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Protein

NKG2D ligand 3

Gene

ULBP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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
  2. peptide antigen binding Source: GO_Central

GO - Biological processi

  1. antigen processing and presentation of peptide antigen via MHC class I Source: GO_Central
  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
Complete GO annotation...

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 Componenti: 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
Complete GO annotation...

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

HPAiHPA063007.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi122673. 5 interactions.
IntActiQ9BZM4. 1 interaction.
STRINGi9606.ENSP00000253335.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000003472.
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

        10         20         30         40         50
MAAAASPAIL PRLAILPYLL FDWSGTGRAD AHSLWYNFTI IHLPRHGQQW
60 70 80 90 100
CEVQSQVDQK NFLSYDCGSD KVLSMGHLEE QLYATDAWGK QLEMLREVGQ
110 120 130 140 150
RLRLELADTE LEDFTPSGPL TLQVRMSCEC EADGYIRGSW QFSFDGRKFL
160 170 180 190 200
LFDSNNRKWT VVHAGARRMK EKWEKDSGLT TFFKMVSMRD CKSWLRDFLM
210 220 230 240
HRKKRLEPTA PPTMAPGLAQ PKAIATTLSP WSFLIILCFI LPGI
Length:244
Mass (Da):27,949
Last modified:June 1, 2001 - v1
Checksum:iBAF07895640B9901
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi122673. 5 interactions.
IntActiQ9BZM4. 1 interaction.
STRINGi9606.ENSP00000253335.

Proteomic databases

MaxQBiQ9BZM4.
PaxDbiQ9BZM4.
PRIDEiQ9BZM4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi79465.
GeneCardsiGC06M150477.
HGNCiHGNC:14895. ULBP3.
HPAiHPA063007.
MIMi605699. gene.
neXtProtiNX_Q9BZM4.
PharmGKBiPA37917.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG75885.
GeneTreeiENSGT00390000003472.
HOGENOMiHOG000070028.
HOVERGENiHBG052564.
InParanoidiQ9BZM4.
KOiK07986.
OMAiWGKQLEM.
OrthoDBiEOG7HB59Z.
PhylomeDBiQ9BZM4.
TreeFamiTF341724.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiQ9BZM4.
GeneWikiiULBP3.
GenomeRNAii79465.
NextBioi68421.
PROiQ9BZM4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BZM4.
CleanExiHS_ULBP3.
GenevestigatoriQ9BZM4.

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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], GPI-ANCHOR.
  2. Onda H., Shintani Y., Ohkubo S., Ogi K.
    Submitted (NOV-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(2003) [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(2002) [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(2003) [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(2000) [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(2001) [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(2001) [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(2002) [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(2009) [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(2000) [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: March 4, 2015
This is version 114 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.