ULBP6_HUMAN
ID ULBP6_HUMAN Reviewed; 246 AA.
AC Q5VY80; A3KME4; Q8TE74;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=UL16-binding protein 6 {ECO:0000303|PubMed:19658097};
DE AltName: Full=Retinoic acid early transcript 1L protein;
DE Flags: Precursor;
GN Name=RAET1L; Synonyms=ULBP6 {ECO:0000303|PubMed:19658097};
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, AND VARIANT THR-85.
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-246, AND VARIANT THR-85.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP VARIANTS GLY-26; THR-85; ARG-106 AND ILE-147, FUNCTION, INTERACTION WITH
RP KLRK1 AND CMV UL16, SUBCELLULAR LOCATION, 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 [5] {ECO:0007744|PDB:4S0U}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 29-203 IN COMPLEX WITH KLRK1,
RP VARIANTS GLY-26; THR-85; ARG-106 AND ILE-147, CHARACTERIZATION OF ALLELES
RP ULBP6*01 AND ULBP6*02, INTERACTION WITH KLRK1, AND TISSUE SPECIFICITY.
RX PubMed=28559451; DOI=10.1126/scisignal.aai8904;
RA Zuo J., Willcox C.R., Mohammed F., Davey M., Hunter S., Khan K., Antoun A.,
RA Katakia P., Croudace J., Inman C., Parry H., Briggs D., Malladi R.,
RA Willcox B.E., Moss P.;
RT "A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell
RT killing by enhancing the stability of NKG2D ligand binding.";
RL Sci. Signal. 10:0-0(2017).
CC -!- FUNCTION: Binds and activates the KLRK1/NKG2D receptor, mediating
CC natural killer cell cytotoxicity. {ECO:0000269|PubMed:19658097,
CC ECO:0000269|PubMed:28559451}.
CC -!- SUBUNIT: Interacts with KLRK1/NKG2D. {ECO:0000269|PubMed:19658097,
CC ECO:0000269|PubMed:28559451}.
CC -!- SUBUNIT: (Microbial infection) In CMV-infected cells, interacts with
CC the viral glycoprotein UL16; this interaction causes relocalization
CC from the cell surface to the cytoplasm and prevents binding to and
CC activation of KLRK1/NKG2D, providing CMV with an immune evasion
CC mechanism. {ECO:0000269|PubMed:19658097}.
CC -!- INTERACTION:
CC Q5VY80; P26718: KLRK1; NbExp=4; IntAct=EBI-16364752, EBI-458344;
CC Q5VY80; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-16364752, EBI-11956541;
CC Q5VY80; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-16364752, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19658097};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:19658097}. Endoplasmic
CC reticulum {ECO:0000250|UniProtKB:Q9BZM6}. Note=In CMV-infected
CC fibroblasts, detected intracellularly. {ECO:0000269|PubMed:19658097}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11827464). Expressed in
CC trachea (PubMed:19658097). Constitutively expressed in peripheral blood
CC mononuclear cells, including B-cells and natural killer cells, as well
CC as CD4+ and CD8+ T-cells and monocytes. Tends to be up-regulated in
CC various lymphoid malignancies, including chronic lymphocytic leukemia
CC (PubMed:28559451). {ECO:0000269|PubMed:11827464,
CC ECO:0000269|PubMed:19658097, ECO:0000269|PubMed:28559451}.
CC -!- POLYMORPHISM: 4 alleles have been identified in 32 Caucasian
CC individuals: ULBP6*01 (frequency 0.483), ULBP6*02 (frequency 0.424),
CC ULBP6*03 (frequency 0.069) and ULBP6*04 (frequency 0.024). The sequence
CC shown is that of ULBP6*03 (PubMed:19658097). Allele ULBP6*02 has a much
CC higher affinity for KLRK1/NKG2D than allele ULBP6*01, but elicits less-
CC efficient cytotoxicity. This high binding affinity and limited
CC functional potency may depend upon the presence of the Leu residue at
CC position 106 (PubMed:28559451). {ECO:0000269|PubMed:19658097,
CC ECO:0000269|PubMed:28559451}.
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.
CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
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DR EMBL; AY039682; AAK91503.1; -; mRNA.
DR EMBL; AL355497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC131600; AAI31601.1; -; mRNA.
DR CCDS; CCDS5224.1; -.
DR RefSeq; NP_570970.2; NM_130900.2.
DR RefSeq; XP_011533788.1; XM_011535486.2.
DR PDB; 4S0U; X-ray; 2.35 A; C=29-203.
DR PDBsum; 4S0U; -.
DR AlphaFoldDB; Q5VY80; -.
DR SMR; Q5VY80; -.
DR BioGRID; 127532; 14.
DR IntAct; Q5VY80; 4.
DR STRING; 9606.ENSP00000356310; -.
DR GlyGen; Q5VY80; 2 sites.
DR iPTMnet; Q5VY80; -.
DR PhosphoSitePlus; Q5VY80; -.
DR BioMuta; RAET1L; -.
DR DMDM; 74747619; -.
DR jPOST; Q5VY80; -.
DR MassIVE; Q5VY80; -.
DR MaxQB; Q5VY80; -.
DR PaxDb; Q5VY80; -.
DR PeptideAtlas; Q5VY80; -.
DR PRIDE; Q5VY80; -.
DR Antibodypedia; 77385; 4 antibodies from 3 providers.
DR DNASU; 154064; -.
DR Ensembl; ENST00000286380.2; ENSP00000286380.2; ENSG00000155918.8.
DR Ensembl; ENST00000367341.6; ENSP00000356310.1; ENSG00000155918.8.
DR GeneID; 154064; -.
DR KEGG; hsa:154064; -.
DR MANE-Select; ENST00000367341.6; ENSP00000356310.1; NM_130900.3; NP_570970.2.
DR UCSC; uc011eei.2; human.
DR CTD; 154064; -.
DR DisGeNET; 154064; -.
DR GeneCards; RAET1L; -.
DR HGNC; HGNC:16798; RAET1L.
DR HPA; ENSG00000155918; Group enriched (esophagus, vagina).
DR MIM; 611047; gene.
DR neXtProt; NX_Q5VY80; -.
DR OpenTargets; ENSG00000155918; -.
DR PharmGKB; PA134918665; -.
DR VEuPathDB; HostDB:ENSG00000155918; -.
DR eggNOG; ENOG502TM6M; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q5VY80; -.
DR OMA; CKSWMEY; -.
DR OrthoDB; 1092787at2759; -.
DR PhylomeDB; Q5VY80; -.
DR TreeFam; TF341724; -.
DR PathwayCommons; Q5VY80; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; Q5VY80; -.
DR BioGRID-ORCS; 154064; 13 hits in 991 CRISPR screens.
DR GenomeRNAi; 154064; -.
DR Pharos; Q5VY80; Tbio.
DR PRO; PR:Q5VY80; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q5VY80; protein.
DR Bgee; ENSG00000155918; Expressed in lower esophagus mucosa and 37 other tissues.
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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
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 3D-structure; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; GPI-anchor; Host-virus interaction; Immunity; Lipoprotein;
KW Membrane; Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..218
FT /note="UL16-binding protein 6"
FT /id="PRO_0000320324"
FT PROPEP 219..246
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000320325"
FT REGION 29..117
FT /note="MHC class I alpha-1 like"
FT /evidence="ECO:0000250"
FT REGION 118..210
FT /note="MHC class I alpha-2 like"
FT /evidence="ECO:0000250"
FT LIPID 218
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000250"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 50..66
FT /evidence="ECO:0000250"
FT DISULFID 127..190
FT /evidence="ECO:0000250"
FT VARIANT 26
FT /note="R -> G (in allele ULBP6*01 and allele ULBP6*04;
FT dbSNP:rs1543547)"
FT /evidence="ECO:0000269|PubMed:19658097,
FT ECO:0000269|PubMed:28559451"
FT /id="VAR_039183"
FT VARIANT 85
FT /note="M -> T (in allele ULBP6*01, allele ULBP6*02 and
FT allele ULBP6*04; dbSNP:rs912565)"
FT /evidence="ECO:0000269|PubMed:11827464,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:19658097,
FT ECO:0000269|PubMed:28559451"
FT /id="VAR_039184"
FT VARIANT 106
FT /note="L -> R (in allele ULBP6*01; affects KLRK1-binding
FT affinity and KLRK1-mediated cytotoxic response;
FT dbSNP:rs1555696)"
FT /evidence="ECO:0000269|PubMed:19658097,
FT ECO:0000269|PubMed:28559451"
FT /id="VAR_039185"
FT VARIANT 147
FT /note="T -> I (in allele ULBP6*01; no effect on KLRK1-
FT binding affinity; dbSNP:rs61730071)"
FT /evidence="ECO:0000269|PubMed:19658097,
FT ECO:0000269|PubMed:28559451"
FT /id="VAR_079132"
FT STRAND 31..39
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 50..56
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 86..106
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 121..129
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 146..152
FT /evidence="ECO:0007829|PDB:4S0U"
FT TURN 153..156
FT /evidence="ECO:0007829|PDB:4S0U"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 166..174
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 176..187
FT /evidence="ECO:0007829|PDB:4S0U"
FT HELIX 189..202
FT /evidence="ECO:0007829|PDB:4S0U"
SQ SEQUENCE 246 AA; 27509 MW; 5FBBEA2289E32690 CRC64;
MAAAAIPALL LCLPLLFLLF GWSRARRDDP HSLCYDITVI PKFRPGPRWC AVQGQVDEKT
FLHYDCGNKT VTPVSPLGKK LNVTMAWKAQ NPVLREVVDI LTEQLLDIQL ENYTPKEPLT
LQARMSCEQK AEGHSSGSWQ FSIDGQTFLL FDSEKRMWTT VHPGARKMKE KWENDKDVAM
SFHYISMGDC IGWLEDFLMG MDSTLEPSAG APLAMSSGTT QLRATATTLI LCCLLIILPC
FILPGI
