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Showing Protein Carcinoembryonic antigen-related cell adhesion molecule 1 (HMDBP12673)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12673
Secondary Accession Numbers None
Name Carcinoembryonic antigen-related cell adhesion molecule 1
Synonyms
  1. Biliary glycoprotein 1
  2. BGP-1
Gene Name CEACAM1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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. Downregulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating 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). Downregulates 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).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).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
cell-cell adhesion via plasma-membrane adhesion molecules
regulation of cell growth
granulocyte colony-stimulating factor signaling pathway
insulin catabolic process
insulin receptor internalization
negative regulation of cytotoxic T cell degranulation
negative regulation of granulocyte differentiation
negative regulation of hepatocyte proliferation
negative regulation of interleukin-1 production
negative regulation of lipid biosynthetic process
negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
negative regulation of platelet aggregation
regulation of blood vessel remodeling
regulation of endothelial cell differentiation
neutrophil degranulation
regulation of endothelial cell migration
regulation of epidermal growth factor receptor signaling pathway
regulation of homophilic cell adhesion
regulation of sprouting angiogenesis
wound healing, spreading of cells
leukocyte migration
cell migration
integrin-mediated signaling pathway
cell adhesion
common myeloid progenitor cell proliferation
regulation of phosphatidylinositol 3-kinase cascade
cellular response to insulin stimulus
angiogenesis
regulation of ERK1 and ERK2 cascade
regulation of cell migration
bile acid and bile salt transport
homophilic cell adhesion
positive regulation of vasculogenesis
blood vessel development
negative regulation of T cell receptor signaling pathway
negative regulation of vascular permeability
negative regulation of fatty acid biosynthetic process
negative regulation of T cell mediated cytotoxicity
negative regulation of protein kinase activity
Cellular Component
microvillus membrane
cell surface
specific granule membrane
extracellular vesicular exosome
plasma membrane
cell junction
basal plasma membrane
tertiary granule membrane
cell-cell junction
adherens junction
lateral plasma membrane
apical plasma membrane
transport vesicle membrane
membrane
integral to membrane
integral to plasma membrane
Molecular Function
actin binding
kinase binding
protein homodimerization activity
bile acid transmembrane transporter activity
identical protein binding
calmodulin binding
protein dimerization activity
filamin binding
protein phosphatase binding
protein tyrosine kinase binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 526
Molecular Weight 57559.965
Theoretical pI 5.977
Pfam Domain Function
Signals
  • 1-34;
Transmembrane Regions
  • 429-452;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P13688
UniProtKB/Swiss-Prot Entry Name CEAM1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952 ]
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  5. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569 ]
  7. Beauchemin N, Draber P, Dveksler G, Gold P, Gray-Owen S, Grunert F, Hammarstrom S, Holmes KV, Karlsson A, Kuroki M, Lin SH, Lucka L, Najjar SM, Neumaier M, Obrink B, Shively JE, Skubitz KM, Stanners CP, Thomas P, Thompson JA, Virji M, von Kleist S, Wagener C, Watt S, Zimmermann W: Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res. 1999 Nov 1;252(2):243-9. doi: 10.1006/excr.1999.4610. [PubMed:11501563 ]
  8. Singer BB, Scheffrahn I, Heymann R, Sigmundsson K, Kammerer R, Obrink B: Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes. J Immunol. 2002 May 15;168(10):5139-46. doi: 10.4049/jimmunol.168.10.5139. [PubMed:11994468 ]
  9. Abou-Rjaily GA, Lee SJ, May D, Al-Share QY, Deangelis AM, Ruch RJ, Neumaier M, Kalthoff H, Lin SH, Najjar SM: CEACAM1 modulates epidermal growth factor receptor--mediated cell proliferation. J Clin Invest. 2004 Oct;114(7):944-52. doi: 10.1172/JCI21786. [PubMed:15467833 ]
  10. Hosomi S, Chen Z, Baker K, Chen L, Huang YH, Olszak T, Zeissig S, Wang JH, Mandelboim O, Beauchemin N, Lanier LL, Blumberg RS: CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. Eur J Immunol. 2013 Sep;43(9):2473-83. doi: 10.1002/eji.201242676. Epub 2013 Jun 18. [PubMed:23696226 ]
  11. Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T, Clayton KL, Raab M, Chen Q, Beauchemin N, Yazaki PJ, Pyzik M, Ostrowski MA, Glickman JN, Rudd CE, Ploegh HL, Franke A, Petsko GA, Kuchroo VK, Blumberg RS: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature. 2015 Jan 15;517(7534):386-90. doi: 10.1038/nature13848. Epub 2014 Oct 26. [PubMed:25363763 ]
  12. Barnett TR, Kretschmer A, Austen DA, Goebel SJ, Hart JT, Elting JJ, Kamarck ME: Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family. J Cell Biol. 1989 Feb;108(2):267-76. doi: 10.1083/jcb.108.2.267. [PubMed:2537311 ]
  13. Hinoda Y, Neumaier M, Hefta SA, Drzeniek Z, Wagener C, Shively L, Hefta LJ, Shively JE, Paxton RJ: Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6959-63. doi: 10.1073/pnas.85.18.6959. [PubMed:2457922 ]
  14. Kuroki M, Arakawa F, Matsuo Y, Oikawa S, Nakazato H, Matsuoka Y: Three novel molecular forms of biliary glycoprotein deduced from cDNA clones from a human leukocyte library. Biochem Biophys Res Commun. 1991 Apr 30;176(2):578-85. doi: 10.1016/s0006-291x(05)80223-2. [PubMed:2025273 ]
  15. Watt SM, Fawcett J, Murdoch SJ, Teixeira AM, Gschmeissner SE, Hajibagheri NM, Simmons DL: CD66 identifies the biliary glycoprotein (BGP) adhesion molecule: cloning, expression, and adhesion functions of the BGPc splice variant. Blood. 1994 Jul 1;84(1):200-10. [PubMed:8018919 ]
  16. Hauck W, Nedellec P, Turbide C, Stanners CP, Barnett TR, Beauchemin N: Transcriptional control of the human biliary glycoprotein gene, a CEA gene family member down-regulated in colorectal carcinomas. Eur J Biochem. 1994 Jul 15;223(2):529-41. doi: 10.1111/j.1432-1033.1994.tb19022.x. [PubMed:8055923 ]
  17. Nedellec P, Turbide C, Beauchemin N: Characterization and transcriptional activity of the mouse biliary glycoprotein 1 gene, a carcinoembryonic antigen-related gene. Eur J Biochem. 1995 Jul 1;231(1):104-14. doi: 10.1111/j.1432-1033.1995.tb20676.x. [PubMed:7628460 ]
  18. Brummer J, Neumaier M, Gopfert C, Wagener C: Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas. Oncogene. 1995 Oct 19;11(8):1649-55. [PubMed:7478590 ]
  19. Frangsmyr L, Baranov V, Hammarstrom S: Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2, selectively expressed in the normal human colonic epithelium, are integral components of the fuzzy coat. Tumour Biol. 1999 Sep-Oct;20(5):277-92. doi: 10.1159/000030075. [PubMed:10436421 ]
  20. Kirshner J, Schumann D, Shively JE: CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II in a three-dimensional model of mammary morphogenesis. J Biol Chem. 2003 Dec 12;278(50):50338-45. doi: 10.1074/jbc.M309115200. Epub 2003 Sep 30. [PubMed:14522961 ]
  21. van Gisbergen KP, Ludwig IS, Geijtenbeek TB, van Kooyk Y: Interactions of DC-SIGN with Mac-1 and CEACAM1 regulate contact between dendritic cells and neutrophils. FEBS Lett. 2005 Nov 7;579(27):6159-68. doi: 10.1016/j.febslet.2005.09.089. Epub 2005 Oct 13. [PubMed:16246332 ]
  22. Klaile E, Muller MM, Kannicht C, Singer BB, Lucka L: CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration. J Cell Sci. 2005 Dec 1;118(Pt 23):5513-24. doi: 10.1242/jcs.02660. Epub 2005 Nov 15. [PubMed:16291724 ]
  23. Chen Z, Chen L, Qiao SW, Nagaishi T, Blumberg RS: Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70. J Immunol. 2008 May 1;180(9):6085-93. doi: 10.4049/jimmunol.180.9.6085. [PubMed:18424730 ]
  24. Bonsor DA, Gunther S, Beadenkopf R, Beckett D, Sundberg EJ: Diverse oligomeric states of CEACAM IgV domains. Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13561-6. doi: 10.1073/pnas.1509511112. Epub 2015 Oct 19. [PubMed:26483485 ]
  25. Fedarovich A, Tomberg J, Nicholas RA, Davies C: Structure of the N-terminal domain of human CEACAM1: binding target of the opacity proteins during invasion of Neisseria meningitidis and N. gonorrhoeae. Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):971-9. doi: 10.1107/S0907444906020737. Epub 2006 Aug 19. [PubMed:16929097 ]