RAE1E_HUMAN
ID RAE1E_HUMAN Reviewed; 263 AA.
AC Q8TD07; A6YF59; Q5VYB7; Q5VYB8; Q8TEZ2; Q96L41;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Retinoic acid early transcript 1E {ECO:0000303|PubMed:11827464, ECO:0000312|HGNC:HGNC:16793};
DE AltName: Full=Lymphocyte effector toxicity activation ligand {ECO:0000303|PubMed:14508119};
DE AltName: Full=NKG2D ligand 4;
DE Short=N2DL-4;
DE Short=NKG2DL4;
DE AltName: Full=RAE-1-like transcript 4 {ECO:0000303|Ref.5};
DE AltName: Full=UL16-binding protein 4;
DE Flags: Precursor;
GN Name=RAET1E {ECO:0000303|PubMed:11827464, ECO:0000312|HGNC:HGNC:16793};
GN Synonyms=LETAL {ECO:0000303|PubMed:14508119}, N2DL4,
GN ULBP4 {ECO:0000303|PubMed:12732206};
GN ORFNames=UNQ1867/PRO4303 {ECO:0000303|PubMed:12975309};
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), AND TISSUE SPECIFICITY.
RC TISSUE=Ovarian carcinoma;
RX PubMed=14508119; DOI=10.4161/cbt.2.4.479;
RA Conejo-Garcia J.-R., Benencia F., Courreges M.C., Khang E., Zhang L.,
RA Mohamed-Hadley A., Vinocur J.M., Buckanovich R.J., Thompson C.B.,
RA Levine B., Coukos G.;
RT "Letal, a tumor-associated NKG2D immunoreceptor ligand, induces activation
RT and expansion of effector immune cells.";
RL Cancer Biol. Ther. 2:446-451(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Esophagus;
RX PubMed=12732206; DOI=10.1016/s0006-291x(03)00714-9;
RA Chalupny N.J., Sutherland C.L., Lawrence W.A., Rein-Weston A., Cosman D.;
RT "ULBP4 is a novel ligand for human NKG2D.";
RL Biochem. Biophys. Res. Commun. 305:129-135(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH KLRK1, LACK OF
RP INTERACTION WITH CMV UL16, AND SUBCELLULAR LOCATION.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND ALTERNATIVE SPLICING.
RX PubMed=17470428; DOI=10.1074/jbc.m702504200;
RA Cao W., Xi X., Hao Z., Li W., Kong Y., Cui L., Ma C., Ba D., He W.;
RT "RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by
RT tumor cells, inhibits NKG2D-mediated NK cytotoxicity.";
RL J. Biol. Chem. 282:18922-18928(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Lanier L.L., Cerwenka A.;
RT "Homo sapiens RAE-1-like transcript 4 (RL-4) mRNA.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ASN-82.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-222 (ISOFORM 1), AND VARIANTS ASN-82 AND
RP HIS-128.
RX PubMed=11827464; DOI=10.1006/geno.2001.6673;
RA Radosavljevic M., Cuillerier B., Wilson M.J., Clement O., Wicker S.,
RA Gilfillan S., Beck S., Trowsdale J., Bahram S.;
RT "A cluster of ten novel MHC class I related genes on human chromosome
RT 6q24.2-q25.3.";
RL Genomics 79:114-123(2002).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS 2; 5 AND 6), INTERACTION WITH KLRK1,
RP FUNCTION, REGION, AND DOMAIN.
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).
CC -!- FUNCTION: Binds and activates the KLRK1/NKG2D receptor, mediating
CC natural killer cell cytotoxicity. {ECO:0000269|PubMed:15240696,
CC ECO:0000269|PubMed:18544572}.
CC -!- SUBUNIT: Binds to KLRK1/NKG2D. {ECO:0000269|PubMed:15240696,
CC ECO:0000269|PubMed:18544572}.
CC -!- SUBUNIT: (Microbial infection) Contrary to other family members, does
CC not interact with CMV glycoprotein UL16. {ECO:0000269|PubMed:15240696}.
CC -!- INTERACTION:
CC Q8TD07; P26718: KLRK1; NbExp=4; IntAct=EBI-16365677, EBI-458344;
CC Q8TD07-1; P26718: KLRK1; NbExp=2; IntAct=EBI-16747021, EBI-458344;
CC Q8TD07-2; P26718: KLRK1; NbExp=2; IntAct=EBI-16417277, EBI-458344;
CC Q8TD07-5; P26718: KLRK1; NbExp=2; IntAct=EBI-16747044, EBI-458344;
CC Q8TD07-6; P26718: KLRK1; NbExp=2; IntAct=EBI-16747033, EBI-458344;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15240696}; Single-
CC pass type I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=ULBP4 {ECO:0000303|PubMed:12732206}, RAET1E
CC {ECO:0000303|PubMed:15240696};
CC IsoId=Q8TD07-1; Sequence=Displayed;
CC Name=2; Synonyms=RL-4 {ECO:0000303|Ref.5}, ULBP4-II
CC {ECO:0000303|PubMed:18544572};
CC IsoId=Q8TD07-2; Sequence=VSP_010441;
CC Name=3;
CC IsoId=Q8TD07-3; Sequence=VSP_010442, VSP_010443;
CC Name=4; Synonyms=RAET1E2 {ECO:0000303|PubMed:17470428};
CC IsoId=Q8TD07-4; Sequence=VSP_045012;
CC Name=5; Synonyms=ULBP4-III {ECO:0000303|PubMed:18544572};
CC IsoId=Q8TD07-5; Sequence=VSP_059263;
CC Name=6; Synonyms=ULBP4-I {ECO:0000303|PubMed:18544572};
CC IsoId=Q8TD07-6; Sequence=VSP_059262;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the skin, but also
CC expressed in testis and trachea. Up-regulated in tumor cells of
CC different origins. Expression progressively decreased after treatment
CC of tumor cells with retinoic acid. {ECO:0000269|PubMed:12732206,
CC ECO:0000269|PubMed:14508119}.
CC -!- DOMAIN: MHC class I alpha-1 like and MHC class I alpha- like regions
CC down-regulate the cell surface expression of KLRK1.
CC {ECO:0000269|PubMed:18544572}.
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:0000305}.
CC -!- CAUTION: Contrary to other family members, does not interact with CMV
CC glycoprotein UL16. {ECO:0000269|PubMed:15240696}.
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DR EMBL; AY069961; AAL58090.1; -; mRNA.
DR EMBL; AY252119; AAP15166.1; -; mRNA.
DR EMBL; AY176317; AAO22240.1; -; mRNA.
DR EMBL; EF489426; ABR29881.1; -; mRNA.
DR EMBL; AY054974; AAL11005.1; -; mRNA.
DR EMBL; AY359075; AAQ89434.1; -; mRNA.
DR EMBL; AL355312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF359243; AAL76417.1; -; mRNA.
DR CCDS; CCDS5221.1; -. [Q8TD07-1]
DR CCDS; CCDS59042.1; -. [Q8TD07-4]
DR CCDS; CCDS59043.1; -. [Q8TD07-3]
DR CCDS; CCDS59044.1; -. [Q8TD07-2]
DR RefSeq; NP_001230254.1; NM_001243325.1. [Q8TD07-2]
DR RefSeq; NP_001230256.1; NM_001243327.1. [Q8TD07-4]
DR RefSeq; NP_001230257.1; NM_001243328.1. [Q8TD07-3]
DR RefSeq; NP_631904.1; NM_139165.2. [Q8TD07-1]
DR RefSeq; XP_011533781.1; XM_011535479.2. [Q8TD07-3]
DR AlphaFoldDB; Q8TD07; -.
DR SMR; Q8TD07; -.
DR BioGRID; 126425; 25.
DR IntAct; Q8TD07; 19.
DR STRING; 9606.ENSP00000349709; -.
DR GlyGen; Q8TD07; 3 sites.
DR PhosphoSitePlus; Q8TD07; -.
DR BioMuta; RAET1E; -.
DR EPD; Q8TD07; -.
DR jPOST; Q8TD07; -.
DR MassIVE; Q8TD07; -.
DR PaxDb; Q8TD07; -.
DR PeptideAtlas; Q8TD07; -.
DR PRIDE; Q8TD07; -.
DR ProteomicsDB; 1774; -.
DR ProteomicsDB; 74206; -. [Q8TD07-1]
DR ProteomicsDB; 74207; -. [Q8TD07-2]
DR ProteomicsDB; 74208; -. [Q8TD07-3]
DR Antibodypedia; 33297; 291 antibodies from 21 providers.
DR DNASU; 135250; -.
DR Ensembl; ENST00000357183.9; ENSP00000349709.4; ENSG00000164520.12. [Q8TD07-1]
DR Ensembl; ENST00000367363.3; ENSP00000356332.3; ENSG00000164520.12. [Q8TD07-2]
DR Ensembl; ENST00000529948.1; ENSP00000432366.1; ENSG00000164520.12. [Q8TD07-4]
DR Ensembl; ENST00000532335.5; ENSP00000437067.1; ENSG00000164520.12. [Q8TD07-3]
DR GeneID; 135250; -.
DR KEGG; hsa:135250; -.
DR MANE-Select; ENST00000357183.9; ENSP00000349709.4; NM_001394057.1; NP_001380986.1.
DR UCSC; uc003qnj.3; human. [Q8TD07-1]
DR CTD; 135250; -.
DR DisGeNET; 135250; -.
DR GeneCards; RAET1E; -.
DR HGNC; HGNC:16793; RAET1E.
DR HPA; ENSG00000164520; Tissue enhanced (esophagus, skin, vagina).
DR MIM; 609243; gene.
DR neXtProt; NX_Q8TD07; -.
DR OpenTargets; ENSG00000164520; -.
DR PharmGKB; PA134913788; -.
DR VEuPathDB; HostDB:ENSG00000164520; -.
DR eggNOG; ENOG502TM6M; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q8TD07; -.
DR OMA; GHREAMP; -.
DR OrthoDB; 1092787at2759; -.
DR PhylomeDB; Q8TD07; -.
DR TreeFam; TF339658; -.
DR PathwayCommons; Q8TD07; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q8TD07; -.
DR BioGRID-ORCS; 135250; 10 hits in 1063 CRISPR screens.
DR GeneWiki; RAET1E; -.
DR GenomeRNAi; 135250; -.
DR Pharos; Q8TD07; Tbio.
DR PRO; PR:Q8TD07; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8TD07; protein.
DR Bgee; ENSG00000164520; Expressed in esophagus mucosa and 91 other tissues.
DR ExpressionAtlas; Q8TD07; baseline and differential.
DR Genevisible; Q8TD07; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
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:0005886; C:plasma membrane; TAS:Reactome.
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:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; 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; Disulfide bond; Glycoprotein; Immunity; Membrane;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..263
FT /note="Retinoic acid early transcript 1E"
FT /id="PRO_0000019021"
FT TOPO_DOM 31..225
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 31..116
FT /note="MHC class I alpha-1 like; down-regulates the cell
FT surface expression of KLRK1"
FT /evidence="ECO:0000269|PubMed:18544572"
FT REGION 117..207
FT /note="MHC class I alpha-2 like; down-regulates the cell
FT surface expression of KLRK1"
FT /evidence="ECO:0000269|PubMed:18544572"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 126..189
FT /evidence="ECO:0000250"
FT VAR_SEQ 28..63
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_010441"
FT VAR_SEQ 29
FT /note="G -> GECPEHKNWLRTRRREKG (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:18544572"
FT /id="VSP_059262"
FT VAR_SEQ 165..208
FT /note="SKIKETWKKDRGLEKYFRKLSKGDCDHWLREFLGHWEAMPEPTV -> M
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:18544572"
FT /id="VSP_059263"
FT VAR_SEQ 208..263
FT /note="VSPVNASDIHWSSSSLPDRWIILGAFILLVLMGIVLICVWWQNGEWQAGLWP
FT LRTS -> GN (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17470428"
FT /id="VSP_045012"
FT VAR_SEQ 208..212
FT /note="VSPVN -> GRRST (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_010442"
FT VAR_SEQ 213..263
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_010443"
FT VARIANT 12
FT /note="R -> H (in dbSNP:rs9383583)"
FT /id="VAR_024534"
FT VARIANT 82
FT /note="Y -> N (in dbSNP:rs2151910)"
FT /evidence="ECO:0000269|PubMed:11827464,
FT ECO:0000269|PubMed:12975309"
FT /id="VAR_020271"
FT VARIANT 128
FT /note="R -> H (in dbSNP:rs6925151)"
FT /evidence="ECO:0000269|PubMed:11827464"
FT /id="VAR_024535"
FT VARIANT 141
FT /note="A -> T (in dbSNP:rs9383921)"
FT /id="VAR_050408"
FT VARIANT 142
FT /note="T -> I (in dbSNP:rs9371533)"
FT /id="VAR_050409"
FT VARIANT 194
FT /note="R -> G (in dbSNP:rs57292884)"
FT /id="VAR_061483"
FT VARIANT 237
FT /note="V -> L (in dbSNP:rs2342767)"
FT /id="VAR_024536"
FT CONFLICT 141..142
FT /note="AT -> TI (in Ref. 8; AAL76417)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 263 AA; 30122 MW; 3309279B51B603C8 CRC64;
MRRISLTSSP VRLLLFLLLL LIALEIMVGG HSLCFNFTIK SLSRPGQPWC EAQVFLNKNL
FLQYNSDNNM VKPLGLLGKK VYATSTWGEL TQTLGEVGRD LRMLLCDIKP QIKTSDPSTL
QVEMFCQREA ERCTGASWQF ATNGEKSLLF DAMNMTWTVI NHEASKIKET WKKDRGLEKY
FRKLSKGDCD HWLREFLGHW EAMPEPTVSP VNASDIHWSS SSLPDRWIIL GAFILLVLMG
IVLICVWWQN GEWQAGLWPL RTS
