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Q9BZM4

- N2DL3_HUMAN

UniProt

Q9BZM4 - N2DL3_HUMAN

Protein

NKG2D ligand 3

Gene

ULBP3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    Functioni

    Ligand for the KLRK1/NKG2D receptor, together with at least ULBP1 and ULBP2. ULBPs activate multiple signaling pathways in primary NK cells, resulting in the production of cytokines and chemokines. Binding of ULBPs ligands to KLRK1/NKG2D induces calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. Has lower affinity for KLRK1/NKG2D compared to ULBP1 and ULBP2 and induces weaker signaling responses than does ULBP2 or ULBP1.1 Publication

    GO - Molecular functioni

    1. natural killer cell lectin-like receptor binding Source: UniProtKB

    GO - Biological processi

    1. antigen processing and presentation Source: InterPro
    2. natural killer cell activation Source: UniProtKB
    3. natural killer cell mediated cytotoxicity Source: UniProtKB
    4. regulation of immune response Source: Reactome
    5. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Host-virus interaction

    Enzyme and pathway databases

    ReactomeiREACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NKG2D ligand 3
    Short name:
    N2DL-3
    Short name:
    NKG2DL3
    Alternative name(s):
    ALCAN-gamma
    Retinoic acid early transcript 1N
    Gene namesi
    Name:ULBP3
    Synonyms:N2DL3, RAET1N
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:14895. ULBP3.

    Subcellular locationi

    GO - Cellular componenti

    1. anchored component of plasma membrane Source: UniProtKB
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA37917.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2929Sequence AnalysisAdd
    BLAST
    Chaini30 – 217188NKG2D ligand 3PRO_0000019019Add
    BLAST
    Propeptidei218 – 24427Removed in mature formSequence AnalysisPRO_0000019020Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi37 – 371N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi51 ↔ 67
    Disulfide bondi128 ↔ 191
    Lipidationi217 – 2171GPI-anchor amidated glycineSequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

    Proteomic databases

    MaxQBiQ9BZM4.
    PaxDbiQ9BZM4.
    PRIDEiQ9BZM4.

    Expressioni

    Gene expression databases

    BgeeiQ9BZM4.
    CleanExiHS_ULBP3.
    GenevestigatoriQ9BZM4.

    Organism-specific databases

    HPAiHPA046558.
    HPA063007.

    Interactioni

    Subunit structurei

    Does not bind to beta2-microglobulin. Interacts with human cytomegalovirus/HHV-5 protein UL142.3 Publications

    Protein-protein interaction databases

    IntActiQ9BZM4. 1 interaction.
    STRINGi9606.ENSP00000253335.

    Structurei

    Secondary structure

    1
    244
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi32 – 4312
    Beta strandi50 – 578
    Beta strandi60 – 667
    Turni67 – 704
    Beta strandi83 – 853
    Helixi86 – 10722
    Beta strandi121 – 13010
    Beta strandi137 – 15317
    Turni154 – 1574
    Beta strandi158 – 1636
    Helixi164 – 1663
    Helixi167 – 1759
    Helixi177 – 18812
    Helixi190 – 20617

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KCGX-ray2.60C30-207[»]
    ProteinModelPortaliQ9BZM4.
    SMRiQ9BZM4. Positions 30-207.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BZM4.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni30 – 11889MHC class I alpha-1 likeAdd
    BLAST
    Regioni119 – 20991MHC class I alpha-2 likeAdd
    BLAST

    Sequence similaritiesi

    Belongs to the MHC class I family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG75885.
    HOGENOMiHOG000070028.
    HOVERGENiHBG052564.
    InParanoidiQ9BZM4.
    KOiK07986.
    OMAiWGKQLEM.
    OrthoDBiEOG7HB59Z.
    PhylomeDBiQ9BZM4.
    TreeFamiTF341724.

    Family and domain databases

    Gene3Di3.30.500.10. 1 hit.
    InterProiIPR011161. MHC_I-like_Ag-recog.
    IPR011162. MHC_I/II-like_Ag-recog.
    IPR001039. MHC_I_a_a1/a2.
    [Graphical view]
    PfamiPF00129. MHC_I. 1 hit.
    [Graphical view]
    SUPFAMiSSF54452. SSF54452. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9BZM4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAAASPAIL PRLAILPYLL FDWSGTGRAD AHSLWYNFTI IHLPRHGQQW    50
    CEVQSQVDQK NFLSYDCGSD KVLSMGHLEE QLYATDAWGK QLEMLREVGQ 100
    RLRLELADTE LEDFTPSGPL TLQVRMSCEC EADGYIRGSW QFSFDGRKFL 150
    LFDSNNRKWT VVHAGARRMK EKWEKDSGLT TFFKMVSMRD CKSWLRDFLM 200
    HRKKRLEPTA PPTMAPGLAQ PKAIATTLSP WSFLIILCFI LPGI 244
    Length:244
    Mass (Da):27,949
    Last modified:June 1, 2001 - v1
    Checksum:iBAF07895640B9901
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF304379 mRNA. Translation: AAK13083.1.
    AB052908 mRNA. Translation: BAB61050.1.
    AK315275 mRNA. Translation: BAG37687.1.
    AL355497 Genomic DNA. Translation: CAH74128.1.
    CH471051 Genomic DNA. Translation: EAW47772.1.
    BC098127 mRNA. Translation: AAH98127.1.
    AF346596 mRNA. Translation: AAN40839.1.
    AY027538 mRNA. Translation: AAK13049.1.
    CCDSiCCDS5225.1.
    RefSeqiNP_078794.1. NM_024518.1.
    XP_005267194.1. XM_005267137.2.
    UniGeneiHs.326556.

    Genome annotation databases

    EnsembliENST00000367339; ENSP00000356308; ENSG00000131019.
    ENST00000438272; ENSP00000403562; ENSG00000131019.
    GeneIDi79465.
    KEGGihsa:79465.
    UCSCiuc003qns.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF304379 mRNA. Translation: AAK13083.1 .
    AB052908 mRNA. Translation: BAB61050.1 .
    AK315275 mRNA. Translation: BAG37687.1 .
    AL355497 Genomic DNA. Translation: CAH74128.1 .
    CH471051 Genomic DNA. Translation: EAW47772.1 .
    BC098127 mRNA. Translation: AAH98127.1 .
    AF346596 mRNA. Translation: AAN40839.1 .
    AY027538 mRNA. Translation: AAK13049.1 .
    CCDSi CCDS5225.1.
    RefSeqi NP_078794.1. NM_024518.1.
    XP_005267194.1. XM_005267137.2.
    UniGenei Hs.326556.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KCG X-ray 2.60 C 30-207 [» ]
    ProteinModelPortali Q9BZM4.
    SMRi Q9BZM4. Positions 30-207.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9BZM4. 1 interaction.
    STRINGi 9606.ENSP00000253335.

    Proteomic databases

    MaxQBi Q9BZM4.
    PaxDbi Q9BZM4.
    PRIDEi Q9BZM4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000367339 ; ENSP00000356308 ; ENSG00000131019 .
    ENST00000438272 ; ENSP00000403562 ; ENSG00000131019 .
    GeneIDi 79465.
    KEGGi hsa:79465.
    UCSCi uc003qns.3. human.

    Organism-specific databases

    CTDi 79465.
    GeneCardsi GC06M150477.
    HGNCi HGNC:14895. ULBP3.
    HPAi HPA046558.
    HPA063007.
    MIMi 605699. gene.
    neXtProti NX_Q9BZM4.
    PharmGKBi PA37917.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG75885.
    HOGENOMi HOG000070028.
    HOVERGENi HBG052564.
    InParanoidi Q9BZM4.
    KOi K07986.
    OMAi WGKQLEM.
    OrthoDBi EOG7HB59Z.
    PhylomeDBi Q9BZM4.
    TreeFami TF341724.

    Enzyme and pathway databases

    Reactomei REACT_11152. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

    Miscellaneous databases

    EvolutionaryTracei Q9BZM4.
    GeneWikii ULBP3.
    GenomeRNAii 79465.
    NextBioi 68421.
    PROi Q9BZM4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9BZM4.
    CleanExi HS_ULBP3.
    Genevestigatori Q9BZM4.

    Family and domain databases

    Gene3Di 3.30.500.10. 1 hit.
    InterProi IPR011161. MHC_I-like_Ag-recog.
    IPR011162. MHC_I/II-like_Ag-recog.
    IPR001039. MHC_I_a_a1/a2.
    [Graphical view ]
    Pfami PF00129. MHC_I. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54452. SSF54452. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor."
      Cosman D., Mullberg J., Sutherland C.L., Chin W., Armitage R., Fanslow W., Kubin M., Chalupny N.J.
      Immunity 14:123-133(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], GPI-ANCHOR.
    2. Onda H., Shintani Y., Ohkubo S., Ogi K.
      Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    4. "The DNA sequence and analysis of human chromosome 6."
      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.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. "Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family."
      Steinle A., Li P., Morris D.L., Groh V., Lanier L.L., Strong R.K., Spies T.
      Immunogenetics 53:279-287(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-244, INTERACTION WITH KLRK1.
    8. "A cluster of ten novel MHC class I related genes on human chromosome 6q24.2-q25.3."
      Radosavljevic M., Cuillerier B., Wilson M.J., Clement O., Wicker S., Gilfillan S., Beck S., Trowsdale J., Bahram S.
      Genomics 79:114-123(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-244.
    9. "UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells."
      Sutherland C.L., Chalupny N.J., Schooley K., VandenBos T., Kubin M., Cosman D.
      J. Immunol. 168:671-679(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A LIGAND FOR KLRK1.
    10. "NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer."
      Cerwenka A., Lanier L.L.
      Tissue Antigens 61:335-343(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    11. "Intracellular sequestration of the NKG2D ligand ULBP3 by human cytomegalovirus."
      Bennett N.J., Ashiru O., Morgan F.J., Pang Y., Okecha G., Eagle R.A., Trowsdale J., Sissons J.G., Wills M.R.
      J. Immunol. 185:1093-1102(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HHV-5 PROTEIN UL142.
    12. "Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3."
      Radaev S., Rostro B., Brooks A.G., Colonna M., Sun P.D.
      Immunity 15:1039-1049(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 30-207 IN COMPLEX WITH THE EXTRACELLULAR DOMAIN OF KLRK1.

    Entry informationi

    Entry nameiN2DL3_HUMAN
    AccessioniPrimary (citable) accession number: Q9BZM4
    Secondary accession number(s): Q5VY82, Q8IZX5, Q8TE75
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2004
    Last sequence update: June 1, 2001
    Last modified: October 1, 2014
    This is version 109 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    The ULBPs are unusual members of the extended MHC class I superfamily, because they do not contain the alpha 3 domain and they lack a transmembrane domain. They are unlikely to present peptides.
    The region from chromosome 6q24.1-6q25.3 contains as many as 10 ULBP-related sequences, many of which are pseudogenes.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3