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Q9BZW8 (CD244_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Natural killer cell receptor 2B4
Alternative name(s):
NK cell activation-inducing ligand
Short name=NAIL
NK cell type I receptor protein 2B4
Short name=NKR2B4
Short name=h2B4
SLAM family member 4
Short name=SLAMF4
Signaling lymphocytic activation molecule 4
CD_antigen=CD244
Gene names
Name:CD244
Synonyms:2B4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Modulate other receptor-ligand interactions to enhance leukocyte activation. CD244/2B4 is the only heterophilic receptor of SLAM family. Ref.1

Subunit structure

Interacts with CD48. Following phosphorylation, it is able to recruit PTPN11/SHP-2 and SH2D1A/SAP. Binding of SH2D1A/SAP to CD244 prevents its association with PTPN11/SHP-2. Ref.1 Ref.2 Ref.4

Subcellular location

Membrane; Single-pass type I membrane protein Potential.

Tissue specificity

Expressed in spleen, PBL, followed by lung, liver, testis and small intestine. Expressed not only in NK cells, but also on monocytes and basophils. Ref.2

Post-translational modification

N-linked glycosylation is essential for the binding to its ligand CD48. Also O-glycosylated, in contrast, O-linked sialylation has a negative impact on ligand binding. Ref.14

Sequence similarities

Contains 2 Ig-like (immunoglobulin-like) domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CD48P093262EBI-1580565,EBI-714770

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BZW8-1)

Also known as: H2B4-B;

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.
Isoform 2 (identifier: Q9BZW8-2)

Also known as: H2B4-A;

The sequence of this isoform differs from the canonical sequence as follows:
     127-131: Missing.
Note: Binds to CD48 with a sronger affinity than isoform 1, and interactions induces greater cytotoxicity and intracellular calcium release.
Isoform 3 (identifier: Q9BZW8-3)

Also known as: H2B4;

The sequence of this isoform differs from the canonical sequence as follows:
     127-131: Missing.
     326-334: SGSRKRNHS → GDRFYSFSG
     335-370: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9BZW8-4)

Also known as: H2B4b;

The sequence of this isoform differs from the canonical sequence as follows:
     128-224: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.2 Ref.12
Chain22 – 370349Natural killer cell receptor 2B4
PRO_0000014668

Regions

Topological domain22 – 229208Extracellular Potential
Transmembrane230 – 25021Helical; Potential
Topological domain251 – 370120Cytoplasmic Potential
Domain22 – 127106Ig-like 1
Domain131 – 21585Ig-like 2

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Ref.14
Glycosylation771N-linked (GlcNAc...) Ref.14
Glycosylation891N-linked (GlcNAc...) Ref.14
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation1811N-linked (GlcNAc...) Potential
Glycosylation1921N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Potential
Glycosylation2131N-linked (GlcNAc...) Potential
Disulfide bond157 ↔ 199 Potential

Natural variations

Alternative sequence127 – 1315Missing in isoform 2 and isoform 3.
VSP_010397
Alternative sequence128 – 22497Missing in isoform 4.
VSP_010398
Alternative sequence326 – 3349SGSRKRNHS → GDRFYSFSG in isoform 3.
VSP_010399
Alternative sequence335 – 37036Missing in isoform 3.
VSP_010400
Natural variant891N → D.
Corresponds to variant rs34846692 [ dbSNP | Ensembl ].
VAR_056036
Natural variant3231S → F.
Corresponds to variant rs12064925 [ dbSNP | Ensembl ].
VAR_056037

Experimental info

Sequence conflict127 – 1337ESLLPDK → GMAMCPM in AAK50015. Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (H2B4-B) [UniParc].

Last modified May 24, 2004. Version 2.
Checksum: 959FF8DBB0BACC87

FASTA37041,616
        10         20         30         40         50         60 
MLGQVVTLIL LLLLKVYQGK GCQGSADHVV SISGVPLQLQ PNSIQTKVDS IAWKKLLPSQ 

        70         80         90        100        110        120 
NGFHHILKWE NGSLPSNTSN DRFSFIVKNL SLLIKAAQQQ DSGLYCLEVT SISGKVQTAT 

       130        140        150        160        170        180 
FQVFVFESLL PDKVEKPRLQ GQGKILDRGR CQVALSCLVS RDGNVSYAWY RGSKLIQTAG 

       190        200        210        220        230        240 
NLTYLDEEVD INGTHTYTCN VSNPVSWESH TLNLTQDCQN AHQEFRFWPF LVIIVILSAL 

       250        260        270        280        290        300 
FLGTLACFCV WRRKRKEKQS ETSPKEFLTI YEDVKDLKTR RNHEQEQTFP GGGSTIYSMI 

       310        320        330        340        350        360 
QSQSSAPTSQ EPAYTLYSLI QPSRKSGSRK RNHSPSFNST IYEVIGKSQP KAQNPARLSR 

       370 
KELENFDVYS 

« Hide

Isoform 2 (H2B4-A) [UniParc].

Checksum: 7DEDD0EBF2E19322
Show »

FASTA36541,077
Isoform 3 (H2B4) [UniParc].

Checksum: 639FE10EA76F074E
Show »

FASTA32936,987
Isoform 4 (H2B4b) [UniParc].

Checksum: 036514F046E2099C
Show »

FASTA27330,784

References

« Hide 'large scale' references
[1]"Activating interactions in human NK cell recognition: the role of 2B4-CD48."
Nakajima H., Cella M., Langen H., Friedlein A., Colonna M.
Eur. J. Immunol. 29:1676-1683(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH CD48.
[2]"Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48."
Kubin M.Z., Parshley D.L., Din W., Waugh J.Y., Davis-Smith T., Smith C.A., Macduff B.M., Armitage R.J., Chin W., Cassiano L., Borges L., Petersen M., Trinchieri G., Goodwin R.G.
Eur. J. Immunol. 29:3466-3477(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF N-TERMINUS, TISSUE SPECIFICITY, INTERACTION WITH CD48.
[3]"Human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP."
Tangye S.G., Lazetic S., Woollatt E., Sutherland G.R., Lanier L.L., Phillips J.H.
J. Immunol. 162:6981-6985(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PHOSPHORYLATION.
[4]"Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4."
Boles K.S., Nakajima H., Colonna M., Chuang S.S., Stepp S.E., Bennett M., Kumar V., Mathew P.A.
Tissue Antigens 54:27-34(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH CD48.
Tissue: Natural killer cell.
[5]"Structure of the human natural killer cell receptor 2B4 gene and identification of a novel alternative transcript."
Kumaresan P.R., Mathew P.A.
Immunogenetics 51:987-992(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]"X-linked lymphoproliferative disease: 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells."
Parolini S., Bottino C., Falco M., Augugliaro R., Giliani S., Franceschini R., Ochs H.D., Wolf H., Bonnefoy J.-Y., Biassoni R., Moretta L., Notarangelo L.D., Moretta A.
J. Exp. Med. 192:337-346(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
Tissue: Lymphoid tissue.
[7]"Activating NK receptor homolog to the murine 2B4."
Biassoni R., Falco M.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Lymphoid tissue.
[8]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.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. expand/collapse author list , 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].
[10]"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] (ISOFORM 2).
Tissue: Blood.
[11]Lennon G.P., Eccleston D.W., Pridgeon C., Pazmany L., Moots R.J.
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-133.
[12]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36.
[13]"Functional role of human NK cell receptor 2B4 (CD244) isoforms."
Mathew S.O., Rao K.K., Kim J.R., Bambard N.D., Mathew P.A.
Eur. J. Immunol. 39:1632-1641(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[14]"Glycosylation affects ligand binding and function of the activating natural killer cell receptor 2B4 (CD244) protein."
Margraf-Schonfeld S., Bohm C., Watzl C.
J. Biol. Chem. 286:24142-24149(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-71; ASN-77 AND ASN-89.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF105261 mRNA. Translation: AAD32538.1.
AF117711 mRNA. Translation: AAF28833.1.
AF145782 mRNA. Translation: AAD38951.1.
AF107761 mRNA. Translation: AAD37838.1.
AF242540 mRNA. Translation: AAK00233.1.
AJ245376 mRNA. Translation: CAC00648.1.
AJ245377 mRNA. Translation: CAC00649.1.
AJ245375 mRNA. Translation: CAC00647.1.
AL354714 Genomic DNA. Translation: CAH72353.1.
AL354714 Genomic DNA. Translation: CAH72354.1.
AL354714 Genomic DNA. Translation: CAH72355.1.
CH471121 Genomic DNA. Translation: EAW52691.1.
CH471121 Genomic DNA. Translation: EAW52692.1.
CH471121 Genomic DNA. Translation: EAW52693.1.
BC028073 mRNA. Translation: AAH28073.1.
BC053985 mRNA. Translation: AAH53985.1.
AF363452 mRNA. Translation: AAK50015.1.
RefSeqNP_001160135.1. NM_001166663.1.
NP_001160136.1. NM_001166664.1.
NP_057466.1. NM_016382.3.
UniGeneHs.157872.

3D structure databases

ProteinModelPortalQ9BZW8.
SMRQ9BZW8. Positions 22-215.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119709. 2 interactions.
IntActQ9BZW8. 4 interactions.
MINTMINT-3371787.
STRING9606.ENSP00000357013.

PTM databases

PhosphoSiteQ9BZW8.

Polymorphism databases

DMDM47605541.

Proteomic databases

PaxDbQ9BZW8.
PRIDEQ9BZW8.

Protocols and materials databases

DNASU51744.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322302; ENSP00000313619; ENSG00000122223. [Q9BZW8-4]
ENST00000368032; ENSP00000357011; ENSG00000122223. [Q9BZW8-3]
ENST00000368033; ENSP00000357012; ENSG00000122223. [Q9BZW8-1]
ENST00000368034; ENSP00000357013; ENSG00000122223. [Q9BZW8-2]
ENST00000492063; ENSP00000432636; ENSG00000122223. [Q9BZW8-3]
GeneID51744.
KEGGhsa:51744.
UCSCuc001fxa.3. human. [Q9BZW8-2]
uc009wtq.3. human. [Q9BZW8-1]
uc009wtr.3. human. [Q9BZW8-4]

Organism-specific databases

CTD51744.
GeneCardsGC01M160799.
HGNCHGNC:18171. CD244.
HPAHPA010628.
MIM605554. gene.
neXtProtNX_Q9BZW8.
PharmGKBPA134905192.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46473.
HOVERGENHBG050850.
InParanoidQ9BZW8.
KOK06582.
OMAHTYTCNV.
OrthoDBEOG7QVM45.
TreeFamTF334964.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkQ9BZW8.

Gene expression databases

BgeeQ9BZW8.
CleanExHS_CD244.
GenevestigatorQ9BZW8.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR024304. NK_rcpt_2B4.
IPR024303. NK_rcpt_2B4_Ig_dom.
IPR015631. SLAM_fam_rcpts.
[Graphical view]
PANTHERPTHR12080. PTHR12080. 1 hit.
PTHR12080:SF11. PTHR12080:SF11. 1 hit.
PfamPF11465. Receptor_2B4. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCD244.
GenomeRNAi51744.
NextBio55826.
PROQ9BZW8.
SOURCESearch...

Entry information

Entry nameCD244_HUMAN
AccessionPrimary (citable) accession number: Q9BZW8
Secondary accession number(s): Q5VYI2 expand/collapse secondary AC list , Q5VYI6, Q5VYI7, Q96T47, Q9NQD2, Q9NQD3, Q9Y288
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: March 19, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries