Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NKG2D ligand 4

Gene

RAET1E

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

Functioni

Ligand for the KLRK1 receptor. Delivers activating signals to NK cells and promotes tumor immune surveillance by inducing the expansion of anti-tumor cytotoxic lymphocytes.

GO - Molecular functioni

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

GO - Biological processi

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 4
Short name:
N2DL-4
Short name:
NKG2DL4
Alternative name(s):
Lymphocyte effector toxicity activation ligand
RAE-1-like transcript 4
Short name:
RL-4
Retinoic acid early transcript 1E
Gene namesi
Name:RAET1E
Synonyms:LETAL, N2DL4, ULBP4
ORF Names:UNQ1867/PRO4303
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:16793. RAET1E.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 225195ExtracellularSequence analysisAdd
BLAST
Transmembranei226 – 24823HelicalSequence analysisAdd
BLAST
Topological domaini249 – 26315CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134913788.

Polymorphism and mutation databases

BioMutaiRAET1E.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Sequence analysisAdd
BLAST
Chaini31 – 263233NKG2D ligand 4PRO_0000019021Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi36 – 361N-linked (GlcNAc...)Sequence analysis
Disulfide bondi126 ↔ 189By similarity
Glycosylationi154 – 1541N-linked (GlcNAc...)Sequence analysis
Glycosylationi212 – 2121N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8TD07.
PRIDEiQ8TD07.

PTM databases

PhosphoSiteiQ8TD07.

Expressioni

Tissue specificityi

Predominantly expressed in the skin, but also expressed in testis and trachea. Up-regulated in tumor cells of different origins. Expression progressively decreased after treatment of tumor cells with retinoic acid.2 Publications

Gene expression databases

BgeeiQ8TD07.
CleanExiHS_RAET1E.
ExpressionAtlasiQ8TD07. baseline and differential.
GenevisibleiQ8TD07. HS.

Organism-specific databases

HPAiHPA054022.

Interactioni

Subunit structurei

Binds to KLRK1/NKG2D. Does not interacts with the CMV glycoprotein UL16.1 Publication

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi126425. 18 interactions.
STRINGi9606.ENSP00000349709.

Structurei

3D structure databases

ProteinModelPortaliQ8TD07.
SMRiQ8TD07. Positions 30-199.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 11686MHC class I alpha-1 likeAdd
BLAST
Regioni117 – 20791MHC class I alpha-2 likeAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi219 – 2224Poly-Ser

Sequence similaritiesi

Belongs to the MHC class I family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410JBPA. Eukaryota.
ENOG411150N. LUCA.
GeneTreeiENSGT00390000003472.
HOGENOMiHOG000070028.
HOVERGENiHBG052564.
InParanoidiQ8TD07.
KOiK07987.
OMAiQFAINGE.
OrthoDBiEOG79CZ03.
PhylomeDBiQ8TD07.
TreeFamiTF339658.

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.

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TD07-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRRISLTSSP VRLLLFLLLL LIALEIMVGG HSLCFNFTIK SLSRPGQPWC
60 70 80 90 100
EAQVFLNKNL FLQYNSDNNM VKPLGLLGKK VYATSTWGEL TQTLGEVGRD
110 120 130 140 150
LRMLLCDIKP QIKTSDPSTL QVEMFCQREA ERCTGASWQF ATNGEKSLLF
160 170 180 190 200
DAMNMTWTVI NHEASKIKET WKKDRGLEKY FRKLSKGDCD HWLREFLGHW
210 220 230 240 250
EAMPEPTVSP VNASDIHWSS SSLPDRWIIL GAFILLVLMG IVLICVWWQN
260
GEWQAGLWPL RTS
Length:263
Mass (Da):30,122
Last modified:June 1, 2002 - v1
Checksum:i3309279B51B603C8
GO
Isoform 2 (identifier: Q8TD07-2) [UniParc]FASTAAdd to basket

Also known as: RL-4

The sequence of this isoform differs from the canonical sequence as follows:
     28-63: Missing.

Show »
Length:227
Mass (Da):26,059
Checksum:iF1644DD3F54FBD81
GO
Isoform 3 (identifier: Q8TD07-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     208-212: VSPVN → GRRST
     213-263: Missing.

Note: No experimental confirmation available.
Show »
Length:212
Mass (Da):24,364
Checksum:i371CA577033747DC
GO
Isoform RAET1E2 (identifier: Q8TD07-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     208-263: VSPVNASDIHWSSSSLPDRWIILGAFILLVLMGIVLICVWWQNGEWQAGLWPLRTS → GN

Show »
Length:209
Mass (Da):23,978
Checksum:iA7433747DC7581C6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti141 – 1422AT → TI in AAL76417 (PubMed:11827464).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121R → H.
Corresponds to variant rs9383583 [ dbSNP | Ensembl ].
VAR_024534
Natural varianti82 – 821Y → N.2 Publications
Corresponds to variant rs2151910 [ dbSNP | Ensembl ].
VAR_020271
Natural varianti128 – 1281R → H.1 Publication
Corresponds to variant rs6925151 [ dbSNP | Ensembl ].
VAR_024535
Natural varianti141 – 1411A → T.
Corresponds to variant rs9383921 [ dbSNP | Ensembl ].
VAR_050408
Natural varianti142 – 1421T → I.
Corresponds to variant rs9371533 [ dbSNP | Ensembl ].
VAR_050409
Natural varianti194 – 1941R → G.
Corresponds to variant rs57292884 [ dbSNP | Ensembl ].
VAR_061483
Natural varianti237 – 2371V → L.
Corresponds to variant rs2342767 [ dbSNP | Ensembl ].
VAR_024536

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei28 – 6336Missing in isoform 2. 1 PublicationVSP_010441Add
BLAST
Alternative sequencei208 – 26356VSPVN…PLRTS → GN in isoform RAET1E2. 1 PublicationVSP_045012Add
BLAST
Alternative sequencei208 – 2125VSPVN → GRRST in isoform 3. 1 PublicationVSP_010442
Alternative sequencei213 – 26351Missing in isoform 3. 1 PublicationVSP_010443Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY069961 mRNA. Translation: AAL58090.1.
AY252119 mRNA. Translation: AAP15166.1.
AY176317 mRNA. Translation: AAO22240.1.
EF489426 mRNA. Translation: ABR29881.1.
AY054974 mRNA. Translation: AAL11005.1.
AY359075 mRNA. Translation: AAQ89434.1.
AL355312 Genomic DNA. Translation: CAH72868.1.
AL355312 Genomic DNA. Translation: CAH72869.1.
AF359243 mRNA. Translation: AAL76417.1.
CCDSiCCDS5221.1. [Q8TD07-1]
CCDS59042.1. [Q8TD07-4]
CCDS59043.1. [Q8TD07-3]
CCDS59044.1. [Q8TD07-2]
RefSeqiNP_001230254.1. NM_001243325.1. [Q8TD07-2]
NP_001230256.1. NM_001243327.1. [Q8TD07-4]
NP_001230257.1. NM_001243328.1. [Q8TD07-3]
NP_631904.1. NM_139165.2. [Q8TD07-1]
XP_011533781.1. XM_011535479.1. [Q8TD07-3]
UniGeneiHs.511818.

Genome annotation databases

EnsembliENST00000357183; ENSP00000349709; ENSG00000164520. [Q8TD07-1]
ENST00000367363; ENSP00000356332; ENSG00000164520. [Q8TD07-2]
ENST00000529948; ENSP00000432366; ENSG00000164520. [Q8TD07-4]
ENST00000532335; ENSP00000437067; ENSG00000164520. [Q8TD07-3]
GeneIDi135250.
KEGGihsa:135250.
UCSCiuc003qnj.3. human. [Q8TD07-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY069961 mRNA. Translation: AAL58090.1.
AY252119 mRNA. Translation: AAP15166.1.
AY176317 mRNA. Translation: AAO22240.1.
EF489426 mRNA. Translation: ABR29881.1.
AY054974 mRNA. Translation: AAL11005.1.
AY359075 mRNA. Translation: AAQ89434.1.
AL355312 Genomic DNA. Translation: CAH72868.1.
AL355312 Genomic DNA. Translation: CAH72869.1.
AF359243 mRNA. Translation: AAL76417.1.
CCDSiCCDS5221.1. [Q8TD07-1]
CCDS59042.1. [Q8TD07-4]
CCDS59043.1. [Q8TD07-3]
CCDS59044.1. [Q8TD07-2]
RefSeqiNP_001230254.1. NM_001243325.1. [Q8TD07-2]
NP_001230256.1. NM_001243327.1. [Q8TD07-4]
NP_001230257.1. NM_001243328.1. [Q8TD07-3]
NP_631904.1. NM_139165.2. [Q8TD07-1]
XP_011533781.1. XM_011535479.1. [Q8TD07-3]
UniGeneiHs.511818.

3D structure databases

ProteinModelPortaliQ8TD07.
SMRiQ8TD07. Positions 30-199.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126425. 18 interactions.
STRINGi9606.ENSP00000349709.

PTM databases

PhosphoSiteiQ8TD07.

Polymorphism and mutation databases

BioMutaiRAET1E.

Proteomic databases

PaxDbiQ8TD07.
PRIDEiQ8TD07.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357183; ENSP00000349709; ENSG00000164520. [Q8TD07-1]
ENST00000367363; ENSP00000356332; ENSG00000164520. [Q8TD07-2]
ENST00000529948; ENSP00000432366; ENSG00000164520. [Q8TD07-4]
ENST00000532335; ENSP00000437067; ENSG00000164520. [Q8TD07-3]
GeneIDi135250.
KEGGihsa:135250.
UCSCiuc003qnj.3. human. [Q8TD07-1]

Organism-specific databases

CTDi135250.
GeneCardsiRAET1E.
H-InvDBHIX0032797.
HGNCiHGNC:16793. RAET1E.
HPAiHPA054022.
MIMi609243. gene.
neXtProtiNX_Q8TD07.
PharmGKBiPA134913788.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBPA. Eukaryota.
ENOG411150N. LUCA.
GeneTreeiENSGT00390000003472.
HOGENOMiHOG000070028.
HOVERGENiHBG052564.
InParanoidiQ8TD07.
KOiK07987.
OMAiQFAINGE.
OrthoDBiEOG79CZ03.
PhylomeDBiQ8TD07.
TreeFamiTF339658.

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiRAET1E.
GenomeRNAii135250.
PROiQ8TD07.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TD07.
CleanExiHS_RAET1E.
ExpressionAtlasiQ8TD07. baseline and differential.
GenevisibleiQ8TD07. 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. "Letal, a tumor-associated NKG2D immunoreceptor ligand, induces activation and expansion of effector immune cells."
    Conejo-Garcia J.-R., Benencia F., Courreges M.C., Khang E., Zhang L., Mohamed-Hadley A., Vinocur J.M., Buckanovich R.J., Thompson C.B., Levine B., Coukos G.
    Cancer Biol. Ther. 2:446-451(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Ovarian carcinoma.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Esophagus.
  3. "Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D."
    Bacon L., Eagle R.A., Meyer M., Easom N., Young N.T., Trowsdale J.
    J. Immunol. 173:1078-1084(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH KLRK1.
  4. "RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity."
    Cao W., Xi X., Hao Z., Li W., Kong Y., Cui L., Ma C., Ba D., He W.
    J. Biol. Chem. 282:18922-18928(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RAET1E2), ALTERNATIVE SPLICING.
  5. "Homo sapiens RAE-1-like transcript 4 (RL-4) mRNA."
    Lanier L.L., Cerwenka A.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ASN-82.
  7. "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].
  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 1-222 (ISOFORM 1), VARIANTS ASN-82 AND HIS-128.

Entry informationi

Entry nameiN2DL4_HUMAN
AccessioniPrimary (citable) accession number: Q8TD07
Secondary accession number(s): A6YF59
, Q5VYB7, Q5VYB8, Q8TEZ2, Q96L41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: June 1, 2002
Last modified: June 8, 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.