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Showing Protein Carcinoembryonic antigen-related cell adhesion molecule 1 (HMDBP12672)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12672
Secondary Accession Numbers None
Name Carcinoembryonic antigen-related cell adhesion molecule 1
Synonyms
  1. Biliary glycoprotein 1
  2. Biliary glycoprotein D
  3. MHVR1
  4. Murine hepatitis virus receptor
  5. BGP-1
  6. MHV-R
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:16680193, PubMed:17081782, PubMed:18544705, PubMed:21029969, PubMed:21081647, PubMed:22496641, PubMed:22962327, PubMed:23696226). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors (PubMed:17081782, PubMed:21029969, PubMed:22496641). Plays a role in immune response, of T-cells, natural killer (NK) and neutrophils (PubMed:17081782, PubMed:23696226, PubMed:22496641, PubMed:21029969). 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:22496641). 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:17081782). 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 (PubMed:22496641). Downregulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (PubMed:21029969). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (PubMed:18544705). 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 (PubMed:16680193, PubMed:22962327). Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (PubMed:21081647). 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 (PubMed:15467833). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (PubMed:19008452). Inhibits cell migration and cell scattering through interaction with FLNA; interfers with the interaction of FLNA with RALA (By similarity). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (PubMed:25490771).Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (PubMed:1633107). Promotes populations of T-cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens (PubMed:23123061).(Microbial infection) In case of murine coronavirus (MHV) infection, serves as receptor for MHV S1 spike glycoprotein.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
cell-cell junction organization
regulation of cell growth
granulocyte colony-stimulating factor signaling pathway
insulin catabolic process
insulin receptor internalization
negative regulation of cytokine production
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
negative regulation of bone resorption
regulation of blood vessel remodeling
regulation of endothelial cell differentiation
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
common myeloid progenitor cell proliferation
regulation of phosphatidylinositol 3-kinase cascade
cellular response to insulin stimulus
regulation of ERK1 and ERK2 cascade
bile acid and bile salt transport
negative regulation of JNK cascade
positive regulation of vasculogenesis
blood vessel development
positive regulation of JNK cascade
negative regulation of osteoclast differentiation
negative regulation of T cell receptor signaling pathway
negative regulation of vascular permeability
negative regulation of T cell proliferation
positive regulation of MAP kinase activity
negative regulation of fatty acid biosynthetic process
negative regulation of T cell mediated cytotoxicity
negative regulation of interleukin-2 production
negative regulation of protein kinase activity
Cellular Component
microvillus membrane
cell surface
plasma membrane
cell junction
basal plasma membrane
cell-cell junction
adherens junction
lateral plasma membrane
apical plasma membrane
external side of plasma membrane
transport vesicle
integral to membrane
ciliary membrane
Molecular Function
protein kinase binding
viral receptor activity
actin binding
Toll-like receptor binding
kinase binding
protein homodimerization activity
bile acid transmembrane transporter activity
identical protein binding
calmodulin binding
protein dimerization activity
filamin binding
granulocyte colony-stimulating factor receptor 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 521
Molecular Weight 57015.32
Theoretical pI 5.582
Pfam Domain Function
Signals
  • 1-34;
Transmembrane Regions
  • 429-447;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P31809
UniProtKB/Swiss-Prot Entry Name CEAM1_MOUSE
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. [PubMed:19349973 ]
  2. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  3. Ghesquiere B, Van Damme J, Martens L, Vandekerckhove J, Gevaert K: Proteome-wide characterization of N-glycosylation events by diagonal chromatography. J Proteome Res. 2006 Sep;5(9):2438-47. doi: 10.1021/pr060186m. [PubMed:16944957 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. Dveksler GS, Pensiero MN, Cardellichio CB, Williams RK, Jiang GS, Holmes KV, Dieffenbach CW: Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. J Virol. 1991 Dec;65(12):6881-91. doi: 10.1128/JVI.65.12.6881-6891.1991. [PubMed:1719235 ]
  8. McCuaig K, Turbide C, Beauchemin N: mmCGM1a: a mouse carcinoembryonic antigen gene family member, generated by alternative splicing, functions as an adhesion molecule. Cell Growth Differ. 1992 Mar;3(3):165-74. [PubMed:1633107 ]
  9. McCuaig K, Rosenberg M, Nedellec P, Turbide C, Beauchemin N: Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms. Gene. 1993 May 30;127(2):173-83. doi: 10.1016/0378-1119(93)90716-g. [PubMed:8500759 ]
  10. Dveksler GS, Dieffenbach CW, Cardellichio CB, McCuaig K, Pensiero MN, Jiang GS, Beauchemin N, Holmes KV: Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol. 1993 Jan;67(1):1-8. doi: 10.1128/JVI.67.1.1-8.1993. [PubMed:8380065 ]
  11. Huber M, Izzi L, Grondin P, Houde C, Kunath T, Veillette A, Beauchemin N: The carboxyl-terminal region of biliary glycoprotein controls its tyrosine phosphorylation and association with protein-tyrosine phosphatases SHP-1 and SHP-2 in epithelial cells. J Biol Chem. 1999 Jan 1;274(1):335-44. doi: 10.1074/jbc.274.1.335. [PubMed:9867848 ]
  12. Hemmila E, Turbide C, Olson M, Jothy S, Holmes KV, Beauchemin N: Ceacam1a-/- mice are completely resistant to infection by murine coronavirus mouse hepatitis virus A59. J Virol. 2004 Sep;78(18):10156-65. doi: 10.1128/JVI.78.18.10156-10165.2004. [PubMed:15331748 ]
  13. Nagaishi T, Pao L, Lin SH, Iijima H, Kaser A, Qiao SW, Chen Z, Glickman J, Najjar SM, Nakajima A, Neel BG, Blumberg RS: SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity. 2006 Nov;25(5):769-81. doi: 10.1016/j.immuni.2006.08.026. Epub 2006 Nov 2. [PubMed:17081782 ]
  14. Horst AK, Ito WD, Dabelstein J, Schumacher U, Sander H, Turbide C, Brummer J, Meinertz T, Beauchemin N, Wagener C: Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo. J Clin Invest. 2006 Jun;116(6):1596-605. doi: 10.1172/JCI24340. Epub 2006 May 4. [PubMed:16680193 ]
  15. DeAngelis AM, Heinrich G, Dai T, Bowman TA, Patel PR, Lee SJ, Hong EG, Jung DY, Assmann A, Kulkarni RN, Kim JK, Najjar SM: Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolism. Diabetes. 2008 Sep;57(9):2296-303. doi: 10.2337/db08-0379. Epub 2008 Jun 10. [PubMed:18544705 ]
  16. Wong C, Liu Y, Yip J, Chand R, Wee JL, Oates L, Nieswandt B, Reheman A, Ni H, Beauchemin N, Jackson DE: CEACAM1 negatively regulates platelet-collagen interactions and thrombus growth in vitro and in vivo. Blood. 2009 Feb 19;113(8):1818-28. doi: 10.1182/blood-2008-06-165043. Epub 2008 Nov 13. [PubMed:19008452 ]
  17. Pan H, Shively JE: Carcinoembryonic antigen-related cell adhesion molecule-1 regulates granulopoiesis by inhibition of granulocyte colony-stimulating factor receptor. Immunity. 2010 Oct 29;33(4):620-31. doi: 10.1016/j.immuni.2010.10.009. [PubMed:21029969 ]
  18. Nouvion AL, Oubaha M, Leblanc S, Davis EC, Jastrow H, Kammerer R, Breton V, Turbide C, Ergun S, Gratton JP, Beauchemin N: CEACAM1: a key regulator of vascular permeability. J Cell Sci. 2010 Dec 15;123(Pt 24):4221-30. doi: 10.1242/jcs.073635. Epub 2010 Nov 16. [PubMed:21081647 ]
  19. Bickert T, Marshall RP, Zhang Z, Ludewig P, Binder M, Klinke A, Rottbauer W, Amling M, Wagener C, Ito WD, Horst AK: Acceleration of collateral development by carcinoembryonic antigen-related cell adhesion molecule 1 expression on CD11b/(+)Gr-1(+) myeloid cells--brief report. Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2566-8. doi: 10.1161/ATVBAHA.112.300015. Epub 2012 Sep 6. [PubMed:22962327 ]
  20. Chen L, Chen Z, Baker K, Halvorsen EM, da Cunha AP, Flak MB, Gerber G, Huang YH, Hosomi S, Arthur JC, Dery KJ, Nagaishi T, Beauchemin N, Holmes KV, Ho JW, Shively JE, Jobin C, Onderdonk AB, Bry L, Weiner HL, Higgins DE, Blumberg RS: The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction. Immunity. 2012 Nov 16;37(5):930-46. doi: 10.1016/j.immuni.2012.07.016. Epub 2012 Nov 1. [PubMed:23123061 ]
  21. Lu R, Pan H, Shively JE: CEACAM1 negatively regulates IL-1beta production in LPS activated neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex. PLoS Pathog. 2012;8(4):e1002597. doi: 10.1371/journal.ppat.1002597. Epub 2012 Apr 5. [PubMed:22496641 ]
  22. 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 ]
  23. Heckt T, Bickert T, Jeschke A, Seitz S, Schulze J, Ito WD, Zimmermann W, Amling M, Schinke T, Horst AK, Keller J: Increased osteoclastogenesis in mice lacking the carcinoembryonic antigen-related cell adhesion molecule 1. PLoS One. 2014 Dec 9;9(12):e114360. doi: 10.1371/journal.pone.0114360. eCollection 2014. [PubMed:25490771 ]
  24. Kitamura Y, Murata Y, Park JH, Kotani T, Imada S, Saito Y, Okazawa H, Azuma T, Matozaki T: Regulation by gut commensal bacteria of carcinoembryonic antigen-related cell adhesion molecule expression in the intestinal epithelium. Genes Cells. 2015 Jul;20(7):578-89. doi: 10.1111/gtc.12247. Epub 2015 Apr 23. [PubMed:25908210 ]
  25. 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 ]
  26. Tan K, Zelus BD, Meijers R, Liu JH, Bergelson JM, Duke N, Zhang R, Joachimiak A, Holmes KV, Wang JH: Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family. EMBO J. 2002 May 1;21(9):2076-86. doi: 10.1093/emboj/21.9.2076. [PubMed:11980704 ]