ULBP1_HUMAN
ID ULBP1_HUMAN Reviewed; 244 AA.
AC Q9BZM6; Q5VY81; Q8IZW3; Q8IZX6;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=UL16-binding protein 1;
DE AltName: Full=ALCAN-beta;
DE AltName: Full=NKG2D ligand 1;
DE Short=N2DL-1;
DE Short=NKG2DL1;
DE AltName: Full=Retinoic acid early transcript 1I;
DE Flags: Precursor;
GN Name=ULBP1; Synonyms=N2DL1, RAET1I;
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.
RC TISSUE=B-cell lymphoma;
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].
RA Onda H., Shintani Y., Ohkubo S., Ogi K.;
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
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].
RC TISSUE=Cerebellum, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
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., 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=Testis;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 6-244.
RA Larson J.H., Rebeiz M., Stiening C.M., Windish R., Beever J.E., Lewin H.A.;
RT "The ULBP proteins are highly divergent among mammals.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-244.
RX PubMed=11491531; DOI=10.1007/s002510100325;
RA Steinle A., Li P., Morris D.L., Groh V., Lanier L.L., Strong R.K.,
RA Spies T.;
RT "Interactions of human NKG2D with its ligands MICA, MICB, and homologs of
RT the mouse RAE-1 protein family.";
RL Immunogenetics 53:279-287(2001).
RN [10]
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 [11]
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 [12]
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 ULBP1 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 Q9BZM6; P26718: KLRK1; NbExp=2; IntAct=EBI-16365037, EBI-458344;
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}. Note=In CMV-infected
CC fibroblasts, detected in the endoplasmic reticulum/cis-Golgi.
CC {ECO:0000269|PubMed:12782710}.
CC -!- TISSUE SPECIFICITY: Expressed in T-cells, B-cells, erythroleukemia cell
CC lines and in a wide range of tissues including heart, brain, lung,
CC liver, testis, lymph node, thymus, tonsil and bone marrow. Also found
CC in fetal heart, brain, lung and liver.
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}.
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DR EMBL; AF304377; AAK13081.1; -; mRNA.
DR EMBL; AB052907; BAB61049.1; -; mRNA.
DR EMBL; AF346416; AAL76416.1; -; mRNA.
DR EMBL; AK292519; BAF85208.1; -; mRNA.
DR EMBL; AK316582; BAG38170.1; -; mRNA.
DR EMBL; AL355497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47776.1; -; Genomic_DNA.
DR EMBL; BC035416; AAH35416.1; -; mRNA.
DR EMBL; AF425265; AAN32759.1; -; mRNA.
DR EMBL; AF346595; AAN40838.1; -; mRNA.
DR CCDS; CCDS5223.1; -.
DR RefSeq; NP_001304018.1; NM_001317089.1.
DR RefSeq; NP_079494.1; NM_025218.3.
DR AlphaFoldDB; Q9BZM6; -.
DR SMR; Q9BZM6; -.
DR BioGRID; 123241; 18.
DR CORUM; Q9BZM6; -.
DR IntAct; Q9BZM6; 7.
DR STRING; 9606.ENSP00000229708; -.
DR GlyGen; Q9BZM6; 1 site.
DR BioMuta; ULBP1; -.
DR jPOST; Q9BZM6; -.
DR MassIVE; Q9BZM6; -.
DR PaxDb; Q9BZM6; -.
DR PeptideAtlas; Q9BZM6; -.
DR PRIDE; Q9BZM6; -.
DR ProteomicsDB; 79879; -.
DR Antibodypedia; 2344; 273 antibodies from 27 providers.
DR DNASU; 80329; -.
DR Ensembl; ENST00000229708.4; ENSP00000229708.2; ENSG00000111981.5.
DR GeneID; 80329; -.
DR KEGG; hsa:80329; -.
DR MANE-Select; ENST00000229708.4; ENSP00000229708.2; NM_025218.4; NP_079494.1.
DR UCSC; uc003qnp.5; human.
DR CTD; 80329; -.
DR DisGeNET; 80329; -.
DR GeneCards; ULBP1; -.
DR HGNC; HGNC:14893; ULBP1.
DR HPA; ENSG00000111981; Group enriched (brain, lung, testis).
DR MIM; 605697; gene.
DR neXtProt; NX_Q9BZM6; -.
DR OpenTargets; ENSG00000111981; -.
DR PharmGKB; PA37915; -.
DR VEuPathDB; HostDB:ENSG00000111981; -.
DR eggNOG; ENOG502TM6M; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q9BZM6; -.
DR OMA; VDTHCLC; -.
DR OrthoDB; 1092787at2759; -.
DR PhylomeDB; Q9BZM6; -.
DR TreeFam; TF341724; -.
DR PathwayCommons; Q9BZM6; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q9BZM6; -.
DR BioGRID-ORCS; 80329; 11 hits in 1077 CRISPR screens.
DR GeneWiki; ULBP1; -.
DR GenomeRNAi; 80329; -.
DR Pharos; Q9BZM6; Tbio.
DR PRO; PR:Q9BZM6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BZM6; protein.
DR Bgee; ENSG00000111981; Expressed in stromal cell of endometrium and 83 other tissues.
DR Genevisible; Q9BZM6; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0005615; C:extracellular space; IBA:GO_Central.
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; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW GPI-anchor; Host-virus interaction; Immunity; Lipoprotein; Membrane;
KW Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..216
FT /note="UL16-binding protein 1"
FT /id="PRO_0000019015"
FT PROPEP 217..244
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000019016"
FT REGION 26..117
FT /note="MHC class I alpha-1 like"
FT REGION 118..208
FT /note="MHC class I alpha-2 like"
FT LIPID 216
FT /note="GPI-anchor amidated glycine"
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 101
FT /note="L -> I (in dbSNP:rs6903584)"
FT /id="VAR_050407"
SQ SEQUENCE 244 AA; 27997 MW; 6094B17CE383DC6D CRC64;
MAAAASPAFL LCLPLLHLLS GWSRAGWVDT HCLCYDFIIT PKSRPEPQWC EVQGLVDERP
FLHYDCVNHK AKAFASLGKK VNVTKTWEEQ TETLRDVVDF LKGQLLDIQV ENLIPIEPLT
LQARMSCEHE AHGHGRGSWQ FLFNGQKFLL FDSNNRKWTA LHPGAKKMTE KWEKNRDVTM
FFQKISLGDC KMWLEEFLMY WEQMLDPTKP PSLAPGTTQP KAMATTLSPW SLLIIFLCFI
LAGR