CD28 and CTLA4

		CD28	CTLA4
Description		CD28 molecule	cytotoxic T-lymphocyte associated protein 4
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GO Annotations	Cellular Component	Immunological Synapse Cytosol Plasma Membrane External Side Of Plasma Membrane Cell Surface Membrane Protein Complex Involved In Cell Adhesion	Golgi Apparatus Plasma Membrane External Side Of Plasma Membrane Membrane Clathrin-coated Endocytic Vesicle Perinuclear Region Of Cytoplasm Protein Complex Involved In Cell Adhesion
	Molecular Function	Protein Binding Coreceptor Activity Protein Kinase Binding Identical Protein Binding	Protein Binding
	Biological Process	Positive Regulation Of Cytokine Production Immune System Process Positive Regulation Of Inflammatory Response To Antigenic Stimulus Transcription By RNA Polymerase II Immune Response Humoral Immune Response Cell Surface Receptor Signaling Pathway Positive Regulation Of Gene Expression Negative Regulation Of Gene Expression T Cell Costimulation Positive Regulation Of Interleukin-10 Production Positive Regulation Of Interleukin-2 Production Positive Regulation Of Interleukin-4 Production CD4-positive, Alpha-beta T Cell Proliferation T Cell Proliferation Positive Regulation Of T Cell Proliferation T Cell Activation Regulation Of T Cell Proliferation Negative Regulation Of Apoptotic Process Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction Negative Thymic T Cell Selection Regulatory T Cell Differentiation Positive Regulation Of Viral Genome Replication Regulation Of Regulatory T Cell Differentiation Positive Regulation Of Translation Positive Regulation Of Mitotic Nuclear Division Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of Isotype Switching To IgG Isotypes T Cell Receptor Signaling Pathway Positive Regulation Of T Cell Activation Positive Regulation Of Phosphatidylinositol 3-kinase/protein Kinase B Signal Transduction Apoptotic Signaling Pathway Positive Regulation Of CD4-positive, Alpha-beta T Cell Proliferation	Adaptive Immune Response Immune System Process Immune Response DNA Damage Response Negative Regulation Of B Cell Proliferation Regulation Of T Cell Proliferation Negative Regulation Of T Cell Proliferation Positive Regulation Of Apoptotic Process Negative Regulation Of Regulatory T Cell Differentiation T Cell Receptor Signaling Pathway B Cell Receptor Signaling Pathway
Pathways		PIP3 activates AKT signaling Nef mediated downregulation of CD28 cell surface expression Constitutive Signaling by Aberrant PI3K in Cancer Co-stimulation by CD28 CD28 dependent PI3K/Akt signaling CD28 dependent Vav1 pathway PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	Co-stimulation by CD28 Co-inhibition by CTLA4 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
Drugs			Abatacept Ipilimumab Tremelimumab
Diseases			Graves' disease Allograft rejection Type I diabetes mellitus Hashimoto's thyroiditis
GWAS		Alopecia areata ( 25608926) Autoimmune traits (pleiotropy) ( 30572963) Celiac disease ( 22057235 20190752 25920553) Celiac disease and Rheumatoid arthritis ( 26546613) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Eosinophil count ( 32888494) Eosinophil percentage of white cells ( 32888494) Graves' disease ( 21841780) Heschl's gyrus morphology ( 25130324) Inflammatory bowel disease ( 26192919) Lymphocyte count ( 32888494) Multiple sclerosis ( 24076602 31604244) Primary biliary cholangitis ( 28425483) Primary sclerosing cholangitis ( 27992413 23603763) Rheumatoid arthritis ( 24390342 30423114 23143596) Rheumatoid arthritis (ACPA-positive) ( 24532676 23143596) Subcutaneous adipose tissue ( 29178545) Systemic lupus erythematosus ( 28714469) Ulcerative colitis ( 26192919)	Addison's disease ( 33574239) Alopecia areata ( 25608926 20596022) Autoimmune thyroid disease ( 32581359) Autoimmune traits (pleiotropy) ( 30572963) Basal cell carcinoma ( 31174203 33549134) Celiac disease ( 22057235 30572963 20190752 25920553) Celiac disease and Rheumatoid arthritis ( 26546613) Graves' disease ( 21841780) Heel bone mineral density ( 30598549) Hypothyroidism ( 22493691 27182965) Inflammatory bowel disease ( 26192919) Keratinocyte cancer (MTAG) ( 31174203) Medication use (thyroid preparations) ( 31015401) Multiple sclerosis ( 24076602) Myasthenia gravis ( 25643325) Primary biliary cholangitis ( 28425483) Rheumatoid arthritis ( 24390342 30423114 30572963 23143596 19503088) Rheumatoid arthritis (ACPA-positive) ( 24532676 23143596) Subcutaneous adipose tissue ( 29178545) Systemic lupus erythematosus ( 33536424) Type 1 diabetes ( 19430480 30659077 30572963 25751624 21829393 18978792) Ulcerative colitis ( 26192919) Vitiligo ( 27723757)
Interacting Genes		17 interacting genes: CD247 CD4 CD80 CD86 DUSP14 GRAP2 GRB2 IL12A ITK LCK LRRC23 NSF PIK3CG PIK3R1 PIK3R2 PLCG1 PTPRC	17 interacting genes: AP1M1 AP2M1 CD80 CD86 CTXN3 FYN JAK2 LCK LYN MALL PIK3R1 PPP2R5A PTPN11 STAT5A STAT5B TMEM218 TXK
Entrez ID		940	1493
HPRD ID		01727	00474
Ensembl ID		ENSG00000178562	ENSG00000163599
Uniprot IDs		B4E0L1 P10747	P16410
PDB IDs		1YJD 3WA4 5AUL 5GJH 5GJI 6O8D 7PPN 7VU5 8S6Z 8W2V	1AH1 1H6E 1I85 1I8L 2X44 3BX7 3OSK 5GGV 5TRU 5XJ3 6RP8 6RPJ 6RQM 6XY2 7CIO 7DV4 7ELX 7SU0 7SU1 8GAB 8HIT 9DQ3
Enriched GO Terms of Interacting Partners?		T Cell Activation Lymphocyte Activation Cell Activation Leukocyte Activation Positive Regulation Of Immune Response Antigen Receptor-mediated Signaling Pathway T Cell Differentiation Regulation Of Immune Response Positive Regulation Of Immune System Process Regulation Of Cell Adhesion Phosphotyrosine Residue Binding Cell Surface Receptor Signaling Pathway T Cell Receptor Signaling Pathway Mononuclear Cell Differentiation B Cell Receptor Signaling Pathway Gamma-delta T Cell Activation Immune Response-activating Cell Surface Receptor Signaling Pathway Immune System Process Leukocyte Differentiation Regulation Of Leukocyte Cell-cell Adhesion Lymphocyte Differentiation Regulation Of T Cell Activation Neurotrophin TRKA Receptor Binding Positive Regulation Of T Cell Activation Immune Response-regulating Cell Surface Receptor Signaling Pathway Positive Regulation Of Leukocyte Cell-cell Adhesion Positive Regulation Of Interleukin-2 Production Phosphatidylinositol 3-kinase Complex, Class IA Alpha-beta T Cell Activation Immune Response Positive Regulation Of Cell Adhesion Positive Regulation Of Cell-cell Adhesion Regulation Of Cell-cell Adhesion Positive Regulation Of Lymphocyte Activation Positive Regulation Of Cytokine Production Regulation Of Lymphocyte Activation T Cell Costimulation Immune Response-activating Signaling Pathway Regulation Of Immune System Process Extrinsic Apoptotic Signaling Pathway Positive Regulation Of Cell Activation Positive Regulation Of Multicellular Organismal Process Regulation Of Mononuclear Cell Proliferation Immune Response-regulating Signaling Pathway Activation Of Immune Response Regulation Of Hemopoiesis Positive Regulation Of Metabolic Process Regulation Of Interleukin-2 Production Regulation Of Leukocyte Proliferation Intracellular Signal Transduction	T Cell Costimulation Positive Regulation Of T Cell Activation Positive Regulation Of Leukocyte Cell-cell Adhesion Positive Regulation Of Lymphocyte Activation Positive Regulation Of Cell-cell Adhesion Non-membrane Spanning Protein Tyrosine Kinase Activity Regulation Of Leukocyte Cell-cell Adhesion Regulation Of T Cell Activation Positive Regulation Of Cell Activation Growth Hormone Receptor Signaling Pathway Leukocyte Activation T Cell Activation Lymphocyte Activation Cell Activation Positive Regulation Of Cell Adhesion Regulation Of Cell-cell Adhesion Regulation Of Lymphocyte Activation Positive Regulation Of Interleukin-2 Production Regulation Of Mononuclear Cell Proliferation Regulation Of Immune Response Positive Regulation Of Leukocyte Proliferation Growth Hormone Receptor Signaling Pathway Via JAK-STAT Regulation Of Leukocyte Proliferation Phosphatidylinositol 3-kinase Binding Regulation Of T Cell Proliferation Positive Regulation Of Immune System Process Positive Regulation Of T Cell Proliferation Regulation Of Cell Adhesion Regulation Of Cell Activation Positive Regulation Of Immune Response Protein Tyrosine Kinase Activity Regulation Of Interleukin-2 Production Positive Regulation Of Cytokine Production Interleukin-5-mediated Signaling Pathway Positive Regulation Of Lymphocyte Proliferation Positive Regulation Of Mononuclear Cell Proliferation T Cell Differentiation Regulation Of Hemopoiesis Regulation Of Cytokine Production Cell Surface Receptor Protein Tyrosine Kinase Signaling Pathway Activated T Cell Proliferation Positive Regulation Of Gamma-delta T Cell Differentiation Regulation Of T Cell Differentiation Mononuclear Cell Differentiation Peptide Hormone Receptor Binding Positive Regulation Of Gamma-delta T Cell Activation Gamma-delta T Cell Differentiation Regulation Of Gamma-delta T Cell Differentiation Lymphocyte Proliferation Regulation Of Lymphocyte Differentiation
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