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UniProtKB - Q9BZW8 (CD244_HUMAN)

Protein

Natural killer cell receptor 2B4

Gene

CD244

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

Functioni

Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor (PubMed:10359122, PubMed:8376943, PubMed:11714776). Activating function implicates association with SH2D1A and FYN (PubMed:15713798). Downstreaming signaling involves predominantly VAV1, and, to a lesser degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of SH2D1A is proposed to be dependent on INPP5D and to a lesser extent PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10934222, PubMed:15713798). Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis (PubMed:8376943, PubMed:11714776). Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells (By similarity). Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1 (PubMed:10741393). At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self-tolerance of developing NK cells (PubMed:11917118). Involved in the regulation of CD8+ T-cell proliferation; expression on activated T-cells and binding to CD488 provides costimulatory-like function for neighboring T-cells (By similarity). Inhibits inflammatory responses in dendritic cells (DCs) (By similarity).By similarity1 Publication6 Publications

GO - Molecular functioni

  • MHC class I protein binding Source: UniProtKB
  • signaling receptor activity Source: ProtInc
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-202733 Cell surface interactions at the vascular wall
SignaLinkiQ9BZW8

Names & Taxonomyi

Protein namesi
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 namesi
Name:CD244
Synonyms:2B4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000122223.12
HGNCiHGNC:18171 CD244
MIMi605554 gene
neXtProtiNX_Q9BZW8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 229ExtracellularSequence analysisAdd BLAST208
Transmembranei230 – 250HelicalSequence analysisAdd BLAST21
Topological domaini251 – 370CytoplasmicSequence analysisAdd BLAST120

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68K → A: Disrupts interaction with CD48; when associated with A-70. 1 Publication1
Mutagenesisi70E → A: Disrupts interaction with CD48; when associated with A-68. 1 Publication1

Organism-specific databases

DisGeNETi51744
MalaCardsiCD244
OpenTargetsiENSG00000122223
PharmGKBiPA134905192

Polymorphism and mutation databases

BioMutaiCD244
DMDMi47605541

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 212 PublicationsAdd BLAST21
ChainiPRO_000001466822 – 370Natural killer cell receptor 2B4Add BLAST349

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi77N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi89N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi157 ↔ 199PROSITE-ProRule annotation
Glycosylationi164N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi181N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi192N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi200N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei271Phosphotyrosine3 Publications1
Modified residuei297Phosphotyrosine; by FYN3 Publications1
Modified residuei317Phosphotyrosine2 Publications1
Modified residuei342Phosphotyrosine; by FYN2 Publications1

Post-translational modificationi

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.1 Publication
Phosphorylated by FYN and CSK on tyrosine residues following activation. Coligation with inhibitory receptors such as KIR2DL1 inhibits phosphorylation upon contact of NK cells with sensitive target cells.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9BZW8
PeptideAtlasiQ9BZW8
PRIDEiQ9BZW8
ProteomicsDBi79913
79914 [Q9BZW8-2]
79915 [Q9BZW8-3]
79916 [Q9BZW8-4]

PTM databases

iPTMnetiQ9BZW8
PhosphoSitePlusiQ9BZW8

Expressioni

Tissue specificityi

Expressed in spleen, PBL, followed by lung, liver, testis and small intestine. Expressed in all natural killer (NK) cells, monocytes and basophils, TCR-gamma/delta+ T-cells, monocytes, basophils, and on a subset of CD8+ T-cells.3 Publications

Gene expression databases

BgeeiENSG00000122223 Expressed in 96 organ(s), highest expression level in leukocyte
CleanExiHS_CD244
GenevisibleiQ9BZW8 HS

Interactioni

Subunit structurei

Interacts with CD48 (PubMed:9841922). Interacts (via phosphorylated ITSM 1-4) with SH2D1A (via SH2 domain); SH2D1A probably mediates association with FYN. Interacts (via phosphorylated ITSM 3) with PTPN11/SHP-2, INPP5D/SHIP1, PTPN6/SHP-1 and CSK; binding of SH2D1A/SAP prevents association with PTPN11, PTPN6 and CSK; conflictingly a similar association has been described for phosphorylated ITSM 1 also including GRB2 and PLCG1. Interacts weakly (via phosphorylated ITSM 2) with PTPN11/SHP-2 and CSK (PubMed:10358138, PubMed:10934222, PubMed:12458214, PubMed:24642916, PubMed:26221972, PubMed:15713798). Interacts with SH2D1B (PubMed:12458214, PubMed:24642916). Interacts with PIK3R1; PI3K recruits SH2D1A (PubMed:11815622). Interacts with MHC class I proteins; the interaction is proposed to prevent self-killing of NK cells.By similarity12 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi119709, 24 interactors
DIPiDIP-40331N
ELMiQ9BZW8
IntActiQ9BZW8, 16 interactors
MINTiQ9BZW8
STRINGi9606.ENSP00000357012

Structurei

3D structure databases

ProteinModelPortaliQ9BZW8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 127Ig-like 1Add BLAST106
Domaini131 – 215Ig-like 2Add BLAST85

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi269 – 274ITSM 1By similarity6
Motifi295 – 300ITSM 2By similarity6
Motifi315 – 320ITSM 3By similarity6
Motifi340 – 345ITSM 4By similarity6

Domaini

The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).By similarity2 Publications

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKYZ Eukaryota
ENOG410Y74Q LUCA
GeneTreeiENSGT00510000049238
HOVERGENiHBG050850
InParanoidiQ9BZW8
KOiK06582
OMAiQDCQNAH
OrthoDBiEOG091G0DZW
PhylomeDBiQ9BZW8
TreeFamiTF334964

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR024304 NK_rcpt_2B4
IPR024303 NK_rcpt_2B4_Ig_dom
PANTHERiPTHR12080:SF56 PTHR12080:SF56, 2 hits
PfamiView protein in Pfam
PF13895 Ig_2, 1 hit
PF11465 Receptor_2B4, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 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: Q9BZW8-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MLGQVVTLIL LLLLKVYQGK GCQGSADHVV SISGVPLQLQ PNSIQTKVDS 
        60         70         80         90        100
IAWKKLLPSQ NGFHHILKWE NGSLPSNTSN DRFSFIVKNL SLLIKAAQQQ 
       110        120        130        140        150
DSGLYCLEVT SISGKVQTAT FQVFVFESLL PDKVEKPRLQ GQGKILDRGR 
       160        170        180        190        200
CQVALSCLVS RDGNVSYAWY RGSKLIQTAG NLTYLDEEVD INGTHTYTCN 
       210        220        230        240        250
VSNPVSWESH TLNLTQDCQN AHQEFRFWPF LVIIVILSAL FLGTLACFCV 
       260        270        280        290        300
WRRKRKEKQS ETSPKEFLTI YEDVKDLKTR RNHEQEQTFP GGGSTIYSMI 
       310        320        330        340        350
QSQSSAPTSQ EPAYTLYSLI QPSRKSGSRK RNHSPSFNST IYEVIGKSQP 
       360        370
KAQNPARLSR KELENFDVYS
Length:370
Mass (Da):41,616
Last modified:May 24, 2004 - v2
Checksum:i959FF8DBB0BACC87
GO
Isoform 2 (identifier: Q9BZW8-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:365
Mass (Da):41,077
Checksum:i7DEDD0EBF2E19322
GO
Isoform 3 (identifier: Q9BZW8-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:329
Mass (Da):36,987
Checksum:i639FE10EA76F074E
GO
Isoform 4 (identifier: Q9BZW8-4) [UniParc]FASTAAdd to basket
Also known as: H2B4b

The sequence of this isoform differs from the canonical sequence as follows:
     128-224: Missing.

Note: No experimental confirmation available.
Show »
Length:273
Mass (Da):30,784
Checksum:i036514F046E2099C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127 – 133ESLLPDK → GMAMCPM in AAK50015 (PubMed:15489334).Curated7

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05603689N → D. Corresponds to variant dbSNP:rs34846692Ensembl.1
Natural variantiVAR_056037323S → F. Corresponds to variant dbSNP:rs12064925Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010397127 – 131Missing in isoform 2 and isoform 3. 7 Publications5
Alternative sequenceiVSP_010398128 – 224Missing in isoform 4. 1 PublicationAdd BLAST97
Alternative sequenceiVSP_010399326 – 334SGSRKRNHS → GDRFYSFSG in isoform 3. 1 Publication9
Alternative sequenceiVSP_010400335 – 370Missing in isoform 3. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
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
CCDSiCCDS1210.1 [Q9BZW8-2]
CCDS53398.1 [Q9BZW8-4]
CCDS53399.1 [Q9BZW8-1]
RefSeqiNP_001160135.1, NM_001166663.1 [Q9BZW8-1]
NP_001160136.1, NM_001166664.1 [Q9BZW8-4]
NP_057466.1, NM_016382.3 [Q9BZW8-2]
XP_011507924.1, XM_011509622.2 [Q9BZW8-3]
UniGeneiHs.157872

Genome annotation databases

EnsembliENST00000322302; ENSP00000313619; ENSG00000122223 [Q9BZW8-4]
ENST00000368033; ENSP00000357012; ENSG00000122223 [Q9BZW8-1]
ENST00000368034; ENSP00000357013; ENSG00000122223 [Q9BZW8-2]
ENST00000492063; ENSP00000432636; ENSG00000122223 [Q9BZW8-3]
GeneIDi51744
KEGGihsa:51744
UCSCiuc001fxa.4 human [Q9BZW8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
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
CCDSiCCDS1210.1 [Q9BZW8-2]
CCDS53398.1 [Q9BZW8-4]
CCDS53399.1 [Q9BZW8-1]
RefSeqiNP_001160135.1, NM_001166663.1 [Q9BZW8-1]
NP_001160136.1, NM_001166664.1 [Q9BZW8-4]
NP_057466.1, NM_016382.3 [Q9BZW8-2]
XP_011507924.1, XM_011509622.2 [Q9BZW8-3]
UniGeneiHs.157872

3D structure databases

ProteinModelPortaliQ9BZW8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119709, 24 interactors
DIPiDIP-40331N
ELMiQ9BZW8
IntActiQ9BZW8, 16 interactors
MINTiQ9BZW8
STRINGi9606.ENSP00000357012

PTM databases

iPTMnetiQ9BZW8
PhosphoSitePlusiQ9BZW8

Polymorphism and mutation databases

BioMutaiCD244
DMDMi47605541

Proteomic databases

PaxDbiQ9BZW8
PeptideAtlasiQ9BZW8
PRIDEiQ9BZW8
ProteomicsDBi79913
79914 [Q9BZW8-2]
79915 [Q9BZW8-3]
79916 [Q9BZW8-4]

Protocols and materials databases

DNASUi51744
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322302; ENSP00000313619; ENSG00000122223 [Q9BZW8-4]
ENST00000368033; ENSP00000357012; ENSG00000122223 [Q9BZW8-1]
ENST00000368034; ENSP00000357013; ENSG00000122223 [Q9BZW8-2]
ENST00000492063; ENSP00000432636; ENSG00000122223 [Q9BZW8-3]
GeneIDi51744
KEGGihsa:51744
UCSCiuc001fxa.4 human [Q9BZW8-1]

Organism-specific databases

CTDi51744
DisGeNETi51744
EuPathDBiHostDB:ENSG00000122223.12
GeneCardsiCD244
HGNCiHGNC:18171 CD244
MalaCardsiCD244
MIMi605554 gene
neXtProtiNX_Q9BZW8
OpenTargetsiENSG00000122223
PharmGKBiPA134905192
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKYZ Eukaryota
ENOG410Y74Q LUCA
GeneTreeiENSGT00510000049238
HOVERGENiHBG050850
InParanoidiQ9BZW8
KOiK06582
OMAiQDCQNAH
OrthoDBiEOG091G0DZW
PhylomeDBiQ9BZW8
TreeFamiTF334964

Enzyme and pathway databases

ReactomeiR-HSA-202733 Cell surface interactions at the vascular wall
SignaLinkiQ9BZW8

Miscellaneous databases

ChiTaRSiCD244 human
GeneWikiiCD244
GenomeRNAii51744
PROiPR:Q9BZW8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000122223 Expressed in 96 organ(s), highest expression level in leukocyte
CleanExiHS_CD244
GenevisibleiQ9BZW8 HS

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR024304 NK_rcpt_2B4
IPR024303 NK_rcpt_2B4_Ig_dom
PANTHERiPTHR12080:SF56 PTHR12080:SF56, 2 hits
PfamiView protein in Pfam
PF13895 Ig_2, 1 hit
PF11465 Receptor_2B4, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCD244_HUMAN
AccessioniPrimary (citable) accession number: Q9BZW8
Secondary accession number(s): Q5VYI2
, Q5VYI6, Q5VYI7, Q96T47, Q9NQD2, Q9NQD3, Q9Y288
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: November 7, 2018
This is version 155 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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