ULBP3_HUMAN
ID ULBP3_HUMAN Reviewed; 244 AA.
AC Q9BZM4; Q5VY82; Q8IZX5; Q8TE75;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=UL16-binding protein 3;
DE AltName: Full=ALCAN-gamma;
DE AltName: Full=NKG2D ligand 3;
DE Short=N2DL-3;
DE Short=NKG2DL3;
DE AltName: Full=Retinoic acid early transcript 1N;
DE Flags: Precursor;
GN Name=ULBP3; Synonyms=N2DL3, RAET1N;
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.
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 [LARGE SCALE MRNA].
RC TISSUE=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 [4]
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-244, AND INTERACTION WITH KLRK1.
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-244.
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 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 [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).
RN [11]
RP INTERACTION WITH CMV UL142.
RX PubMed=20530255; DOI=10.4049/jimmunol.1000789;
RA Bennett N.J., Ashiru O., Morgan F.J., Pang Y., Okecha G., Eagle R.A.,
RA Trowsdale J., Sissons J.G., Wills M.R.;
RT "Intracellular sequestration of the NKG2D ligand ULBP3 by human
RT cytomegalovirus.";
RL J. Immunol. 185:1093-1102(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 30-207 IN COMPLEX WITH THE
RP EXTRACELLULAR DOMAIN OF KLRK1.
RX PubMed=11754823; DOI=10.1016/s1074-7613(01)00241-2;
RA Radaev S., Rostro B., Brooks A.G., Colonna M., Sun P.D.;
RT "Conformational plasticity revealed by the cocrystal structure of NKG2D and
RT its class I MHC-like ligand ULBP3.";
RL Immunity 15:1039-1049(2001).
CC -!- FUNCTION: Binds and activates the KLRK1/NKG2D receptor, mediating
CC natural killer cell cytotoxicity. {ECO:0000269|PubMed:11491531,
CC ECO:0000269|PubMed:11754823, ECO:0000269|PubMed:11777960}.
CC -!- SUBUNIT: Interacts with KLRK1/NKG2D (PubMed:11491531, PubMed:11777960,
CC PubMed:11754823). Does not bind to beta2-microglobulin (By similarity).
CC {ECO:0000250|UniProtKB:Q9BZM6, ECO:0000269|PubMed:11491531,
CC ECO:0000269|PubMed:11754823, ECO:0000269|PubMed:11777960}.
CC -!- SUBUNIT: (Microbial infection) In CMV-infected cells, interacts with
CC the viral glycoprotein UL16 and UL142; this interaction causes ULBP3
CC retention in the endoplasmic reticulum and cis-Golgi and prevents
CC binding to and activation of KLRK1/NKG2D, providing CMV with an immune
CC evasion mechanism. {ECO:0000269|PubMed:20530255}.
CC -!- INTERACTION:
CC Q9BZM4; P01100: FOS; NbExp=3; IntAct=EBI-1032551, EBI-852851;
CC Q9BZM4; P26718: KLRK1; NbExp=4; IntAct=EBI-1032551, EBI-458344;
CC Q9BZM4; P31930: UQCRC1; NbExp=3; IntAct=EBI-1032551, EBI-1052596;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BZM6};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q9BZM6}.
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; AF304379; AAK13083.1; -; mRNA.
DR EMBL; AB052908; BAB61050.1; -; mRNA.
DR EMBL; AK315275; BAG37687.1; -; mRNA.
DR EMBL; AL355497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47772.1; -; Genomic_DNA.
DR EMBL; BC098127; AAH98127.1; -; mRNA.
DR EMBL; AF346596; AAN40839.1; -; mRNA.
DR EMBL; AY027538; AAK13049.1; -; mRNA.
DR CCDS; CCDS5225.1; -.
DR RefSeq; NP_078794.1; NM_024518.2.
DR PDB; 1KCG; X-ray; 2.60 A; C=30-207.
DR PDBsum; 1KCG; -.
DR AlphaFoldDB; Q9BZM4; -.
DR SMR; Q9BZM4; -.
DR BioGRID; 122673; 55.
DR CORUM; Q9BZM4; -.
DR IntAct; Q9BZM4; 24.
DR STRING; 9606.ENSP00000356308; -.
DR GlyGen; Q9BZM4; 2 sites, 2 O-linked glycans (1 site).
DR iPTMnet; Q9BZM4; -.
DR PhosphoSitePlus; Q9BZM4; -.
DR BioMuta; ULBP3; -.
DR jPOST; Q9BZM4; -.
DR MassIVE; Q9BZM4; -.
DR MaxQB; Q9BZM4; -.
DR PaxDb; Q9BZM4; -.
DR PeptideAtlas; Q9BZM4; -.
DR PRIDE; Q9BZM4; -.
DR ProteomicsDB; 79877; -.
DR Antibodypedia; 57233; 140 antibodies from 16 providers.
DR DNASU; 79465; -.
DR Ensembl; ENST00000367339.7; ENSP00000356308.1; ENSG00000131019.11.
DR Ensembl; ENST00000438272.2; ENSP00000403562.2; ENSG00000131019.11.
DR GeneID; 79465; -.
DR KEGG; hsa:79465; -.
DR MANE-Select; ENST00000367339.7; ENSP00000356308.1; NM_024518.3; NP_078794.1.
DR UCSC; uc003qns.4; human.
DR CTD; 79465; -.
DR DisGeNET; 79465; -.
DR GeneCards; ULBP3; -.
DR HGNC; HGNC:14895; ULBP3.
DR HPA; ENSG00000131019; Tissue enhanced (skeletal muscle, testis).
DR MIM; 605699; gene.
DR neXtProt; NX_Q9BZM4; -.
DR OpenTargets; ENSG00000131019; -.
DR PharmGKB; PA37917; -.
DR VEuPathDB; HostDB:ENSG00000131019; -.
DR eggNOG; ENOG502TM6M; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_086235_0_0_1; -.
DR InParanoid; Q9BZM4; -.
DR OMA; WIGGSKP; -.
DR OrthoDB; 1092787at2759; -.
DR PhylomeDB; Q9BZM4; -.
DR TreeFam; TF341724; -.
DR PathwayCommons; Q9BZM4; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q9BZM4; -.
DR BioGRID-ORCS; 79465; 21 hits in 1064 CRISPR screens.
DR EvolutionaryTrace; Q9BZM4; -.
DR GeneWiki; ULBP3; -.
DR GenomeRNAi; 79465; -.
DR Pharos; Q9BZM4; Tbio.
DR PRO; PR:Q9BZM4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BZM4; protein.
DR Bgee; ENSG00000131019; Expressed in epithelial cell of pancreas and 134 other tissues.
DR Genevisible; Q9BZM4; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
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; TAS:Reactome.
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 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Host-virus interaction; Immunity; Lipoprotein; Membrane;
KW Reference proteome; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..217
FT /note="UL16-binding protein 3"
FT /id="PRO_0000019019"
FT PROPEP 218..244
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000019020"
FT REGION 30..118
FT /note="MHC class I alpha-1 like"
FT REGION 119..209
FT /note="MHC class I alpha-2 like"
FT LIPID 217
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..67
FT DISULFID 128..191
FT STRAND 32..43
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:1KCG"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:1KCG"
FT HELIX 86..107
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 121..130
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 137..153
FT /evidence="ECO:0007829|PDB:1KCG"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:1KCG"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:1KCG"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:1KCG"
FT HELIX 167..175
FT /evidence="ECO:0007829|PDB:1KCG"
FT HELIX 177..188
FT /evidence="ECO:0007829|PDB:1KCG"
FT HELIX 190..206
FT /evidence="ECO:0007829|PDB:1KCG"
SQ SEQUENCE 244 AA; 27949 MW; BAF07895640B9901 CRC64;
MAAAASPAIL PRLAILPYLL FDWSGTGRAD AHSLWYNFTI IHLPRHGQQW CEVQSQVDQK
NFLSYDCGSD KVLSMGHLEE QLYATDAWGK QLEMLREVGQ RLRLELADTE LEDFTPSGPL
TLQVRMSCEC EADGYIRGSW QFSFDGRKFL LFDSNNRKWT VVHAGARRMK EKWEKDSGLT
TFFKMVSMRD CKSWLRDFLM HRKKRLEPTA PPTMAPGLAQ PKAIATTLSP WSFLIILCFI
LPGI
