Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP12670
Secondary Accession Numbers None
Name Carcinoembryonic antigen-related cell adhesion molecule 1
Synonyms
  1. ATP-dependent taurocolate-carrier protein
  2. Cell-CAM 105
  3. Ecto-ATPase
  4. GP110
  5. pp120
  6. C-CAM 105
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 (PubMed:8454589, PubMed:2373740). Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:11850617). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors (By similarity). Plays a role in immune response, of T-cells, natural killer (NK) and neutrophils (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (PubMed:11850617). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis (PubMed:7592607, PubMed:9712832). 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 (PubMed:7592607, PubMed:16054098). 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 (PubMed:11694516). 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 (By similarity). 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 (PubMed:15467833). 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 (By similarity). Mediates bile acid transport activity in a phosphorylation dependent manner (PubMed:7518458). Negatively regulates osteoclastogenesis (By similarity).Cell adhesion proteins that mediates homophilic cell adhesion in a calcium-independent manner (PubMed:8536699, PubMed:7774714). 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
calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
cell-cell adhesion via plasma-membrane adhesion molecules
cell-cell junction organization
regulation of cell growth
granulocyte colony-stimulating factor signaling pathway
insulin catabolic process
insulin receptor internalization
signal transduction
negative regulation by host of viral genome replication
negative regulation by host of viral process
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
positive regulation by host of viral process
positive regulation of activation-induced cell death of T cells
positive regulation of calcineurin-NFAT signaling cascade
positive regulation of CD4-positive, alpha-beta T cell activation
negative regulation of bone resorption
positive regulation of CD4-positive, alpha-beta T cell proliferation
viral entry into host cell
positive regulation of CD8-positive, alpha-beta T cell activation
positive regulation of homophilic cell adhesion
positive regulation of immunoglobulin production
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
cell adhesion
positive regulation of T cell proliferation
common myeloid progenitor cell proliferation
regulation of phosphatidylinositol 3-kinase cascade
cellular response to insulin stimulus
regulation of ERK1 and ERK2 cascade
regulation of cell migration
bile acid and bile salt transport
homophilic cell adhesion
calcium-dependent cell-cell adhesion
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
Peyer's patch development
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
extracellular space
brush border membrane
apical plasma membrane
external side of plasma membrane
transport vesicle
membrane
integral to membrane
integral to plasma membrane
ciliary membrane
Molecular Function
virion binding
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 519
Molecular Weight 57409.58
Theoretical pI 5.917
Pfam Domain Function
Signals
  • 1-34;
Transmembrane Regions
  • 426-446;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P16573
UniProtKB/Swiss-Prot Entry Name CEAM1_RAT
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426. [PubMed:15057822 ]
  3. Lin SH, Guidotti G: Cloning and expression of a cDNA coding for a rat liver plasma membrane ecto-ATPase. The primary structure of the ecto-ATPase is similar to that of the human biliary glycoprotein I. J Biol Chem. 1989 Aug 25;264(24):14408-14. [PubMed:2527235 ]
  4. Culic O, Huang QH, Flanagan D, Hixson D, Lin SH: Molecular cloning and expression of a new rat liver cell-CAM105 isoform. Differential phosphorylation of isoforms. Biochem J. 1992 Jul 1;285 ( Pt 1):47-53. doi: 10.1042/bj2850047. [PubMed:1637321 ]
  5. Cheung PH, Culic O, Qiu Y, Earley K, Thompson N, Hixson DC, Lin SH: The cytoplasmic domain of C-CAM is required for C-CAM-mediated adhesion function: studies of a C-CAM transcript containing an unspliced intron. Biochem J. 1993 Oct 15;295 ( Pt 2):427-35. doi: 10.1042/bj2950427. [PubMed:8240240 ]
  6. Edlund M, Gaardsvoll H, Bock E, Obrink B: Different isoforms and stock-specific variants of the cell adhesion molecule C-CAM (cell-CAM 105) in rat liver. Eur J Biochem. 1993 May 1;213(3):1109-16. doi: 10.1111/j.1432-1033.1993.tb17860.x. [PubMed:8504806 ]
  7. Lucka L, Cichocka I, Baumler K, Bechler K, Reutter W: A short isoform of carcinoembryonic-antigen-related rat liver cell-cell adhesion molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing and recombinant functional analysis. Eur J Biochem. 1995 Dec 1;234(2):527-35. doi: 10.1111/j.1432-1033.1995.527_b.x. [PubMed:8536699 ]
  8. Aurivillius M, Hansen OC, Lazrek MB, Bock E, Obrink B: The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of the immunoglobulin superfamily. FEBS Lett. 1990 May 21;264(2):267-9. doi: 10.1016/0014-5793(90)80264-j. [PubMed:2141577 ]
  9. Becker A, Lucka L, Kilian C, Kannicht C, Reutter W: Characterisation of the ATP-dependent taurocholate-carrier protein (gp110) of the hepatocyte canalicular membrane. Eur J Biochem. 1993 Jun 1;214(2):539-48. doi: 10.1111/j.1432-1033.1993.tb17952.x. [PubMed:8513803 ]
  10. Tingstrom A, Blikstad I, Aurivillius M, Obrink B: C-CAM (cell-CAM 105) is an adhesive cell surface glycoprotein with homophilic binding properties. J Cell Sci. 1990 May;96 ( Pt 1):17-25. [PubMed:2373740 ]
  11. Lin SH, Culic O, Flanagan D, Hixson DC: Immunochemical characterization of two isoforms of rat liver ecto-ATPase that show an immunological and structural identity with a glycoprotein cell-adhesion molecule with Mr 105,000. Biochem J. 1991 Aug 15;278 ( Pt 1):155-61. doi: 10.1042/bj2780155. [PubMed:1831973 ]
  12. Cheung PH, Thompson NL, Earley K, Culic O, Hixson D, Lin SH: Cell-CAM105 isoforms with different adhesion functions are coexpressed in adult rat tissues and during liver development. J Biol Chem. 1993 Mar 25;268(9):6139-46. [PubMed:8454589 ]
  13. Najjar SM, Accili D, Philippe N, Jernberg J, Margolis R, Taylor SI: pp120/ecto-ATPase, an endogenous substrate of the insulin receptor tyrosine kinase, is expressed as two variably spliced isoforms. J Biol Chem. 1993 Jan 15;268(2):1201-6. [PubMed:8380406 ]
  14. Sippel CJ, Fallon RJ, Perlmutter DH: Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto-ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine 488 phosphorylation. J Biol Chem. 1994 Jul 29;269(30):19539-45. [PubMed:7518458 ]
  15. Najjar SM, Philippe N, Suzuki Y, Ignacio GA, Formisano P, Accili D, Taylor SI: Insulin-stimulated phosphorylation of recombinant pp120/HA4, an endogenous substrate of the insulin receptor tyrosine kinase. Biochemistry. 1995 Jul 25;34(29):9341-9. doi: 10.1021/bi00029a009. [PubMed:7626603 ]
  16. Formisano P, Najjar SM, Gross CN, Philippe N, Oriente F, Kern-Buell CL, Accili D, Gorden P: Receptor-mediated internalization of insulin. Potential role of pp120/HA4, a substrate of the insulin receptor kinase. J Biol Chem. 1995 Oct 13;270(41):24073-7. doi: 10.1074/jbc.270.41.24073. [PubMed:7592607 ]
  17. Olsson H, Wikstrom K, Kjellstrom G, Obrink B: Cell adhesion activity of the short cytoplasmic domain isoform of C-CAM (C-CAM2) in CHO cells. FEBS Lett. 1995 May 22;365(1):51-6. doi: 10.1016/0014-5793(95)00436-d. [PubMed:7774714 ]
  18. Hunter I, Sawa H, Edlund M, Obrink B: Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in epithelial cells. Biochem J. 1996 Dec 15;320 ( Pt 3):847-53. doi: 10.1042/bj3200847. [PubMed:9003371 ]
  19. Wikstrom K, Kjellstrom G, Obrink B: Homophilic intercellular adhesion mediated by C-CAM is due to a domain 1-domain 1 reciprocal binding. Exp Cell Res. 1996 Sep 15;227(2):360-6. doi: 10.1006/excr.1996.0285. [PubMed:8831574 ]
  20. Edlund M, Blikstad I, Obrink B: Calmodulin binds to specific sequences in the cytoplasmic domain of C-CAM and down-regulates C-CAM self-association. J Biol Chem. 1996 Jan 19;271(3):1393-9. doi: 10.1074/jbc.271.3.1393. [PubMed:8576129 ]
  21. Choice CV, Howard MJ, Poy MN, Hankin MH, Najjar SM: Insulin stimulates pp120 endocytosis in cells co-expressing insulin receptors. J Biol Chem. 1998 Aug 28;273(35):22194-200. doi: 10.1074/jbc.273.35.22194. [PubMed:9712832 ]
  22. 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 ]
  23. Poy MN, Ruch RJ, Fernstrom MA, Okabayashi Y, Najjar SM: Shc and CEACAM1 interact to regulate the mitogenic action of insulin. J Biol Chem. 2002 Jan 11;277(2):1076-84. doi: 10.1074/jbc.M108415200. Epub 2001 Nov 1. [PubMed:11694516 ]
  24. 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 ]
  25. Poy MN, Yang Y, Rezaei K, Fernstrom MA, Lee AD, Kido Y, Erickson SK, Najjar SM: CEACAM1 regulates insulin clearance in liver. Nat Genet. 2002 Mar;30(3):270-6. doi: 10.1038/ng840. Epub 2002 Feb 19. [PubMed:11850617 ]
  26. 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 ]
  27. Najjar SM, Yang Y, Fernstrom MA, Lee SJ, Deangelis AM, Rjaily GA, Al-Share QY, Dai T, Miller TA, Ratnam S, Ruch RJ, Smith S, Lin SH, Beauchemin N, Oyarce AM: Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab. 2005 Jul;2(1):43-53. doi: 10.1016/j.cmet.2005.06.001. [PubMed:16054098 ]
  28. Muller MM, Klaile E, Vorontsova O, Singer BB, Obrink B: Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src. J Cell Biol. 2009 Nov 16;187(4):569-81. doi: 10.1083/jcb.200904150. [PubMed:19948503 ]