TARG1_HUMAN
ID TARG1_HUMAN Reviewed; 177 AA.
AC Q8IXB3; A6NMK4;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Trafficking regulator of GLUT4 1 {ECO:0000312|HGNC:HGNC:29592};
DE AltName: Full=Dispanin subfamily B member 1;
DE Short=DSPB1;
DE AltName: Full=Interferon-induced transmembrane domain-containing protein D3;
DE AltName: Full=Protein located at seventeen-p-thirteen point three 1;
DE AltName: Full=Tumor suppressor candidate 5;
GN Name=TRARG1 {ECO:0000312|HGNC:HGNC:29592};
GN Synonyms=IFITMD3, LOST1, TUSC5 {ECO:0000312|HGNC:HGNC:29592};
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], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP VARIANTS TYR-3; SER-15; THR-18; SER-20; ASP-34 AND GLY-57.
RC TISSUE=Lung;
RX PubMed=12660825; DOI=10.1038/sj.onc.1206304;
RA Konishi H., Sugiyama M., Mizuno K., Saito H., Yatabe Y., Takahashi T.,
RA Osada H., Takahashi T.;
RT "Detailed characterization of a homozygously deleted region corresponding
RT to a candidate tumor suppressor locus at distal 17p13.3 in human lung
RT cancer.";
RL Oncogene 22:1892-1905(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP GENE FAMILY.
RX PubMed=22363774; DOI=10.1371/journal.pone.0031961;
RA Sallman Almen M., Bringeland N., Fredriksson R., Schioth H.B.;
RT "The dispanins: a novel gene family of ancient origin that contains 14
RT human members.";
RL PLoS ONE 7:E31961-E31961(2012).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=26629404; DOI=10.1016/j.molmet.2015.08.003;
RA Beaton N., Rudigier C., Moest H., Mueller S., Mrosek N., Roeder E.,
RA Rudofsky G., Ruelicke T., Ukropec J., Ukropcova B., Augustin R.,
RA Neubauer H., Wolfrum C.;
RT "TUSC5 regulates insulin-mediated adipose tissue glucose uptake by
RT modulation of GLUT4 recycling.";
RL Mol. Metab. 4:795-810(2015).
CC -!- FUNCTION: Regulates insulin-mediated adipose tissue glucose uptake and
CC transport by modulation of SLC2A4 recycling. Not required for SLC2A4
CC membrane fusion upon an initial stimulus, but rather is necessary for
CC proper protein recycling during prolonged insulin stimulation.
CC {ECO:0000250|UniProtKB:Q8C838}.
CC -!- SUBUNIT: Interacts with SLC2A4; the interaction is required for proper
CC SLC2A4 reacycling after insulin stimulation.
CC {ECO:0000250|UniProtKB:Q8C838}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8C838};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q8C838}.
CC Endomembrane system {ECO:0000250|UniProtKB:Q8C838}; Single-pass
CC membrane protein {ECO:0000250|UniProtKB:Q8C838}. Cytoplasm, perinuclear
CC region {ECO:0000250|UniProtKB:Q8C838}. Note=Shifts from low-density
CC microsome vesicles to the cell membrane upon insulin stimulation.
CC {ECO:0000250|UniProtKB:Q8C838}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart, mammary gland,
CC adrenal gland, stomach, smooth muscle and skeletal muscle, and at lower
CC levels in brain and lung. Strongly down-regulated in lung cancer
CC tissues, due to hypermethylation of the corresponding locus
CC (PubMed:12660825). Expressed in adipose tissue (PubMed:26629404).
CC {ECO:0000269|PubMed:12660825, ECO:0000269|PubMed:26629404}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain.
CC {ECO:0000269|PubMed:12660825}.
CC -!- SIMILARITY: Belongs to the CD225/Dispanin family. {ECO:0000305}.
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DR EMBL; AB090231; BAC43751.1; -; mRNA.
DR EMBL; AC032044; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90630.1; -; Genomic_DNA.
DR CCDS; CCDS42225.1; -.
DR RefSeq; NP_758955.2; NM_172367.2.
DR AlphaFoldDB; Q8IXB3; -.
DR BioGRID; 130417; 121.
DR IntAct; Q8IXB3; 6.
DR STRING; 9606.ENSP00000329548; -.
DR iPTMnet; Q8IXB3; -.
DR PhosphoSitePlus; Q8IXB3; -.
DR BioMuta; TUSC5; -.
DR DMDM; 229462764; -.
DR jPOST; Q8IXB3; -.
DR MassIVE; Q8IXB3; -.
DR PaxDb; Q8IXB3; -.
DR PeptideAtlas; Q8IXB3; -.
DR PRIDE; Q8IXB3; -.
DR ProteomicsDB; 70982; -.
DR Antibodypedia; 58595; 157 antibodies from 27 providers.
DR DNASU; 286753; -.
DR Ensembl; ENST00000333813.4; ENSP00000329548.3; ENSG00000184811.4.
DR GeneID; 286753; -.
DR KEGG; hsa:286753; -.
DR MANE-Select; ENST00000333813.4; ENSP00000329548.3; NM_172367.3; NP_758955.2.
DR UCSC; uc002fsi.1; human.
DR CTD; 286753; -.
DR DisGeNET; 286753; -.
DR GeneCards; TRARG1; -.
DR HGNC; HGNC:29592; TRARG1.
DR HPA; ENSG00000184811; Group enriched (adipose tissue, breast).
DR MIM; 612211; gene.
DR neXtProt; NX_Q8IXB3; -.
DR OpenTargets; ENSG00000184811; -.
DR PharmGKB; PA134868023; -.
DR VEuPathDB; HostDB:ENSG00000184811; -.
DR eggNOG; ENOG502RY44; Eukaryota.
DR GeneTree; ENSGT00940000160337; -.
DR HOGENOM; CLU_103195_0_0_1; -.
DR InParanoid; Q8IXB3; -.
DR OMA; MQQGNVD; -.
DR OrthoDB; 1467259at2759; -.
DR PhylomeDB; Q8IXB3; -.
DR TreeFam; TF333012; -.
DR PathwayCommons; Q8IXB3; -.
DR SignaLink; Q8IXB3; -.
DR BioGRID-ORCS; 286753; 14 hits in 1060 CRISPR screens.
DR ChiTaRS; TUSC5; human.
DR GenomeRNAi; 286753; -.
DR Pharos; Q8IXB3; Tbio.
DR PRO; PR:Q8IXB3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8IXB3; protein.
DR Bgee; ENSG00000184811; Expressed in subcutaneous adipose tissue and 73 other tissues.
DR Genevisible; Q8IXB3; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0099638; P:endosome to plasma membrane protein transport; ISS:UniProtKB.
DR GO; GO:0044381; P:glucose import in response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0099500; P:vesicle fusion to plasma membrane; IEA:Ensembl.
DR InterPro; IPR007593; CD225/Dispanin_fam.
DR Pfam; PF04505; CD225; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..177
FT /note="Trafficking regulator of GLUT4 1"
FT /id="PRO_0000263639"
FT TOPO_DOM 1..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8C838"
FT INTRAMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8C838"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..177
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8C838"
FT REGION 71..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2MHH0"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2MHH0"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2MHH0"
FT VARIANT 3
FT /note="H -> Y (in dbSNP:rs75616699)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029589"
FT VARIANT 15
FT /note="P -> S (in dbSNP:rs111587833)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029590"
FT VARIANT 18
FT /note="A -> T (in dbSNP:rs111701043)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029591"
FT VARIANT 20
FT /note="F -> S (in dbSNP:rs6502774)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029592"
FT VARIANT 34
FT /note="E -> D (in dbSNP:rs75025906)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029593"
FT VARIANT 57
FT /note="S -> G (in dbSNP:rs6502776)"
FT /evidence="ECO:0000269|PubMed:12660825"
FT /id="VAR_029594"
SQ SEQUENCE 177 AA; 19254 MW; FCF701E12EDA70A5 CRC64;
MAHPVQSEFP SAQEPGSAAF LDLPEMEILL TKAENKDDKT LNLSKTLSGP LDLEQNSQGL
PFKAISEGHL EAPLPRSPSR ASSRRASSIA TTSYAQDQEA PRDYLILAVV ACFCPVWPLN
LIPLIISIMS RSSMQQGNVD GARRLGRLAR LLSITLIIMG IVIIMVAVTV NFTVQKK