Detail Information for IndEnz0002015634
IED ID IndEnz0002015634
Enzyme Type ID protease015634
Protein Name Membrane cofactor protein
TLX
Trophoblast leukocyte common antigen
CD antigen CD46
Gene Name CD46 MCP MIC10
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MEPPGRRECPFPSWRFPGLLLAAMVLLLYSFSDACEEPPTFEAMELIGKPKPYYEIGERVDYKCKKGYFYIPPLATHTICDRNHTWLPVSDDACYRETCPYIRDPLNGQAVPANGTYEFGYQMHFICNEGYYLIGEEILYCELKGSVAIWSGKPPICEKVLCTPPPKIKNGKHTFSEVEVFEYLDAVTYSCDPAPGPDPFSLIGESTIYCGDNSVWSRAAPECKVVKCRFPVVENGKQISGFGKKFYYKATVMFECDKGFYLDGSDTIVCDSNSTWDPPVPKCLKVLPPSSTKPPALSHSVSTSSTTKSPASSASGPRPTYKPPVSNYPGYPKPEEGILDSLDVWVIAVIVIAIVVGVAVICVVPYRYLQRRKKKGTYLTDETHREVKFTSL
Enzyme Length 392
Uniprot Accession Number P15529
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. {ECO:0000269|PubMed:10843656, ECO:0000269|PubMed:12540904}.; FUNCTION: (Microbial infection) A number of viral and bacterial pathogens seem to bind MCP in order to exploit its immune regulation property and directly induce an immunosuppressive phenotype in T-cells.; FUNCTION: (Microbial infection) Acts as a receptor for Adenovirus subgroup B2 and Ad3. {ECO:0000269|PubMed:12915534, ECO:0000269|PubMed:14566335, ECO:0000269|PubMed:15047806, ECO:0000269|PubMed:15078926, ECO:0000269|PubMed:15919905, ECO:0000269|PubMed:16254377}.; FUNCTION: (Microbial infection) Acts as a receptor for cultured Measles virus. {ECO:0000269|PubMed:10972291}.; FUNCTION: (Microbial infection) Acts as a receptor for Herpesvirus 6/HHV-6. {ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329}.; FUNCTION: (Microbial infection) May act as a receptor for pathogenic bacteria Neisseria and Streptococcus pyogenes (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006).
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Alternative sequence (11); Beta strand (27); Chain (1); Compositional bias (1); Disulfide bond (8); Domain (4); Glycosylation (21); Helix (2); Modified residue (7); Mutagenesis (3); Natural variant (13); Region (1); Sequence conflict (4); Signal peptide (1); Topological domain (2); Transmembrane (1)
Keywords 3D-structure;Alternative splicing;Complement pathway;Cytoplasmic vesicle;Direct protein sequencing;Disease variant;Disulfide bond;Fertilization;Glycoprotein;Hemolytic uremic syndrome;Host cell receptor for virus entry;Host-virus interaction;Immunity;Innate immunity;Membrane;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Sushi;Transmembrane;Transmembrane helix
Interact With P01024; P78504; Q8TD06; Q86W74-2; O60883; Q12837; Q9UEU0
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane {ECO:0000269|PubMed:12112588, ECO:0000269|PubMed:14597734, ECO:0000269|PubMed:15307194}; Single-pass type I membrane protein {ECO:0000269|PubMed:12112588, ECO:0000269|PubMed:14597734, ECO:0000269|PubMed:15307194}. Note=Inner acrosomal membrane of spermatozoa. Internalized upon binding of Measles virus, Herpesvirus 6 or Neisseria gonorrhoeae, which results in an increased susceptibility of infected cells to complement-mediated injury. In cancer cells or cells infected by Neisseria, shedding leads to a soluble peptide.
Modified Residue MOD_RES P15529-2:384; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-3:369; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-4:354; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-5:370; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-6:355; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-7:340; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632; MOD_RES P15529-16:321; /note=Phosphotyrosine; /evidence=ECO:0000269|PubMed:10657632
Post Translational Modification PTM: N-glycosylated on Asn-83; Asn-114 and Asn-273 in most tissues, but probably less N-glycosylated in testis. N-glycosylation on Asn-114 and Asn-273 is required for cytoprotective function. N-glycosylation on Asn-114 is required for Measles virus binding. N-glycosylation on Asn-273 is required for Neisseria binding. N-glycosylation is not required for human adenovirus binding.; PTM: Extensively O-glycosylated in the Ser/Thr-rich domain. O-glycosylation is required for Neisseria binding but not for Measles virus or human adenovirus binding.; PTM: In epithelial cells, isoforms B/D/F/H/J/L/3 are phosphorylated by YES1 in response to infection by Neisseria gonorrhoeae; which promotes infectivity. In T-cells, these isoforms may be phosphorylated by LCK.
Signal Peptide SIGNAL 1..34; /evidence="ECO:0000269|PubMed:1479546, ECO:0000269|PubMed:2298462, ECO:0000269|PubMed:3260937, ECO:0000269|PubMed:8371352"
Structure 3D X-ray crystallography (6)
Cross Reference PDB 1CKL; 2O39; 3INB; 3L89; 3O8E; 5FO8;
Mapped Pubmed ID 12055245; 1386357; 17220899; 17446270; 19367725; 19396169; 20010840; 20071571; 20534589; 20694009; 20711500; 20941397; 23086448; 2481448; 27013439; 6214588; 7391570;
Motif
Gene Encoded By
Mass 43,747
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda