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   04-NOV-2026, entry version 133.
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_172367.3.
DR   AlphaFoldDB; Q8IXB3; -.
DR   BioGRID; 130417; 124.
DR   FunCoup; Q8IXB3; 58.
DR   IntAct; Q8IXB3; 9.
DR   STRING; 9606.ENSP00000329548; -.
DR   iPTMnet; Q8IXB3; -.
DR   PhosphoSitePlus; Q8IXB3; -.
DR   BioMuta; TUSC5; -.
DR   DMDM; 229462764; -.
DR   MassIVE; Q8IXB3; -.
DR   PaxDb; 9606-ENSP00000329548; -.
DR   PeptideAtlas; Q8IXB3; -.
DR   ProteomicsDB; 70982; -.
DR   Antibodypedia; 58595; 161 antibodies from 30 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   AGR; HGNC:29592; -.
DR   ClinPGx; PA134868023; -.
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   OpenTargets; ENSG00000184811; -.
DR   VEuPathDB; HostDB:ENSG00000184811; -.
DR   eggNOG; ENOG502RY44; Eukaryota.
DR   GeneTree; ENSGT00940000160337; -.
DR   HOGENOM; CLU_103195_0_0_1; -.
DR   InParanoid; Q8IXB3; -.
DR   OMA; ADFHETE; -.
DR   OrthoDB; 9049275at2759; -.
DR   PAN-GO; Q8IXB3; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; Q8IXB3; -.
DR   PathwayCommons; Q8IXB3; -.
DR   SignaLink; Q8IXB3; -.
DR   Agora; ENSG00000184811; -.
DR   BioGRID-ORCS; 286753; 14 hits in 1134 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 75 other cell types or tissues.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0012505; C:endomembrane system; ISS:UniProtKB.
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   InterPro; IPR051423; CD225/Dispanin.
DR   InterPro; IPR007593; CD225/Dispanin_fam.
DR   PANTHER; PTHR14948; NG5; 1.
DR   PANTHER; PTHR14948:SF1; TRAFFICKING REGULATOR OF GLUT4 1; 1.
DR   Pfam; PF04505; CD225; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Transmembrane;
KW   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   COMPBIAS        72..88
FT                   /note="Low complexity"
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
//