DegronMD - P13688(CEACAM1)

FUNCTION: [Isoform 1]: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:18424730, PubMed:23696226, PubMed:25363763). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors. Plays a role in immune response, of T cells, natural killer (NK) and neutrophils (PubMed:18424730, PubMed:23696226). Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (PubMed:18424730). Also inhibits T cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T cell through its interaction with HAVCR2 (PubMed:25363763). Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4-CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome. Down-regulates neutrophil production by acting as a coinhibitory receptor for CSF3R by down-regulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (By similarity). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (By similarity). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis. This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis. INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (By similarity). Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia. Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (By similarity). Down-regulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (By similarity). Inhibits cell migration and cell scattering through interaction with FLNA; interfers with the interaction of FLNA with RALA (PubMed:16291724). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730, ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763}.; FUNCTION: [Isoform 8]: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Promotes populations of T cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809}. View more >>

GO - Biological processes (BP): angiogenesis [GO:0001525]; bile acid and bile salt transport [GO:0015721]; blood vessel development [GO:0001568]; cell adhesion [GO:0007155]; cell-cell adhesion via plasma-membrane adhesion molecules [GO:0098742]; cell migration [GO:0016477]; cellular response to insulin stimulus [GO:0032869]; common myeloid progenitor cell proliferation [GO:0035726]; granulocyte colony-stimulating factor signaling pathway [GO:0038158]; homophilic cell adhesion via plasma membrane adhesion molecules [GO:0007156]; insulin catabolic process [GO:1901143]; insulin receptor internalization [GO:0038016]; integrin-mediated signaling pathway [GO:0007229]; negative regulation of cytotoxic T cell degranulation [GO:0043318]; negative regulation of fatty acid biosynthetic process [GO:0045717]; negative regulation of granulocyte differentiation [GO:0030853]; negative regulation of hepatocyte proliferation [GO:2000346]; negative regulation of interleukin-1 production [GO:0032692]; negative regulation of lipid biosynthetic process [GO:0051055]; negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target [GO:0002859]; negative regulation of platelet aggregation [GO:0090331]; negative regulation of protein kinase activity [GO:0006469]; negative regulation of T cell mediated cytotoxicity [GO:0001915]; negative regulation of T cell receptor signaling pathway [GO:0050860]; negative regulation of vascular permeability [GO:0043116]; positive regulation of vasculogenesis [GO:2001214]; regulation of blood vessel remodeling [GO:0060312]; regulation of cell growth [GO:0001558]; regulation of cell migration [GO:0030334]; regulation of endothelial cell differentiation [GO:0045601]; regulation of endothelial cell migration [GO:0010594]; regulation of epidermal growth factor receptor signaling pathway [GO:0042058]; regulation of ERK1 and ERK2 cascade [GO:0070372]; regulation of homophilic cell adhesion [GO:1903385]; regulation of phosphatidylinositol 3-kinase signaling [GO:0014066]; regulation of sprouting angiogenesis [GO:1903670]; wound healing, spreading of cells [GO:0044319] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S151I	TCGA-05-4250	LUAD	TCGA	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1111
p.S151I	DO24457	LUAD	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1111
p.L129F	TCGA-AX-A05Z	UCEC	TCGA	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.0833
p.L129F	DO40884	UCEC	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.0833
p.G252E	TCGA-DA-A1IA	SKCM	TCGA	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.0833
p.G252E	DO38022	SKCM	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.0833
p.G252R	TCGA-DA-A1IA	SKCM	TCGA	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.0833
p.Y235C	TCGA-EO-A22X	UCEC	TCGA	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.2778
p.Y235C	DO43907	UCEC	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.2778
p.A134T	TCGA-VQ-A8PB	STAD	TCGA	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.2222
p.A134T	DO51766	STAD	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.2222
p.R250C	TCGA-VQ-A94R	STAD	TCGA	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.1389
p.R250C	DO222372	STAD	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.1389
p.L129I	DO222884	COCA	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.0833
p.T240K	DO229025	LICA	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation altering degron motif	0.7306
p.T240K	DO229032	LICA	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation altering degron motif	0.7306
p.T247N	DO229045	LICA	ICGC	PDTPTIS	DEG_SCF_FBW7_1	237:243	Mutation rewiring degron network	0.2222
p.P145L	DO220893	MELA	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.2778
p.PE142PK	DO222521	MELA	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation altering degron motif	0.7312
p.E128K	DO37819	SKCM	ICGC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.0556
p.S151T	SIDM00355	Non-Small Cell Lung Carcinoma	GDSC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1111
p.S151T	ACH-000062	Lung Cancer	CCLE	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1111
p.S151T	RERF-LC-MS	lung	COSMIC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1111
p.E143G	SIDM00498	Colorectal Carcinoma	GDSC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation altering degron motif	0.7199
p.E143G	ACH-000970	Colon/Colorectal Cancer	CCLE	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation altering degron motif	0.7199
p.E143G	SNU-C5	large intestine	COSMIC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation altering degron motif	0.7199
p.E132A	SIDM00850	Gastric Carcinoma	GDSC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1667
p.E132A	ACH-000880	Gastric Cancer	CCLE	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1667
p.E132A	AGS	stomach	COSMIC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1667
p.S150P	SIDM01608	Endometrial Carcinoma	GDSC	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1389
p.S150P	ACH-000990	Endometrial/Uterine Cancer	CCLE	FHVYPE	LIG_APCC_ABBA_1	138:143	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

CEACAM1

UniProt ID: P13688

Entrez ID: 634

Protein name: Carcinoembryonic antigen-related cell adhesion molecule 1 (Biliary glycoprotein 1) (BGP-1) (CD antigen CD66a)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for CEACAM1 in