CEAM1_MOUSE
ID CEAM1_MOUSE Reviewed; 521 AA.
AC P31809; Q61350; Q61353;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 1 {ECO:0000250|UniProtKB:P13688};
DE AltName: Full=Biliary glycoprotein 1 {ECO:0000250|UniProtKB:P13688};
DE Short=BGP-1;
DE AltName: Full=Biliary glycoprotein D;
DE AltName: Full=MHVR1;
DE AltName: Full=Murine hepatitis virus receptor;
DE Short=MHV-R;
DE AltName: CD_antigen=CD66a;
DE Flags: Precursor;
GN Name=Ceacam1 {ECO:0000312|MGI:MGI:1347245};
GN Synonyms=Bgp {ECO:0000303|PubMed:8500759}, Bgp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH MHV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RC STRAIN=BALB/cJ, and CD-1; TISSUE=Colon, and Liver;
RX PubMed=1719235; DOI=10.1128/jvi.65.12.6881-6891.1991;
RA Dveksler G.S., Pensiero M.N., Cardellichio C.B., Williams R.K.,
RA Jiang G.-S., Holmes K.V., Dieffenbach C.W.;
RT "Cloning of the mouse hepatitis virus (MHV) receptor: expression in human
RT and hamster cell lines confers susceptibility to MHV.";
RL J. Virol. 65:6881-6891(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND FUNCTION.
RC STRAIN=CD-1; TISSUE=Colon;
RX PubMed=1633107;
RA McCuaig K., Turbide C., Beauchemin N.;
RT "mmCGM1a: a mouse carcinoembryonic antigen gene family member, generated by
RT alternative splicing, functions as an adhesion molecule.";
RL Cell Growth Differ. 3:165-174(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), AND ALTERNATIVE SPLICING.
RC STRAIN=CD-1; TISSUE=Colon;
RX PubMed=8500759; DOI=10.1016/0378-1119(93)90716-g;
RA McCuaig K., Rosenberg M., Nedellec P., Turbide C., Beauchemin N.;
RT "Expression of the Bgp gene and characterization of mouse colon biliary
RT glycoprotein isoforms.";
RL Gene 127:173-183(1993).
RN [4]
RP PROTEIN SEQUENCE OF 35-59.
RX PubMed=1648219; DOI=10.1073/pnas.88.13.5533;
RA Williams R.K., Jiang G.-S., Holmes K.V.;
RT "Receptor for mouse hepatitis virus is a member of the carcinoembryonic
RT antigen family of glycoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5533-5536(1991).
RN [5]
RP PROTEIN SEQUENCE OF 116-130, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [6]
RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, AND INTERACTION WITH MHV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RC STRAIN=CD-1; TISSUE=Colon;
RX PubMed=8380065; DOI=10.1128/jvi.67.1.1-8.1993;
RA Dveksler G.S., Dieffenback C.B., Cardellichio C.B., McCuaig K.,
RA Pensiero M.N., Jiang G.-S., Beauchemin N., Holmes K.V.;
RT "Several members of the mouse carcinoembryonic antigen-related glycoprotein
RT family are functional receptors for the coronavirus mouse hepatitis virus-
RT A59.";
RL J. Virol. 67:1-8(1993).
RN [7]
RP NOMENCLATURE OF ALTERNATIVE SPLICING ISOFORMS.
RX PubMed=11501563; DOI=10.1006/excr.1999.4610;
RA Beauchemin N., Draber P., Dveksler G., Gold P., Gray-Owen S., Grunert F.,
RA Hammarstrom S., Holmes K.V., Karlsson A., Kuroki M., Lin S.H., Lucka L.,
RA Najjar S.M., Neumaier M., Obrink B., Shively J.E., Skubitz K.M.,
RA Stanners C.P., Thomas P., Thompson J.A., Virji M., von Kleist S.,
RA Wagener C., Watt S., Zimmermann W.;
RT "Redefined nomenclature for members of the carcinoembryonic antigen
RT family.";
RL Exp. Cell Res. 252:243-249(1999).
RN [8]
RP INTERACTION WITH PTPN11 AND PTPN6, PHOSPHORYLATION AT TYR-488 AND TYR-515
RP BY SRC, REGION, AND MUTAGENESIS OF TYR-488; TYR-515; 519-LYS--LYS-521 AND
RP VAL-518.
RX PubMed=9867848; DOI=10.1074/jbc.274.1.335;
RA Huber M., Izzi L., Grondin P., Houde C., Kunath T., Veillette A.,
RA Beauchemin N.;
RT "The carboxyl-terminal region of biliary glycoprotein controls its tyrosine
RT phosphorylation and association with protein-tyrosine phosphatases SHP-1
RT and SHP-2 in epithelial cells.";
RL J. Biol. Chem. 274:335-344(1999).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=11994468; DOI=10.4049/jimmunol.168.10.5139;
RA Singer B.B., Scheffrahn I., Heymann R., Sigmundsson K., Kammerer R.,
RA Obrink B.;
RT "Carcinoembryonic antigen-related cell adhesion molecule 1 expression and
RT signaling in human, mouse, and rat leukocytes: evidence for replacement of
RT the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked
RT proteins in human leukocytes.";
RL J. Immunol. 168:5139-5146(2002).
RN [10]
RP INTERACTION WITH SHC1, AND FUNCTION.
RX PubMed=15467833; DOI=10.1172/jci200421786;
RA Abou-Rjaily G.A., Lee S.J., May D., Al-Share Q.Y., Deangelis A.M.,
RA Ruch R.J., Neumaier M., Kalthoff H., Lin S.H., Najjar S.M.;
RT "CEACAM1 modulates epidermal growth factor receptor--mediated cell
RT proliferation.";
RL J. Clin. Invest. 114:944-952(2004).
RN [11]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=15331748; DOI=10.1128/jvi.78.18.10156-10165.2004;
RA Hemmila E., Turbide C., Olson M., Jothy S., Holmes K.V., Beauchemin N.;
RT "Ceacam1a-/- mice are completely resistant to infection by murine
RT coronavirus mouse hepatitis virus A59.";
RL J. Virol. 78:10156-10165(2004).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF TYR-488 AND TYR-515.
RX PubMed=17081782; DOI=10.1016/j.immuni.2006.08.026;
RA Nagaishi T., Pao L., Lin S.H., Iijima H., Kaser A., Qiao S.W., Chen Z.,
RA Glickman J., Najjar S.M., Nakajima A., Neel B.G., Blumberg R.S.;
RT "SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule
RT isoforms.";
RL Immunity 25:769-781(2006).
RN [13]
RP MUTAGENESIS OF TYR-488 AND SER-503, AND FUNCTION.
RX PubMed=16680193; DOI=10.1172/jci24340;
RA Horst A.K., Ito W.D., Dabelstein J., Schumacher U., Sander H., Turbide C.,
RA Bruemmer J., Meinertz T., Beauchemin N., Wagener C.;
RT "Carcinoembryonic antigen-related cell adhesion molecule 1 modulates
RT vascular remodeling in vitro and in vivo.";
RL J. Clin. Invest. 116:1596-1605(2006).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-206.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [15]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18544705; DOI=10.2337/db08-0379;
RA DeAngelis A.M., Heinrich G., Dai T., Bowman T.A., Patel P.R., Lee S.J.,
RA Hong E.G., Jung D.Y., Assmann A., Kulkarni R.N., Kim J.K., Najjar S.M.;
RT "Carcinoembryonic antigen-related cell adhesion molecule 1: a link between
RT insulin and lipid metabolism.";
RL Diabetes 57:2296-2303(2008).
RN [16]
RP DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19008452; DOI=10.1182/blood-2008-06-165043;
RA Wong C., Liu Y., Yip J., Chand R., Wee J.L., Oates L., Nieswandt B.,
RA Reheman A., Ni H., Beauchemin N., Jackson D.E.;
RT "CEACAM1 negatively regulates platelet-collagen interactions and thrombus
RT growth in vitro and in vivo.";
RL Blood 113:1818-1828(2009).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-71; ASN-89; ASN-317; ASN-333
RP AND ASN-375.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE, PHOSPHORYLATION BY
RP CSF3R, AND INTERACTION WITH CSF3R.
RX PubMed=21029969; DOI=10.1016/j.immuni.2010.10.009;
RA Pan H., Shively J.E.;
RT "Carcinoembryonic antigen-related cell adhesion molecule-1 regulates
RT granulopoiesis by inhibition of granulocyte colony-stimulating factor
RT receptor.";
RL Immunity 33:620-631(2010).
RN [20]
RP FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF TYR-488 AND TYR-515, AND
RP PHOSPHORYLATION AT TYR-488 AND TYR-515.
RX PubMed=21081647; DOI=10.1242/jcs.073635;
RA Nouvion A.L., Oubaha M., Leblanc S., Davis E.C., Jastrow H., Kammerer R.,
RA Breton V., Turbide C., Ergun S., Gratton J.P., Beauchemin N.;
RT "CEACAM1: a key regulator of vascular permeability.";
RL J. Cell Sci. 123:4221-4230(2010).
RN [21]
RP FUNCTION.
RX PubMed=22962327; DOI=10.1161/atvbaha.112.300015;
RA Bickert T., Marshall R.P., Zhang Z., Ludewig P., Binder M., Klinke A.,
RA Rottbauer W., Amling M., Wagener C., Ito W.D., Horst A.K.;
RT "Acceleration of collateral development by carcinoembryonic antigen-related
RT cell adhesion molecule 1 expression on CD11b/[?]Gr-1[?] myeloid cells--
RT brief report.";
RL Arterioscler. Thromb. Vasc. Biol. 32:2566-2568(2012).
RN [22]
RP TISSUE SPECIFICITY, FUNCTION, AND INDUCTION.
RX PubMed=23123061; DOI=10.1016/j.immuni.2012.07.016;
RA Chen L., Chen Z., Baker K., Halvorsen E.M., da Cunha A.P., Flak M.B.,
RA Gerber G., Huang Y.H., Hosomi S., Arthur J.C., Dery K.J., Nagaishi T.,
RA Beauchemin N., Holmes K.V., Ho J.W., Shively J.E., Jobin C.,
RA Onderdonk A.B., Bry L., Weiner H.L., Higgins D.E., Blumberg R.S.;
RT "The short isoform of the CEACAM1 receptor in intestinal T cells regulates
RT mucosal immunity and homeostasis via Tfh cell induction.";
RL Immunity 37:930-946(2012).
RN [23]
RP FUNCTION, INTERACTION WITH SYK, PTPN6; TLR4 AND LYN, AND MUTAGENESIS OF
RP TYR-488 AND TYR-515.
RX PubMed=22496641; DOI=10.1371/journal.ppat.1002597;
RA Lu R., Pan H., Shively J.E.;
RT "CEACAM1 negatively regulates IL-1beta production in LPS activated
RT neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex.";
RL PLoS Pathog. 8:E1002597-E1002597(2012).
RN [24]
RP FUNCTION, AND INDUCTION.
RX PubMed=23696226; DOI=10.1002/eji.201242676;
RA Hosomi S., Chen Z., Baker K., Chen L., Huang Y.H., Olszak T., Zeissig S.,
RA Wang J.H., Mandelboim O., Beauchemin N., Lanier L.L., Blumberg R.S.;
RT "CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function
RT and signaling.";
RL Eur. J. Immunol. 43:2473-2483(2013).
RN [25]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND
RP FUNCTION.
RX PubMed=25490771; DOI=10.1371/journal.pone.0114360;
RA Heckt T., Bickert T., Jeschke A., Seitz S., Schulze J., Ito W.D.,
RA Zimmermann W., Amling M., Schinke T., Horst A.K., Keller J.;
RT "Increased osteoclastogenesis in mice lacking the carcinoembryonic antigen-
RT related cell adhesion molecule 1.";
RL PLoS ONE 9:E114360-E114360(2014).
RN [26]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=25908210; DOI=10.1111/gtc.12247;
RA Kitamura Y., Murata Y., Park J.H., Kotani T., Imada S., Saito Y.,
RA Okazawa H., Azuma T., Matozaki T.;
RT "Regulation by gut commensal bacteria of carcinoembryonic antigen-related
RT cell adhesion molecule expression in the intestinal epithelium.";
RL Genes Cells 20:578-589(2015).
RN [27]
RP INTERACTION WITH HAVCR2.
RX PubMed=25363763; DOI=10.1038/nature13848;
RA Huang Y.H., Zhu C., Kondo Y., Anderson A.C., Gandhi A., Russell A.,
RA Dougan S.K., Petersen B.S., Melum E., Pertel T., Clayton K.L., Raab M.,
RA Chen Q., Beauchemin N., Yazaki P.J., Pyzik M., Ostrowski M.A.,
RA Glickman J.N., Rudd C.E., Ploegh H.L., Franke A., Petsko G.A.,
RA Kuchroo V.K., Blumberg R.S.;
RT "CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.";
RL Nature 517:386-390(2015).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.32 ANGSTROMS) OF 35-236 (ISOFORM 3), GLYCOSYLATION
RP AT ASN-71; ASN-89; ASN-104 AND ASN-333, DISULFIDE BOND, AND INTERACTION
RP WITH MURINE CORONAVIRUS MHV S1 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=11980704; DOI=10.1093/emboj/21.9.2076;
RA Tan K., Zelus B.D., Meijers R., Liu J.-H., Bergelson J.M., Duke N.,
RA Zhang R., Joachimiak A., Holmes K.V., Wang J.-H.;
RT "Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the
RT CEA family.";
RL EMBO J. 21:2076-2086(2002).
CC -!- FUNCTION: [Isoform 1]: Cell adhesion protein that mediates homophilic
CC cell adhesion in a calcium-independent manner (By similarity). Plays a
CC role as coinhibitory receptor in immune response, insulin action and
CC functions also as an activator during angiogenesis (PubMed:16680193,
CC PubMed:17081782, PubMed:18544705, PubMed:21029969, PubMed:21081647,
CC PubMed:22496641, PubMed:22962327, PubMed:23696226). Its coinhibitory
CC receptor function is phosphorylation- and PTPN6 -dependent, which in
CC turn, suppress signal transduction of associated receptors by
CC dephosphorylation of their downstream effectors (PubMed:17081782,
CC PubMed:21029969, PubMed:22496641). Plays a role in immune response, of
CC T-cells, natural killer (NK) and neutrophils (PubMed:17081782,
CC PubMed:23696226, PubMed:22496641, PubMed:21029969). Upon TCR/CD3
CC complex stimulation, inhibits TCR-mediated cytotoxicity by blocking
CC granule exocytosis by mediating homophilic binding to adjacent cells,
CC allowing interaction with and phosphorylation by LCK and interaction
CC with the TCR/CD3 complex which recruits PTPN6 resulting in
CC dephosphorylation of CD247 and ZAP70 (PubMed:22496641). Also inhibits
CC T-cell proliferation and cytokine production through inhibition of JNK
CC cascade and plays a crucial role in regulating autoimmunity and anti-
CC tumor immunity by inhibiting T-cell through its interaction with HAVCR2
CC (PubMed:17081782). Upon natural killer (NK) cells activation, inhibit
CC KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-
CC homophilic interactions with CEACAM1 on the target cell and lead to
CC cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment
CC and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils
CC activation negatively regulates IL1B production by recruiting PTPN6 to
CC a SYK-TLR4-CEACAM1 complex, that dephosphorylates SYK, reducing the
CC production of reactive oxygen species (ROS) and lysosome disruption,
CC which in turn, reduces the activity of the inflammasome
CC (PubMed:22496641). Down-regulates neutrophil production by acting as a
CC coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3
CC pathway through recruitment of PTPN6 that dephosphorylates CSF3R
CC (PubMed:21029969). Also regulates insulin action by promoting INS
CC clearance and regulating lipogenesis in liver through regulating
CC insulin signaling (PubMed:18544705). Upon INS stimulation, undergoes
CC phosphorylation by INSR leading to INS clearance by increasing
CC receptor-mediated insulin endocytosis. This inernalization promotes
CC interaction with FASN leading to receptor-mediated insulin degradation
CC and to reduction of FASN activity leading to negative regulation of
CC fatty acid synthesis. INSR-mediated phosphorylation also provokes a
CC down-regulation of cell proliferation through SHC1 interaction
CC resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and
CC phosphatidylinositol 3-kinase pathways (By similarity). Functions as
CC activator in angiogenesis by promoting blood vessel remodeling through
CC endothelial cell differentiation and migration and in arteriogenesis by
CC increasing the number of collateral arteries and collateral vessel
CC calibers after ischemia (PubMed:16680193, PubMed:22962327). Also
CC regulates vascular permeability through the VEGFR2 signaling pathway
CC resulting in control of nitric oxide production (PubMed:21081647).
CC Down-regulates cell growth in response to EGF through its interaction
CC with SHC1 that mediates interaction with EGFR resulting in decrease
CC coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway
CC (PubMed:15467833). Negatively regulates platelet aggregation by
CC decreasing platelet adhesion on type I collagen through the GPVI-
CC FcRgamma complex (PubMed:19008452). Inhibits cell migration and cell
CC scattering through interaction with FLNA; interfers with the
CC interaction of FLNA with RALA (By similarity). Mediates bile acid
CC transport activity in a phosphorylation dependent manner (By
CC similarity). Negatively regulates osteoclastogenesis (PubMed:25490771).
CC {ECO:0000250|UniProtKB:P13688, ECO:0000250|UniProtKB:P16573,
CC ECO:0000269|PubMed:15467833, ECO:0000269|PubMed:16680193,
CC ECO:0000269|PubMed:17081782, ECO:0000269|PubMed:18544705,
CC ECO:0000269|PubMed:19008452, ECO:0000269|PubMed:21029969,
CC ECO:0000269|PubMed:21081647, ECO:0000269|PubMed:22496641,
CC ECO:0000269|PubMed:22962327, ECO:0000269|PubMed:23696226,
CC ECO:0000269|PubMed:25490771}.
CC -!- FUNCTION: [Isoform 2]: Cell adhesion protein that mediates homophilic
CC cell adhesion in a calcium-independent manner (PubMed:1633107).
CC Promotes populations of T-cells regulating IgA production and secretion
CC associated with control of the commensal microbiota and resistance to
CC enteropathogens (PubMed:23123061). {ECO:0000269|PubMed:1633107,
CC ECO:0000269|PubMed:23123061}.
CC -!- FUNCTION: (Microbial infection) In case of murine coronavirus (MHV)
CC infection, serves as receptor for MHV S1 spike glycoprotein.
CC {ECO:0000269|PubMed:15331748, ECO:0000269|PubMed:1719235}.
CC -!- SUBUNIT: (Microbial infection) Interacts with MHV S1 spike
CC glycoprotein. {ECO:0000269|PubMed:11980704, ECO:0000269|PubMed:1719235,
CC ECO:0000269|PubMed:8380065}.
CC -!- SUBUNIT: Monomer. Oligomer. Heterodimer. Homodimer (By similarity).
CC Cis-dimer/oligomer (via Ig-like C2-type and/or via cytoplasmic
CC domains); induced by trans-homophilic cell adhesion through an
CC allosteric mechanism transmitted by the Ig-like V-type domain, and is
CC regulated by intracellular calcium and calmodulin. Interacts (via
CC cytoplasmic domain) with calmodulin in a calcium dependent manner;
CC reduces homophilic cell adhesion through dissociation of dimer (By
CC similarity). Isoform 1 interacts (via cytoplasmic domain) with PTPN11
CC (preferentially) and PTPN6; cis-homodimer form is preferred; this
CC interaction is decreased by formation of isoform 1 / isoform 2 cis-
CC heterodimers and is dependent on the monomer/dimer equilibrium; this
CC interaction is phosphorylation-dependent (PubMed:9867848). Isoform 1
CC interacts with LYN (PubMed:22496641). Isoform 1 interacts (via
CC cytoplasmic domain) with SRC (via SH2 domain); this interaction is
CC regulated by trans-homophilic cell adhesion (By similarity). Isoform 1
CC interacts with LCK; mediates phosphorylation at Tyr-488 and Tyr-515
CC resulting in PTPN6 association. Isoform 1 interacts with PTPN6; this
CC interaction is phosphorylation-dependent and causes a profound decrease
CC in TCR stimulation-induced CD247 and ZAP70 phosphorylation. Isoform 1
CC interacts with TCR/CD3 complex through TCR beta chain and CD3E;
CC colocalizes at the cell surface and upon stimulation of the TCR/CD3
CC complex recruits PTPN6 in the TCR/CD3 complex, resulting in
CC dephosphorylation of CD247 and ZAP70 (By similarity). Isoform 1
CC interacts (via cytoplasmic domain) with SHC1 (via SH2 domain); SHC1
CC mediates interaction with INSR or EGFR in a Ser-503 phosphorylation-
CC dependent manner (PubMed:15467833). Isoform 1 interacts with EGFR; the
CC interaction is indirect (By similarity). Isoform 1 interacts with
CC CSF3R; down-regulates the CSF3R-STAT3 pathway through recruitment of
CC PTPN6 that dephosphorylates CSF3R (PubMed:21029969). Isoform 1
CC (phosphorylated form) interacts with TLR4 and SYK; recruits PTPN6 that
CC dephosphorylates SYK, reducing the production of reactive oxygen
CC species (ROS) and lysosome disruption, leading to a reduction of the
CC inflammasome activity (PubMed:22496641). Isoform 1 interacts with FLNA;
CC inhibits cell migration and cell scattering by interfering with the
CC interaction of FLNA with RALA. Isoform 1 interacts (via cytoplasmic
CC domain) with PXN; the interaction is phosphotyrosyl-dependent. Isoform
CC 1 interacts with KLRK1; recruits PTPN6 that dephosphorylates VAV1.
CC Isoform 1 interacts with CEACAM8 (By similarity). Isoform 1 interacts
CC with FASN; this interaction is insulin and phosphorylation-dependent;
CC reduces fatty-acid synthase activity (By similarity). Interacts (via
CC Ig-like V-type) with HAVCR2 (via Ig-like V-type); facilitates the
CC maturation and cell surface expression of HAVCR2 thereby regulating T-
CC cell tolerance induction (By similarity) (PubMed:25363763). Isoform 2
CC interacts (via the cytoplasmic domain) with ANXA2; this interaction is
CC regulated by phosphorylation and appears in the AIIt complex. Interacts
CC (via Lewis X moieties) with CD209 (via C-type lectin domain); this
CC interaction is regulated by the glycosylation pattern of CEACAM1 on
CC cell types and regulates contact between dendritic cells and
CC neutrophils (By similarity). {ECO:0000250|UniProtKB:P13688,
CC ECO:0000250|UniProtKB:P16573, ECO:0000269|PubMed:15467833,
CC ECO:0000269|PubMed:21029969, ECO:0000269|PubMed:22496641,
CC ECO:0000269|PubMed:25363763, ECO:0000269|PubMed:9867848}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:19008452, ECO:0000269|PubMed:8380065}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:P16573}. Lateral cell
CC membrane {ECO:0000250|UniProtKB:P16573}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Basal cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Cell junction
CC {ECO:0000250|UniProtKB:P16573}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P16573}. Note=Canalicular domain of hepatocyte
CC plasma membranes. Found as a mixture of monomer, dimer and oligomer in
CC the plasma membrane. Occurs predominantly as cis-dimers and/or small
CC cis-oligomers in the cell junction regions. Found as dimer in the
CC solution. Predominantly localized to the lateral cell membranes.
CC {ECO:0000250|UniProtKB:P16573}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:1633107, ECO:0000269|PubMed:8380065}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:P16573}. Lateral cell
CC membrane {ECO:0000250|UniProtKB:P16573}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Basal cell membrane
CC {ECO:0000250|UniProtKB:P16573}. Cell junction
CC {ECO:0000250|UniProtKB:P16573}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P16573}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:P13688}. Note=Predominantly localized to the
CC lateral cell membranes. Found as a mixture of monomer, dimer and
CC oligomer in the plasma membrane. Occurs predominantly as cis-dimers
CC and/or small cis-oligomers in the cell junction regions (By
CC similarity). Co-localizes with ANXA2 in secretory vesicles and with
CC S100A10/p11 at the plasma membrane (By similarity).
CC {ECO:0000250|UniProtKB:P13688, ECO:0000250|UniProtKB:P16573}.
CC -!- SUBCELLULAR LOCATION: Cell projection, microvillus membrane
CC {ECO:0000269|PubMed:25908210}; Single-pass type I membrane protein
CC {ECO:0000305}. Apical cell membrane {ECO:0000269|PubMed:25908210};
CC Single-pass type I membrane protein {ECO:0000305}. Note=Localized to
CC the apical glycocalyx surface (By similarity). Colocalizes with
CC CEACAM20 at the apical brush border of intestinal cells
CC (PubMed:25908210). {ECO:0000250|UniProtKB:P13688,
CC ECO:0000269|PubMed:25908210}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Ceacam1-4L {ECO:0000303|PubMed:11501563}, Bgpd;
CC IsoId=P31809-1; Sequence=Displayed;
CC Name=2; Synonyms=Ceacam1-4S {ECO:0000303|PubMed:11501563}, Bgpa,
CC mmCGM1a;
CC IsoId=P31809-2; Sequence=VSP_002484, VSP_002485;
CC Name=3; Synonyms=Ceacam1-2L {ECO:0000303|PubMed:11501563}, Bgpg;
CC IsoId=P31809-3; Sequence=VSP_036040, VSP_036041;
CC Name=4; Synonyms=Ceacam1-2S {ECO:0000303|PubMed:11501563}, Bgpc;
CC IsoId=P31809-4; Sequence=VSP_058517, VSP_002484, VSP_002485;
CC -!- TISSUE SPECIFICITY: Expressed in granulocytes, lymphocytes,
CC granulocytes, B cells, and T-cells (PubMed:11994468). Expressed in
CC bone. Highly expressed in liver and femur (PubMed:25490771). Highly
CC expressed in neutrophils, and to a lesser extent inmonocytes, and
CC macrophages. Slightly higher expressed in peripheral blood neutrophils
CC (PBNs) (PubMed:21029969). Intestinal T-cells predominantly express
CC isoform 2 while extraintestinal T-cells mainly express isoform 1
CC (PubMed:23123061). Expressed in small intestine and colon
CC (PubMed:25908210). {ECO:0000269|PubMed:11994468,
CC ECO:0000269|PubMed:21029969, ECO:0000269|PubMed:23123061,
CC ECO:0000269|PubMed:25490771, ECO:0000269|PubMed:25908210}.
CC -!- DEVELOPMENTAL STAGE: Expression increases during the early stages of
CC osteoblast differentiation, and decreases towards terminal osteoblast
CC differentiation. In addition, expression markedly decreases during the
CC course of osteoclastogenesis. {ECO:0000269|PubMed:25490771}.
CC -!- INDUCTION: In intestinal epithelium, up-regulated in the presence of
CC Gram-positive commensal gut bacteria (PubMed:25908210). May also be up-
CC regulated by interferon gamma (IFNG) and TNF (TNF-alpha)
CC (PubMed:25908210). Isoform 2: Expression is promoted and maintained by
CC the mucosal environment (PubMed:23123061). Induced by IL2 on natural
CC killer cell (PubMed:23696226). {ECO:0000269|PubMed:23123061,
CC ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25908210}.
CC -!- DOMAIN: Ig-like V-type domain mediates trans-homophilic cell adhesion
CC through homodimerization and this active process is regulated by
CC tyrosine kinase, PTPN11 AND PTPN6. Ig-like C2-type and/or cytoplasmic
CC domains mediate cis-dimer/oligomer. {ECO:0000250|UniProtKB:P16573}.
CC -!- PTM: [Isoform 1]: Phosphorylated on serine and tyrosine (By
CC similarity). Isoform 1 is phosphorylated on tyrosine by Src family
CC kinases like SRC and LCK and by receptor like CSF3R, EGFR and INSR upon
CC stimulation (PubMed:9867848, PubMed:21029969). Phosphorylated at Ser-
CC 503; mediates activity. Phosphorylated at Tyr-488; regulates activity
CC (By similarity). Phosphorylated at Tyr-488 by EGFR and INSR upon
CC stimulation; this phosphorylation is Ser-503-phosphorylation-dependent;
CC mediates cellular internalization; increases interaction with FASN (By
CC similarity). Phosphorylated at Tyr-488 and Tyr-515 by LCK; mediates
CC PTPN6 association and is regulated by homophilic ligation of CEACAM1 in
CC the absence of T-cell activation (By similarity). Phosphorylated at
CC Tyr-515; mediates interaction with PTPN11 (PubMed:9867848).
CC {ECO:0000250|UniProtKB:P13688, ECO:0000250|UniProtKB:P16573,
CC ECO:0000269|PubMed:21029969, ECO:0000269|PubMed:9867848}.
CC -!- PTM: [Isoform 2]: Phosphorylated on serine and threonine.
CC {ECO:0000250|UniProtKB:P13688, ECO:0000250|UniProtKB:P16573}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice exhibit impairment of insulin
CC clearance and hyperinsulinemia, which cause insulin resistance; develop
CC insulin resistance primarily in liver (PubMed:18544705). Display normal
CC white blood cell, red blood cell, hemoglobin and platelet. On the other
CC hand, mice have a high number of neutrophils. Display also increased
CC thrombus growth, and enhanced susceptibility to type I collagen induced
CC pulmonary thromboembolism (PubMed:19008452). Spontaneously develop
CC systemic neutrophilia. Upon Listeria Monocytogenes (LM) infection mice
CC die dramatically faster within 7 days and display an improved bacterial
CC clearance accompanied by severe tissue damage and necrosis in the liver
CC (PubMed:21029969). Knockout mice present an increased basal
CC permeability (PubMed:21081647). Knockout mice show a reduced bone mass
CC namely a decreased trabecular bone volume accompanied by a reduction in
CC trabecular number and an increase in trabecular separation
CC (PubMed:25490771). {ECO:0000269|PubMed:18544705,
CC ECO:0000269|PubMed:19008452, ECO:0000269|PubMed:21029969,
CC ECO:0000269|PubMed:21081647, ECO:0000269|PubMed:25490771}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.
CC {ECO:0000305}.
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DR EMBL; M77196; AAA37858.1; -; mRNA.
DR EMBL; X15351; CAA33409.1; -; mRNA.
DR EMBL; X67278; CAA47695.1; -; mRNA.
DR EMBL; X67279; CAA47696.1; -; mRNA.
DR EMBL; X67282; CAA47699.1; -; mRNA.
DR CCDS; CCDS20984.1; -. [P31809-1]
DR CCDS; CCDS20985.1; -. [P31809-3]
DR CCDS; CCDS39839.1; -. [P31809-2]
DR CCDS; CCDS85244.1; -. [P31809-4]
DR PIR; JC1505; WMMSR1.
DR PIR; JC1508; JC1508.
DR PIR; JC1511; JC1511.
DR RefSeq; NP_001034274.1; NM_001039185.1.
DR RefSeq; NP_001034275.1; NM_001039186.1. [P31809-2]
DR PDB; 1L6Z; X-ray; 3.32 A; A=35-416.
DR PDB; 3R4D; X-ray; 3.10 A; A/C=35-416.
DR PDB; 5VST; X-ray; 3.10 A; A=35-416.
DR PDB; 6VSJ; EM; 3.94 A; D/E/F=35-416.
DR PDBsum; 1L6Z; -.
DR PDBsum; 3R4D; -.
DR PDBsum; 5VST; -.
DR PDBsum; 6VSJ; -.
DR AlphaFoldDB; P31809; -.
DR SMR; P31809; -.
DR CORUM; P31809; -.
DR DIP; DIP-61461N; -.
DR IntAct; P31809; 3.
DR MINT; P31809; -.
DR STRING; 10090.ENSMUSP00000096266; -.
DR GlyGen; P31809; 17 sites.
DR iPTMnet; P31809; -.
DR PhosphoSitePlus; P31809; -.
DR jPOST; P31809; -.
DR MaxQB; P31809; -.
DR PaxDb; P31809; -.
DR PeptideAtlas; P31809; -.
DR PRIDE; P31809; -.
DR ProteomicsDB; 281454; -. [P31809-1]
DR ProteomicsDB; 281455; -. [P31809-2]
DR ProteomicsDB; 281456; -. [P31809-3]
DR ProteomicsDB; 281457; -. [P31809-4]
DR DNASU; 26365; -.
DR Ensembl; ENSMUST00000098666; ENSMUSP00000096263; ENSMUSG00000074272. [P31809-2]
DR Ensembl; ENSMUST00000206171; ENSMUSP00000145584; ENSMUSG00000074272. [P31809-2]
DR Ensembl; ENSMUST00000206687; ENSMUSP00000146066; ENSMUSG00000074272. [P31809-4]
DR GeneID; 26365; -.
DR KEGG; mmu:26365; -.
DR UCSC; uc009fsv.1; mouse. [P31809-2]
DR UCSC; uc009fta.1; mouse. [P31809-1]
DR CTD; 634; -.
DR MGI; MGI:1347245; Ceacam1.
DR VEuPathDB; HostDB:ENSMUSG00000074272; -.
DR eggNOG; ENOG502RXPD; Eukaryota.
DR GeneTree; ENSGT00960000186634; -.
DR InParanoid; P31809; -.
DR OrthoDB; 998214at2759; -.
DR PhylomeDB; P31809; -.
DR Reactome; R-MMU-1566977; Fibronectin matrix formation.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 26365; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ceacam1; mouse.
DR EvolutionaryTrace; P31809; -.
DR PRO; PR:P31809; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P31809; protein.
DR Bgee; ENSMUSG00000074272; Expressed in prostate gland ventral lobe and 172 other tissues.
DR ExpressionAtlas; P31809; baseline and differential.
DR Genevisible; P31809; MM.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0031225; C:anchored component of membrane; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0071575; C:integral component of external side of plasma membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0042101; C:T cell receptor complex; ISO:MGI.
DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; ISO:MGI.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0031005; F:filamin binding; ISO:MGI.
DR GO; GO:0034235; F:GPI anchor binding; ISO:MGI.
DR GO; GO:0005130; F:granulocyte colony-stimulating factor receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0035325; F:Toll-like receptor binding; IPI:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISO:MGI.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISO:MGI.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; IMP:UniProtKB.
DR GO; GO:0038158; P:granulocyte colony-stimulating factor signaling pathway; IMP:UniProtKB.
DR GO; GO:1901143; P:insulin catabolic process; IMP:UniProtKB.
DR GO; GO:0038016; P:insulin receptor internalization; ISS:UniProtKB.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:MGI.
DR GO; GO:0043318; P:negative regulation of cytotoxic T cell degranulation; ISS:UniProtKB.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IMP:UniProtKB.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IMP:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IMP:UniProtKB.
DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IMP:UniProtKB.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IMP:MGI.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:0001915; P:negative regulation of T cell mediated cytotoxicity; ISS:UniProtKB.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP:UniProtKB.
DR GO; GO:1903387; P:positive regulation of homophilic cell adhesion; ISO:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IMP:UniProtKB.
DR GO; GO:0060312; P:regulation of blood vessel remodeling; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0045601; P:regulation of endothelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:1903385; P:regulation of homophilic cell adhesion; ISS:UniProtKB.
DR GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Host cell receptor for virus entry;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000269|PubMed:1648219"
FT CHAIN 35..521
FT /note="Carcinoembryonic antigen-related cell adhesion
FT molecule 1"
FT /id="PRO_0000014563"
FT TOPO_DOM 35..428
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 429..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 448..521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..142
FT /note="Ig-like V-type"
FT /evidence="ECO:0000250|UniProtKB:P31997"
FT DOMAIN 147..234
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 239..319
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 323..411
FT /note="Ig-like C2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REGION 39..142
FT /note="Required for homophilic binding"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 445..457
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 447..521
FT /note="Interaction with FLNA"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT REGION 455..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..521
FT /note="Required for interaction with PTPN11 and PTPN6 and
FT for control of phosphorylation level"
FT /evidence="ECO:0000269|PubMed:9867848"
FT REGION 515..518
FT /note="Essential for interaction with PTPN11 and PTPN6"
FT /evidence="ECO:0000269|PubMed:9867848"
FT COMPBIAS 467..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 488
FT /note="Phosphotyrosine; by SRC, LCK, INSR and EGFR"
FT /evidence="ECO:0000269|PubMed:21081647,
FT ECO:0000269|PubMed:9867848"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16573"
FT MOD_RES 515
FT /note="Phosphotyrosine; by INSR, SRC and LCK"
FT /evidence="ECO:0000269|PubMed:21081647,
FT ECO:0000269|PubMed:9867848"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:11980704, ECO:0000269|PubMed:19349973"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:11980704, ECO:0000269|PubMed:19349973"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:11980704"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P13688,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:16944957"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P13688,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P13688,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19349973"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:11980704, ECO:0000269|PubMed:19349973"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:19349973"
FT DISULFID 167..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000305|PubMed:11980704"
FT DISULFID 261..301
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000305|PubMed:11980704"
FT DISULFID 346..394
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:11980704"
FT VAR_SEQ 142..322
FT /note="PILLKPNITSNNSNPVEGDDSVSLTCDSYTDPDNINYLWSRNGESLSEGDRL
FT KLSEGNRTLTLLNVTRNDTGPYVCETRNPVSVNRSDPFSLNIIYGPDTPIISPSDIYLH
FT PGSNLNLSCHAASNPPAQYFWLINEKPHASSQELFIPNITTNNSGTYTCFVNNSVTGLS
FT RTTVKNITVLE -> Q (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:8500759"
FT /id="VSP_058517"
FT VAR_SEQ 142
FT /note="P -> Q (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8500759"
FT /id="VSP_036040"
FT VAR_SEQ 143..322
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8500759"
FT /id="VSP_036041"
FT VAR_SEQ 455..458
FT /note="GSDQ -> SGSF (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:1633107,
FT ECO:0000303|PubMed:1719235, ECO:0000303|PubMed:8500759"
FT /id="VSP_002484"
FT VAR_SEQ 459..521
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:1633107,
FT ECO:0000303|PubMed:1719235, ECO:0000303|PubMed:8500759"
FT /id="VSP_002485"
FT MUTAGEN 488
FT /note="Y->F: Phosphorylated on tyrosine. Abrogates
FT interaction with PTPN11. Abrogates interaction with PTPN11
FT and phosphorylation; when associated with F-515. Reduces
FT endothelial cell migration and differentiation. Suppresses
FT T cell proliferation; when associated with F-515. Increases
FT cytokine production; when associated with F-515. Activates
FT JNK cascade; when associated with F-515. Abrogates CEACAM1-
FT L phosphorylation in endothelial cells and decreases
FT amounts of released nitric oxide upon VEGF stimulation.
FT Impairs interaction with and inactivation of SYK; when
FT associated with F-515."
FT /evidence="ECO:0000269|PubMed:16680193,
FT ECO:0000269|PubMed:17081782, ECO:0000269|PubMed:21081647,
FT ECO:0000269|PubMed:22496641, ECO:0000269|PubMed:9867848"
FT MUTAGEN 503
FT /note="S->A: Reduces endothelial cell migration and
FT differentiation."
FT /evidence="ECO:0000269|PubMed:16680193"
FT MUTAGEN 515
FT /note="Y->F: Phosphorylated on tyrosine. Abrogates
FT interaction with PTPN11. Abrogates interaction with PTPN11
FT and phosphorylation; when associated with F-488. Suppresses
FT T cell proliferation; when associated with F-488. Increases
FT cytokine production; when associated with F-488. Activates
FT JNK cascade; when associated with F-488. Abrogates CEACAM1-
FT L phosphorylation in endothelial cells upon VEGF
FT stimulation. Impairs interaction with and inactivation of
FT SYK; when associated with F-488."
FT /evidence="ECO:0000269|PubMed:17081782,
FT ECO:0000269|PubMed:21081647, ECO:0000269|PubMed:22496641,
FT ECO:0000269|PubMed:9867848"
FT MUTAGEN 518
FT /note="V->A: Impairs interaction with PTPN11 and PTPN6.
FT Doesn't affect phosphorylation."
FT /evidence="ECO:0000269|PubMed:9867848"
FT MUTAGEN 519..521
FT /note="Missing: Reduces Tyr phosphorylation by at least 50%
FT and almost completely abrogates interaction with PTPN11 and
FT PTPN6."
FT /evidence="ECO:0000269|PubMed:9867848"
FT CONFLICT 361..362
FT /note="SQ -> RE (in Ref. 3; CAA47699/CAA47695)"
FT /evidence="ECO:0000305"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:3R4D"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:3R4D"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:3R4D"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 130..141
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:1L6Z"
FT STRAND 342..347
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:3R4D"
FT TURN 374..377
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 378..383
FT /evidence="ECO:0007829|PDB:3R4D"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 390..397
FT /evidence="ECO:0007829|PDB:3R4D"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:3R4D"
SQ SEQUENCE 521 AA; 57016 MW; 1C8F71FAC47DD54E CRC64;
MELASAHLHK GQVPWGGLLL TASLLASWSP ATTAEVTIEA VPPQVAEDNN VLLLVHNLPL
ALGAFAWYKG NTTAIDKEIA RFVPNSNMNF TGQAYSGREI IYSNGSLLFQ MITMKDMGVY
TLDMTDENYR RTQATVRFHV HPILLKPNIT SNNSNPVEGD DSVSLTCDSY TDPDNINYLW
SRNGESLSEG DRLKLSEGNR TLTLLNVTRN DTGPYVCETR NPVSVNRSDP FSLNIIYGPD
TPIISPSDIY LHPGSNLNLS CHAASNPPAQ YFWLINEKPH ASSQELFIPN ITTNNSGTYT
CFVNNSVTGL SRTTVKNITV LEPVTQPFLQ VTNTTVKELD SVTLTCLSND IGANIQWLFN
SQSLQLTERM TLSQNNSILR IDPIKREDAG EYQCEISNPV SVRRSNSIKL DIIFDPTQGG
LSDGAIAGIV IGVVAGVALI AGLAYFLYSR KSGGGSDQRD LTEHKPSTSN HNLAPSDNSP
NKVDDVAYTV LNFNSQQPNR PTSAPSSPRA TETVYSEVKK K
