UniProtKB - Q9BZW8 (CD244_HUMAN)
Natural killer cell receptor 2B4
CD244
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 PublicationsGO - Molecular functioni
- MHC class I protein binding Source: UniProtKB
- signaling receptor activity Source: ProtInc
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- natural killer cell activation involved in immune response Source: UniProtKB
- positive regulation of granzyme B production Source: UniProtKB
- positive regulation of inositol phosphate biosynthetic process Source: UniProtKB
- positive regulation of interferon-gamma production Source: UniProtKB
- positive regulation of interleukin-8 production Source: UniProtKB
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Receptor |
Biological process | Adaptive immunity, Immunity, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | Q9BZW8 |
Reactomei | R-HSA-202733, Cell surface interactions at the vascular wall |
SignaLinki | Q9BZW8 |
Names & Taxonomyi
Protein namesi | Recommended name: Natural killer cell receptor 2B4Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18171, CD244 |
MIMi | 605554, gene |
neXtProti | NX_Q9BZW8 |
VEuPathDBi | HostDB:ENSG00000122223 |
Subcellular locationi
Plasma membrane
- Cell membrane Curated
Other locations
- Membrane Curated; Single-pass type I membrane protein Curated
Note: Receptor engagement results in a recruitment to lipid drafts essential for the subsequent tyrosine phosphorylation of the ITSMs.1 Publication
Plasma Membrane
- external side of plasma membrane Source: MGI
- plasma membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 22 – 229 | ExtracellularSequence analysisAdd BLAST | 208 | |
Transmembranei | 230 – 250 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 251 – 370 | CytoplasmicSequence analysisAdd BLAST | 120 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 68 | K → A: Disrupts interaction with CD48; when associated with A-70. 1 Publication | 1 | |
Mutagenesisi | 70 | E → A: Disrupts interaction with CD48; when associated with A-68. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 51744 |
MalaCardsi | CD244 |
OpenTargetsi | ENSG00000122223 |
PharmGKBi | PA134905192 |
Miscellaneous databases
Pharosi | Q9BZW8, Tbio |
Genetic variation databases
BioMutai | CD244 |
DMDMi | 47605541 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | 2 PublicationsAdd BLAST | 21 | |
ChainiPRO_0000014668 | 22 – 370 | Natural killer cell receptor 2B4Add BLAST | 349 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 71 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 77 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 89 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 157 ↔ 199 | PROSITE-ProRule annotation | ||
Glycosylationi | 164 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 181 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 192 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 200 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 213 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 271 | Phosphotyrosine3 Publications | 1 | |
Modified residuei | 297 | Phosphotyrosine; by FYN3 Publications | 1 | |
Modified residuei | 317 | Phosphotyrosine2 Publications | 1 | |
Modified residuei | 342 | Phosphotyrosine; by FYN2 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q9BZW8 |
MassIVEi | Q9BZW8 |
PaxDbi | Q9BZW8 |
PeptideAtlasi | Q9BZW8 |
PRIDEi | Q9BZW8 |
ProteomicsDBi | 79913 [Q9BZW8-1] 79914 [Q9BZW8-2] 79915 [Q9BZW8-3] 79916 [Q9BZW8-4] |
PTM databases
GlyGeni | Q9BZW8, 8 sites |
iPTMneti | Q9BZW8 |
PhosphoSitePlusi | Q9BZW8 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000122223, Expressed in granulocyte and 122 other tissues |
Genevisiblei | Q9BZW8, HS |
Organism-specific databases
HPAi | ENSG00000122223, Tissue enhanced (bone marrow, lymphoid tissue) |
Interactioni
Subunit structurei
Interacts with CD48 (PubMed:9841922,PubMed:27249817).
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 similarity13 PublicationsBinary interactionsi
Q9BZW8
GO - Molecular functioni
- MHC class I protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119709, 37 interactors |
DIPi | DIP-40331N |
ELMi | Q9BZW8 |
IntActi | Q9BZW8, 34 interactors |
MINTi | Q9BZW8 |
STRINGi | 9606.ENSP00000357012 |
Miscellaneous databases
RNActi | Q9BZW8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 22 – 127 | Ig-like 1Add BLAST | 106 | |
Domaini | 131 – 215 | Ig-like 2Add BLAST | 85 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 324 – 370 | DisorderedSequence analysisAdd BLAST | 47 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 269 – 274 | ITSM 1By similarity | 6 | |
Motifi | 295 – 300 | ITSM 2By similarity | 6 | |
Motifi | 315 – 320 | ITSM 3By similarity | 6 | |
Motifi | 340 – 345 | ITSM 4By similarity | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 332 – 355 | Polar residuesSequence analysisAdd BLAST | 24 |
Domaini
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502S7N7, Eukaryota |
GeneTreei | ENSGT01030000234540 |
HOGENOMi | CLU_065827_0_0_1 |
InParanoidi | Q9BZW8 |
OMAi | VDIHGTH |
OrthoDBi | 1532935at2759 |
PhylomeDBi | Q9BZW8 |
TreeFami | TF334964 |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View 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 |
PANTHERi | PTHR12080:SF56, PTHR12080:SF56, 1 hit |
Pfami | View protein in Pfam PF13895, Ig_2, 1 hit PF11465, Receptor_2B4, 1 hit |
SUPFAMi | SSF48726, SSF48726, 2 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
127-131: Missing.
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 127 – 133 | ESLLPDK → GMAMCPM in AAK50015 (PubMed:15489334).Curated | 7 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_056036 | 89 | N → D. Corresponds to variant dbSNP:rs34846692Ensembl. | 1 | |
Natural variantiVAR_056037 | 323 | S → F. Corresponds to variant dbSNP:rs12064925Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010397 | 127 – 131 | Missing in isoform 2 and isoform 3. 7 Publications | 5 | |
Alternative sequenceiVSP_010398 | 128 – 224 | Missing in isoform 4. 1 PublicationAdd BLAST | 97 | |
Alternative sequenceiVSP_010399 | 326 – 334 | SGSRKRNHS → GDRFYSFSG in isoform 3. 1 Publication | 9 | |
Alternative sequenceiVSP_010400 | 335 – 370 | Missing in isoform 3. 1 PublicationAdd BLAST | 36 |
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 |
CCDSi | CCDS1210.1 [Q9BZW8-2] CCDS53398.1 [Q9BZW8-4] CCDS53399.1 [Q9BZW8-1] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000322302; ENSP00000313619; ENSG00000122223 [Q9BZW8-4] ENST00000368033; ENSP00000357012; ENSG00000122223 ENST00000368034; ENSP00000357013; ENSG00000122223 [Q9BZW8-2] ENST00000492063; ENSP00000432636; ENSG00000122223 [Q9BZW8-3] |
GeneIDi | 51744 |
KEGGi | hsa:51744 |
MANE-Selecti | ENST00000368034.9; ENSP00000357013.4; NM_016382.4; NP_057466.1 [Q9BZW8-2] |
UCSCi | uc001fxa.4, human [Q9BZW8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS1210.1 [Q9BZW8-2] CCDS53398.1 [Q9BZW8-4] CCDS53399.1 [Q9BZW8-1] |
RefSeqi | NP_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] |
3D structure databases
SMRi | Q9BZW8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119709, 37 interactors |
DIPi | DIP-40331N |
ELMi | Q9BZW8 |
IntActi | Q9BZW8, 34 interactors |
MINTi | Q9BZW8 |
STRINGi | 9606.ENSP00000357012 |
PTM databases
GlyGeni | Q9BZW8, 8 sites |
iPTMneti | Q9BZW8 |
PhosphoSitePlusi | Q9BZW8 |
Genetic variation databases
BioMutai | CD244 |
DMDMi | 47605541 |
Proteomic databases
jPOSTi | Q9BZW8 |
MassIVEi | Q9BZW8 |
PaxDbi | Q9BZW8 |
PeptideAtlasi | Q9BZW8 |
PRIDEi | Q9BZW8 |
ProteomicsDBi | 79913 [Q9BZW8-1] 79914 [Q9BZW8-2] 79915 [Q9BZW8-3] 79916 [Q9BZW8-4] |
Protocols and materials databases
Antibodypediai | 2392, 822 antibodies from 42 providers |
DNASUi | 51744 |
Genome annotation databases
Ensembli | ENST00000322302; ENSP00000313619; ENSG00000122223 [Q9BZW8-4] ENST00000368033; ENSP00000357012; ENSG00000122223 ENST00000368034; ENSP00000357013; ENSG00000122223 [Q9BZW8-2] ENST00000492063; ENSP00000432636; ENSG00000122223 [Q9BZW8-3] |
GeneIDi | 51744 |
KEGGi | hsa:51744 |
MANE-Selecti | ENST00000368034.9; ENSP00000357013.4; NM_016382.4; NP_057466.1 [Q9BZW8-2] |
UCSCi | uc001fxa.4, human [Q9BZW8-1] |
Organism-specific databases
CTDi | 51744 |
DisGeNETi | 51744 |
GeneCardsi | CD244 |
HGNCi | HGNC:18171, CD244 |
HPAi | ENSG00000122223, Tissue enhanced (bone marrow, lymphoid tissue) |
MalaCardsi | CD244 |
MIMi | 605554, gene |
neXtProti | NX_Q9BZW8 |
OpenTargetsi | ENSG00000122223 |
PharmGKBi | PA134905192 |
VEuPathDBi | HostDB:ENSG00000122223 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S7N7, Eukaryota |
GeneTreei | ENSGT01030000234540 |
HOGENOMi | CLU_065827_0_0_1 |
InParanoidi | Q9BZW8 |
OMAi | VDIHGTH |
OrthoDBi | 1532935at2759 |
PhylomeDBi | Q9BZW8 |
TreeFami | TF334964 |
Enzyme and pathway databases
PathwayCommonsi | Q9BZW8 |
Reactomei | R-HSA-202733, Cell surface interactions at the vascular wall |
SignaLinki | Q9BZW8 |
Miscellaneous databases
BioGRID-ORCSi | 51744, 10 hits in 1027 CRISPR screens |
GeneWikii | CD244 |
GenomeRNAii | 51744 |
Pharosi | Q9BZW8, Tbio |
PROi | PR:Q9BZW8 |
RNActi | Q9BZW8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000122223, Expressed in granulocyte and 122 other tissues |
Genevisiblei | Q9BZW8, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View 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 |
PANTHERi | PTHR12080:SF56, PTHR12080:SF56, 1 hit |
Pfami | View protein in Pfam PF13895, Ig_2, 1 hit PF11465, Receptor_2B4, 1 hit |
SUPFAMi | SSF48726, SSF48726, 2 hits |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CD244_HUMAN | |
Accessioni | Q9BZW8Primary (citable) accession number: Q9BZW8 Secondary accession number(s): Q5VYI2 Q9Y288 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 24, 2004 |
Last sequence update: | May 24, 2004 | |
Last modified: | February 23, 2022 | |
This is version 177 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot