ID   ULBP5_HUMAN             Reviewed;         334 AA.
AC   Q6H3X3; Q6H3X2;
DT   21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 152.
DE   RecName: Full=UL-16 binding protein 5;
DE   AltName: Full=Retinoic acid early transcript 1G protein {ECO:0000312|HGNC:HGNC:16795};
DE   Flags: Precursor;
GN   Name=RAET1G {ECO:0000303|PubMed:19223974,
GN   ECO:0000312|HGNC:HGNC:16795};
GN   Synonyms=ULBP5 {ECO:0000303|PubMed:19223974};
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] {ECO:0000305, ECO:0000312|EMBL:AAO22238.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP   LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH KLRK1 AND CMV UL16.
RX   PubMed=15240696; DOI=10.4049/jimmunol.173.2.1078;
RA   Bacon L., Eagle R.A., Meyer M., Easom N., Young N.T., Trowsdale J.;
RT   "Two human ULBP/RAET1 molecules with transmembrane regions are ligands for
RT   NKG2D.";
RL   J. Immunol. 173:1078-1084(2004).
RN   [2]
RP   ALTERNATIVE SPLICING (ISOFORM 3), AND INTERACTION WITH KLRK1.
RX   PubMed=18544572; DOI=10.1093/intimm/dxn057;
RA   Cao W., Xi X., Wang Z., Dong L., Hao Z., Cui L., Ma C., He W.;
RT   "Four novel ULBP splice variants are ligands for human NKG2D.";
RL   Int. Immunol. 20:981-991(2008).
RN   [3]
RP   FUNCTION, INTERACTION WITH KLRK1 AND CMV UL16, AND TISSUE SPECIFICITY.
RX   PubMed=19658097; DOI=10.1002/eji.200939502;
RA   Eagle R.A., Traherne J.A., Hair J.R., Jafferji I., Trowsdale J.;
RT   "ULBP6/RAET1L is an additional human NKG2D ligand.";
RL   Eur. J. Immunol. 39:3207-3216(2009).
RN   [4]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-82.
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19349973; DOI=10.1038/nbt.1532;
RA   Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA   Schiess R., Aebersold R., Watts J.D.;
RT   "Mass-spectrometric identification and relative quantification of N-linked
RT   cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [5]
RP   SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX   PubMed=19223974; DOI=10.1371/journal.pone.0004503;
RA   Eagle R.A., Flack G., Warford A., Martinez-Borra J., Jafferji I.,
RA   Traherne J.A., Ohashi M., Boyle L.H., Barrow A.D., Caillat-Zucman S.,
RA   Young N.T., Trowsdale J.;
RT   "Cellular expression, trafficking, and function of two isoforms of human
RT   ULBP5/RAET1G.";
RL   PLoS ONE 4:E4503-E4503(2009).
RN   [6]
RP   SUBCELLULAR LOCATION, GPI-ANCHOR AT GLY-218, PROTEOLYTIC PROCESSING, AND
RP   MUTAGENESIS OF SER-217.
RX   PubMed=20304922; DOI=10.1074/jbc.m109.077636;
RA   Ohashi M., Eagle R.A., Trowsdale J.;
RT   "Post-translational modification of the NKG2D ligand RAET1G leads to cell
RT   surface expression of a glycosylphosphatidylinositol-linked isoform.";
RL   J. Biol. Chem. 285:16408-16415(2010).
CC   -!- FUNCTION: [Isoform 1]: Binds and activates the KLRK1/NKG2D receptor,
CC       mediating natural killer cell cytotoxicity.
CC       {ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:18544572,
CC       ECO:0000269|PubMed:19658097}.
CC   -!- FUNCTION: [Isoform 3]: Down-regulates the expression of KLRK1 and
CC       stimulates natural killer cells to secrete IFNG.
CC       {ECO:0000269|PubMed:18544572}.
CC   -!- FUNCTION: [Isoform 2]: Stimulates natural killer cells to secrete IFNG.
CC       {ECO:0000269|PubMed:18544572}.
CC   -!- SUBUNIT: Interacts with KLRK1/NKG2D. {ECO:0000269|PubMed:15240696,
CC       ECO:0000269|PubMed:18544572, ECO:0000269|PubMed:19658097}.
CC   -!- SUBUNIT: (Microbial infection) In CMV-infected cells, interacts with
CC       the viral glycoprotein UL16; this interaction causes RAET1G retention
CC       in the endoplasmic reticulum and cis-Golgi and prevents binding to and
CC       activation of KLRK1/NKG2D, providing CMV with an immune evasion
CC       mechanism. {ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:19658097}.
CC   -!- INTERACTION:
CC       Q6H3X3; P26718: KLRK1; NbExp=6; IntAct=EBI-458334, EBI-458344;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC       {ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:19223974,
CC       ECO:0000269|PubMed:20304922}; Lipid-anchor, GPI-anchor
CC       {ECO:0000269|PubMed:20304922}. Endoplasmic reticulum
CC       {ECO:0000269|PubMed:19223974, ECO:0000269|PubMed:20304922}. Note=Mainly
CC       found intracellularly. {ECO:0000269|PubMed:15240696,
CC       ECO:0000269|PubMed:19223974, ECO:0000269|PubMed:20304922}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC       {ECO:0000269|PubMed:19223974}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1 {ECO:0000269|PubMed:15240696}; Synonyms=RAET1G1
CC       {ECO:0000303|PubMed:15240696};
CC         IsoId=Q6H3X3-1; Sequence=Displayed;
CC       Name=2 {ECO:0000269|PubMed:15240696}; Synonyms=RAET1G2
CC       {ECO:0000303|PubMed:15240696};
CC         IsoId=Q6H3X3-2; Sequence=VSP_051621, VSP_051622;
CC       Name=3; Synonyms=RAET1G3 {ECO:0000303|PubMed:18544572};
CC         IsoId=Q6H3X3-3; Sequence=VSP_059264, VSP_051622;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is highly expressed in colon and in a
CC       number of tumor cell lines and highly restricted in normal tissues.
CC       Both isoforms are frequently expressed in cell lines derived from
CC       epithelial cancers, and in primary breast cancers.
CC       {ECO:0000269|PubMed:15240696, ECO:0000269|PubMed:19223974,
CC       ECO:0000269|PubMed:19658097}.
CC   -!- PTM: The functional form is cleaved C-terminally of the GPI-anchor and
CC       yields a 28 kDa protein. {ECO:0000269|PubMed:20304922}.
CC   -!- MISCELLANEOUS: UL16-binding proteins (ULBPs) are unusual members of the
CC       extended MHC class I superfamily. They do not contain the alpha 3
CC       domain and lack a transmembrane domain. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000255}.
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DR   EMBL; AY172579; AAO22238.1; -; mRNA.
DR   EMBL; AY172580; AAO22239.1; -; mRNA.
DR   CCDS; CCDS43514.1; -. [Q6H3X3-1]
DR   RefSeq; NP_001001788.2; NM_001001788.3. [Q6H3X3-1]
DR   AlphaFoldDB; Q6H3X3; -.
DR   SMR; Q6H3X3; -.
DR   BioGRID; 131627; 1.
DR   IntAct; Q6H3X3; 2.
DR   STRING; 9606.ENSP00000356329; -.
DR   GlyCosmos; Q6H3X3; 1 site, No reported glycans.
DR   GlyGen; Q6H3X3; 1 site.
DR   iPTMnet; Q6H3X3; -.
DR   PhosphoSitePlus; Q6H3X3; -.
DR   BioMuta; RAET1G; -.
DR   DMDM; 56749591; -.
DR   EPD; Q6H3X3; -.
DR   jPOST; Q6H3X3; -.
DR   MassIVE; Q6H3X3; -.
DR   MaxQB; Q6H3X3; -.
DR   PaxDb; 9606-ENSP00000356329; -.
DR   PeptideAtlas; Q6H3X3; -.
DR   ProteomicsDB; 66338; -. [Q6H3X3-1]
DR   ProteomicsDB; 66339; -. [Q6H3X3-2]
DR   Pumba; Q6H3X3; -.
DR   TopDownProteomics; Q6H3X3-1; -. [Q6H3X3-1]
DR   Antibodypedia; 33303; 33 antibodies from 8 providers.
DR   DNASU; 353091; -.
DR   Ensembl; ENST00000367360.7; ENSP00000356329.2; ENSG00000203722.8. [Q6H3X3-1]
DR   Ensembl; ENST00000367361.6; ENSP00000356330.2; ENSG00000203722.8. [Q6H3X3-2]
DR   GeneID; 353091; -.
DR   KEGG; hsa:353091; -.
DR   MANE-Select; ENST00000367360.7; ENSP00000356329.2; NM_001001788.4; NP_001001788.2.
DR   UCSC; uc010kii.1; human. [Q6H3X3-1]
DR   AGR; HGNC:16795; -.
DR   CTD; 353091; -.
DR   DisGeNET; 353091; -.
DR   GeneCards; RAET1G; -.
DR   HGNC; HGNC:16795; RAET1G.
DR   HPA; ENSG00000203722; Tissue enhanced (adrenal gland, esophagus).
DR   MIM; 609244; gene.
DR   neXtProt; NX_Q6H3X3; -.
DR   OpenTargets; ENSG00000203722; -.
DR   PharmGKB; PA134897742; -.
DR   VEuPathDB; HostDB:ENSG00000203722; -.
DR   eggNOG; ENOG502TM6M; Eukaryota.
DR   GeneTree; ENSGT01100000263517; -.
DR   HOGENOM; CLU_086235_0_0_1; -.
DR   InParanoid; Q6H3X3; -.
DR   OMA; NNGAARH; -.
DR   OrthoDB; 5267070at2759; -.
DR   PhylomeDB; Q6H3X3; -.
DR   TreeFam; TF341724; -.
DR   PathwayCommons; Q6H3X3; -.
DR   Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR   SignaLink; Q6H3X3; -.
DR   BioGRID-ORCS; 353091; 13 hits in 1105 CRISPR screens.
DR   GenomeRNAi; 353091; -.
DR   Pharos; Q6H3X3; Tbio.
DR   PRO; PR:Q6H3X3; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q6H3X3; Protein.
DR   Bgee; ENSG00000203722; Expressed in esophagus mucosa and 90 other cell types or tissues.
DR   ExpressionAtlas; Q6H3X3; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0046703; F:natural killer cell lectin-like receptor binding; IPI:UniProtKB.
DR   GO; GO:0002486; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent; IBA:GO_Central.
DR   GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IBA:GO_Central.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR   GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IDA:UniProtKB.
DR   GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IBA:GO_Central.
DR   Gene3D; 3.30.500.10; MHC class I-like antigen recognition-like; 1.
DR   InterPro; IPR011161; MHC_I-like_Ag-recog.
DR   InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR   InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR   PANTHER; PTHR16675; MHC CLASS I-RELATED; 1.
DR   PANTHER; PTHR16675:SF232; UL-16 BINDING PROTEIN 5; 1.
DR   Pfam; PF00129; MHC_I; 1.
DR   SUPFAM; SSF54452; MHC antigen-recognition domain; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW   Glycoprotein; GPI-anchor; Host-virus interaction; Immunity; Lipoprotein;
KW   Membrane; Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000250|UniProtKB:Q9BZM5"
FT   CHAIN           26..218
FT                   /note="UL-16 binding protein 5"
FT                   /id="PRO_0000019022"
FT   PROPEP          219..334
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000429932"
FT   TOPO_DOM        26..223
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        224..243
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        244..334
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          29..117
FT                   /note="MHC class I alpha-1 like"
FT   REGION          118..210
FT                   /note="MHC class I alpha-2 like"
FT   LIPID           218
FT                   /note="GPI-anchor amidated glycine"
FT                   /evidence="ECO:0000305|PubMed:20304922"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973"
FT   DISULFID        50..66
FT                   /evidence="ECO:0000250|UniProtKB:Q9BZM4"
FT   DISULFID        127..190
FT                   /evidence="ECO:0000250|UniProtKB:Q9BZM4"
FT   VAR_SEQ         118..154
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:18544572"
FT                   /id="VSP_059264"
FT   VAR_SEQ         211..213
FT                   /note="APP -> GTV (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15240696"
FT                   /id="VSP_051621"
FT   VAR_SEQ         214..334
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15240696"
FT                   /id="VSP_051622"
FT   VARIANT         70
FT                   /note="T -> R (in dbSNP:rs9397449)"
FT                   /id="VAR_033449"
FT   MUTAGEN         217
FT                   /note="S->P: Reduced cell surface expression."
FT                   /evidence="ECO:0000269|PubMed:20304922"
SQ   SEQUENCE   334 AA;  37106 MW;  3F8350036951BA69 CRC64;
     MAAAASPAFL LRLPLLLLLS SWCRTGLADP HSLCYDITVI PKFRPGPRWC AVQGQVDEKT
     FLHYDCGSKT VTPVSPLGKK LNVTTAWKAQ NPVLREVVDI LTEQLLDIQL ENYIPKEPLT
     LQARMSCEQK AEGHGSGSWQ LSFDGQIFLL FDSENRMWTT VHPGARKMKE KWENDKDMTM
     SFHYISMGDC TGWLEDFLMG MDSTLEPSAG APPTMSSGTA QPRATATTLI LCCLLIMCLL
     ICSRHSLTQS HGHHPQSLQP PPHPPLLHPT WLLRRVLWSD SYQIAKRPLS GGHVTRVTLP
     IIGDDSHSLP CPLALYTINN GAARYSEPLQ VSIS
//