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Retinoic acid early transcript 1E (Lymphocyte effector toxicity activation ligand) (NKG2D ligand 4) (N2DL-4) (NKG2DL4) (RAE-1-like transcript 4) (UL16-binding protein 4)

 RAE1E_HUMAN             Reviewed;         263 AA.
Q8TD07; A6YF59; Q5VYB7; Q5VYB8; Q8TEZ2; Q96L41;
24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
01-JUN-2002, sequence version 1.
20-JUN-2018, entry version 140.
RecName: Full=Retinoic acid early transcript 1E {ECO:0000303|PubMed:11827464, ECO:0000312|HGNC:HGNC:16793};
AltName: Full=Lymphocyte effector toxicity activation ligand {ECO:0000303|PubMed:14508119};
AltName: Full=NKG2D ligand 4;
Short=N2DL-4;
Short=NKG2DL4;
AltName: Full=RAE-1-like transcript 4 {ECO:0000303|Ref.5};
AltName: Full=UL16-binding protein 4;
Flags: Precursor;
Name=RAET1E {ECO:0000303|PubMed:11827464,
ECO:0000312|HGNC:HGNC:16793};
Synonyms=LETAL {ECO:0000303|PubMed:14508119}, N2DL4,
ULBP4 {ECO:0000303|PubMed:12732206};
ORFNames=UNQ1867/PRO4303 {ECO:0000303|PubMed:12975309};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
TISSUE=Ovarian carcinoma;
PubMed=14508119; DOI=10.4161/cbt.2.4.479;
Conejo-Garcia J.-R., Benencia F., Courreges M.C., Khang E., Zhang L.,
Mohamed-Hadley A., Vinocur J.M., Buckanovich R.J., Thompson C.B.,
Levine B., Coukos G.;
"Letal, a tumor-associated NKG2D immunoreceptor ligand, induces
activation and expansion of effector immune cells.";
Cancer Biol. Ther. 2:446-451(2003).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
TISSUE=Esophagus;
PubMed=12732206; DOI=10.1016/S0006-291X(03)00714-9;
Chalupny N.J., Sutherland C.L., Lawrence W.A., Rein-Weston A.,
Cosman D.;
"ULBP4 is a novel ligand for human NKG2D.";
Biochem. Biophys. Res. Commun. 305:129-135(2003).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH KLRK1, LACK
OF INTERACTION WITH CMV UL16, AND SUBCELLULAR LOCATION.
PubMed=15240696; DOI=10.4049/jimmunol.173.2.1078;
Bacon L., Eagle R.A., Meyer M., Easom N., Young N.T., Trowsdale J.;
"Two human ULBP/RAET1 molecules with transmembrane regions are ligands
for NKG2D.";
J. Immunol. 173:1078-1084(2004).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND ALTERNATIVE SPLICING.
PubMed=17470428; DOI=10.1074/jbc.M702504200;
Cao W., Xi X., Hao Z., Li W., Kong Y., Cui L., Ma C., Ba D., He W.;
"RAET1E2, a soluble isoform of the UL16-binding protein RAET1E
produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity.";
J. Biol. Chem. 282:18922-18928(2007).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Lanier L.L., Cerwenka A.;
"Homo sapiens RAE-1-like transcript 4 (RL-4) mRNA.";
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT
ASN-82.
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=14574404; DOI=10.1038/nature02055;
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-222 (ISOFORM 1), AND VARIANTS ASN-82
AND HIS-128.
PubMed=11827464; DOI=10.1006/geno.2001.6673;
Radosavljevic M., Cuillerier B., Wilson M.J., Clement O., Wicker S.,
Gilfillan S., Beck S., Trowsdale J., Bahram S.;
"A cluster of ten novel MHC class I related genes on human chromosome
6q24.2-q25.3.";
Genomics 79:114-123(2002).
[9]
ALTERNATIVE SPLICING (ISOFORMS 2; 5 AND 6), INTERACTION WITH KLRK1,
FUNCTION, REGION, AND DOMAIN.
PubMed=18544572; DOI=10.1093/intimm/dxn057;
Cao W., Xi X., Wang Z., Dong L., Hao Z., Cui L., Ma C., He W.;
"Four novel ULBP splice variants are ligands for human NKG2D.";
Int. Immunol. 20:981-991(2008).
-!- FUNCTION: Binds and activates the KLRK1/NKG2D receptor, mediating
natural killer cell cytotoxicity. {ECO:0000269|PubMed:15240696,
ECO:0000269|PubMed:18544572}.
-!- SUBUNIT: Binds to KLRK1/NKG2D. {ECO:0000269|PubMed:15240696,
ECO:0000269|PubMed:18544572}.
-!- SUBUNIT: (Microbial infection) Contrary to other family members,
does not interact with CMV glycoprotein UL16.
{ECO:0000269|PubMed:15240696}.
-!- INTERACTION:
P26718:KLRK1; NbExp=4; IntAct=EBI-16365677, EBI-458344;
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15240696};
Single-pass type I membrane protein.
-!- SUBCELLULAR LOCATION: Isoform 4: Secreted.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=6;
Name=1; Synonyms=ULBP4 {ECO:0000303|PubMed:12732206}, RAET1E
{ECO:0000303|PubMed:15240696};
IsoId=Q8TD07-1; Sequence=Displayed;
Name=2; Synonyms=RL-4 {ECO:0000303|Ref.5}, ULBP4-II
{ECO:0000303|PubMed:18544572};
IsoId=Q8TD07-2; Sequence=VSP_010441;
Name=3;
IsoId=Q8TD07-3; Sequence=VSP_010442, VSP_010443;
Note=No experimental confirmation available.;
Name=4; Synonyms=RAET1E2 {ECO:0000303|PubMed:17470428};
IsoId=Q8TD07-4; Sequence=VSP_045012;
Name=5; Synonyms=ULBP4-III {ECO:0000303|PubMed:18544572};
IsoId=Q8TD07-5; Sequence=VSP_059263;
Name=6; Synonyms=ULBP4-I {ECO:0000303|PubMed:18544572};
IsoId=Q8TD07-6; Sequence=VSP_059262;
-!- TISSUE SPECIFICITY: Predominantly expressed in the skin, but also
expressed in testis and trachea. Up-regulated in tumor cells of
different origins. Expression progressively decreased after
treatment of tumor cells with retinoic acid.
{ECO:0000269|PubMed:12732206, ECO:0000269|PubMed:14508119}.
-!- DOMAIN: MHC class I alpha-1 like and MHC class I alpha- like
regions down-regulate the cell surface expression of KLRK1.
{ECO:0000269|PubMed:18544572}.
-!- MISCELLANEOUS: UL16-binding proteins (ULBPs) are unusual members
of the extended MHC class I superfamily. They do not contain the
alpha 3 domain and lack a transmembrane domain. {ECO:0000305}.
-!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
-!- CAUTION: Contrary to other family members, does not interact with
CMV glycoprotein UL16. {ECO:0000269|PubMed:15240696}.
-----------------------------------------------------------------------
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EMBL; AY069961; AAL58090.1; -; mRNA.
EMBL; AY252119; AAP15166.1; -; mRNA.
EMBL; AY176317; AAO22240.1; -; mRNA.
EMBL; EF489426; ABR29881.1; -; mRNA.
EMBL; AY054974; AAL11005.1; -; mRNA.
EMBL; AY359075; AAQ89434.1; -; mRNA.
EMBL; AL355312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AF359243; AAL76417.1; -; mRNA.
CCDS; CCDS5221.1; -. [Q8TD07-1]
CCDS; CCDS59042.1; -. [Q8TD07-4]
CCDS; CCDS59043.1; -. [Q8TD07-3]
CCDS; CCDS59044.1; -. [Q8TD07-2]
RefSeq; NP_001230254.1; NM_001243325.1. [Q8TD07-2]
RefSeq; NP_001230256.1; NM_001243327.1. [Q8TD07-4]
RefSeq; NP_001230257.1; NM_001243328.1. [Q8TD07-3]
RefSeq; NP_631904.1; NM_139165.2. [Q8TD07-1]
RefSeq; XP_011533781.1; XM_011535479.2. [Q8TD07-3]
UniGene; Hs.511818; -.
ProteinModelPortal; Q8TD07; -.
SMR; Q8TD07; -.
BioGrid; 126425; 19.
IntAct; Q8TD07; 1.
STRING; 9606.ENSP00000349709; -.
PhosphoSitePlus; Q8TD07; -.
BioMuta; RAET1E; -.
PaxDb; Q8TD07; -.
PeptideAtlas; Q8TD07; -.
PRIDE; Q8TD07; -.
ProteomicsDB; 74206; -.
ProteomicsDB; 74207; -. [Q8TD07-2]
ProteomicsDB; 74208; -. [Q8TD07-3]
Ensembl; ENST00000357183; ENSP00000349709; ENSG00000164520. [Q8TD07-1]
Ensembl; ENST00000367363; ENSP00000356332; ENSG00000164520. [Q8TD07-2]
Ensembl; ENST00000529948; ENSP00000432366; ENSG00000164520. [Q8TD07-4]
Ensembl; ENST00000532335; ENSP00000437067; ENSG00000164520. [Q8TD07-3]
GeneID; 135250; -.
KEGG; hsa:135250; -.
UCSC; uc003qnj.3; human. [Q8TD07-1]
CTD; 135250; -.
DisGeNET; 135250; -.
EuPathDB; HostDB:ENSG00000164520.11; -.
GeneCards; RAET1E; -.
H-InvDB; HIX0032797; -.
HGNC; HGNC:16793; RAET1E.
HPA; HPA054022; -.
MIM; 609243; gene.
neXtProt; NX_Q8TD07; -.
OpenTargets; ENSG00000164520; -.
PharmGKB; PA134913788; -.
eggNOG; ENOG410JBPA; Eukaryota.
eggNOG; ENOG411150N; LUCA.
GeneTree; ENSGT00390000003472; -.
HOGENOM; HOG000070028; -.
HOVERGEN; HBG052564; -.
InParanoid; Q8TD07; -.
KO; K07987; -.
OMA; WQFAING; -.
OrthoDB; EOG091G0NI5; -.
PhylomeDB; Q8TD07; -.
TreeFam; TF339658; -.
Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
GeneWiki; RAET1E; -.
GenomeRNAi; 135250; -.
PRO; PR:Q8TD07; -.
Proteomes; UP000005640; Chromosome 6.
Bgee; ENSG00000164520; -.
CleanEx; HS_RAET1E; -.
ExpressionAtlas; Q8TD07; baseline and differential.
Genevisible; Q8TD07; HS.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
GO; GO:0046703; F:natural killer cell lectin-like receptor binding; IPI:UniProtKB.
GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:UniProtKB.
GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB.
GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
GO; GO:0001913; P:T cell mediated cytotoxicity; IBA:GO_Central.
Gene3D; 3.30.500.10; -; 1.
InterPro; IPR011161; MHC_I-like_Ag-recog.
InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
InterPro; IPR011162; MHC_I/II-like_Ag-recog.
Pfam; PF00129; MHC_I; 1.
SUPFAM; SSF54452; SSF54452; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Disulfide bond; Glycoprotein;
Immunity; Membrane; Polymorphism; Reference proteome; Secreted;
Signal; Transmembrane; Transmembrane helix.
SIGNAL 1 30 {ECO:0000255}.
CHAIN 31 263 Retinoic acid early transcript 1E.
/FTId=PRO_0000019021.
TOPO_DOM 31 225 Extracellular. {ECO:0000255}.
TRANSMEM 226 248 Helical. {ECO:0000255}.
TOPO_DOM 249 263 Cytoplasmic. {ECO:0000255}.
REGION 31 116 MHC class I alpha-1 like; down-regulates
the cell surface expression of KLRK1.
{ECO:0000269|PubMed:18544572}.
REGION 117 207 MHC class I alpha-2 like; down-regulates
the cell surface expression of KLRK1.
{ECO:0000269|PubMed:18544572}.
COMPBIAS 219 222 Poly-Ser.
CARBOHYD 36 36 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 154 154 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 212 212 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 126 189 {ECO:0000250}.
VAR_SEQ 28 63 Missing (in isoform 2).
{ECO:0000303|Ref.5}.
/FTId=VSP_010441.
VAR_SEQ 29 29 G -> GECPEHKNWLRTRRREKG (in isoform 6).
{ECO:0000303|PubMed:18544572}.
/FTId=VSP_059262.
VAR_SEQ 165 208 SKIKETWKKDRGLEKYFRKLSKGDCDHWLREFLGHWEAMPE
PTV -> M (in isoform 5).
{ECO:0000303|PubMed:18544572}.
/FTId=VSP_059263.
VAR_SEQ 208 263 VSPVNASDIHWSSSSLPDRWIILGAFILLVLMGIVLICVWW
QNGEWQAGLWPLRTS -> GN (in isoform 4).
{ECO:0000303|PubMed:17470428}.
/FTId=VSP_045012.
VAR_SEQ 208 212 VSPVN -> GRRST (in isoform 3).
{ECO:0000303|PubMed:12975309}.
/FTId=VSP_010442.
VAR_SEQ 213 263 Missing (in isoform 3).
{ECO:0000303|PubMed:12975309}.
/FTId=VSP_010443.
VARIANT 12 12 R -> H (in dbSNP:rs9383583).
/FTId=VAR_024534.
VARIANT 82 82 Y -> N (in dbSNP:rs2151910).
{ECO:0000269|PubMed:11827464,
ECO:0000269|PubMed:12975309}.
/FTId=VAR_020271.
VARIANT 128 128 R -> H (in dbSNP:rs6925151).
{ECO:0000269|PubMed:11827464}.
/FTId=VAR_024535.
VARIANT 141 141 A -> T (in dbSNP:rs9383921).
/FTId=VAR_050408.
VARIANT 142 142 T -> I (in dbSNP:rs9371533).
/FTId=VAR_050409.
VARIANT 194 194 R -> G (in dbSNP:rs57292884).
/FTId=VAR_061483.
VARIANT 237 237 V -> L (in dbSNP:rs2342767).
/FTId=VAR_024536.
CONFLICT 141 142 AT -> TI (in Ref. 8; AAL76417).
{ECO:0000305}.
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


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