Q9BZM4 (N2DL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NKG2D ligand 3
Short name=N2DL-3
Short name=NKG2DL3

Alternative name(s):
ALCAN-gamma
Retinoic acid early transcript 1N

Gene names

Name:	ULBP3
Synonyms:	N2DL3, RAET1N

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	244 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand for the 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 NKG2D induces calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. Has lower affinity for NKG2D compared to ULBP1 and ULBP2 and induces weaker signaling responses than does ULBP2 or ULBP1.
Subunit structure	Does not bind to beta2-microglobulin. Interacts with human cytomegalovirus/HHV-5 protein UL142. Ref.7 Ref.10
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor Ref.1.
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.
Sequence similarities	Belongs to the MHC class I family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Membrane
Domain	Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation Inferred from electronic annotation. Source: InterPro natural killer cell activation Inferred from direct assay Ref.1. Source: UniProtKB natural killer cell mediated cytotoxicity Inferred from direct assay Ref.1. Source: UniProtKB regulation of immune response Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	MHC class I protein complex Inferred from electronic annotation. Source: InterPro anchored to plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	natural killer cell lectin-like receptor binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Potential

Chain

30 – 217

188

NKG2D ligand 3

PRO_0000019019

Propeptide

218 – 244

27

Removed in mature form Potential

PRO_0000019020

Regions

Region

30 – 118

89

MHC class I alpha-1 like

Region

119 – 209

91

MHC class I alpha-2 like

Amino acid modifications

Lipidation

217

1

GPI-anchor amidated glycine Potential

Glycosylation

37

1

N-linked (GlcNAc...) Potential

Disulfide bond

51 ↔ 67

Disulfide bond

128 ↔ 191

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

244

Helix Strand Turn

Details...

Beta strand

32 – 43

12

Beta strand

50 – 57

8

Beta strand

60 – 66

7

Turn

67 – 70

4

Beta strand

83 – 85

3

Helix

86 – 107

22

Beta strand

121 – 130

10

Beta strand

137 – 153

17

Turn

154 – 157

4

Beta strand

158 – 163

6

Helix

164 – 166

3

Helix

167 – 175

9

Helix

177 – 188

12

Helix

190 – 206

17

Sequences

	Sequence		Length	Mass (Da)
	Q9BZM4 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: BAF07895640B9901	FASTA	244	27,949
	10 20 30 40 50 60 MAAAASPAIL PRLAILPYLL FDWSGTGRAD AHSLWYNFTI IHLPRHGQQW CEVQSQVDQK 70 80 90 100 110 120 NFLSYDCGSD KVLSMGHLEE QLYATDAWGK QLEMLREVGQ RLRLELADTE LEDFTPSGPL 130 140 150 160 170 180 TLQVRMSCEC EADGYIRGSW QFSFDGRKFL LFDSNNRKWT VVHAGARRMK EKWEKDSGLT 190 200 210 220 230 240 TFFKMVSMRD CKSWLRDFLM HRKKRLEPTA PPTMAPGLAQ PKAIATTLSP WSFLIILCFI LPGI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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 NKG2D.
[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]	"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.
[10]	"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.
[11]	"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 NKG2D.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00001602.

RefSeq

NP_078794.1. NM_024518.1.

UniGene

Hs.326556.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KCG	X-ray	2.60	C	30-207	[»]

ProteinModelPortal

Q9BZM4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BZM4. 1 interaction.

STRING

9606.ENSP00000253335.

Polymorphism databases

DMDM

47605922.

Proteomic databases

PaxDb

Q9BZM4.

PRIDE

Q9BZM4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000367339; ENSP00000356308; ENSG00000131019.
ENST00000438272; ENSP00000403562; ENSG00000131019.

GeneID

79465.

KEGG

hsa:79465.

UCSC

uc003qns.3. human.

Organism-specific databases

CTD

79465.

GeneCards

GC06M150477.

HGNC

HGNC:14895. ULBP3.

MIM

605699. gene.

neXtProt

NX_Q9BZM4.

PharmGKB

PA37917.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG75885.

HOGENOM

HOG000070028.

HOVERGEN

HBG052564.

InParanoid

Q9BZM4.

KO

K07986.

OMA

SMGHLEE.

OrthoDB

EOG4FBHTV.

PhylomeDB

Q9BZM4.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9BZM4.

Bgee

Q9BZM4.

CleanEx

HS_ULBP3.

Genevestigator

Q9BZM4.

GermOnline

ENSG00000131019. Homo sapiens.

Family and domain databases

Gene3D

3.30.500.10. 1 hit.

InterPro

IPR011161. MHC_I-like_Ag-recog.
IPR011162. MHC_I/II-like_Ag-recog.
IPR001039. MHC_I_a_a1/a2.
[Graphical view]

Pfam

PF00129. MHC_I. 1 hit.
[Graphical view]

SUPFAM

SSF54452. MHC_I/II-like_Ag-recog. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9BZM4.

GenomeRNAi

79465.

NextBio

68421.

SOURCE

Search...

Entry information

Entry name

N2DL3_HUMAN

Accession

Primary (citable) accession number: Q9BZM4
Secondary accession number(s): Q5VY82, Q8IZX5, Q8TE75

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.