ULBP5_HUMAN
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 03-AUG-2022, entry version 144.
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, 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 IntAct; Q6H3X3; 2.
DR STRING; 9606.ENSP00000356329; -.
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; Q6H3X3; -.
DR PeptideAtlas; Q6H3X3; -.
DR PRIDE; Q6H3X3; -.
DR ProteomicsDB; 66338; -. [Q6H3X3-1]
DR ProteomicsDB; 66339; -. [Q6H3X3-2]
DR TopDownProteomics; Q6H3X3-1; -. [Q6H3X3-1]
DR Antibodypedia; 33303; 22 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 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; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q6H3X3; -.
DR OMA; MCPRHSP; -.
DR OrthoDB; 1092787at2759; -.
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 1027 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 89 other tissues.
DR ExpressionAtlas; Q6H3X3; baseline and differential.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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 Gene3D; 3.30.500.10; -; 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 Pfam; PF00129; MHC_I; 1.
DR SUPFAM; SSF54452; SSF54452; 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
