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Protein

Natural killer cell receptor 2B4

Gene

Cd244

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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:8326140, PubMed:12734329, PubMed:19648922, PubMed:20962259). Activating function implicates association with SH2D1A and FYN. 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. Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis (PubMed:8326140, PubMed:15169881, PubMed:15998796, PubMed:22683124). Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells (PubMed:15905190). Regulation of NK cell activity by adapters Sh2d1b and Sh2d1b2 is reported conflictingly (PubMed:16127454, PubMed:16425036). Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1. At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self-tolerance of developing NK cells (By similarity). 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 (PubMed:11739483). Inhibits inflammatory responses in dendritic cells (DCs) (PubMed:25643613).By similarity2 Publications8 Publications

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • myeloid dendritic cell activation Source: UniProtKB
  • natural killer cell activation involved in immune response Source: UniProtKB
  • positive regulation of CD8-positive, alpha-beta T cell proliferation Source: UniProtKB
  • positive regulation of granzyme B production Source: MGI
  • positive regulation of inositol phosphate biosynthetic process Source: MGI
  • positive regulation of interferon-gamma secretion Source: MGI
  • positive regulation of interleukin-8 secretion Source: MGI
  • positive regulation of natural killer cell proliferation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-202733. Cell surface interactions at the vascular wall.

Names & Taxonomyi

Protein namesi
Recommended name:
Natural killer cell receptor 2B4
Alternative name(s):
NK cell type I receptor protein 2B4
Short name:
NKR2B4
Non-MHC restricted killing associated
SLAM family member 4
Short name:
SLAMF4
Signaling lymphocytic activation molecule 4
CD_antigen: CD244
Gene namesi
Name:Cd244
Synonyms:2b4, Nmrk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:109294. Cd244.

Subcellular locationi

  • Membrane Curated; Single-pass type I membrane protein Curated
  • Cell membrane Curated

  • Note: Receptor engagement results in a recruitment to lipid drafts essential for the subsequent tyrosine phosphorylation of the ITSMs.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 226ExtracellularSequence analysisAdd BLAST207
Transmembranei227 – 247HelicalSequence analysisAdd BLAST21
Topological domaini248 – 397CytoplasmicSequence analysisAdd BLAST150

GO - Cellular componenti

  • external side of plasma membrane Source: MGI
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi266Y → F: Abolishes downstream phosphorylation of CBL and VAV1; when associated with F-325, F-344 and F-369. 1 Publication1
Mutagenesisi266Y → F: Decreases downstream phosphorylation of CBL and VAV1. 1 Publication1
Mutagenesisi325Y → F: Abolishes downstream phosphorylation of CBL and VAV1; when associated with F-266, F-344 and F-369. 1 Publication1
Mutagenesisi325Y → F: Weakly decreases downstream phosphorylation of CBL and VAV1; when associated with F-344 and F-369. 1 Publication1
Mutagenesisi344Y → F: Abolishes downstream phosphorylation of CBL and VAV1; when associated with F-266, F-325 and F-369. 1 Publication1
Mutagenesisi344Y → F: Weakly decreases downstream phosphorylation of CBL and VAV1; when associated with F-325 and F-369. 1 Publication1
Mutagenesisi369Y → F: Abolishes downstream phosphorylation of CBL and VAV1; when associated with F-266, F-325 and F-344. 1 Publication1
Mutagenesisi369Y → F: Weakly decreases downstream phosphorylation of CBL and VAV1; when associated with F-325 and F-344. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001466920 – 397Natural killer cell receptor 2B4Add BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi22 ↔ 1192 Publications
Glycosylationi78N-linked (GlcNAc...)Sequence analysis1
Glycosylationi145N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi154 ↔ 196By similarity
Glycosylationi161N-linked (GlcNAc...)Sequence analysis1
Glycosylationi178N-linked (GlcNAc...)Sequence analysis1
Glycosylationi197N-linked (GlcNAc...)Sequence analysis1
Glycosylationi206N-linked (GlcNAc...)Sequence analysis1
Glycosylationi210N-linked (GlcNAc...)Sequence analysis1
Modified residuei266PhosphotyrosineBy similarity1 Publication1
Modified residuei325Phosphotyrosine; by FYNBy similarity1 Publication1
Modified residuei344Phosphotyrosine1 Publication1
Modified residuei369Phosphotyrosine; by FYN1 Publication1

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 (By similarity).By similarity
Phosphorylated by FYN and CSK at tyrosine residues following activation. Coligation with inhibitory receptors such as KIR2DL1 inhibits phosphorylation upon contact of NK cells with sensitive target cells.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ07763.
PRIDEiQ07763.

PTM databases

iPTMnetiQ07763.
PhosphoSitePlusiQ07763.

Expressioni

Tissue specificityi

Expressed in natural killer (NK) cells, T cells and dendritic cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000004709.
CleanExiMM_CD244.
ExpressionAtlasiQ07763. baseline and differential.
GenevisibleiQ07763. MM.

Interactioni

Subunit structurei

Interacts with CD48 (PubMed:9841922, PubMed:15905190). Interacts (via phosphorylated ITSM 1-4) with SH2D1A/SAP (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 prevents association with PTPN11, PTPN6 and CSK. Interacts weakly (via phosphorylated ITSM 2) with PTPN11 and CSK. Interacts with SH2D1B and SH2D1B2. Interacts with MHC class I proteins; the interaction is proposed to prevent self-killing of NK cells (By similarity).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201792. 2 interactors.
STRINGi10090.ENSMUSP00000004829.

Structurei

Secondary structure

1397
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 31Combined sources7
Beta strandi37 – 39Combined sources3
Beta strandi50 – 56Combined sources7
Beta strandi60 – 62Combined sources3
Beta strandi63 – 73Combined sources11
Beta strandi76 – 78Combined sources3
Helixi79 – 83Combined sources5
Beta strandi85 – 87Combined sources3
Turni89 – 91Combined sources3
Beta strandi94 – 98Combined sources5
Helixi101 – 103Combined sources3
Beta strandi105 – 112Combined sources8
Beta strandi117 – 127Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z2KNMR-A21-129[»]
2PTTX-ray1.63B19-129[»]
2PTUX-ray2.38A/B/C/D19-129[»]
ProteinModelPortaliQ07763.
SMRiQ07763.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ07763.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 129Ig-like 1Add BLAST108
Domaini131 – 215Ig-like 2Add BLAST85

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi264 – 269ITSM 1By similarity6
Motifi323 – 328ITSM 2By similarity6
Motifi342 – 347ITSM 3By similarity6
Motifi367 – 372ITSM 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 similarity1 Publication

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKYZ. Eukaryota.
ENOG410Y74Q. LUCA.
GeneTreeiENSGT00510000049238.
HOVERGENiHBG050850.
InParanoidiQ07763.
KOiK06582.
OMAiTIYEDVK.
OrthoDBiEOG091G0DZW.
TreeFamiTF334964.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR024304. NK_rcpt_2B4.
IPR024303. NK_rcpt_2B4_Ig_dom.
[Graphical view]
PANTHERiPTHR12080:SF56. PTHR12080:SF56. 1 hit.
PfamiPF11465. Receptor_2B4. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q07763-1) [UniParc]FASTAAdd to basket
Also known as: m2B4L

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
MLGQAVLFTT FLLLRAHQGQ DCPDSSEEVV GVSGKPVQLR PSNIQTKDVS
60 70 80 90 100
VQWKKTEQGS HRKIEILNWY NDGPSWSNVS FSDIYGFDYG DFALSIKSAK
110 120 130 140 150
LQDSGHYLLE ITNTGGKVCN KNFQLLILDH VETPNLKAQW KPWTNGTCQL
160 170 180 190 200
FLSCLVTKDD NVSYALYRGS TLISNQRNST HWENQIDASS LHTYTCNVSN
210 220 230 240 250
RASWANHTLN FTHGCQSVPS NFRFLPFGVI IVILVTLFLG AIICFCVWTK
260 270 280 290 300
KRKQLQFSPK EPLTIYEYVK DSRASRDQQG CSRASGSPSA VQEDGRGQRE
310 320 330 340 350
LDRRVSEVLE QLPQQTFPGD RGTMYSMIQC KPSDSTSQEK CTVYSVVQPS
360 370 380 390
RKSGSKKRNQ NSSLSCTVYE EVGNPWLKAH NPARLSRREL ENFDVYS
Length:397
Mass (Da):44,836
Last modified:July 27, 2011 - v3
Checksum:i0E2F0D946F7B63A7
GO
Isoform 2 (identifier: Q07763-2) [UniParc]FASTAAdd to basket
Also known as: m2B4S

The sequence of this isoform differs from the canonical sequence as follows:
     309-340: LEQLPQQTFPGDRGTMYSMIQCKPSDSTSQEK → MFSSLLAFLLHQFPGSTQRGKEKRERAEKNGK
     341-397: Missing.

Note: No experimental confirmation available.
Show »
Length:340
Mass (Da):38,397
Checksum:i0D5275A1A354FC1E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti38Q → P in AAF91290 (PubMed:10941850).Curated1
Sequence conflicti156V → A in AAF91290 (PubMed:10941850).Curated1
Sequence conflicti166L → FW in AAA16353 (PubMed:8228228).Curated1
Sequence conflicti362S → Y in AAA16353 (PubMed:8228228).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010401309 – 340LEQLP…TSQEK → MFSSLLAFLLHQFPGSTQRG KEKRERAEKNGK in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_010402341 – 397Missing in isoform 2. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19057 mRNA. Translation: AAA16353.1.
AF234831 mRNA. Translation: AAF91290.1.
AF082803 mRNA. Translation: AAC34859.1.
AK137505 mRNA. Translation: BAE23386.1.
CCDSiCCDS35778.1. [Q07763-1]
PIRiI49443.
RefSeqiNP_061199.2. NM_018729.2. [Q07763-1]
UniGeneiMm.2299.

Genome annotation databases

EnsembliENSMUST00000004829; ENSMUSP00000004829; ENSMUSG00000004709. [Q07763-1]
GeneIDi18106.
KEGGimmu:18106.
UCSCiuc007dor.1. mouse. [Q07763-2]
uc007dos.1. mouse. [Q07763-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19057 mRNA. Translation: AAA16353.1.
AF234831 mRNA. Translation: AAF91290.1.
AF082803 mRNA. Translation: AAC34859.1.
AK137505 mRNA. Translation: BAE23386.1.
CCDSiCCDS35778.1. [Q07763-1]
PIRiI49443.
RefSeqiNP_061199.2. NM_018729.2. [Q07763-1]
UniGeneiMm.2299.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z2KNMR-A21-129[»]
2PTTX-ray1.63B19-129[»]
2PTUX-ray2.38A/B/C/D19-129[»]
ProteinModelPortaliQ07763.
SMRiQ07763.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201792. 2 interactors.
STRINGi10090.ENSMUSP00000004829.

PTM databases

iPTMnetiQ07763.
PhosphoSitePlusiQ07763.

Proteomic databases

PaxDbiQ07763.
PRIDEiQ07763.

Protocols and materials databases

DNASUi18106.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004829; ENSMUSP00000004829; ENSMUSG00000004709. [Q07763-1]
GeneIDi18106.
KEGGimmu:18106.
UCSCiuc007dor.1. mouse. [Q07763-2]
uc007dos.1. mouse. [Q07763-1]

Organism-specific databases

CTDi51744.
MGIiMGI:109294. Cd244.

Phylogenomic databases

eggNOGiENOG410IKYZ. Eukaryota.
ENOG410Y74Q. LUCA.
GeneTreeiENSGT00510000049238.
HOVERGENiHBG050850.
InParanoidiQ07763.
KOiK06582.
OMAiTIYEDVK.
OrthoDBiEOG091G0DZW.
TreeFamiTF334964.

Enzyme and pathway databases

ReactomeiR-MMU-202733. Cell surface interactions at the vascular wall.

Miscellaneous databases

EvolutionaryTraceiQ07763.
PROiQ07763.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004709.
CleanExiMM_CD244.
ExpressionAtlasiQ07763. baseline and differential.
GenevisibleiQ07763. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR024304. NK_rcpt_2B4.
IPR024303. NK_rcpt_2B4_Ig_dom.
[Graphical view]
PANTHERiPTHR12080:SF56. PTHR12080:SF56. 1 hit.
PfamiPF11465. Receptor_2B4. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCD244_MOUSE
AccessioniPrimary (citable) accession number: Q07763
Secondary accession number(s): O88654, Q3UV86, Q9JIE0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.