UniProt functional annotation for P15529



	UniProt functional annotation for P15529

UniProt code: P15529.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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).

Subunit: Interacts with C3b (PubMed:3260937, PubMed:1717583). Interacts with C4b (PubMed:1717583). Interacts with moesin/MSN (PubMed:7884872). {ECO:0000269|PubMed:1717583, ECO:0000269|PubMed:3260937, ECO:0000269|PubMed:7884872}.

Subunit: (Microbial infection) Interacts with measles virus H protein. {ECO:0000269|PubMed:10972291}.

Subunit: (Microbial infection) Interacts with human herpesvirus 6 GH protein (PubMed:12663806, PubMed:12724329). {ECO:0000269|PubMed:12663806, ECO:0000269|PubMed:12724329}.

Subunit: (Microbial infection) Interacts with human adenovirus B/D fiber protein (PubMed:12915534, PubMed:14566335, PubMed:15047806, PubMed:15078926, PubMed:15919905, PubMed:16254377). {ECO:0000269|PubMed:12915534, ECO:0000269|PubMed:14566335, ECO:0000269|PubMed:15047806, ECO:0000269|PubMed:15078926, ECO:0000269|PubMed:15919905, ECO:0000269|PubMed:16254377}.

Subunit: (Microbial infection) Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006). {ECO:0000269|PubMed:11260136, ECO:0000269|PubMed:11971006, ECO:0000269|PubMed:7708671, ECO:0000269|PubMed:9379894}.

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.

Tissue specificity: Expressed by all cells except erythrocytes.

Domain: Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b.

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.

Disease: Hemolytic uremic syndrome atypical 2 (AHUS2) [MIM:612922]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:14566051, ECO:0000269|PubMed:16386793, ECO:0000269|PubMed:16621965, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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).


Subunit:		Interacts with C3b (PubMed:3260937, PubMed:1717583). Interacts with C4b (PubMed:1717583). Interacts with moesin/MSN (PubMed:7884872). {ECO:0000269\|PubMed:1717583, ECO:0000269\|PubMed:3260937, ECO:0000269\|PubMed:7884872}.
Subunit:		(Microbial infection) Interacts with measles virus H protein. {ECO:0000269\|PubMed:10972291}.
Subunit:		(Microbial infection) Interacts with human herpesvirus 6 GH protein (PubMed:12663806, PubMed:12724329). {ECO:0000269\|PubMed:12663806, ECO:0000269\|PubMed:12724329}.
Subunit:		(Microbial infection) Interacts with human adenovirus B/D fiber protein (PubMed:12915534, PubMed:14566335, PubMed:15047806, PubMed:15078926, PubMed:15919905, PubMed:16254377). {ECO:0000269\|PubMed:12915534, ECO:0000269\|PubMed:14566335, ECO:0000269\|PubMed:15047806, ECO:0000269\|PubMed:15078926, ECO:0000269\|PubMed:15919905, ECO:0000269\|PubMed:16254377}.
Subunit:		(Microbial infection) Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria (PubMed:7708671, PubMed:9379894, PubMed:11260136, PubMed:11971006). {ECO:0000269\|PubMed:11260136, ECO:0000269\|PubMed:11971006, ECO:0000269\|PubMed:7708671, ECO:0000269\|PubMed:9379894}.
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.
Tissue specificity:		Expressed by all cells except erythrocytes.
Domain:		Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b.
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.
Disease:		Hemolytic uremic syndrome atypical 2 (AHUS2) [MIM:612922]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269\|PubMed:14566051, ECO:0000269\|PubMed:16386793, ECO:0000269\|PubMed:16621965, ECO:0000269\|PubMed:20513133}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.