CEAM8_HUMAN
ID CEAM8_HUMAN Reviewed; 349 AA.
AC P31997; O60399; Q16574;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 8;
DE AltName: Full=CD67 antigen;
DE AltName: Full=Carcinoembryonic antigen CGM6;
DE AltName: Full=Non-specific cross-reacting antigen NCA-95;
DE AltName: CD_antigen=CD66b;
DE Flags: Precursor;
GN Name=CEACAM8; Synonyms=CGM6;
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], AND GPI-ANCHOR AT ASP-320.
RC TISSUE=Spleen;
RX PubMed=2208113;
RA Berling B., Kolbinger F., Grunert F., Thompson J.A., Brombacher F.,
RA Buchegger F., Vkleist S., Zimmermann W.;
RT "Cloning of a carcinoembryonic antigen gene family member expressed in
RT leukocytes of chronic myeloid leukemia patients and bone marrow.";
RL Cancer Res. 50:6534-6539(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-322.
RX PubMed=2306228; DOI=10.1016/0006-291x(90)90975-s;
RA Arakawa F., Kuroki M., Misumi Y., Oikawa S., Nakazato H., Matsuoka Y.;
RT "Characterization of a cDNA clone encoding a new species of the nonspecific
RT cross-reacting antigen (NCA), a member of the CEA gene family.";
RL Biochem. Biophys. Res. Commun. 166:1063-1071(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [GENOMIC DNA] OF 1-21.
RX PubMed=9427723;
RA Eades-Perner A., Thompson J., van der Putten H., Zimmermann W.;
RT "Mice transgenic for the human CGM6 gene express its product, the
RT granulocyte marker CD66b, exclusively in granulocytes.";
RL Blood 91:663-672(1998).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8776764; DOI=10.1006/prep.1996.0065;
RA Yamanaka T., Kuroki M., Kinugasa T., Matsuo Y., Matsuoka Y.;
RT "Preparation and characterization of two human carcinoembryonic antigen
RT family proteins of neutrophils, CD66b and c, in silkworm larvae.";
RL Protein Expr. Purif. 7:438-446(1996).
RN [8]
RP FUNCTION.
RX PubMed=2022629; DOI=10.1016/s0021-9258(18)92930-3;
RA Oikawa S., Inuzuka C., Kuroki M., Arakawa F., Matsuoka Y., Kosaki G.,
RA Nakazato H.;
RT "A specific heterotypic cell adhesion activity between members of
RT carcinoembryonic antigen family, W272 and NCA, is mediated by N-domains.";
RL J. Biol. Chem. 266:7995-8001(1991).
RN [9]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 40-ALA--ALA-45; 61-ASP--ARG-63;
RP ASN-66; 72-THR--ALA-75; ARG-78; 85-SER--ILE-89 AND ASN-97.
RX PubMed=11590190;
RA Kuroki M., Abe H., Imakiirei T., Liao S., Uchida H., Yamauchi Y.,
RA Oikawa S., Kuroki M.;
RT "Identification and comparison of residues critical for cell-adhesion
RT activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8.";
RL J. Leukoc. Biol. 70:543-550(2001).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-288.
RC TISSUE=Saliva;
RX PubMed=16740002; DOI=10.1021/pr050492k;
RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
RT "Identification of N-linked glycoproteins in human saliva by glycoprotein
RT capture and mass spectrometry.";
RL J. Proteome Res. 5:1493-1503(2006).
RN [11]
RP STRUCTURE BY NMR OF 33-154.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first Ig-like domain of human carcinoembryonic
RT antigen related cell adhesion molecule 8.";
RL Submitted (MAY-2007) to the PDB data bank.
RN [12] {ECO:0007744|PDB:4WTZ}
RP X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 34-141 IN COMPLEX WITH CEACAM6.
RA Kirouac K.N., Prive G.G.;
RT "Human CEACAM6-CEACAM8 N-domain heterodimer complex.";
RL Submitted (OCT-2014) to the PDB data bank.
RN [13] {ECO:0007744|PDB:4Y88, ECO:0007744|PDB:4YIQ}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 34-141 IN COMPLEX WITH CEACAM6,
RP SUBUNIT, GLYCOSYLATION, AND MUTAGENESIS OF ARG-78; GLN-123 AND LEU-129.
RX PubMed=26483485; DOI=10.1073/pnas.1509511112;
RA Bonsor D.A., Gunther S., Beadenkopf R., Beckett D., Sundberg E.J.;
RT "Diverse oligomeric states of CEACAM IgV domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:13561-13566(2015).
CC -!- FUNCTION: Cell surface glycoprotein that plays a role in cell adhesion
CC in a calcium-independent manner (PubMed:8776764, PubMed:2022629,
CC PubMed:11590190). Mediates heterophilic cell adhesion with other
CC carcinoembryonic antigen-related cell adhesion molecules, such as
CC CEACAM6 (PubMed:8776764, PubMed:2022629, PubMed:11590190). Heterophilic
CC interaction with CEACAM8 occurs in activated neutrophils
CC (PubMed:8776764). {ECO:0000269|PubMed:11590190,
CC ECO:0000269|PubMed:2022629, ECO:0000269|PubMed:8776764}.
CC -!- SUBUNIT: Monomer. Heterodimer with CEACAM6; heterodimerizes via its Ig-
CC like V-type domain. {ECO:0000269|PubMed:26483485}.
CC -!- INTERACTION:
CC P31997; P40199: CEACAM6; NbExp=5; IntAct=EBI-4314540, EBI-4314501;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2208113};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:2208113}. Cell surface
CC {ECO:0000269|PubMed:8776764}.
CC -!- TISSUE SPECIFICITY: Expressed in leukocytes of chronic myeloid Leukemia
CC patients and bone marrow.
CC -!- DOMAIN: The N-terminus Ig-like V-type domain is necessary for
CC heterophilic intercellular adhesion. {ECO:0000269|PubMed:11590190}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:26483485}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. CEA family.
CC {ECO:0000305}.
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DR EMBL; X52378; CAA36604.1; -; mRNA.
DR EMBL; M33326; AAA59914.1; -; mRNA.
DR EMBL; D90064; BAA14108.1; -; mRNA.
DR EMBL; AC004558; AAC13659.1; -; Genomic_DNA.
DR EMBL; BC026263; AAH26263.1; -; mRNA.
DR EMBL; Z95119; CAB08298.1; -; Genomic_DNA.
DR CCDS; CCDS12610.1; -.
DR PIR; S13524; A34815.
DR RefSeq; NP_001807.2; NM_001816.3.
DR RefSeq; XP_016881684.1; XM_017026195.1.
DR PDB; 2DKS; NMR; -; A=33-149.
DR PDB; 4WTZ; X-ray; 2.52 A; G/H/I/J/K/L=34-141.
DR PDB; 4Y88; X-ray; 1.45 A; A=34-141.
DR PDB; 4YIQ; X-ray; 1.85 A; A/C=34-141.
DR PDBsum; 2DKS; -.
DR PDBsum; 4WTZ; -.
DR PDBsum; 4Y88; -.
DR PDBsum; 4YIQ; -.
DR AlphaFoldDB; P31997; -.
DR SMR; P31997; -.
DR BioGRID; 107514; 122.
DR IntAct; P31997; 4.
DR STRING; 9606.ENSP00000244336; -.
DR GlyConnect; 1072; 5 N-Linked glycans (2 sites).
DR GlyGen; P31997; 11 sites, 5 N-linked glycans (2 sites).
DR iPTMnet; P31997; -.
DR PhosphoSitePlus; P31997; -.
DR BioMuta; CEACAM8; -.
DR DMDM; 6166048; -.
DR CPTAC; CPTAC-1306; -.
DR jPOST; P31997; -.
DR MassIVE; P31997; -.
DR PaxDb; P31997; -.
DR PeptideAtlas; P31997; -.
DR PRIDE; P31997; -.
DR ProteomicsDB; 54829; -.
DR ABCD; P31997; 2 sequenced antibodies.
DR Antibodypedia; 17485; 539 antibodies from 39 providers.
DR CPTC; P31997; 2 antibodies.
DR DNASU; 1088; -.
DR Ensembl; ENST00000244336.10; ENSP00000244336.5; ENSG00000124469.12.
DR GeneID; 1088; -.
DR KEGG; hsa:1088; -.
DR MANE-Select; ENST00000244336.10; ENSP00000244336.5; NM_001816.4; NP_001807.2.
DR CTD; 1088; -.
DR DisGeNET; 1088; -.
DR GeneCards; CEACAM8; -.
DR HGNC; HGNC:1820; CEACAM8.
DR HPA; ENSG00000124469; Tissue enriched (bone).
DR MIM; 615747; gene.
DR neXtProt; NX_P31997; -.
DR OpenTargets; ENSG00000124469; -.
DR PharmGKB; PA26364; -.
DR VEuPathDB; HostDB:ENSG00000124469; -.
DR eggNOG; ENOG502RXPD; Eukaryota.
DR GeneTree; ENSGT00960000186634; -.
DR InParanoid; P31997; -.
DR OMA; APPCRIC; -.
DR OrthoDB; 998214at2759; -.
DR PhylomeDB; P31997; -.
DR TreeFam; TF336859; -.
DR PathwayCommons; P31997; -.
DR Reactome; R-HSA-1566977; Fibronectin matrix formation.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P31997; -.
DR BioGRID-ORCS; 1088; 15 hits in 1063 CRISPR screens.
DR EvolutionaryTrace; P31997; -.
DR GeneWiki; CEACAM8; -.
DR GenomeRNAi; 1088; -.
DR Pharos; P31997; Tbio.
DR PRO; PR:P31997; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P31997; protein.
DR Bgee; ENSG00000124469; Expressed in trabecular bone tissue and 91 other tissues.
DR ExpressionAtlas; P31997; baseline and differential.
DR Genevisible; P31997; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 3.
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; 2.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell membrane; Disulfide bond; Glycoprotein;
KW GPI-anchor; Immunoglobulin domain; Lipoprotein; Membrane;
KW Reference proteome; Repeat; Signal.
FT SIGNAL 1..34
FT CHAIN 35..320
FT /note="Carcinoembryonic antigen-related cell adhesion
FT molecule 8"
FT /id="PRO_0000014572"
FT PROPEP 321..349
FT /note="Removed in mature form"
FT /id="PRO_0000014573"
FT DOMAIN 35..142
FT /note="Ig-like V-type"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:2208113"
FT DOMAIN 145..232
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 237..319
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT LIPID 320
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000269|PubMed:2208113"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 115
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 274
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 ECO:0000269|PubMed:16740002"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="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 VARIANT 17
FT /note="G -> V (in dbSNP:rs28367882)"
FT /id="VAR_049849"
FT VARIANT 45
FT /note="A -> V (in dbSNP:rs35221575)"
FT /id="VAR_049850"
FT VARIANT 114
FT /note="R -> K (in dbSNP:rs1041997)"
FT /id="VAR_011721"
FT VARIANT 322
FT /note="L -> V (in dbSNP:rs1126458)"
FT /evidence="ECO:0000269|PubMed:2306228"
FT /id="VAR_049851"
FT VARIANT 340
FT /note="I -> M (in dbSNP:rs8103051)"
FT /id="VAR_049852"
FT MUTAGEN 40..45
FT /note="AVPSNA->STPFNV: No effect on heterophilic cell
FT adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 61..63
FT /note="DPR->NRI: No effect on heterophilic cell adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 66
FT /note="N->S: Inhibits heterophilic cell adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 72..75
FT /note="TVDA->RVDG: No effect on heterophilic cell
FT adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 78
FT /note="R->A: Does not affect the monomeric structure. Loss
FT of heterodimerization with CEACAM6."
FT /evidence="ECO:0000269|PubMed:26483485"
FT MUTAGEN 78
FT /note="R->Q: Inhibits heterophilic cell adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 85..89
FT /note="SNQQI->GTQQA: No effect on heterophilic cell
FT adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 97
FT /note="N->G: No effect on heterophilic cell adhesion."
FT /evidence="ECO:0000269|PubMed:11590190"
FT MUTAGEN 123
FT /note="Q->A: Does not affect the monomeric structure.
FT Decreases heterodimerization with CEACAM6."
FT /evidence="ECO:0000269|PubMed:26483485"
FT MUTAGEN 129
FT /note="L->A: Does not affect the monomeric structure. Loss
FT of heterodimerization with CEACAM6."
FT /evidence="ECO:0000269|PubMed:26483485"
FT STRAND 37..46
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 64..72
FT /evidence="ECO:0007829|PDB:4Y88"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:4Y88"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:4Y88"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:4Y88"
FT STRAND 118..125
FT /evidence="ECO:0007829|PDB:4Y88"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:2DKS"
FT STRAND 131..141
FT /evidence="ECO:0007829|PDB:4Y88"
SQ SEQUENCE 349 AA; 38154 MW; AACF74DA1AC839D8 CRC64;
MGPISAPSCR WRIPWQGLLL TASLFTFWNP PTTAQLTIEA VPSNAAEGKE VLLLVHNLPQ
DPRGYNWYKG ETVDANRRII GYVISNQQIT PGPAYSNRET IYPNASLLMR NVTRNDTGSY
TLQVIKLNLM SEEVTGQFSV HPETPKPSIS SNNSNPVEDK DAVAFTCEPE TQNTTYLWWV
NGQSLPVSPR LQLSNGNRTL TLLSVTRNDV GPYECEIQNP ASANFSDPVT LNVLYGPDAP
TISPSDTYYH AGVNLNLSCH AASNPPSQYS WSVNGTFQQY TQKLFIPNIT TKNSGSYACH
TTNSATGRNR TTVRMITVSD ALVQGSSPGL SARATVSIMI GVLARVALI
