Browse CD244

Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane Single-pass type I membrane protein Cell membrane Note=Receptor engagement results in a recruitment to lipid drafts essential for the subsequent tyrosine phosphorylation of the ITSMs.
Domain PF13895 Immunoglobulin domain
PF11465 Natural killer cell receptor 2B4
Function

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).

> Gene Ontology
 
Biological Process GO:0001773 myeloid dendritic cell activation
GO:0001787 natural killer cell proliferation
GO:0001819 positive regulation of cytokine production
GO:0002250 adaptive immune response
GO:0002263 cell activation involved in immune response
GO:0002274 myeloid leukocyte activation
GO:0002285 lymphocyte activation involved in immune response
GO:0002323 natural killer cell activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002440 production of molecular mediator of immune response
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0006066 alcohol metabolic process
GO:0006109 regulation of carbohydrate metabolic process
GO:0007159 leukocyte cell-cell adhesion
GO:0009306 protein secretion
GO:0010675 regulation of cellular carbohydrate metabolic process
GO:0010676 positive regulation of cellular carbohydrate metabolic process
GO:0010919 regulation of inositol phosphate biosynthetic process
GO:0016051 carbohydrate biosynthetic process
GO:0019751 polyol metabolic process
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030101 natural killer cell activation
GO:0032609 interferon-gamma production
GO:0032637 interleukin-8 production
GO:0032649 regulation of interferon-gamma production
GO:0032677 regulation of interleukin-8 production
GO:0032729 positive regulation of interferon-gamma production
GO:0032757 positive regulation of interleukin-8 production
GO:0032814 regulation of natural killer cell activation
GO:0032816 positive regulation of natural killer cell activation
GO:0032817 regulation of natural killer cell proliferation
GO:0032819 positive regulation of natural killer cell proliferation
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0032958 inositol phosphate biosynthetic process
GO:0035740 CD8-positive, alpha-beta T cell proliferation
GO:0036037 CD8-positive, alpha-beta T cell activation
GO:0042098 T cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0043255 regulation of carbohydrate biosynthetic process
GO:0043647 inositol phosphate metabolic process
GO:0044262 cellular carbohydrate metabolic process
GO:0044283 small molecule biosynthetic process
GO:0044723 single-organism carbohydrate metabolic process
GO:0045785 positive regulation of cell adhesion
GO:0045913 positive regulation of carbohydrate metabolic process
GO:0046165 alcohol biosynthetic process
GO:0046173 polyol biosynthetic process
GO:0046631 alpha-beta T cell activation
GO:0046633 alpha-beta T cell proliferation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046640 regulation of alpha-beta T cell proliferation
GO:0046641 positive regulation of alpha-beta T cell proliferation
GO:0046651 lymphocyte proliferation
GO:0050663 cytokine secretion
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050900 leukocyte migration
GO:0051047 positive regulation of secretion
GO:0051222 positive regulation of protein transport
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0060732 positive regulation of inositol phosphate biosynthetic process
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0071613 granzyme B production
GO:0071661 regulation of granzyme B production
GO:0071663 positive regulation of granzyme B production
GO:0072606 interleukin-8 secretion
GO:0072643 interferon-gamma secretion
GO:1901615 organic hydroxy compound metabolic process
GO:1901617 organic hydroxy compound biosynthetic process
GO:1902713 regulation of interferon-gamma secretion
GO:1902715 positive regulation of interferon-gamma secretion
GO:1902930 regulation of alcohol biosynthetic process
GO:1902932 positive regulation of alcohol biosynthetic process
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903532 positive regulation of secretion by cell
GO:1904951 positive regulation of establishment of protein localization
GO:2000482 regulation of interleukin-8 secretion
GO:2000484 positive regulation of interleukin-8 secretion
GO:2000564 regulation of CD8-positive, alpha-beta T cell proliferation
GO:2000566 positive regulation of CD8-positive, alpha-beta T cell proliferation
GO:2001185 regulation of CD8-positive, alpha-beta T cell activation
GO:2001187 positive regulation of CD8-positive, alpha-beta T cell activation
Molecular Function GO:0042287 MHC protein binding
GO:0042288 MHC class I protein binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0098552 side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-109582: Hemostasis
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CD244 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CD244 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24510590Ovarian CarcinomaPromote immunity (T and NK cell function)Most tumor-associated NK cells displayed a CD56(bright) , CD16(neg) or CD56(bright) , CD16(dim) phenotype, and very poor cytolytic activities, despite an increased expression of the activation marker CD69. They also showed downregulation of DNAM-1, 2B4, and NTB-A activating receptors, and an altered chemokine receptor repertoire.
23536636MelanomaInhibit immunity (T cell function); essential for immunotherapyConcomitantly, tumor-specific CD4(+) T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression.
19638467Neuroblastoma; LeukemiaPromote immunity (T cell function)2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. The signaling lymphocyte activation molecule-related receptor 2B4 (CD244) is an important regulator of NK cell activation.
23225218Hepatocellular CarcinomaInhibit immunityThe monocytes from HCC tissues, but not from nontumoral liver, strongly express CD48 proteins; and such monocyte-induced NK cell dysfunction was markedly attenuated by blocking CD48 receptor 2B4 on NK cells, but not by blockade of NKG2D and NKp30.
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CD244 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CD244 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0930.794
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1690.784
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.040.939
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0960.87
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.320.759
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1740.873
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2740.583
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4940.523
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0550.949
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.90.269
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3970.738
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2240.253
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CD244 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.72.711
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.73.40.31
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916012.5-12.50.52
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD244. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD244. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD244.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD244. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CD244 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CD244 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCD244
NameCD244 molecule, natural killer cell receptor 2B4
Aliases 2B4; NAIL; NKR2B4; Nmrk; SLAMF4; natural killer cell receptor 2B4; CD244 natural killer cell receptor 2B4; N ......
Chromosomal Location1q23.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CD244 collected from DrugBank database.
> Drugs from DrugBank database
 

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