P16573 · CEAM1_RAT
- ProteinCarcinoembryonic antigen-related cell adhesion molecule 1
- GeneCeacam1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids519 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform 1
Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:11850617).
Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors (By similarity).
Plays a role in immune response, of T-cells, natural killer (NK) and neutrophils (By similarity).
Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (By similarity).
Also inhibits T-cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T-cell through its interaction with HAVCR2 (By similarity).
Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (By similarity).
Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4-CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (By similarity).
Down-regulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (By similarity).
Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (PubMed:11850617).
Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis (PubMed:7592607, PubMed:9712832).
This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis (PubMed:16054098, PubMed:7592607).
INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (PubMed:11694516).
Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia (By similarity).
Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (By similarity).
Down-regulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (PubMed:15467833).
Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (By similarity).
Inhibits cell migration and cell scattering through interaction with FLNA; interferes with the interaction of FLNA with RALA (By similarity).
Mediates bile acid transport activity in a phosphorylation dependent manner (PubMed:7518458).
Negatively regulates osteoclastogenesis (By similarity).
Isoform 2
Promotes populations of T-cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens (By similarity).
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCarcinoembryonic antigen-related cell adhesion molecule 1
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP16573
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Colocalizes with CEACAM20 at the apical brush border of intestinal cells (By similarity).
Isoform 1
Found as a mixture of monomer, dimer and oligomer in the plasma membrane. Occurs predominantly as cis-dimers and/or small cis-oligomers in the cell junction regions (PubMed:19948503).
Found as dimer in the solution (PubMed:9003371).
Predominantly localized to the lateral cell membranes (PubMed:7774714).
Isoform 2
Found as a mixture of monomer, dimer and oligomer in the plasma membrane. Occurs predominantly as cis-dimers and/or small cis-oligomers in the cell junction regions (PubMed:19948503).
Co-localizes with ANXA2 in secretory vesicles and with S100A10/p11 at the plasma membrane (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 35-425 | Extracellular | ||||
Sequence: QVTVDAVPPNVVEEKSVLLLAHNLPQEFQVFYWYKGTTLNPDSEIARYIRSDNMSKTGPAYSGRETIYSNGSLFFQNVNKTDERAYTLSVFDQQFNPIQTSVQFRVYPALQKPNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNRSDPFNLDVIYGPDAPVISPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNITVFEPVTQPSIQITNTTVKELGSVTLTCFSKDTGVSVRWLFNSQSLQLTDRMTLSQDNSTLRIDPIKREDAGDYQCEISNPVSFRISHPIKLDVIPDPTQGNSGLSEGA | ||||||
Transmembrane | 426-446 | Helical | ||||
Sequence: IAGIVIGSVAGVALIAALAYF | ||||||
Topological domain | 447-519 | Cytoplasmic | ||||
Sequence: LYSRKTGGGSDHRDLTEHKPSTSSHNLGPSDDSPNKVDDVSYSVLNFNAQQSKRPTSASSSPTETVYSVVKKK |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 49 | in allele b | ||||
Sequence: K → S | ||||||
Natural variant | 55 | in allele b | ||||
Sequence: A → T | ||||||
Natural variant | 70 | in allele b | ||||
Sequence: G → V | ||||||
Natural variant | 73 | in allele b | ||||
Sequence: L → T | ||||||
Natural variant | 74 | in allele b | ||||
Sequence: N → G | ||||||
Natural variant | 75 | in allele b | ||||
Sequence: P → L | ||||||
Natural variant | 76 | in allele b | ||||
Sequence: D → N | ||||||
Natural variant | 86 | in allele b | ||||
Sequence: D → S | ||||||
Natural variant | 88 | in allele b | ||||
Sequence: M → T | ||||||
Natural variant | 90 | in allele b | ||||
Sequence: K → Q | ||||||
Natural variant | 92 | in allele b | ||||
Sequence: G → E | ||||||
Natural variant | 99 | in allele b | ||||
Sequence: E → V | ||||||
Natural variant | 118 | in allele b | ||||
Sequence: R → G | ||||||
Natural variant | 119 | in allele b | ||||
Sequence: A → P | ||||||
Natural variant | 125 | in allele b | ||||
Sequence: F → I | ||||||
Natural variant | 127 | in allele b | ||||
Sequence: Q → K | ||||||
Mutagenesis | 488 | Phosphorylated on serine. Decreases bile acid transport Doesn't phosphorylated by EGFR. Doesn't increase interaction with SHC1. Completely inhibits insulin-stimulated phosphorylation. No effect on INSR internalization and INS degradation. Prevents CEACAM1 phosphorylation and the increase in its binding to FASN in the presence of INSR. No effect on cell-surface expression in response to INS. Abolishes phosphorylation by INSR. Abolishes indirect interaction with INSR. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 502-503 | Phosphorylated on tyrosine. Impairs bile acid transport. | ||||
Sequence: TS → AA | ||||||
Mutagenesis | 503 | Abolishes phosphorylation by EGFR. Reduces interaction with SHC1. Completely inhibits insulin-stimulated phosphorylation. No effect on INSR internalization and INS degradation. In L-SACC1; completely inhibits insulin-stimulated phosphorylation; develops hyperinsulinemia resulting from impaired insulin clearance; the hyperinsulinemia causes secondary insulin resistance with impaired glucose tolerance and random, but not fasting, hyperglycemia; insulin doesn't significantly decrease FASN activity in liver. Prevents CEACAM1 phosphorylation and the increase in its binding to FASN in the presence of INSR. No effect on cell-surface expression in response to INS. | ||||
Sequence: S → A | ||||||
Mutagenesis | 503 | Preserves the ability of INSR to induce CEACAM1 phosphorylation. | ||||
Sequence: S → D | ||||||
Mutagenesis | 513 | Increases INSR internalization and INS degradation. Phosphorylated by INSR. Prevents the increase in CEACAM1 binding to FASN by INSR. Decreases cell-surface expression in response to INS. Doesn't affect phosphorylation by INSR. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 17 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, modified residue, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-34 | |||||
Sequence: MELASARLLRGQIPWRGLLLTASLLTYWSPLTTA | ||||||
Modified residue | 35 | Pyrrolidone carboxylic acid | ||||
Sequence: Q | ||||||
Chain | PRO_0000014564 | 35-519 | Carcinoembryonic antigen-related cell adhesion molecule 1 | |||
Sequence: QVTVDAVPPNVVEEKSVLLLAHNLPQEFQVFYWYKGTTLNPDSEIARYIRSDNMSKTGPAYSGRETIYSNGSLFFQNVNKTDERAYTLSVFDQQFNPIQTSVQFRVYPALQKPNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNRSDPFNLDVIYGPDAPVISPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNITVFEPVTQPSIQITNTTVKELGSVTLTCFSKDTGVSVRWLFNSQSLQLTDRMTLSQDNSTLRIDPIKREDAGDYQCEISNPVSFRISHPIKLDVIPDPTQGNSGLSEGAIAGIVIGSVAGVALIAALAYFLYSRKTGGGSDHRDLTEHKPSTSSHNLGPSDDSPNKVDDVSYSVLNFNAQQSKRPTSASSSPTETVYSVVKKK | ||||||
Glycosylation | 87 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 104 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 113 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 148 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 152 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 167↔215 | |||||
Sequence: CEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYEC | ||||||
Glycosylation | 173 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 197 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 224 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 256 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 259↔299 | |||||
Sequence: CHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYAC | ||||||
Glycosylation | 288 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 292 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 302 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 315 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 331 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 344↔392 | |||||
Sequence: CFSKDTGVSVRWLFNSQSLQLTDRMTLSQDNSTLRIDPIKREDAGDYQC | ||||||
Glycosylation | 374 | N-linked (GlcNAc...) asparagine; atypical | ||||
Sequence: N | ||||||
Modified residue | 488 | Phosphotyrosine; by SRC, LCK, INSR and EGFR | ||||
Sequence: Y | ||||||
Modified residue | 503 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 513 | Phosphotyrosine; by INSR, SRC and LCK | ||||
Sequence: Y |
Post-translational modification
Isoform 1
Isoform 1 is phosphorylated on tyrosine by Src family kinases like SRC and LCK and by receptor like CSF3R, EGFR and INSR upon stimulation (PubMed:15467833, PubMed:16054098, PubMed:7626603, PubMed:9712832).
Phosphorylated at Ser-503; mediates activity. Phosphorylated at Tyr-488; regulates activity (PubMed:7518458).
Phosphorylated at Tyr-488 by EGFR and INSR upon stimulation; this phosphorylation is Ser-503-phosphorylation-dependent; mediates cellular internalization; increases interaction with FASN (PubMed:15467833, PubMed:16054098, PubMed:7626603, PubMed:9712832).
Phosphorylated at Tyr-488 and Tyr-513 by LCK; mediates PTPN6 association and is regulated by homophilic ligation of CEACAM1 in the absence of T-cell activation (By similarity).
Phosphorylated at Tyr-513; mediates interaction with PTPN11 (By similarity).
Isoform 2
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in granulocytes, lymphocytes, granulocytes, B cells, and T-cells (PubMed:11994468).
Gene expression databases
Interaction
Subunit
Oligomer. Heterodimer. Homodimer (PubMed:19948503).
Cis-dimer/oligomer (via Ig-like C2-type and/or via cytoplasmic domains); induced by trans-homophilic cell adhesion through an allosteric mechanism transmitted by the Ig-like V-type domain, and is regulated by intracellular calcium and calmodulin (PubMed:19948503, PubMed:2373740, PubMed:8831574, PubMed:9003371).
Interacts (via cytoplasmic domain) with calmodulin in a calcium dependent manner; reduces homophilic cell adhesion through dissociation of dimer (PubMed:8576129).
Isoform 1 interacts (via cytoplasmic domain) with PTPN11 (preferentially) and PTPN6; cis-homodimer form is preferred; this interaction is decreased by formation of isoform 1 / isoform 2 cis-heterodimers and is dependent on the monomer/dimer equilibrium; this interaction is phosphorylation-dependent (PubMed:19948503).
Isoform 1 interacts with LYN (By similarity).
Isoform 1 interacts (via cytoplasmic domain) with SRC (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (PubMed:19948503).
Isoform 1 interacts (via cytoplasmic domain) with LCK; mediates phosphorylation at Tyr-488 and Tyr-513 resulting in PTPN6 association. Isoform 1 interacts with PTPN6; this interaction is phosphorylation-dependent and causes a profound decrease in TCR stimulation-induced CD247 and ZAP70 phosphorylation. Isoform 1 interacts with TCR/CD3 complex through TCR beta chain and CD3E; colocalizes at the cell surface and upon stimulation of the TCR/CD3 complex recruits PTPN6 in the TCR/CD3 complex, resulting in dephosphorylation of CD247 and ZAP70 (By similarity).
Isoform 1 interacts (via cytoplasmic domain) with SHC1 (via SH2 domain); SHC1 mediates interaction with INSR or EGFR in a Ser-503 phosphorylation-dependent manner (PubMed:11694516).
Isoform 1 interacts with EGFR; the interaction is indirect (PubMed:15467833).
Isoform 1 interacts with CSF3R; down-regulates the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R. Isoform 1 (phosphorylated form) interacts with TLR4 and SYK; recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity (By similarity).
Isoform 1 interacts with FLNA; inhibits cell migration and cell scattering by interfering with the interaction of FLNA with RALA (PubMed:16291724).
Isoform 1 interacts (via cytoplasmic domain) with PXN; the interaction is phosphotyrosyl-dependent. Isoform 1 interacts with KLRK1; recruits PTPN6 that dephosphorylates VAV1. Isoform 1 interacts with CEACAM8 (By similarity).
Isoform 1 interacts with FASN; this interaction is insulin and phosphorylation-dependent; reduces fatty-acid synthase activity (PubMed:16054098).
Interacts (via Ig-like V-type) with HAVCR2 (via Ig-like V-type); facilitates the maturation and cell surface expression of HAVCR2 thereby regulating T-cell tolerance induction. Isoform 2 interacts (via the cytoplasmic domain) with ANXA2; this interaction is regulated by phosphorylation and appears in the AIIt complex. Interacts (via Lewis X moieties) with CD209 (via C-type lectin domain); this interaction is regulated by the glycosylation pattern of CEACAM1 on cell types and regulates contact between dendritic cells and neutrophils (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 39-142 | Required for homophilic binding | ||||
Sequence: DAVPPNVVEEKSVLLLAHNLPQEFQVFYWYKGTTLNPDSEIARYIRSDNMSKTGPAYSGRETIYSNGSLFFQNVNKTDERAYTLSVFDQQFNPIQTSVQFRVYP | ||||||
Domain | 42-140 | Ig-like V-type | ||||
Sequence: PPNVVEEKSVLLLAHNLPQEFQVFYWYKGTTLNPDSEIARYIRSDNMSKTGPAYSGRETIYSNGSLFFQNVNKTDERAYTLSVFDQQFNPIQTSVQFRV | ||||||
Domain | 147-232 | Ig-like C2-type 1 | ||||
Sequence: PNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNRSDPFNLD | ||||||
Domain | 237-317 | Ig-like C2-type 2 | ||||
Sequence: PDAPVISPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNIT | ||||||
Domain | 325-403 | Ig-like C2-type 3 | ||||
Sequence: PSIQITNTTVKELGSVTLTCFSKDTGVSVRWLFNSQSLQLTDRMTLSQDNSTLRIDPIKREDAGDYQCEISNPVSFRIS | ||||||
Region | 445-457 | Interaction with calmodulin | ||||
Sequence: YFLYSRKTGGGSD | ||||||
Region | 447-519 | Interaction with FLNA | ||||
Sequence: LYSRKTGGGSDHRDLTEHKPSTSSHNLGPSDDSPNKVDDVSYSVLNFNAQQSKRPTSASSSPTETVYSVVKKK | ||||||
Region | 455-519 | Disordered | ||||
Sequence: GSDHRDLTEHKPSTSSHNLGPSDDSPNKVDDVSYSVLNFNAQQSKRPTSASSSPTETVYSVVKKK | ||||||
Compositional bias | 467-513 | Polar residues | ||||
Sequence: STSSHNLGPSDDSPNKVDDVSYSVLNFNAQQSKRPTSASSSPTETVY | ||||||
Region | 484-519 | Required for interaction with PTPN11 and PTPN6 and for control of phosphorylation level | ||||
Sequence: DDVSYSVLNFNAQQSKRPTSASSSPTETVYSVVKKK | ||||||
Region | 513-516 | Essential for interaction with PTPN11 and PTPN6 | ||||
Sequence: YSVV |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing. For each isoform it exists 2 allelic variants, named a and b. The allelic variants differ in 16 amino acids in the Ig-like V-type domain.
P16573-1
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.
- Name1
- SynonymsCEACAM1-4L, C-CAM1, L-form Cell-CAM105
- NoteAllele a.
- Length519
- Mass (Da)57,410
- Last updated2016-10-05 v4
- Checksum9EFE74FD565E7C29
P16573-2
- Name2
- SynonymsCEACAM1-4S, C-CAM2, S-form Cell-CAM105
- NoteAllele a.
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q9JHL6 | Q9JHL6_RAT | Ceacam1 | 459 | ||
Q9JHL7 | Q9JHL7_RAT | Ceacam1 | 448 | ||
A0A8I6ACX8 | A0A8I6ACX8_RAT | Ceacam1 | 341 | ||
F7F6B2 | F7F6B2_RAT | Ceacam1 | 442 | ||
A0A8I6A3J5 | A0A8I6A3J5_RAT | Ceacam1 | 509 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Polymorphism
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J04963 EMBL· GenBank· DDBJ | AAA41104.1 EMBL· GenBank· DDBJ | mRNA | ||
Z12019 EMBL· GenBank· DDBJ | CAA78054.1 EMBL· GenBank· DDBJ | mRNA | ||
M92848 EMBL· GenBank· DDBJ | AAA16783.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
X71122 EMBL· GenBank· DDBJ | CAA50435.1 EMBL· GenBank· DDBJ | mRNA | ||
X91137 EMBL· GenBank· DDBJ | CAA62577.1 EMBL· GenBank· DDBJ | mRNA | ||
AC134759 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH473979 EMBL· GenBank· DDBJ | EDM08020.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC061740 EMBL· GenBank· DDBJ | AAH61740.1 EMBL· GenBank· DDBJ | mRNA |