CEAM3_HUMAN
ID CEAM3_HUMAN Reviewed; 252 AA.
AC P40198; G5E978; Q3KPH9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 3;
DE AltName: Full=Carcinoembryonic antigen CGM1;
DE AltName: CD_antigen=CD66d;
DE Flags: Precursor;
GN Name=CEACAM3; Synonyms=CD66D, CGM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT PRO-7.
RC TISSUE=Leukocyte;
RX PubMed=2050678; DOI=10.1016/s0021-9258(18)99029-0;
RA Kuroki M., Arakawa F., Matsuo Y., Oikawa S., Misumi Y., Nakazato H.,
RA Matsuoka Y.;
RT "Molecular cloning of nonspecific cross-reacting antigens in human
RT granulocytes.";
RL J. Biol. Chem. 266:11810-11817(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RX PubMed=8508798; DOI=10.1111/j.1432-1033.1993.tb17892.x;
RA Nagel G., Grunert F., Kuijpers T.W., Watt S.M., Thompson J.,
RA Zimmermann W.A.;
RT "Genomic organization, splice variants and expression of CGM1, a CD66-
RT related member of the carcinoembryonic antigen gene family.";
RL Eur. J. Biochem. 214:27-35(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-141.
RX PubMed=1427854; DOI=10.1016/s0888-7543(05)80230-7;
RA Khan W.N., Fraengsmyr L., Teglund S., Israelsson A., Bremer K.,
RA Hammarstroem S.;
RT "Identification of three new genes and estimation of the size of the
RT carcinoembryonic antigen family.";
RL Genomics 14:384-390(1992).
RN [7]
RP INTERACTION WITH S100A9, AND TISSUE SPECIFICITY.
RX PubMed=11708798; DOI=10.1006/bbrc.2001.5955;
RA Streichert T., Ebrahimnejad A., Ganzer S., Flayeh R., Wagener C.,
RA Bruemmer J.;
RT "The microbial receptor CEACAM3 is linked to the calprotectin complex in
RT granulocytes.";
RL Biochem. Biophys. Res. Commun. 289:191-197(2001).
RN [8]
RP FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF TYR-230 AND TYR-241.
RX PubMed=12864848; DOI=10.1046/j.1365-2958.2003.03591.x;
RA McCaw S.E., Schneider J., Liao E.H., Zimmermann W., Gray-Owen S.D.;
RT "Immunoreceptor tyrosine-based activation motif phosphorylation during
RT engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3
RT (CD66d) receptor.";
RL Mol. Microbiol. 49:623-637(2003).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF TYR-230 AND TYR-241.
RX PubMed=14707113; DOI=10.1084/jem.20030204;
RA Schmitter T., Agerer F., Peterson L., Muenzner P., Hauck C.R.;
RT "Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system
RT that mediates recognition and elimination of human-specific pathogens.";
RL J. Exp. Med. 199:35-46(2004).
CC -!- FUNCTION: Major granulocyte receptor mediating recognition and
CC efficient opsonin-independent phagocytosis of CEACAM-binding
CC microorganisms, including Neissiria, Moxarella and Haemophilus species,
CC thus playing an important role in the clearance of pathogens by the
CC innate immune system. Responsible for RAC1 stimulation in the course of
CC pathogen phagocytosis. {ECO:0000269|PubMed:12864848,
CC ECO:0000269|PubMed:14707113}.
CC -!- SUBUNIT: Interacts with S100A9/calprotectin. This interaction is
CC calcium-dependent, but independent of CEACAM3 phosphorylation.
CC {ECO:0000269|PubMed:11708798}.
CC -!- INTERACTION:
CC P40198; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-12851752, EBI-12208021;
CC P40198; Q92982: NINJ1; NbExp=3; IntAct=EBI-12851752, EBI-2802124;
CC P40198; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-12851752, EBI-10317425;
CC P40198; Q01453: PMP22; NbExp=3; IntAct=EBI-12851752, EBI-2845982;
CC P40198; Q04883: opaD; Xeno; NbExp=2; IntAct=EBI-12851752, EBI-26495131;
CC P40198; Q04884: opaH; Xeno; NbExp=3; IntAct=EBI-12851752, EBI-26495102;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CGM1A;
CC IsoId=P40198-1; Sequence=Displayed;
CC Name=2; Synonyms=CGM1B;
CC IsoId=P40198-2; Sequence=VSP_002486;
CC Name=3; Synonyms=CGM1C;
CC IsoId=P40198-3; Sequence=VSP_002487;
CC -!- TISSUE SPECIFICITY: CGM1a, the predominant CGM1 transcript, is
CC granulocyte-specific. Not detected out of the granulocytic lineage,
CC such as monocytes, lymphocytes, spleen, testis, colon, brain, liver,
CC pancreas, thymus, ovary, placenta, skeletal muscle, prostate, small
CC intestine, heart, lung and kidney. {ECO:0000269|PubMed:11708798}.
CC -!- DOMAIN: The cytosolic domain is involved in S100A9 interaction.
CC -!- PTM: Tyrosine-phosphorylated in response to microbial binding. Tyr-230
CC and Tyr-241 are both required for phosphorylation to be detected.
CC {ECO:0000269|PubMed:12864848}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.
CC {ECO:0000305}.
CC -!- CAUTION: This is not the ortholog of rat CEACAM3. {ECO:0000305}.
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DR EMBL; D90277; BAA14321.1; -; mRNA.
DR EMBL; D90278; BAA14322.1; -; mRNA.
DR EMBL; L00692; AAA51969.1; -; mRNA.
DR EMBL; L00693; AAA51970.1; -; mRNA.
DR EMBL; AC022516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471126; EAW57062.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57063.1; -; Genomic_DNA.
DR EMBL; BC106728; AAI06729.1; -; mRNA.
DR CCDS; CCDS12586.2; -. [P40198-1]
DR CCDS; CCDS62685.1; -. [P40198-3]
DR PIR; C40428; C40428.
DR PIR; S33323; S33323.
DR PIR; S33324; S33324.
DR RefSeq; NP_001264092.1; NM_001277163.2. [P40198-3]
DR RefSeq; NP_001806.2; NM_001815.4. [P40198-1]
DR PDB; 6AVZ; X-ray; 2.05 A; A=34-141.
DR PDB; 6AW0; X-ray; 2.43 A; A/B=34-141.
DR PDB; 6AW1; X-ray; 2.10 A; A/B=34-141.
DR PDB; 6AW3; X-ray; 2.66 A; A=34-141.
DR PDBsum; 6AVZ; -.
DR PDBsum; 6AW0; -.
DR PDBsum; 6AW1; -.
DR PDBsum; 6AW3; -.
DR AlphaFoldDB; P40198; -.
DR SMR; P40198; -.
DR BioGRID; 107510; 4.
DR IntAct; P40198; 6.
DR MINT; P40198; -.
DR STRING; 9606.ENSP00000349971; -.
DR GlyGen; P40198; 2 sites.
DR iPTMnet; P40198; -.
DR PhosphoSitePlus; P40198; -.
DR BioMuta; CEACAM3; -.
DR DMDM; 218511974; -.
DR MassIVE; P40198; -.
DR MaxQB; P40198; -.
DR PaxDb; P40198; -.
DR PeptideAtlas; P40198; -.
DR PRIDE; P40198; -.
DR ProteomicsDB; 33858; -.
DR ProteomicsDB; 55342; -. [P40198-1]
DR ProteomicsDB; 55343; -. [P40198-2]
DR ProteomicsDB; 55344; -. [P40198-3]
DR Antibodypedia; 30816; 334 antibodies from 29 providers.
DR DNASU; 1084; -.
DR Ensembl; ENST00000344550.4; ENSP00000341725.4; ENSG00000170956.17. [P40198-3]
DR Ensembl; ENST00000357396.8; ENSP00000349971.3; ENSG00000170956.17. [P40198-1]
DR Ensembl; ENST00000415495.5; ENSP00000411641.1; ENSG00000170956.17. [P40198-2]
DR Ensembl; ENST00000630848.2; ENSP00000485920.1; ENSG00000170956.17. [P40198-3]
DR GeneID; 1084; -.
DR KEGG; hsa:1084; -.
DR MANE-Select; ENST00000357396.8; ENSP00000349971.3; NM_001815.5; NP_001806.2.
DR UCSC; uc032hyd.2; human. [P40198-1]
DR CTD; 1084; -.
DR DisGeNET; 1084; -.
DR GeneCards; CEACAM3; -.
DR HGNC; HGNC:1815; CEACAM3.
DR HPA; ENSG00000170956; Tissue enriched (bone).
DR MIM; 609142; gene.
DR neXtProt; NX_P40198; -.
DR OpenTargets; ENSG00000170956; -.
DR Orphanet; 586; Cystic fibrosis.
DR PharmGKB; PA26359; -.
DR VEuPathDB; HostDB:ENSG00000170956; -.
DR eggNOG; ENOG502S42Z; Eukaryota.
DR GeneTree; ENSGT00960000186634; -.
DR HOGENOM; CLU_024555_4_2_1; -.
DR InParanoid; P40198; -.
DR OMA; NIYCRMD; -.
DR OrthoDB; 998214at2759; -.
DR PhylomeDB; P40198; -.
DR TreeFam; TF336859; -.
DR PathwayCommons; P40198; -.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P40198; -.
DR BioGRID-ORCS; 1084; 8 hits in 1044 CRISPR screens.
DR GeneWiki; CEACAM3; -.
DR GenomeRNAi; 1084; -.
DR Pharos; P40198; Tbio.
DR PRO; PR:P40198; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P40198; protein.
DR Bgee; ENSG00000170956; Expressed in blood and 123 other tissues.
DR ExpressionAtlas; P40198; baseline and differential.
DR Genevisible; P40198; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Glycoprotein; Immunoglobulin domain;
KW Membrane; Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..34
FT /evidence="ECO:0000250"
FT CHAIN 35..252
FT /note="Carcinoembryonic antigen-related cell adhesion
FT molecule 3"
FT /id="PRO_0000014565"
FT TOPO_DOM 35..155
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..142
FT /note="Ig-like V-type"
FT REGION 188..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 142..252
FT /note="QENAPGLPVGAVAGIVTGVLVGVALVAALVCFLLLAKTGRTSIQRDLKEQQP
FT QALAPGRGPSHSSAFSMSPLSTAQAPLPNPRTAASIYEELLKHDTNIYCRMDHKAEVAS
FT -> PELPKPSISSNNSNPKEDKDAVAFTCEPEIHSTTCL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2050678"
FT /id="VSP_002486"
FT VAR_SEQ 182..252
FT /note="TSIQRDLKEQQPQALAPGRGPSHSSAFSMSPLSTAQAPLPNPRTAASIYEEL
FT LKHDTNIYCRMDHKAEVAS -> PWSLPQLCLLDVPSLHCPGPPTQPQDSSFHL (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:8508798"
FT /id="VSP_002487"
FT VARIANT 7
FT /note="S -> P (in dbSNP:rs1041999)"
FT /evidence="ECO:0000269|PubMed:2050678"
FT /id="VAR_003905"
FT MUTAGEN 230
FT /note="Y->F: Loss of phosphorylation and 30% reduction in
FT bacterial uptake. More than 60% reduction in bacterial
FT uptake and loss of RAC1 stimulation; when associated with
FT F-241."
FT /evidence="ECO:0000269|PubMed:12864848,
FT ECO:0000269|PubMed:14707113"
FT MUTAGEN 241
FT /note="Y->F: Loss of phosphorylation and 30% reduction in
FT bacterial uptake. More than 60% reduction in bacterial
FT uptake and loss of RAC1 stimulation; when associated with
FT F-230."
FT /evidence="ECO:0000269|PubMed:12864848,
FT ECO:0000269|PubMed:14707113"
FT CONFLICT 49
FT /note="K -> N (in Ref. 1; BAA14321)"
FT /evidence="ECO:0000305"
FT CONFLICT 84
FT /note="I -> T (in Ref. 1; BAA14322)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="Q -> H (in Ref. 1; BAA14322)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="T -> S (in Ref. 2; AAA51969)"
FT /evidence="ECO:0000305"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 60..72
FT /evidence="ECO:0007829|PDB:6AVZ"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:6AVZ"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:6AW1"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:6AW1"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6AVZ"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 118..126
FT /evidence="ECO:0007829|PDB:6AVZ"
FT STRAND 129..141
FT /evidence="ECO:0007829|PDB:6AVZ"
FT CONFLICT P40198-3:199
FT /note="P -> L (in Ref. 2; AAA51970)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 252 AA; 27091 MW; 179F0C51C6A062A1 CRC64;
MGPPSASPHR ECIPWQGLLL TASLLNFWNP PTTAKLTIES MPLSVAEGKE VLLLVHNLPQ
HLFGYSWYKG ERVDGNSLIV GYVIGTQQAT PGAAYSGRET IYTNASLLIQ NVTQNDIGFY
TLQVIKSDLV NEEATGQFHV YQENAPGLPV GAVAGIVTGV LVGVALVAAL VCFLLLAKTG
RTSIQRDLKE QQPQALAPGR GPSHSSAFSM SPLSTAQAPL PNPRTAASIY EELLKHDTNI
YCRMDHKAEV AS
