ID TM165_HUMAN Reviewed; 324 AA.
AC Q9HC07; A8K3P8; B4DHW1; Q9BTN9; Q9NZ34;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 27-MAR-2024, entry version 153.
DE RecName: Full=Putative divalent cation/proton antiporter TMEM165 {ECO:0000305|PubMed:32047108};
DE AltName: Full=Transmembrane protein 165;
DE AltName: Full=Transmembrane protein PT27;
DE AltName: Full=Transmembrane protein TPARL;
DE Flags: Precursor;
GN Name=TMEM165 {ECO:0000303|PubMed:32047108, ECO:0000312|HGNC:HGNC:30760};
GN Synonyms=TPARL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Yue P., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA homologous to Mus musculus transmembrane
RT protein.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, Lung, and Uterus;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-124; LEU-127 AND 209-LEU-LEU-210,
RP CHARACTERIZATION OF VARIANTS CDG2K HIS-126; CYS-126 AND ARG-304, AND
RP TOPOLOGY.
RX PubMed=23575229; DOI=10.1093/hmg/ddt146;
RA Rosnoblet C., Legrand D., Demaegd D., Hacine-Gherbi H., de Bettignies G.,
RA Bammens R., Borrego C., Duvet S., Morsomme P., Matthijs G., Foulquier F.;
RT "Impact of disease-causing mutations on TMEM165 subcellular localization, a
RT recently identified protein involved in CDG-II.";
RL Hum. Mol. Genet. 22:2914-2928(2013).
RN [9]
RP FUNCTION.
RX PubMed=27008884; DOI=10.1093/hmg/ddw026;
RA Potelle S., Morelle W., Dulary E., Duvet S., Vicogne D., Spriet C.,
RA Krzewinski-Recchi M.A., Morsomme P., Jaeken J., Matthijs G.,
RA De Bettignies G., Foulquier F.;
RT "Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a
RT defect in Golgi manganese homeostasis.";
RL Hum. Mol. Genet. 25:1489-1500(2016).
RN [10]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARATERIZATION OF VARIANTS CDG2K GLY-108; CYS-126; HIS-126 AND ARG-304.
RX PubMed=32047108; DOI=10.1074/jbc.ra119.012249;
RA Stribny J., Thines L., Deschamps A., Goffin P., Morsomme P.;
RT "The human Golgi protein TMEM165 transports calcium and manganese in yeast
RT and bacterial cells.";
RL J. Biol. Chem. 295:3865-3874(2020).
RN [11]
RP INVOLVEMENT IN CDG2K.
RX PubMed=23430531; DOI=10.1007/8904_2012_172;
RA Zeevaert R., de Zegher F., Sturiale L., Garozzo D., Smet M., Moens M.,
RA Matthijs G., Jaeken J.;
RT "Bone dysplasia as a key feature in three patients with a novel congenital
RT disorder of glycosylation (CDG) type II due to a deep intronic splice
RT mutation in TMEM165.";
RL JIMD Rep. 8:145-152(2013).
RN [12]
RP FUNCTION IN CALCIUM AND PH HOMEOSTASIS.
RX PubMed=23569283; DOI=10.1073/pnas.1219871110;
RA Demaegd D., Foulquier F., Colinet A.S., Gremillon L., Legrand D.,
RA Mariot P., Peiter E., Van Schaftingen E., Matthijs G., Morsomme P.;
RT "Newly characterized Golgi-localized family of proteins is involved in
RT calcium and pH homeostasis in yeast and human cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6859-6864(2013).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP VARIANTS CDG2K HIS-126; CYS-126 AND ARG-304, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22683087; DOI=10.1016/j.ajhg.2012.05.002;
RA Foulquier F., Amyere M., Jaeken J., Zeevaert R., Schollen E., Race V.,
RA Bammens R., Morelle W., Rosnoblet C., Legrand D., Demaegd D., Buist N.,
RA Cheillan D., Guffon N., Morsomme P., Annaert W., Freeze H.H.,
RA Van Schaftingen E., Vikkula M., Matthijs G.;
RT "TMEM165 deficiency causes a congenital disorder of glycosylation.";
RL Am. J. Hum. Genet. 91:15-26(2012).
CC -!- FUNCTION: Putative divalent cation:proton antiporter that exchanges
CC calcium or manganese ions for protons across the Golgi membrane.
CC Mediates the reversible transport of calcium or manganese to the Golgi
CC lumen driven by the proton gradient and possibly the membrane potential
CC generated by V-ATPase. Provides calcium or manganese cofactors to
CC resident Golgi enzymes and contributes to the maintenance of an acidic
CC luminal Golgi pH required for proper functioning of the secretory
CC pathway (PubMed:32047108, PubMed:23569283, PubMed:22683087,
CC PubMed:27008884) (By similarity). Promotes Ca(2+) storage within the
CC Golgi lumen of the mammary epithelial cells to be then secreted into
CC milk (By similarity). The transport mechanism and stoichiometry remains
CC to be elucidated. {ECO:0000250|UniProtKB:P38301,
CC ECO:0000250|UniProtKB:P52875, ECO:0000269|PubMed:22683087,
CC ECO:0000269|PubMed:23569283, ECO:0000269|PubMed:27008884,
CC ECO:0000269|PubMed:32047108}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) + n H(+)(out) = Ca(2+)(out) + n H(+)(in);
CC Xref=Rhea:RHEA:76631, ChEBI:CHEBI:15378, ChEBI:CHEBI:29108;
CC Evidence={ECO:0000305|PubMed:32047108};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=n H(+)(out) + Mn(2+)(in) = n H(+)(in) + Mn(2+)(out);
CC Xref=Rhea:RHEA:76635, ChEBI:CHEBI:15378, ChEBI:CHEBI:29035;
CC Evidence={ECO:0000305|PubMed:32047108};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for Ca(2+) {ECO:0000269|PubMed:32047108};
CC KM=170 uM for Mn(2+) {ECO:0000269|PubMed:32047108};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P52875}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HC07-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HC07-2; Sequence=VSP_056691;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:22683087}.
CC -!- DISEASE: Congenital disorder of glycosylation 2K (CDG2K) [MIM:614727]:
CC An autosomal recessive disorder with a variable phenotype. Affected
CC individuals show psychomotor retardation and growth retardation, and
CC most have short stature. Other features include dysmorphism, hypotonia,
CC eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal
CC dysplasia. Congenital disorders of glycosylation are caused by a defect
CC in glycoprotein biosynthesis and characterized by under-glycosylated
CC serum glycoproteins and a wide variety of clinical features. The broad
CC spectrum of features reflects the critical role of N-glycoproteins
CC during embryonic development, differentiation, and maintenance of cell
CC functions. {ECO:0000269|PubMed:22683087, ECO:0000269|PubMed:23430531,
CC ECO:0000269|PubMed:23575229, ECO:0000269|PubMed:32047108}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the GDT1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF67653.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF132746; AAL75947.1; -; mRNA.
DR EMBL; AF183409; AAG09678.1; -; mRNA.
DR EMBL; AF220188; AAF67653.1; ALT_FRAME; mRNA.
DR EMBL; AK290663; BAF83352.1; -; mRNA.
DR EMBL; AK295289; BAG58273.1; -; mRNA.
DR EMBL; AC069200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05467.1; -; Genomic_DNA.
DR EMBL; BC003545; AAH03545.2; -; mRNA.
DR EMBL; BC104980; AAI04981.1; -; mRNA.
DR EMBL; BC104978; AAI04979.1; -; mRNA.
DR EMBL; BC107582; AAI07583.1; -; mRNA.
DR CCDS; CCDS3499.1; -. [Q9HC07-1]
DR RefSeq; NP_060945.2; NM_018475.4. [Q9HC07-1]
DR RefSeq; XP_016863901.1; XM_017008412.1. [Q9HC07-2]
DR AlphaFoldDB; Q9HC07; -.
DR BioGRID; 120960; 119.
DR IntAct; Q9HC07; 48.
DR MINT; Q9HC07; -.
DR STRING; 9606.ENSP00000370736; -.
DR TCDB; 2.A.106.2.2; the ca(2+):h(+) antiporter-2 (caca2) family.
DR GlyCosmos; Q9HC07; 1 site, 1 glycan.
DR GlyGen; Q9HC07; 3 sites, 3 O-linked glycans (3 sites).
DR iPTMnet; Q9HC07; -.
DR MetOSite; Q9HC07; -.
DR PhosphoSitePlus; Q9HC07; -.
DR SwissPalm; Q9HC07; -.
DR BioMuta; TMEM165; -.
DR DMDM; 74718825; -.
DR EPD; Q9HC07; -.
DR jPOST; Q9HC07; -.
DR MassIVE; Q9HC07; -.
DR MaxQB; Q9HC07; -.
DR PaxDb; 9606-ENSP00000370736; -.
DR PeptideAtlas; Q9HC07; -.
DR ProteomicsDB; 4251; -.
DR ProteomicsDB; 81617; -. [Q9HC07-1]
DR Pumba; Q9HC07; -.
DR Antibodypedia; 44090; 136 antibodies from 22 providers.
DR DNASU; 55858; -.
DR Ensembl; ENST00000381334.10; ENSP00000370736.5; ENSG00000134851.13. [Q9HC07-1]
DR GeneID; 55858; -.
DR KEGG; hsa:55858; -.
DR MANE-Select; ENST00000381334.10; ENSP00000370736.5; NM_018475.5; NP_060945.2.
DR UCSC; uc003hax.4; human. [Q9HC07-1]
DR AGR; HGNC:30760; -.
DR CTD; 55858; -.
DR DisGeNET; 55858; -.
DR GeneCards; TMEM165; -.
DR GeneReviews; TMEM165; -.
DR HGNC; HGNC:30760; TMEM165.
DR HPA; ENSG00000134851; Low tissue specificity.
DR MalaCards; TMEM165; -.
DR MIM; 614726; gene.
DR MIM; 614727; phenotype.
DR neXtProt; NX_Q9HC07; -.
DR OpenTargets; ENSG00000134851; -.
DR Orphanet; 314667; TMEM165-CDG.
DR PharmGKB; PA147357214; -.
DR VEuPathDB; HostDB:ENSG00000134851; -.
DR eggNOG; KOG2881; Eukaryota.
DR GeneTree; ENSGT00390000005261; -.
DR HOGENOM; CLU_040186_0_1_1; -.
DR InParanoid; Q9HC07; -.
DR OMA; KSQLVCM; -.
DR OrthoDB; 180756at2759; -.
DR PhylomeDB; Q9HC07; -.
DR TreeFam; TF105960; -.
DR PathwayCommons; Q9HC07; -.
DR SignaLink; Q9HC07; -.
DR BioGRID-ORCS; 55858; 103 hits in 1178 CRISPR screens.
DR ChiTaRS; TMEM165; human.
DR GenomeRNAi; 55858; -.
DR Pharos; Q9HC07; Tbio.
DR PRO; PR:Q9HC07; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9HC07; Protein.
DR Bgee; ENSG00000134851; Expressed in corpus callosum and 196 other cell types or tissues.
DR ExpressionAtlas; Q9HC07; baseline and differential.
DR Genevisible; Q9HC07; HS.
DR GO; GO:0033106; C:cis-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015085; F:calcium ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR GO; GO:0032468; P:Golgi calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0032472; P:Golgi calcium ion transport; IDA:UniProtKB.
DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IGI:UniProtKB.
DR GO; GO:0071421; P:manganese ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006828; P:manganese ion transport; IDA:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; IMP:UniProtKB.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; IMP:UniProtKB.
DR InterPro; IPR001727; GDT1-like.
DR InterPro; IPR049555; GDT1-like_CS.
DR PANTHER; PTHR12608:SF1; TRANSMEMBRANE PROTEIN 165; 1.
DR PANTHER; PTHR12608; TRANSMEMBRANE PROTEIN HTP-1 RELATED; 1.
DR Pfam; PF01169; UPF0016; 2.
DR PROSITE; PS01214; UPF0016; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiport; Coiled coil;
KW Congenital disorder of glycosylation; Disease variant; Golgi apparatus;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..324
FT /note="Putative divalent cation/proton antiporter TMEM165"
FT /id="PRO_0000247334"
FT TOPO_DOM 34..89
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..126
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 148..151
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..267
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..324
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 35..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 184..211
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..69
FT /note="MAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQ
FT LQPQPVAVQGPEPARVE -> MEIPMQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056691"
FT VARIANT 108
FT /note="E -> G (in CDG2K; does not affect the affinity for
FT Ca(2+) and Mn(2+) ions)"
FT /evidence="ECO:0000269|PubMed:32047108"
FT /id="VAR_088436"
FT VARIANT 126
FT /note="R -> C (in CDG2K; alters subcellular location;
FT displays decreased affinity for Ca(2+) ions; does not
FT affect the affinity for Mn(2+) ions; dbSNP:rs387907222)"
FT /evidence="ECO:0000269|PubMed:22683087,
FT ECO:0000269|PubMed:23575229, ECO:0000269|PubMed:32047108"
FT /id="VAR_068446"
FT VARIANT 126
FT /note="R -> H (in CDG2K; alters subcellular location; does
FT not affect the affinity for Ca(2+) and Mn(2+) ions;
FT dbSNP:rs387907221)"
FT /evidence="ECO:0000269|PubMed:22683087,
FT ECO:0000269|PubMed:23575229, ECO:0000269|PubMed:32047108"
FT /id="VAR_068447"
FT VARIANT 304
FT /note="G -> R (in CDG2K; accumulates in Golgi compartment;
FT displays decreased affinity for Ca(2+) ions; does not
FT affect the affinity for Mn(2+) ions; dbSNP:rs886037631)"
FT /evidence="ECO:0000269|PubMed:22683087,
FT ECO:0000269|PubMed:23575229, ECO:0000269|PubMed:32047108"
FT /id="VAR_068448"
FT MUTAGEN 124
FT /note="Y->S: Alters subcellular location."
FT /evidence="ECO:0000269|PubMed:23575229"
FT MUTAGEN 127
FT /note="L->G: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:23575229"
FT MUTAGEN 209..210
FT /note="LL->GG: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:23575229"
SQ SEQUENCE 324 AA; 34906 MW; A0E6C8BBFF189D72 CRC64;
MAAAAPGNGR ASAPRLLLLF LVPLLWAPAA VRAGPDEDLS HRNKEPPAPA QQLQPQPVAV
QGPEPARVEK IFTPAAPVHT NKEDPATQTN LGFIHAFVAA ISVIIVSELG DKTFFIAAIM
AMRYNRLTVL AGAMLALGLM TCLSVLFGYA TTVIPRVYTY YVSTVLFAIF GIRMLREGLK
MSPDEGQEEL EEVQAELKKK DEEFQRTKLL NGPGDVETGT SITVPQKKWL HFISPIFVQA
LTLTFLAEWG DRSQLTTIVL AAREDPYGVA VGGTVGHCLC TGLAVIGGRM IAQKISVRTV
TIIGGIVFLA FAFSALFISP DSGF
//
