Reviewed, UniProtKB/Swiss-Prot P40198 (CEAM3_HUMAN)

Names and origin

Protein names

Recommended name:
    Carcinoembryonic antigen-related cell adhesion molecule 3
Alternative name(s):
    Carcinoembryonic antigen CGM1
    CD_antigen=CD66d

Gene names

Name:	CEACAM3
Synonyms:	CD66D, CGM1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	252 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Major granulocyte receptor mediating recognition and efficient opsonin-independent phagocytosis of CEACAM-binding microorganisms, including Neissiria, Moxarella and Haemophilus species, thus playing an important role in the clearance of pathogens by the innate immune system. Responsible for RAC1 stimulation in the course of pathogen phagocytosis. Ref.8 Ref.9
Subunit structure	Interacts with S100A9/calprotectin. This interaction is calcium-dependent, but independent of CEACAM3 phosphorylation. Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	CGM1a, the predominant CGM1 transcript, is granulocyte-specific. Not detected out of the granulocytic lineage, such as monocytes, lymphocytes, spleen, testis, colon, brain, liver, pancreas, thymus, ovary, placenta, skeletal muscle, prostate, small intestine, heart, lung and kidney. Ref.7
Domain	The cytosolic domain is involved in S100A9 interaction.
Post-translational modification	Tyrosine-phosphorylated in response to microbial binding. Tyr-230 and Tyr-241 are both required for phosphorylation to be detected. Ref.8
Sequence similarities	Belongs to the immunoglobulin superfamily. CEA family. Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Caution	This is not the ortholog of rat CEACAM3.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P40198-1)

Also known as: CGM1A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P40198-2)

Also known as: CGM1B;

The sequence of this isoform differs from the canonical sequence as follows:
     142-252: QENAPGLPVG...RMDHKAEVAS → PELPKPSISS...EPEIHSTTCL

Isoform 3 (identifier: P40198-3)

Also known as: CGM1C;

The sequence of this isoform differs from the canonical sequence as follows:
     182-252: TSIQRDLKEQ...RMDHKAEVAS → PWSLPQLCLLDVPSLHCLGPPTQPQDSSFHL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 34	34	By similarity
	Chain	35 – 252	218	Carcinoembryonic antigen-related cell adhesion molecule 3		PRO_0000014565
Regions
	Topological domain	35 – 155	121	Extracellular Potential
	Transmembrane	156 – 176	21	Potential
	Topological domain	177 – 252	76	Cytoplasmic Potential
	Domain	35 – 142	108	Ig-like V-type
Amino acid modifications
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	111	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	142 – 252	111	QENAP…AEVAS → PELPKPSISSNNSNPKEDKD AVAFTCEPEIHSTTCL in isoform 2.		VSP_002486
	Alternative sequence	182 – 252	71	TSIQR…AEVAS → PWSLPQLCLLDVPSLHCLGP PTQPQDSSFHL in isoform 3.		VSP_002487
	Natural variant	7	1	S → P: dbSNP rs1041999. Ref.1		VAR_003905
Experimental info
	Mutagenesis	230	1	Y → F: Loss of phosphorylation and 30% reduction in bacterial uptake. More than 60% reduction in bacterial uptake and loss of RAC1 stimulation; when associated with F-241. Ref.8 Ref.9
	Mutagenesis	241	1	Y → F: Loss of phosphorylation and 30% reduction in bacterial uptake. More than 60% reduction in bacterial uptake and loss of RAC1 stimulation; when associated with F-230. Ref.8 Ref.9
	Sequence conflict	49	1	K → N in BAA14321. Ref.1
	Sequence conflict	84	1	I → T in BAA14322. Ref.1
	Sequence conflict	137	1	Q → H in BAA14322. Ref.1
	Sequence conflict	215	1	T → S in AAA51969. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CGM1A) [UniParc]. Last modified December 16, 2008. Version 2. Checksum: 179F0C51C6A062A1	FASTA	252	27,091
	10 20 30 40 50 60 MGPPSASPHR ECIPWQGLLL TASLLNFWNP PTTAKLTIES MPLSVAEGKE VLLLVHNLPQ 70 80 90 100 110 120 HLFGYSWYKG ERVDGNSLIV GYVIGTQQAT PGAAYSGRET IYTNASLLIQ NVTQNDIGFY 130 140 150 160 170 180 TLQVIKSDLV NEEATGQFHV YQENAPGLPV GAVAGIVTGV LVGVALVAAL VCFLLLAKTG 190 200 210 220 230 240 RTSIQRDLKE QQPQALAPGR GPSHSSAFSM SPLSTAQAPL PNPRTAASIY EELLKHDTNI 250 YCRMDHKAEV AS
	Isoform 2 (CGM1B). Checksum: C0BF243D56686F8C	FASTA	177	19,403
	10 20 30 40 50 60 MGPPSASPHR ECIPWQGLLL TASLLNFWNP PTTAKLTIES MPLSVAEGKE VLLLVHNLPQ 70 80 90 100 110 120 HLFGYSWYKG ERVDGNSLIV GYVIGTQQAT PGAAYSGRET IYTNASLLIQ NVTQNDIGFY 130 140 150 160 170 TLQVIKSDLV NEEATGQFHV YPELPKPSIS SNNSNPKEDK DAVAFTCEPE IHSTTCL
	Isoform 3 (CGM1C). Checksum: A146AF256C846762	FASTA	212	22,770
	10 20 30 40 50 60 MGPPSASPHR ECIPWQGLLL TASLLNFWNP PTTAKLTIES MPLSVAEGKE VLLLVHNLPQ 70 80 90 100 110 120 HLFGYSWYKG ERVDGNSLIV GYVIGTQQAT PGAAYSGRET IYTNASLLIQ NVTQNDIGFY 130 140 150 160 170 180 TLQVIKSDLV NEEATGQFHV YQENAPGLPV GAVAGIVTGV LVGVALVAAL VCFLLLAKTG 190 200 210 RPWSLPQLCL LDVPSLHCLG PPTQPQDSSF HL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of nonspecific cross-reacting antigens in human granulocytes." Kuroki M., Arakawa F., Matsuo Y., Oikawa S., Misumi Y., Nakazato H., Matsuoka Y. J. Biol. Chem. 266:11810-11817(1991) [PubMed: 2050678] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT PRO-7. Tissue: Leukocyte.
[2]	"Genomic organization, splice variants and expression of CGM1, a CD66-related member of the carcinoembryonic antigen gene family." Nagel G., Grunert F., Kuijpers T.W., Watt S.M., Thompson J., Zimmermann W.A. Eur. J. Biochem. 214:27-35(1993) [PubMed: 8508798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Identification of three new genes and estimation of the size of the carcinoembryonic antigen family." Khan W.N., Fraengsmyr L., Teglund S., Israelsson A., Bremer K., Hammarstroem S. Genomics 14:384-390(1992) [PubMed: 1427854] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-141.
[7]	"The microbial receptor CEACAM3 is linked to the calprotectin complex in granulocytes." Streichert T., Ebrahimnejad A., Ganzer S., Flayeh R., Wagener C., Bruemmer J. Biochem. Biophys. Res. Commun. 289:191-197(2001) [PubMed: 11708798] [Abstract] Cited for: INTERACTION WITH S100A9, TISSUE SPECIFICITY.
[8]	"Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor." McCaw S.E., Schneider J., Liao E.H., Zimmermann W., Gray-Owen S.D. Mol. Microbiol. 49:623-637(2003) [PubMed: 12864848] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF TYR-230 AND TYR-241.
[9]	"Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens." Schmitter T., Agerer F., Peterson L., Muenzner P., Hauck C.R. J. Exp. Med. 199:35-46(2004) [PubMed: 14707113] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-230 AND TYR-241.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D90277 mRNA. Translation: BAA14321.1. D90278 mRNA. Translation: BAA14322.1. L00692 mRNA. Translation: AAA51969.1. L00693 mRNA. Translation: AAA51970.1. AC022516 Genomic DNA. No translation available. CH471126 Genomic DNA. Translation: EAW57063.1. BC106728 mRNA. Translation: AAI06729.1.
IPI	IPI00027411. IPI00289794. IPI00411778.
PIR	C40428. S33323. S33324.
RefSeq	NP_001806.2.
UniGene	Hs.11
3D structure databases
HSSP	HSSP built from PDB template 1L6Z based on UniProtKB Q61353.
SMR	P40198. Positions 34-141.
ModBase	Search...
PTM databases
PhosphoSite	P40198.
Proteomic databases
PRIDE	P40198.
Genome annotation databases
Ensembl	ENSG00000170956. Homo sapiens. [Contig view]
GeneID	1084.
Organism-specific databases
GeneCards	GC19P046992.
H-InvDB	HIX0040150.
HGNC	HGNC:1815. CEACAM3.
HPA	HPA011041.
MIM	609142. gene.
PharmGKB	PA26359.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P40198.
HOVERGEN	P40198.
OMA	P40198. GPSHSSA.
Gene expression databases
ArrayExpress	P40198.
Bgee	P40198.
CleanEx	HS_CEACAM3.
GermOnline	ENSG00000170956. Homo sapiens.
Family and domain databases
InterPro	IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

CEAM3_HUMAN

Accession

Primary (citable) accession number: P40198
Secondary accession number(s): Q3KPH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	December 16, 2008
Last modified:	June 16, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)