CEAM1_RAT
ID CEAM1_RAT Reviewed; 519 AA.
AC P16573; Q63093;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2016, sequence version 4.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 1 {ECO:0000250|UniProtKB:P13688};
DE AltName: Full=ATP-dependent taurocolate-carrier protein;
DE AltName: Full=Cell-CAM 105 {ECO:0000303|PubMed:8504806};
DE Short=C-CAM 105;
DE AltName: Full=Ecto-ATPase {ECO:0000303|PubMed:2527235};
DE AltName: Full=GP110 {ECO:0000303|PubMed:8536699};
DE AltName: Full=pp120;
DE AltName: CD_antigen=CD66a;
DE Flags: Precursor;
GN Name=Ceacam1 {ECO:0000312|RGD:67396};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE A) (ISOFORM 1), AND PROTEIN SEQUENCE OF
RP 50-68.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2527235; DOI=10.1016/s0021-9258(18)71694-3;
RA Lin S.-H., Guidotti G.;
RT "Cloning and expression of a cDNA coding for a rat liver plasma membrane
RT ecto-ATPase. The primary structure of the ecto-ATPase is similar to that of
RT the human biliary glycoprotein I.";
RL J. Biol. Chem. 264:14408-14414(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B) (ISOFORM 2), AND VARIANTS SER-49;
RP THR-55; VAL-70; THR-73; GLY-74; LEU-75; ASN-76; SER-86; THR-88; GLN-90;
RP GLU-92; VAL-99; GLY-118; PRO-119; ILE-125 AND LYS-127.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1637321; DOI=10.1042/bj2850047;
RA Culic O., Huang Q., Flanagan D., Hixon D., Lin S.-H.;
RT "Molecular cloning and expression of a new rat liver cell-CAM105 isoform.
RT Differential phosphorylation of isoforms.";
RL Biochem. J. 285:47-53(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-454 (ALLELE A) (ISOFORM 1).
RC TISSUE=Intestine;
RX PubMed=8240240; DOI=10.1042/bj2950427;
RA Cheung P.H., Culic O., Qiu Y., Earley K., Thompson N., Hixson D.C.,
RA Lin S.-H.;
RT "The cytoplasmic domain of C-CAM is required for C-CAM-mediated adhesion
RT function: studies of a C-CAM transcript containing an unspliced intron.";
RL Biochem. J. 295:427-435(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B) (ISOFORM 2), AND VARIANTS SER-49;
RP THR-55; VAL-70; THR-73; GLY-74; LEU-75; ASN-76; SER-86; THR-88; GLN-90;
RP GLU-92; VAL-99; GLY-118; PRO-119; ILE-125 AND LYS-127.
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Liver;
RX PubMed=8504806; DOI=10.1111/j.1432-1033.1993.tb17860.x;
RA Edlund M., Gaardsvoll H., Bock E., Oebrink B.;
RT "Different isoforms and stock-specific variants of the cell adhesion
RT molecule C-CAM (cell-CAM 105) in rat liver.";
RL Eur. J. Biochem. 213:1109-1116(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE (ALLELE A) (ISOFORM 2), SUBCELLULAR LOCATION, AND
RP FUNCTION.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8536699; DOI=10.1111/j.1432-1033.1995.527_b.x;
RA Lucka L., Cichocka I., Baeumler K., Bechler K., Reutter W.;
RT "A short isoform of carcinoembryonic-antigen-related rat liver cell-cell
RT adhesion molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing
RT and recombinant functional analysis.";
RL Eur. J. Biochem. 234:527-535(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND IDENTIFICATION.
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE B) (ISOFORM 1), AND VARIANTS
RP SER-49; THR-55; VAL-70; THR-73; GLY-74; LEU-75; ASN-76; SER-86; THR-88;
RP GLN-90; GLU-92; VAL-99; GLY-118; PRO-119; ILE-125 AND LYS-127.
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 58-66 AND 119-138.
RX PubMed=2141577; DOI=10.1016/0014-5793(90)80264-j;
RA Aurivillius M., Hansen O.C., Lazrek M.B.S., Bock E., Oebrink B.;
RT "The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of
RT the immunoglobulin superfamily.";
RL FEBS Lett. 264:267-269(1990).
RN [10]
RP PARTIAL PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8513803; DOI=10.1111/j.1432-1033.1993.tb17952.x;
RA Becker A., Lucka L., Kilian C., Kannicht C., Reutter W.;
RT "Characterisation of the ATP-dependent taurocholate-carrier protein (gp110)
RT of the hepatocyte canalicular membrane.";
RL Eur. J. Biochem. 214:539-548(1993).
RN [11]
RP PROTEIN SEQUENCE OF 110-138 AND 148-150, AND PHOSPHORYLATION.
RX PubMed=8420979; DOI=10.1016/s0021-9258(18)53965-x;
RA Sippel C.J., Suchy F.J., Ananthanarayanan M., Perlmutter D.H.;
RT "The rat liver ecto-ATPase is also a canalicular bile acid transport
RT protein.";
RL J. Biol. Chem. 268:2083-2091(1993).
RN [12]
RP HOMODIMERIZATION, AND FUNCTION.
RX PubMed=2373740; DOI=10.1242/jcs.96.1.17;
RA Tingstroem A., Blikstad I., Aurivillius M., Obrink B.;
RT "C-CAM (cell-CAM 105) is an adhesive cell surface glycoprotein with
RT homophilic binding properties.";
RL J. Cell Sci. 96:17-25(1990).
RN [13]
RP CHARACTERIZATION.
RX PubMed=1831973; DOI=10.1042/bj2780155;
RA Lin S.-H., Culic O., Flanagan D., Hixson D.C.;
RT "Immunochemical characterization of two isoforms of rat liver ecto-ATPase
RT that show an immunological and structural identity with a glycoprotein
RT cell-adhesion molecule with Mr 105,000.";
RL Biochem. J. 278:155-161(1991).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8454589; DOI=10.1016/s0021-9258(18)53230-0;
RA Cheung P.H., Thompson N.L., Earley K., Culic O., Hixson D., Lin S.H.;
RT "Cell-CAM105 isoforms with different adhesion functions are coexpressed in
RT adult rat tissues and during liver development.";
RL J. Biol. Chem. 268:6139-6146(1993).
RN [15]
RP ALTERNATIVE SPLICING.
RX PubMed=8380406; DOI=10.1016/s0021-9258(18)54060-6;
RA Najjae S.M., Accili D., Philippe N., Jernberg J., Margolis R., Taylor S.I.;
RT "pp120/ecto-ATPase, an endogenous substrate of the insulin receptor
RT tyrosine kinase, is expressed as two variably spliced isoforms.";
RL J. Biol. Chem. 268:1201-1206(1993).
RN [16]
RP FUNCTION, PHOSPHORYLATION AT TYR-488 AND SER-503, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF TYR-488 AND 502-THR-SER-503.
RX PubMed=7518458; DOI=10.1016/s0021-9258(17)32202-0;
RA Sippel C.J., Fallon R.J., Perlmutter D.H.;
RT "Bile acid efflux mediated by the rat liver canalicular bile acid
RT transport/ecto-ATPase protein requires serine 503 phosphorylation and is
RT regulated by tyrosine 488 phosphorylation.";
RL J. Biol. Chem. 269:19539-19545(1994).
RN [17]
RP PHOSPHORYLATION AT TYR-488 BY INSR, AND MUTAGENESIS OF TYR-488 AND SER-503.
RX PubMed=7626603; DOI=10.1021/bi00029a009;
RA Najjar S.M., Philippe N., Suzuki Y., Ignacio G.A., Formisano P., Accili D.,
RA Taylor S.I.;
RT "Insulin-stimulated phosphorylation of recombinant pp120/HA4, an endogenous
RT substrate of the insulin receptor tyrosine kinase.";
RL Biochemistry 34:9341-9349(1995).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF TYR-488; SER-503 AND TYR-513.
RX PubMed=7592607; DOI=10.1074/jbc.270.41.24073;
RA Formisano P., Najjar S.M., Gross C.N., Philippe N., Oriente F.,
RA Kern-Buell C.L., Accili D., Gorden P.;
RT "Receptor-mediated internalization of insulin. Potential role of pp120/HA4,
RT a substrate of the insulin receptor kinase.";
RL J. Biol. Chem. 270:24073-24077(1995).
RN [19]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=7774714; DOI=10.1016/0014-5793(95)00436-d;
RA Olsson H., Wikstroem K., Kjellstroem G., Obrink B.;
RT "Cell adhesion activity of the short cytoplasmic domain isoform of C-CAM
RT (C-CAM2) in CHO cells.";
RL FEBS Lett. 365:51-56(1995).
RN [20]
RP SUBCELLULAR LOCATION, AND HOMODIMERIZATION.
RX PubMed=9003371; DOI=10.1042/bj3200847;
RA Hunter I., Sawa H., Edlund M., Obrink B.;
RT "Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM)
RT in epithelial cells.";
RL Biochem. J. 320:847-853(1996).
RN [21]
RP DOMAIN, AND HOMODIMERIZATION.
RX PubMed=8831574; DOI=10.1006/excr.1996.0285;
RA Wikstroem K., Kjellstroem G., Obrink B.;
RT "Homophilic intercellular adhesion mediated by C-CAM is due to a domain 1-
RT domain 1 reciprocal binding.";
RL Exp. Cell Res. 227:360-366(1996).
RN [22]
RP INTERACTION WITH CALMODULIN, AND REGION.
RX PubMed=8576129; DOI=10.1074/jbc.271.3.1393;
RA Edlund M., Blikstad I., Obrink B.;
RT "Calmodulin binds to specific sequences in the cytoplasmic domain of C-CAM
RT and down-regulates C-CAM self-association.";
RL J. Biol. Chem. 271:1393-1399(1996).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-488; SER-503 AND
RP TYR-513, AND PHOSPHORYLATION AT TYR-488 BY INSR.
RX PubMed=9712832; DOI=10.1074/jbc.273.35.22194;
RA Choice C.V., Howard M.J., Poy M.N., Hankin M.H., Najjar S.M.;
RT "Insulin stimulates pp120 endocytosis in cells co-expressing insulin
RT receptors.";
RL J. Biol. Chem. 273:22194-22200(1998).
RN [24]
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 [25]
RP INTERACTION WITH SHC1, FUNCTION, AND MUTAGENESIS OF TYR-488 AND SER-503.
RX PubMed=11694516; DOI=10.1074/jbc.m108415200;
RA Poy M.N., Ruch R.J., Fernstrom M.A., Okabayashi Y., Najjar S.M.;
RT "Shc and CEACAM1 interact to regulate the mitogenic action of insulin.";
RL J. Biol. Chem. 277:1076-1084(2002).
RN [26]
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 [27]
RP MUTAGENESIS OF SER-503, AND FUNCTION.
RX PubMed=11850617; DOI=10.1038/ng840;
RA Poy M.N., Yang Y., Rezaei K., Fernstroem M.A., Lee A.D., Kido Y.,
RA Erickson S.K., Najjar S.M.;
RT "CEACAM1 regulates insulin clearance in liver.";
RL Nat. Genet. 30:270-276(2002).
RN [28]
RP PHOSPHORYLATION AT TYR-488 BY EGFR, FUNCTION, MUTAGENESIS OF TYR-488 AND
RP SER-503, AND INTERACTION WITH EGFR.
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 [29]
RP INTERACTION WITH FASN, MUTAGENESIS OF TYR-488; SER-503 AND TYR-513,
RP SUBCELLULAR LOCATION, FUNCTION, AND PHOSPHORYLATION AT TYR-488 AND TYR-513
RP BY INSR.
RX PubMed=16054098; DOI=10.1016/j.cmet.2005.06.001;
RA Najjar S.M., Yang Y., Fernstroem M.A., Lee S.J., Deangelis A.M.,
RA Rjaily G.A., Al-Share Q.Y., Dai T., Miller T.A., Ratnam S., Ruch R.J.,
RA Smith S., Lin S.H., Beauchemin N., Oyarce A.M.;
RT "Insulin acutely decreases hepatic fatty acid synthase activity.";
RL Cell Metab. 2:43-53(2005).
RN [30]
RP INTERACTION WITH FLNA, AND REGION.
RX PubMed=16291724; DOI=10.1242/jcs.02660;
RA Klaile E., Mueller M.M., Kannicht C., Singer B.B., Lucka L.;
RT "CEACAM1 functionally interacts with filamin A and exerts a dual role in
RT the regulation of cell migration.";
RL J. Cell Sci. 118:5513-5524(2005).
RN [31]
RP SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH PTPN11; PTPN6 AND SRC, AND
RP SUBUNIT.
RX PubMed=19948503; DOI=10.1083/jcb.200904150;
RA Mueller M.M., Klaile E., Vorontsova O., Singer B.B., Obrink B.;
RT "Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and
RT recruitment of SHP-2 and c-Src.";
RL J. Cell Biol. 187:569-581(2009).
CC -!- FUNCTION: [Isoform 1]: Cell adhesion protein that mediates homophilic
CC cell adhesion in a calcium-independent manner (PubMed:8454589,
CC PubMed:2373740). Plays a role as coinhibitory receptor in immune
CC response, insulin action and functions also as an activator during
CC angiogenesis (PubMed:11850617). Its coinhibitory receptor function is
CC phosphorylation- and PTPN6 -dependent, which in turn, suppress signal
CC transduction of associated receptors by dephosphorylation of their
CC downstream effectors (By similarity). Plays a role in immune response,
CC of T-cells, natural killer (NK) and neutrophils (By similarity). Upon
CC TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by
CC blocking granule exocytosis by mediating homophilic binding to adjacent
CC cells, allowing interaction with and phosphorylation by LCK and
CC interaction with the TCR/CD3 complex which recruits PTPN6 resulting in
CC dephosphorylation of CD247 and ZAP70 (By similarity). Also inhibits T-
CC 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 (By similarity). 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 (By similarity). 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 (By
CC similarity). 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 (By
CC similarity). Also regulates insulin action by promoting INS clearance
CC and regulating lipogenesis in liver through regulating insulin
CC signaling (PubMed:11850617). Upon INS stimulation, undergoes
CC phosphorylation by INSR leading to INS clearance by increasing
CC receptor-mediated insulin endocytosis (PubMed:7592607, PubMed:9712832).
CC This inernalization promotes interaction with FASN leading to receptor-
CC mediated insulin degradation and to reduction of FASN activity leading
CC to negative regulation of fatty acid synthesis (PubMed:7592607,
CC PubMed:16054098). INSR-mediated phosphorylation also provokes a down-
CC regulation of cell proliferation through SHC1 interaction resulting in
CC decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and
CC phosphatidylinositol 3-kinase pathways (PubMed:11694516). 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 (By similarity). Also regulates vascular
CC permeability through the VEGFR2 signaling pathway resulting in control
CC of nitric oxide production (By similarity). Down-regulates cell growth
CC in response to EGF through its interaction with SHC1 that mediates
CC interaction with EGFR resulting in decrease coupling of SHC1 to the
CC MAPK3/ERK1-MAPK1/ERK2 pathway (PubMed:15467833). Negatively regulates
CC platelet aggregation by decreasing platelet adhesion on type I collagen
CC through the GPVI-FcRgamma complex (By similarity). Inhibits cell
CC migration and cell scattering through interaction with FLNA; interfers
CC with the interaction of FLNA with RALA (By similarity). Mediates bile
CC acid transport activity in a phosphorylation dependent manner
CC (PubMed:7518458). Negatively regulates osteoclastogenesis (By
CC similarity). {ECO:0000250|UniProtKB:P13688,
CC ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:11694516,
CC ECO:0000269|PubMed:11850617, ECO:0000269|PubMed:15467833,
CC ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:2373740,
CC ECO:0000269|PubMed:7518458, ECO:0000269|PubMed:7592607,
CC ECO:0000269|PubMed:8454589, ECO:0000269|PubMed:9712832}.
CC -!- FUNCTION: [Isoform 2]: Cell adhesion proteins that mediates homophilic
CC cell adhesion in a calcium-independent manner (PubMed:8536699,
CC PubMed:7774714). Promotes populations of T-cells regulating IgA
CC production and secretion associated with control of the commensal
CC microbiota and resistance to enteropathogens (By similarity).
CC {ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:7774714,
CC ECO:0000269|PubMed:8536699}.
CC -!- SUBUNIT: Monomer (PubMed:9003371, PubMed:19948503). Oligomer.
CC Heterodimer. Homodimer (PubMed:19948503). Cis-dimer/oligomer (via Ig-
CC like C2-type and/or via cytoplasmic domains); induced by trans-
CC homophilic cell adhesion through an allosteric mechanism transmitted by
CC the Ig-like V-type domain, and is regulated by intracellular calcium
CC and calmodulin (PubMed:19948503, PubMed:2373740, PubMed:8831574,
CC PubMed:9003371). Interacts (via cytoplasmic domain) with calmodulin in
CC a calcium dependent manner; reduces homophilic cell adhesion through
CC dissociation of dimer (PubMed:8576129). Isoform 1 interacts (via
CC cytoplasmic domain) with PTPN11 (preferentially) and PTPN6; cis-
CC homodimer form is preferred; this interaction is decreased by formation
CC of isoform 1 / isoform 2 cis-heterodimers and is dependent on the
CC monomer/dimer equilibrium; this interaction is phosphorylation-
CC dependent (PubMed:19948503). Isoform 1 interacts with LYN (By
CC similarity). Isoform 1 interacts (via cytoplasmic domain) with SRC (via
CC SH2 domain); this interaction is regulated by trans-homophilic cell
CC adhesion (PubMed:19948503). Isoform 1 interacts (via cytoplasmic
CC domain) with LCK; mediates phosphorylation at Tyr-488 and Tyr-513
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:11694516). Isoform 1 interacts with EGFR; the
CC interaction is indirect (PubMed:15467833). Isoform 1 interacts with
CC CSF3R; down-regulates the CSF3R-STAT3 pathway through recruitment of
CC PTPN6 that dephosphorylates CSF3R. Isoform 1 (phosphorylated form)
CC interacts with TLR4 and SYK; recruits PTPN6 that dephosphorylates SYK,
CC reducing the production of reactive oxygen species (ROS) and lysosome
CC disruption, leading to a reduction of the inflammasome activity (By
CC similarity). Isoform 1 interacts with FLNA; inhibits cell migration and
CC cell scattering by interfering with the interaction of FLNA with RALA
CC (PubMed:16291724). Isoform 1 interacts (via cytoplasmic domain) with
CC PXN; the interaction is phosphotyrosyl-dependent. Isoform 1 interacts
CC with KLRK1; recruits PTPN6 that dephosphorylates VAV1. Isoform 1
CC interacts with CEACAM8 (By similarity). Isoform 1 interacts with FASN;
CC this interaction is insulin and phosphorylation-dependent; reduces
CC fatty-acid synthase activity (PubMed:16054098). Interacts (via Ig-like
CC V-type) with HAVCR2 (via Ig-like V-type); facilitates the maturation
CC and cell surface expression of HAVCR2 thereby regulating T-cell
CC tolerance induction. Isoform 2 interacts (via the cytoplasmic domain)
CC with ANXA2; this interaction is regulated by phosphorylation and
CC appears in the AIIt complex. Interacts (via Lewis X moieties) with
CC CD209 (via C-type lectin domain); this interaction is regulated by the
CC glycosylation pattern of CEACAM1 on cell types and regulates contact
CC between dendritic cells and neutrophils (By similarity).
CC {ECO:0000250|UniProtKB:P13688, ECO:0000250|UniProtKB:P31809,
CC ECO:0000269|PubMed:11694516, ECO:0000269|PubMed:15467833,
CC ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:16291724,
CC ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:2373740,
CC ECO:0000269|PubMed:8576129, ECO:0000269|PubMed:8831574,
CC ECO:0000269|PubMed:9003371}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:7518458,
CC ECO:0000269|PubMed:7774714, ECO:0000269|PubMed:8536699,
CC ECO:0000269|PubMed:9003371, ECO:0000269|PubMed:9712832}; Single-pass
CC type I membrane protein. Lateral cell membrane
CC {ECO:0000269|PubMed:7774714}. Apical cell membrane
CC {ECO:0000269|PubMed:7774714}. Basal cell membrane
CC {ECO:0000269|PubMed:7774714}. Cell junction
CC {ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:9003371}. Cell
CC junction, adherens junction {ECO:0000269|PubMed:19948503}.
CC Note=Canalicular domain of hepatocyte plasma membranes
CC (PubMed:8513803). 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 (PubMed:19948503). Found as
CC dimer in the solution (PubMed:9003371). Predominantly localized to the
CC lateral cell membranes (PubMed:7774714). {ECO:0000269|PubMed:19948503,
CC ECO:0000269|PubMed:7774714, ECO:0000269|PubMed:8513803,
CC ECO:0000269|PubMed:9003371}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:7774714, ECO:0000269|PubMed:9003371}; Single-pass
CC type I membrane protein. Lateral cell membrane
CC {ECO:0000269|PubMed:7774714}. Apical cell membrane
CC {ECO:0000269|PubMed:7774714}. Basal cell membrane
CC {ECO:0000269|PubMed:7774714}. Cell junction
CC {ECO:0000269|PubMed:19948503}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:19948503}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:P13688}. Note=Predominantly localized to the
CC lateral cell membranes (PubMed:7774714). Found as a mixture of monomer,
CC dimer and oligomer in the plasma membrane. Occurs predominantly as cis-
CC dimers and/or small cis-oligomers in the cell junction regions
CC (PubMed:19948503). Co-localizes with ANXA2 in secretory vesicles and
CC with S100A10/p11 at the plasma membrane (By similarity).
CC {ECO:0000250|UniProtKB:P13688, ECO:0000269|PubMed:19948503,
CC ECO:0000269|PubMed:7774714}.
CC -!- SUBCELLULAR LOCATION: Cell projection, microvillus membrane
CC {ECO:0000250|UniProtKB:P31809}; Single-pass type I membrane protein
CC {ECO:0000305}. Apical cell membrane {ECO:0000250|UniProtKB:P31809};
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 (By
CC similarity). {ECO:0000250|UniProtKB:P13688,
CC ECO:0000250|UniProtKB:P31809}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=For each isoform it exists 2 allelic variants, named a and b.
CC The allelic variants differ in 16 amino acids in the Ig-like V-type
CC domain. {ECO:0000305|PubMed:8504806};
CC Name=1; Synonyms=CEACAM1-4L {ECO:0000303|PubMed:11501563}, C-CAM1,
CC L-form Cell-CAM105;
CC IsoId=P16573-1; Sequence=Displayed;
CC Name=2; Synonyms=CEACAM1-4S {ECO:0000303|PubMed:11501563}, C-CAM2,
CC S-form Cell-CAM105;
CC IsoId=P16573-2; Sequence=VSP_002504, VSP_002505;
CC -!- TISSUE SPECIFICITY: Expressed in epithelia, vessel endothelia,
CC leukocytes and platelets. Isoform 1 and isoform 2 are highly expressed
CC in liver and intestine, moderately in lung, and weakly in muscle,
CC kidney, and spleen (PubMed:8454589). Expressed in granulocytes,
CC lymphocytes, granulocytes, B cells, and T-cells (PubMed:11994468).
CC {ECO:0000269|PubMed:11994468, ECO:0000269|PubMed:8454589}.
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:0000269|PubMed:19948503,
CC ECO:0000269|PubMed:8831574}.
CC -!- PTM: [Isoform 1]: Phosphorylated on serine and tyrosine
CC (PubMed:8420979). 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:15467833, PubMed:7626603, PubMed:9712832,
CC PubMed:16054098). Phosphorylated at Ser-503; mediates activity.
CC Phosphorylated at Tyr-488; regulates activity (PubMed:7518458).
CC Phosphorylated at Tyr-488 by EGFR and INSR upon stimulation; this
CC phosphorylation is Ser-503-phosphorylation-dependent; mediates cellular
CC internalization; increases interaction with FASN (PubMed:16054098,
CC PubMed:15467833, PubMed:7626603, PubMed:9712832). Phosphorylated at
CC Tyr-488 and Tyr-513 by LCK; mediates PTPN6 association and is regulated
CC by homophilic ligation of CEACAM1 in the absence of T-cell activation
CC (By similarity). Phosphorylated at Tyr-513; mediates interaction with
CC PTPN11 (By similarity). {ECO:0000250|UniProtKB:P13688,
CC ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:15467833,
CC ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:7518458,
CC ECO:0000269|PubMed:7626603, ECO:0000269|PubMed:8420979,
CC ECO:0000269|PubMed:9712832}.
CC -!- PTM: [Isoform 2]: Phosphorylated on serine and threonine.
CC {ECO:0000269|PubMed:8420979}.
CC -!- POLYMORPHISM: There are two different allelic variants of CEACAM1,
CC named a and b. The allelic variants differ in 16 amino acids in the Ig-
CC like V-type domain. The sequence shown here, corresponds to allele A.
CC {ECO:0000269|PubMed:8504806}.
CC -!- MISCELLANEOUS: [Isoform 1]: Allele a.
CC -!- MISCELLANEOUS: [Isoform 2]: Allele a. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA16783.1; Type=Miscellaneous discrepancy; Note=Dubious isoform. Probable cloning artifact lacking polyadenylation evidence.; Evidence={ECO:0000305};
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DR EMBL; J04963; AAA41104.1; -; mRNA.
DR EMBL; Z12019; CAA78054.1; -; mRNA.
DR EMBL; M92848; AAA16783.1; ALT_SEQ; mRNA.
DR EMBL; X71122; CAA50435.1; -; mRNA.
DR EMBL; X91137; CAA62577.1; -; mRNA.
DR EMBL; AC134759; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473979; EDM08020.1; -; Genomic_DNA.
DR EMBL; BC061740; AAH61740.1; -; mRNA.
DR PIR; A44783; A44783.
DR PIR; S23969; S23969.
DR PIR; S68177; S68177.
DR RefSeq; NP_001029032.1; NM_001033860.1. [P16573-1]
DR RefSeq; NP_001029033.1; NM_001033861.1.
DR RefSeq; NP_001029034.1; NM_001033862.1. [P16573-2]
DR RefSeq; NP_113943.1; NM_031755.2.
DR AlphaFoldDB; P16573; -.
DR SMR; P16573; -.
DR MINT; P16573; -.
DR STRING; 10116.ENSRNOP00000046654; -.
DR TCDB; 8.A.23.1.4; the basigin (basigin) family.
DR GlyGen; P16573; 15 sites.
DR iPTMnet; P16573; -.
DR PhosphoSitePlus; P16573; -.
DR PaxDb; P16573; -.
DR PRIDE; P16573; -.
DR Ensembl; ENSRNOT00000051892; ENSRNOP00000046654; ENSRNOG00000020578. [P16573-1]
DR Ensembl; ENSRNOT00000090629; ENSRNOP00000074820; ENSRNOG00000020578. [P16573-2]
DR GeneID; 81613; -.
DR KEGG; rno:81613; -.
DR UCSC; RGD:67396; rat. [P16573-1]
DR CTD; 634; -.
DR RGD; 67396; Ceacam1.
DR eggNOG; ENOG502RXPD; Eukaryota.
DR GeneTree; ENSGT00960000186634; -.
DR InParanoid; P16573; -.
DR OMA; NTSYLWS; -.
DR TreeFam; TF336859; -.
DR Reactome; R-RNO-1566977; Fibronectin matrix formation.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P16573; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000020578; Expressed in jejunum and 18 other tissues.
DR ExpressionAtlas; P16573; baseline and differential.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:RGD.
DR GO; GO:0060170; C:ciliary membrane; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:RGD.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; ISO:RGD.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0031005; F:filamin binding; ISO:RGD.
DR GO; GO:0005130; F:granulocyte colony-stimulating factor receptor binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IMP:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:RGD.
DR GO; GO:0046790; F:virion binding; ISO:RGD.
DR GO; GO:0015721; P:bile acid and bile salt transport; IDA:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IDA:UniProtKB.
DR GO; GO:0045216; P:cell-cell junction organization; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISS:UniProtKB.
DR GO; GO:0038158; P:granulocyte colony-stimulating factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IDA:UniProtKB.
DR GO; GO:1901143; P:insulin catabolic process; IMP:UniProtKB.
DR GO; GO:0038016; P:insulin receptor internalization; IDA:UniProtKB.
DR GO; GO:0045779; P:negative regulation of bone resorption; ISO:RGD.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:RGD.
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; IMP:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IMP:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; ISS:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:0051055; P:negative regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0002859; P:negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISS:UniProtKB.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISO:RGD.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS: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; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:1903387; P:positive regulation of homophilic cell adhesion; IDA:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:MGI.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0060312; P:regulation of blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0045601; P:regulation of endothelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS: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; IDA:UniProtKB.
DR GO; GO:1903385; P:regulation of homophilic cell adhesion; IDA: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; IDA:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IDA:RGD.
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 InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell adhesion; Cell junction; Cell membrane;
KW Cell projection; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Pyrrolidone carboxylic acid; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..519
FT /note="Carcinoembryonic antigen-related cell adhesion
FT molecule 1"
FT /id="PRO_0000014564"
FT TOPO_DOM 35..425
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..519
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 42..140
FT /note="Ig-like V-type"
FT /evidence="ECO:0000250|UniProtKB:P31997"
FT DOMAIN 147..232
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 237..317
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 325..403
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:0000269|PubMed:8831574"
FT REGION 445..457
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000269|PubMed:8576129"
FT REGION 447..519
FT /note="Interaction with FLNA"
FT /evidence="ECO:0000269|PubMed:16291724"
FT REGION 455..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..519
FT /note="Required for interaction with PTPN11 and PTPN6 and
FT for control of phosphorylation level"
FT /evidence="ECO:0000250|UniProtKB:P31809"
FT REGION 513..516
FT /note="Essential for interaction with PTPN11 and PTPN6"
FT /evidence="ECO:0000250|UniProtKB:P31809"
FT COMPBIAS 467..513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 35
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P13688"
FT MOD_RES 488
FT /note="Phosphotyrosine; by SRC, LCK, INSR and EGFR"
FT /evidence="ECO:0000269|PubMed:15467833,
FT ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:7518458,
FT ECO:0000269|PubMed:7626603, ECO:0000269|PubMed:9712832"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16054098,
FT ECO:0000269|PubMed:7518458"
FT MOD_RES 513
FT /note="Phosphotyrosine; by INSR, SRC and LCK"
FT /evidence="ECO:0000269|PubMed:16054098"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
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:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine; atypical"
FT /evidence="ECO:0000250|UniProtKB:P31809,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 167..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 259..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 344..392
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 455..458
FT /note="GSDH -> SGSF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1637321,
FT ECO:0000303|PubMed:8504806, ECO:0000303|PubMed:8536699"
FT /id="VSP_002504"
FT VAR_SEQ 459..519
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1637321,
FT ECO:0000303|PubMed:8504806, ECO:0000303|PubMed:8536699"
FT /id="VSP_002505"
FT VARIANT 49
FT /note="K -> S (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 55
FT /note="A -> T (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 70
FT /note="G -> V (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 73
FT /note="L -> T (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 74
FT /note="N -> G (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 75
FT /note="P -> L (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 76
FT /note="D -> N (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 86
FT /note="D -> S (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 88
FT /note="M -> T (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 90
FT /note="K -> Q (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 92
FT /note="G -> E (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 99
FT /note="E -> V (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 118
FT /note="R -> G (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 119
FT /note="A -> P (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 125
FT /note="F -> I (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT VARIANT 127
FT /note="Q -> K (in allele b)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1637321, ECO:0000269|PubMed:8504806"
FT MUTAGEN 488
FT /note="Y->F: Phosphorylated on serine. Decreases bile acid
FT transport Doesn't phosphorylated by EGFR. Doesn't increase
FT interaction with SHC1. Completely inhibits insulin-
FT stimulated phosphorylation. No effect on INSR
FT internalization and INS degradation. Prevents CEACAM1
FT phosphorylation and the increase in its binding to FASN in
FT the presence of INSR. No effect on cell-surface expression
FT in response to INS. Abolishes phosphorylation by INSR.
FT Abolishes indirect interaction with INSR."
FT /evidence="ECO:0000269|PubMed:15467833,
FT ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:7518458,
FT ECO:0000269|PubMed:7592607, ECO:0000269|PubMed:7626603,
FT ECO:0000269|PubMed:9712832"
FT MUTAGEN 502..503
FT /note="TS->AA: Phosphorylated on tyrosine. Impairs bile
FT acid transport."
FT /evidence="ECO:0000269|PubMed:7518458"
FT MUTAGEN 503
FT /note="S->A: Abolishes phosphorylation by EGFR. Reduces
FT interaction with SHC1. Completely inhibits insulin-
FT stimulated phosphorylation. No effect on INSR
FT internalization and INS degradation. In L-SACC1; completely
FT inhibits insulin-stimulated phosphorylation; develops
FT hyperinsulinemia resulting from impaired insulin clearance;
FT the hyperinsulinemia causes secondary insulin resistance
FT with impaired glucose tolerance and random, but not
FT fasting, hyperglycemia; insulin doesn't significantly
FT decrease FASN activity in liver. Prevents CEACAM1
FT phosphorylation and the increase in its binding to FASN in
FT the presence of INSR. No effect on cell-surface expression
FT in response to INS."
FT /evidence="ECO:0000269|PubMed:11694516,
FT ECO:0000269|PubMed:11850617, ECO:0000269|PubMed:15467833,
FT ECO:0000269|PubMed:16054098, ECO:0000269|PubMed:7592607,
FT ECO:0000269|PubMed:7626603, ECO:0000269|PubMed:9712832"
FT MUTAGEN 503
FT /note="S->D: Preserves the ability of INSR to induce
FT CEACAM1 phosphorylation."
FT /evidence="ECO:0000269|PubMed:16054098"
FT MUTAGEN 513
FT /note="Y->F: Increases INSR internalization and INS
FT degradation. Phosphorylated by INSR. Prevents the increase
FT in CEACAM1 binding to FASN by INSR. Decreases cell-surface
FT expression in response to INS. Doesn't affect
FT phosphorylation by INSR."
FT /evidence="ECO:0000269|PubMed:16054098,
FT ECO:0000269|PubMed:7592607, ECO:0000269|PubMed:9712832"
SQ SEQUENCE 519 AA; 57410 MW; 9EFE74FD565E7C29 CRC64;
MELASARLLR GQIPWRGLLL TASLLTYWSP LTTAQVTVDA VPPNVVEEKS VLLLAHNLPQ
EFQVFYWYKG TTLNPDSEIA RYIRSDNMSK TGPAYSGRET IYSNGSLFFQ NVNKTDERAY
TLSVFDQQFN PIQTSVQFRV YPALQKPNVT GNNSNPMEGE PFVSLMCEPY TNNTSYLWSR
NGESLSEGDR VTFSEGNRTL TLLNVRRTDK GYYECEARNP ATFNRSDPFN LDVIYGPDAP
VISPPDIYLH QGSNLNLSCH ADSNPPAQYF WLINEKLQTS SQELFISNIT TNNSGTYACF
VNNTVTGLSR TTVKNITVFE PVTQPSIQIT NTTVKELGSV TLTCFSKDTG VSVRWLFNSQ
SLQLTDRMTL SQDNSTLRID PIKREDAGDY QCEISNPVSF RISHPIKLDV IPDPTQGNSG
LSEGAIAGIV IGSVAGVALI AALAYFLYSR KTGGGSDHRD LTEHKPSTSS HNLGPSDDSP
NKVDDVSYSV LNFNAQQSKR PTSASSSPTE TVYSVVKKK
