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Protein

NKG2D ligand 1

Gene

ULBP1

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 ULBP2 and ULBP3. 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. In CMV infected cells, interacts with soluble CMV glycoprotein UL16. The interaction with UL16 blocked the interaction with the KLRK1/NKG2D receptor, providing a mechanism by which CMV infected cells might escape the immune system. UL16 also causes ULBP1 to be retained in the ER and cis-Golgi apparatus so that it does not reach the cell surface.1 Publication

GO - Molecular functioni

  • antigen binding Source: GO_Central
  • natural killer cell lectin-like receptor binding Source: UniProtKB

GO - Biological processi

  • antigen processing and presentation Source: GO_Central
  • natural killer cell activation Source: UniProtKB
  • natural killer cell mediated cytotoxicity Source: UniProtKB
  • regulation of immune response Source: Reactome
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
NKG2D ligand 1
Short name:
N2DL-1
Short name:
NKG2DL1
Alternative name(s):
ALCAN-beta
Retinoic acid early transcript 1I
UL16-binding protein 1
Gene namesi
Name:ULBP1
Synonyms:N2DL1, RAET1I
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:14893. ULBP1.

Subcellular locationi

GO - Cellular componenti

  • anchored component of plasma membrane Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37915.

Polymorphism and mutation databases

BioMutaiULBP1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525By similarityAdd
BLAST
Chaini26 – 216191NKG2D ligand 1PRO_0000019015Add
BLAST
Propeptidei217 – 24428Removed in mature formSequence analysisPRO_0000019016Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi50 ↔ 66By similarity
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence analysis
Disulfide bondi127 ↔ 190By similarity
Lipidationi216 – 2161GPI-anchor amidated glycineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ9BZM6.
PeptideAtlasiQ9BZM6.
PRIDEiQ9BZM6.

Expressioni

Tissue specificityi

Expressed in T-cells, B-cells, erythroleukemia cell lines and in a wide range of tissues including heart, brain, lung, liver, testis, lymph node, thymus, tonsil and bone marrow. Also found in fetal heart, brain, lung and liver.

Gene expression databases

BgeeiQ9BZM6.
CleanExiHS_ULBP1.
GenevisibleiQ9BZM6. HS.

Organism-specific databases

HPAiHPA007547.

Interactioni

Subunit structurei

Interacts with the CMV glycoprotein UL16. Does not bind to beta2-microglobulin.1 Publication

GO - Molecular functioni

  • natural killer cell lectin-like receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi123241. 8 interactions.
STRINGi9606.ENSP00000229708.

Structurei

3D structure databases

ProteinModelPortaliQ9BZM6.
SMRiQ9BZM6. Positions 29-206.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni26 – 11792MHC class I alpha-1 likeAdd
BLAST
Regioni118 – 20891MHC class I alpha-2 likeAdd
BLAST

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4VC. Eukaryota.
ENOG41113ZC. LUCA.
GeneTreeiENSGT00390000003472.
HOGENOMiHOG000070028.
HOVERGENiHBG052564.
InParanoidiQ9BZM6.
KOiK07986.
OMAiLCYDFII.
OrthoDBiEOG7HB59Z.
PhylomeDBiQ9BZM6.
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.

Q9BZM6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAASPAFL LCLPLLHLLS GWSRAGWVDT HCLCYDFIIT PKSRPEPQWC
60 70 80 90 100
EVQGLVDERP FLHYDCVNHK AKAFASLGKK VNVTKTWEEQ TETLRDVVDF
110 120 130 140 150
LKGQLLDIQV ENLIPIEPLT LQARMSCEHE AHGHGRGSWQ FLFNGQKFLL
160 170 180 190 200
FDSNNRKWTA LHPGAKKMTE KWEKNRDVTM FFQKISLGDC KMWLEEFLMY
210 220 230 240
WEQMLDPTKP PSLAPGTTQP KAMATTLSPW SLLIIFLCFI LAGR
Length:244
Mass (Da):27,997
Last modified:June 1, 2001 - v1
Checksum:i6094B17CE383DC6D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti101 – 1011L → I.
Corresponds to variant rs6903584 [ dbSNP | Ensembl ].
VAR_050407

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304377 mRNA. Translation: AAK13081.1.
AB052907 mRNA. Translation: BAB61049.1.
AF346416 mRNA. Translation: AAL76416.1.
AK292519 mRNA. Translation: BAF85208.1.
AK316582 mRNA. Translation: BAG38170.1.
AL355497 Genomic DNA. Translation: CAH74121.1.
CH471051 Genomic DNA. Translation: EAW47776.1.
BC035416 mRNA. Translation: AAH35416.1.
AF425265 mRNA. Translation: AAN32759.1.
AF346595 mRNA. Translation: AAN40838.1.
CCDSiCCDS5223.1.
RefSeqiNP_001304018.1. NM_001317089.1.
NP_079494.1. NM_025218.3.
UniGeneiHs.653255.

Genome annotation databases

EnsembliENST00000229708; ENSP00000229708; ENSG00000111981.
GeneIDi80329.
KEGGihsa:80329.
UCSCiuc003qnp.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304377 mRNA. Translation: AAK13081.1.
AB052907 mRNA. Translation: BAB61049.1.
AF346416 mRNA. Translation: AAL76416.1.
AK292519 mRNA. Translation: BAF85208.1.
AK316582 mRNA. Translation: BAG38170.1.
AL355497 Genomic DNA. Translation: CAH74121.1.
CH471051 Genomic DNA. Translation: EAW47776.1.
BC035416 mRNA. Translation: AAH35416.1.
AF425265 mRNA. Translation: AAN32759.1.
AF346595 mRNA. Translation: AAN40838.1.
CCDSiCCDS5223.1.
RefSeqiNP_001304018.1. NM_001317089.1.
NP_079494.1. NM_025218.3.
UniGeneiHs.653255.

3D structure databases

ProteinModelPortaliQ9BZM6.
SMRiQ9BZM6. Positions 29-206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123241. 8 interactions.
STRINGi9606.ENSP00000229708.

Polymorphism and mutation databases

BioMutaiULBP1.

Proteomic databases

PaxDbiQ9BZM6.
PeptideAtlasiQ9BZM6.
PRIDEiQ9BZM6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229708; ENSP00000229708; ENSG00000111981.
GeneIDi80329.
KEGGihsa:80329.
UCSCiuc003qnp.5. human.

Organism-specific databases

CTDi80329.
GeneCardsiULBP1.
HGNCiHGNC:14893. ULBP1.
HPAiHPA007547.
MIMi605697. gene.
neXtProtiNX_Q9BZM6.
PharmGKBiPA37915.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J4VC. Eukaryota.
ENOG41113ZC. LUCA.
GeneTreeiENSGT00390000003472.
HOGENOMiHOG000070028.
HOVERGENiHBG052564.
InParanoidiQ9BZM6.
KOiK07986.
OMAiLCYDFII.
OrthoDBiEOG7HB59Z.
PhylomeDBiQ9BZM6.
TreeFamiTF341724.

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Miscellaneous databases

GeneWikiiULBP1.
GenomeRNAii80329.
PROiQ9BZM6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BZM6.
CleanExiHS_ULBP1.
GenevisibleiQ9BZM6. HS.

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(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], GPI-ANCHOR.
    Tissue: B-cell lymphoma.
  2. Onda H., Shintani Y., Ohkubo S., Ogi K.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "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].
  4. "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: Cerebellum and Testis.
  5. "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].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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].
    Tissue: Testis.
  8. "The ULBP proteins are highly divergent among mammals."
    Larson J.H., Rebeiz M., Stiening C.M., Windish R., Beever J.E., Lewin H.A.
    Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-244.
  9. "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 11-244.
  10. "Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity."
    Dunn C., Chalupny N.J., Sutherland C.L., Dosch S., Sivakumar P.V., Johnson D.C., Cosman D.
    J. Exp. Med. 197:1427-1439(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UL16, SUBCELLULAR LOCATION.
  11. "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.
  12. "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.

Entry informationi

Entry nameiN2DL1_HUMAN
AccessioniPrimary (citable) accession number: Q9BZM6
Secondary accession number(s): Q5VY81, Q8IZW3, Q8IZX6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 123 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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.