ULBP2_HUMAN
ID ULBP2_HUMAN Reviewed; 246 AA.
AC Q9BZM5; Q5VUN4;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=UL16-binding protein 2;
DE AltName: Full=ALCAN-alpha;
DE AltName: Full=NKG2D ligand 2;
DE Short=N2DL-2;
DE Short=NKG2DL2;
DE AltName: Full=Retinoic acid early transcript 1H;
DE Flags: Precursor;
GN Name=ULBP2; Synonyms=N2DL2, RAET1H; ORFNames=UNQ463/PRO791;
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], AND GPI-ANCHOR AT SER-216.
RX PubMed=11239445; DOI=10.1016/s1074-7613(01)00095-4;
RA Cosman D., Mullberg J., Sutherland C.L., Chin W., Armitage R., Fanslow W.,
RA Kubin M., Chalupny N.J.;
RT "ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16
RT and stimulate NK cytotoxicity through the NKG2D receptor.";
RL Immunity 14:123-133(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, GPI-ANCHOR AT
RP SER-216, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 208-SER--GLY-210 AND 216-SER--GLY-218.
RC TISSUE=Endometrial tumor;
RX PubMed=11444831; DOI=10.1006/bbrc.2001.5149;
RA Onda H., Ohkubo S., Shintani Y., Ogi K., Kikuchi K., Tanaka H.,
RA Yamamoto K., Tsuji I., Ishibashi Y., Yamada T., Kitada C., Suzuki N.,
RA Sawada H., Nishimura O., Fujino M.;
RT "A novel secreted tumor antigen with a glycosylphosphatidylinositol-
RT anchored structure ubiquitously expressed in human cancers.";
RL Biochem. Biophys. Res. Commun. 285:235-243(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [8]
RP FUNCTION, AND INTERACTION WITH KLRK1.
RX PubMed=11777960; DOI=10.4049/jimmunol.168.2.671;
RA Sutherland C.L., Chalupny N.J., Schooley K., VandenBos T., Kubin M.,
RA Cosman D.;
RT "UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D
RT and activate multiple signaling pathways in primary NK cells.";
RL J. Immunol. 168:671-679(2002).
RN [9]
RP INTERACTION WITH CMV UL16, AND SUBCELLULAR LOCATION.
RX PubMed=12782710; DOI=10.1084/jem.20022059;
RA Dunn C., Chalupny N.J., Sutherland C.L., Dosch S., Sivakumar P.V.,
RA Johnson D.C., Cosman D.;
RT "Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration
RT of NKG2D ligands, protecting against natural killer cell cytotoxicity.";
RL J. Exp. Med. 197:1427-1439(2003).
RN [10]
RP REVIEW.
RX PubMed=12753652; DOI=10.1034/j.1399-0039.2003.00070.x;
RA Cerwenka A., Lanier L.L.;
RT "NKG2D ligands: unconventional MHC class I-like molecules exploited by
RT viruses and cancer.";
RL Tissue Antigens 61:335-343(2003).
CC -!- FUNCTION: Binds and activates the KLRK1/NKG2D receptor, mediating
CC natural killer cell cytotoxicity. {ECO:0000269|PubMed:11777960}.
CC -!- SUBUNIT: Interacts with KLRK1/NKG2D (PubMed:11777960). Does not bind to
CC beta2-microglobulin (PubMed:12782710). {ECO:0000269|PubMed:11777960,
CC ECO:0000269|PubMed:12782710}.
CC -!- SUBUNIT: (Microbial infection) In CMV-infected cells, interacts with
CC the viral glycoprotein UL16; this interaction causes ULBP2 retention in
CC 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:12782710}.
CC -!- INTERACTION:
CC Q9BZM5; Q96Q80: DERL3; NbExp=3; IntAct=EBI-3919993, EBI-12831318;
CC Q9BZM5; P26718: KLRK1; NbExp=6; IntAct=EBI-3919993, EBI-458344;
CC Q9BZM5; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-3919993, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12782710};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:12782710}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:12782710}. Secreted
CC {ECO:0000269|PubMed:11444831}. Note=In CMV-infected fibroblasts,
CC detected in the endoplasmic reticulum/cis-Golgi.
CC {ECO:0000269|PubMed:12782710}.
CC -!- TISSUE SPECIFICITY: Expressed in various types of cancer cell lines and
CC in the fetus, but not in normal tissues. {ECO:0000269|PubMed:11444831}.
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; AF304378; AAK13082.1; -; mRNA.
DR EMBL; AB052906; BAB61048.1; -; mRNA.
DR EMBL; AY026825; AAK07688.1; -; mRNA.
DR EMBL; AY358665; AAQ89028.1; -; mRNA.
DR EMBL; AL583835; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47777.1; -; Genomic_DNA.
DR EMBL; BC034689; AAH34689.1; -; mRNA.
DR CCDS; CCDS5222.1; -.
DR RefSeq; NP_079493.1; NM_025217.3.
DR AlphaFoldDB; Q9BZM5; -.
DR SMR; Q9BZM5; -.
DR BioGRID; 123240; 27.
DR CORUM; Q9BZM5; -.
DR IntAct; Q9BZM5; 21.
DR STRING; 9606.ENSP00000356320; -.
DR GlyGen; Q9BZM5; 2 sites.
DR iPTMnet; Q9BZM5; -.
DR PhosphoSitePlus; Q9BZM5; -.
DR BioMuta; ULBP2; -.
DR EPD; Q9BZM5; -.
DR jPOST; Q9BZM5; -.
DR MassIVE; Q9BZM5; -.
DR MaxQB; Q9BZM5; -.
DR PaxDb; Q9BZM5; -.
DR PeptideAtlas; Q9BZM5; -.
DR PRIDE; Q9BZM5; -.
DR ProteomicsDB; 79878; -.
DR Antibodypedia; 33306; 248 antibodies from 28 providers.
DR DNASU; 80328; -.
DR Ensembl; ENST00000367351.4; ENSP00000356320.3; ENSG00000131015.5.
DR GeneID; 80328; -.
DR KEGG; hsa:80328; -.
DR MANE-Select; ENST00000367351.4; ENSP00000356320.3; NM_025217.4; NP_079493.1.
DR UCSC; uc003qno.4; human.
DR CTD; 80328; -.
DR DisGeNET; 80328; -.
DR GeneCards; ULBP2; -.
DR HGNC; HGNC:14894; ULBP2.
DR HPA; ENSG00000131015; Tissue enhanced (esophagus).
DR MIM; 605698; gene.
DR neXtProt; NX_Q9BZM5; -.
DR OpenTargets; ENSG00000131015; -.
DR PharmGKB; PA37916; -.
DR VEuPathDB; HostDB:ENSG00000131015; -.
DR eggNOG; ENOG502TM6M; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q9BZM5; -.
DR OMA; HYISMAD; -.
DR OrthoDB; 1092787at2759; -.
DR PhylomeDB; Q9BZM5; -.
DR TreeFam; TF341724; -.
DR PathwayCommons; Q9BZM5; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; Q9BZM5; -.
DR SIGNOR; Q9BZM5; -.
DR BioGRID-ORCS; 80328; 33 hits in 1043 CRISPR screens.
DR GeneWiki; ULBP2; -.
DR GenomeRNAi; 80328; -.
DR Pharos; Q9BZM5; Tbio.
DR PRO; PR:Q9BZM5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BZM5; protein.
DR Bgee; ENSG00000131015; Expressed in esophagus squamous epithelium and 128 other tissues.
DR Genevisible; Q9BZM5; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
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; IDA:BHF-UCL.
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; IDA:UniProtKB.
DR GO; GO:0030101; P:natural killer cell activation; IDA:UniProtKB.
DR GO; GO:0042267; P: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 Cell membrane; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; GPI-anchor; Host-virus interaction;
KW Immunity; Lipoprotein; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:11444831"
FT CHAIN 26..216
FT /note="UL16-binding protein 2"
FT /id="PRO_0000019017"
FT PROPEP 217..246
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:11444831"
FT /id="PRO_0000019018"
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 216
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000305|PubMed:11239445,
FT ECO:0000305|PubMed:11444831"
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 MUTAGEN 208..210
FT /note="SAG->TPV: Secreted."
FT /evidence="ECO:0000269|PubMed:11444831"
FT MUTAGEN 216..218
FT /note="SSG->TPV: Not secreted."
FT /evidence="ECO:0000269|PubMed:11444831"
SQ SEQUENCE 246 AA; 27368 MW; 804D1A0D4A9C5CF8 CRC64;
MAAAAATKIL LCLPLLLLLS GWSRAGRADP HSLCYDITVI PKFRPGPRWC AVQGQVDEKT
FLHYDCGNKT VTPVSPLGKK LNVTTAWKAQ NPVLREVVDI LTEQLRDIQL ENYTPKEPLT
LQARMSCEQK AEGHSSGSWQ FSFDGQIFLL FDSEKRMWTT VHPGARKMKE KWENDKVVAM
SFHYFSMGDC IGWLEDFLMG MDSTLEPSAG APLAMSSGTT QLRATATTLI LCCLLIILPC
FILPGI
