source: UniProtKB
  • endosome membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi35 – 351R → A: Impaired potassium channel activity. Curated
Mutagenesisi39 – 391F → V: Impaired potassium channel activity. Curated
Mutagenesisi40 – 401S → A: Impaired potassium channel activity. Curated
Mutagenesisi41 – 411D → A, E or N: Impaired potassium channel activity. Curated

Organism-specific databases

PharmGKBiPA162405946.

Polymorphism and mutation databases

BioMutaiTMEM175.
DMDMi74732981.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 504504Endosomal/lysomomal potassium channel TMEM175PRO_0000282588Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei6 – 61PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9BSA9.
PaxDbiQ9BSA9.
PeptideAtlasiQ9BSA9.
PRIDEiQ9BSA9.

PTM databases

iPTMnetiQ9BSA9.
PhosphoSiteiQ9BSA9.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ9BSA9.
CleanExiHS_TMEM175.
ExpressionAtlasiQ9BSA9. baseline and differential.
GenevisibleiQ9BSA9. HS.

Organism-specific databases

HPAiHPA023327.
HPA057160.

Interactioni

Protein-protein interaction databases

BioGridi124013. 1 interaction.
STRINGi9606.ENSP00000264771.

Structurei

3D structure databases

ProteinModelPortaliQ9BSA9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi39 – 413FSD motif 11 Publication
Motifi264 – 2663FSD motif 21 Publication

Domaini

Probably forms a two-repeat structure, with each repeat containing 6 transmembrane regions. The first transmembrane region of each repeat (named IS1 and IIS1, repectively), which contain the invariant FSD motif probably form the ion filter. Negatively charged residues (Asp/Glu) within the helices may interact with potassium ions to achieve the potassium selectivity.1 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.
PhylomeDBiQ9BSA9.
TreeFamiTF328838.

Family and domain databases

InterProiIPR010617. TMEM175.
[Graphical view]
PfamiPF06736. DUF1211. 2 hits.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti65 – 651Q → P.
Corresponds to variant rs34884217 [ dbSNP | Ensembl ].
VAR_053873
Natural varianti393 – 3931M → T.
Corresponds to variant rs34311866 [ dbSNP | Ensembl ].
VAR_053874

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 116116Missing in isoform 2. 1 PublicationVSP_024213Add
BLAST

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]
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

Cross-referencesi

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]
UniGeneiHs.478936.

3D structure databases

ProteinModelPortaliQ9BSA9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124013. 1 interaction.
STRINGi9606.ENSP00000264771.

Protein family/group databases

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

PTM databases

iPTMnetiQ9BSA9.
PhosphoSiteiQ9BSA9.

Polymorphism and mutation databases

BioMutaiTMEM175.
DMDMi74732981.

Proteomic databases

MaxQBiQ9BSA9.
PaxDbiQ9BSA9.
PeptideAtlasiQ9BSA9.
PRIDEiQ9BSA9.

Protocols and materials databases

DNASUi84286.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi84286.
GeneCardsiTMEM175.
H-InvDBHIX0004008.
HGNCiHGNC:28709. TMEM175.
HPAiHPA023327.
HPA057160.
MIMi616660. gene.
neXtProtiNX_Q9BSA9.
PharmGKBiPA162405946.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiTMEM175. human.
GenomeRNAii84286.
PROiQ9BSA9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BSA9.
CleanExiHS_TMEM175.
ExpressionAtlasiQ9BSA9. baseline and differential.
GenevisibleiQ9BSA9. HS.

Family and domain databases

InterProiIPR010617. TMEM175.
[Graphical view]
PfamiPF06736. DUF1211. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Kidney.
  4. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-6, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  5. "TMEM175 is an organelle K(+) channel regulating lysosomal function."
    Cang C., Aranda K., Seo Y.J., Gasnier B., Ren D.
    Cell 162:1101-1112(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DOMAIN, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-35; PHE-39; SER-40 AND ASP-41.

Entry informationi

Entry nameiTM175_HUMAN
AccessioniPrimary (citable) accession number: Q9BSA9
Secondary accession number(s): D3DVN4, Q8ND13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 97 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.