Q9BZW8 (CD244_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	370 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	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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome signal transduction Traceable author statement Ref.3. Source: ProtInc
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 17213291. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD48	P09326	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.2 Ref.12
	Chain	22 – 370	349	Natural killer cell receptor 2B4		PRO_0000014668
Regions
	Topological domain	22 – 229	208	Extracellular Potential
	Transmembrane	230 – 250	21	Helical; Potential
	Topological domain	251 – 370	120	Cytoplasmic Potential
	Domain	25 – 126	102	Ig-like 1
	Domain	131 – 215	85	Ig-like 2
Amino acid modifications
	Modified residue	369	1	Phosphotyrosine By similarity
	Glycosylation	71	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	77	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	89	1	N-linked (GlcNAc...) Ref.14
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	200	1	N-linked (GlcNAc...) Potential
	Glycosylation	213	1	N-linked (GlcNAc...) Potential
	Disulfide bond	157 ↔ 199		Potential
Natural variations
	Alternative sequence	127 – 131	5	Missing in isoform 2 and isoform 3.		VSP_010397
	Alternative sequence	128 – 224	97	Missing in isoform 4.		VSP_010398
	Alternative sequence	326 – 334	9	SGSRKRNHS → GDRFYSFSG in isoform 3.		VSP_010399
	Alternative sequence	335 – 370	36	Missing in isoform 3.		VSP_010400
	Natural variant	89	1	N → D. Corresponds to variant rs34846692 [ dbSNP | Ensembl ].		VAR_056036
	Natural variant	323	1	S → F. Corresponds to variant rs12064925 [ dbSNP | Ensembl ].		VAR_056037
Experimental info
	Sequence conflict	127 – 133	7	ESLLPDK → GMAMCPM in AAK50015. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (H2B4-B) [UniParc]. Last modified May 24, 2004. Version 2. Checksum: 959FF8DBB0BACC87	FASTA	370	41,616
	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
	Isoform 2 (H2B4-A) [UniParc]. Checksum: 7DEDD0EBF2E19322	FASTA	365	41,077
	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 FQVFVFDKVE KPRLQGQGKI LDRGRCQVAL SCLVSRDGNV SYAWYRGSKL IQTAGNLTYL 190 200 210 220 230 240 DEEVDINGTH TYTCNVSNPV SWESHTLNLT QDCQNAHQEF RFWPFLVIIV ILSALFLGTL 250 260 270 280 290 300 ACFCVWRRKR KEKQSETSPK EFLTIYEDVK DLKTRRNHEQ EQTFPGGGST IYSMIQSQSS 310 320 330 340 350 360 APTSQEPAYT LYSLIQPSRK SGSRKRNHSP SFNSTIYEVI GKSQPKAQNP ARLSRKELEN FDVYS
	Isoform 3 (H2B4) [UniParc]. Checksum: 639FE10EA76F074E	FASTA	329	36,987
	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 FQVFVFDKVE KPRLQGQGKI LDRGRCQVAL SCLVSRDGNV SYAWYRGSKL IQTAGNLTYL 190 200 210 220 230 240 DEEVDINGTH TYTCNVSNPV SWESHTLNLT QDCQNAHQEF RFWPFLVIIV ILSALFLGTL 250 260 270 280 290 300 ACFCVWRRKR KEKQSETSPK EFLTIYEDVK DLKTRRNHEQ EQTFPGGGST IYSMIQSQSS 310 320 APTSQEPAYT LYSLIQPSRK GDRFYSFSG
	Isoform 4 (H2B4b) [UniParc]. Checksum: 036514F046E2099C	FASTA	273	30,784
	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 FQVFVFEFRF WPFLVIIVIL SALFLGTLAC FCVWRRKRKE KQSETSPKEF LTIYEDVKDL 190 200 210 220 230 240 KTRRNHEQEQ TFPGGGSTIY SMIQSQSSAP TSQEPAYTLY SLIQPSRKSG SRKRNHSPSF 250 260 270 NSTIYEVIGK SQPKAQNPAR LSRKELENFD VYS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00015548. IPI00184175. IPI00411526. IPI00411528.
RefSeq	NP_001160135.1. NM_001166663.1. NP_001160136.1. NM_001166664.1. NP_057466.1. NM_016382.3.
UniGene	Hs.157872.
3D structure databases
ProteinModelPortal	Q9BZW8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BZW8. 1 interaction.
MINT	MINT-3371787.
STRING	9606.ENSP00000357013.
PTM databases
PhosphoSite	Q9BZW8.
Polymorphism databases
DMDM	47605541.
Proteomic databases
PaxDb	Q9BZW8.
PRIDE	Q9BZW8.
Protocols and materials databases
DNASU	51744.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322302; ENSP00000313619; ENSG00000122223. ENST00000368032; ENSP00000357011; ENSG00000122223. ENST00000368033; ENSP00000357012; ENSG00000122223. ENST00000368034; ENSP00000357013; ENSG00000122223. ENST00000492063; ENSP00000432636; ENSG00000122223.
GeneID	51744.
KEGG	hsa:51744.
UCSC	uc001fxa.3. human. uc009wtq.3. human. uc009wtr.3. human.
Organism-specific databases
CTD	51744.
GeneCards	GC01M160799.
HGNC	HGNC:18171. CD244.
HPA	HPA010628.
MIM	605554. gene.
neXtProt	NX_Q9BZW8.
PharmGKB	PA134905192.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46473.
HOVERGEN	HBG050850.
InParanoid	Q9BZW8.
KO	K06582.
OMA	TIYSMIQ.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
Bgee	Q9BZW8.
CleanEx	HS_CD244.
Genevestigator	Q9BZW8.
GermOnline	ENSG00000122223. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 2 hits.
InterPro	IPR007110. 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]
PANTHER	PTHR12080. PTHR12080. 1 hit. PTHR12080:SF11. PTHR12080:SF11. 1 hit.
Pfam	PF11465. Receptor_2B4. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	51744.
NextBio	55826.
SOURCE	Search...

Entry information

Entry name

CD244_HUMAN

Accession

Primary (citable) accession number: Q9BZW8
Secondary accession number(s): Q5VYI2 , Q5VYI6, Q5VYI7, Q96T47, Q9NQD2, Q9NQD3, Q9Y288

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	May 24, 2004
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 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.