UniProt functional annotation for P08174



	UniProt functional annotation for P08174

UniProt code: P08174.

Organism: Homo sapiens (Human).

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

Function: This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). {ECO:0000269|PubMed:7525274, ECO:0000305|PubMed:28657829}.

Function: (Microbial infection) Acts as a receptor for Coxsackievirus A21, coxsackieviruses B1, B3 and B5. {ECO:0000269|PubMed:9151867}.

Function: (Microbial infection) Acts as a receptor for Human enterovirus 70 and D68 (Probable). {ECO:0000269|PubMed:8764022}.

Function: (Microbial infection) Acts as a receptor for Human echoviruses 6, 7, 11, 12, 20 and 21. {ECO:0000269|PubMed:7525274, ECO:0000305|PubMed:12409401}.

Subunit: Monomer (major form) and non-disulfide-linked, covalent homodimer (minor form). Interacts with ADGRE5 (PubMed:11297558). {ECO:0000269|PubMed:11297558, ECO:0000269|PubMed:1377029, ECO:0000305|PubMed:12409401}.

Subunit: (Microbial infection) Interacts with coxsackievirus A21, coxsackieviruses B1, B3 and B5 capsid proteins. {ECO:0000269|PubMed:9151867}.

Subunit: (Microbial infection) Interacts with human enterovirus 70 and D68 capsid proteins (Probable). {ECO:0000269|PubMed:8764022}.

Subunit: (Microbial infection) Interacts with human echoviruses 6, 7, 11, 12, 20 and 21 capsid proteins. {ECO:0000269|PubMed:7525274}.

Subcellular location: [Isoform 1]: Cell membrane; Single-pass type I membrane protein.

Subcellular location: [Isoform 2]: Cell membrane; Lipid-anchor, GPI- anchor.

Subcellular location: [Isoform 3]: Secreted {ECO:0000269|PubMed:16503113}.

Subcellular location: [Isoform 4]: Secreted {ECO:0000269|PubMed:16503113}.

Subcellular location: [Isoform 5]: Secreted {ECO:0000269|PubMed:16503113}.

Subcellular location: [Isoform 6]: Cell membrane {ECO:0000305|PubMed:16503113}; Lipid-anchor, GPI-anchor {ECO:0000305|PubMed:16503113}.

Subcellular location: [Isoform 7]: Cell membrane {ECO:0000305|PubMed:16503113}; Lipid-anchor, GPI-anchor {ECO:0000305|PubMed:16503113}.

Tissue specificity: Expressed on the plasma membranes of all cell types that are in intimate contact with plasma complement proteins. It is also found on the surfaces of epithelial cells lining extracellular compartments, and variants of the molecule are present in body fluids and in extracellular matrix.

Domain: The first Sushi domain (SCR1) is not necessary for function. SCR2 and SCR4 provide the proper conformation for the active site on SCR3 (By similarity). {ECO:0000250}.

Ptm: The Ser/Thr-rich domain is heavily O-glycosylated. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:26207632}.

Polymorphism: Responsible for the Cromer blood group system (CROM) [MIM:613793]. It consists of at least 8 high-incidence (Cr(a), Tc(a), Dr(a), Es(a), WES(b), UMC, IFC and GUTI) and three low-incidence (Tc(b), Tc(c) and WES(a)) antigens that reside on DAF. In the Cromer phenotypes Dr(a-) and Inab there is reduced or absent expression of DAF, respectively. In the case of the Dr(a-) phenotype, a single nucleotide substitution within exon 5 accounts for two changes: a simple amino acid substitution, Leu-199 that is the basis of the antigenic variation, and an alternative splicing event that underlies the decreased expression of DAF in this phenotype. The Inab phenotype is a very rare one in which the red blood cells lack all Cromer system antigens. The red blood cells of individuals with Inab phenotype have a deficiency of DAF, but these individuals are not known to have any associated hematologic or other abnormalities (PubMed:12675719). {ECO:0000269|PubMed:12675719}.

Disease: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) [MIM:226300]: An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a. {ECO:0000269|PubMed:28657829, ECO:0000269|PubMed:28657861}. Note=The disease is caused by variants affecting the gene represented in this entry. CHAPLE is caused by biallelic mutations in the CD55 gene.

Miscellaneous: [Isoform 6]: Includes partial sequence of the intron 7. {ECO:0000305}.

Miscellaneous: [Isoform 7]: Includes full sequence of the intron 7. {ECO:0000305}.

Similarity: Belongs to the receptors of complement activation (RCA) family. {ECO:0000305}.

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:		This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade (PubMed:7525274). Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage (PubMed:28657829). {ECO:0000269\|PubMed:7525274, ECO:0000305\|PubMed:28657829}.



Function:		(Microbial infection) Acts as a receptor for Coxsackievirus A21, coxsackieviruses B1, B3 and B5. {ECO:0000269\|PubMed:9151867}.



Function:		(Microbial infection) Acts as a receptor for Human enterovirus 70 and D68 (Probable). {ECO:0000269\|PubMed:8764022}.



Function:		(Microbial infection) Acts as a receptor for Human echoviruses 6, 7, 11, 12, 20 and 21. {ECO:0000269\|PubMed:7525274, ECO:0000305\|PubMed:12409401}.


Subunit:		Monomer (major form) and non-disulfide-linked, covalent homodimer (minor form). Interacts with ADGRE5 (PubMed:11297558). {ECO:0000269\|PubMed:11297558, ECO:0000269\|PubMed:1377029, ECO:0000305\|PubMed:12409401}.
Subunit:		(Microbial infection) Interacts with coxsackievirus A21, coxsackieviruses B1, B3 and B5 capsid proteins. {ECO:0000269\|PubMed:9151867}.
Subunit:		(Microbial infection) Interacts with human enterovirus 70 and D68 capsid proteins (Probable). {ECO:0000269\|PubMed:8764022}.
Subunit:		(Microbial infection) Interacts with human echoviruses 6, 7, 11, 12, 20 and 21 capsid proteins. {ECO:0000269\|PubMed:7525274}.
Subcellular location:		[Isoform 1]: Cell membrane; Single-pass type I membrane protein.
Subcellular location:		[Isoform 2]: Cell membrane; Lipid-anchor, GPI- anchor.
Subcellular location:		[Isoform 3]: Secreted {ECO:0000269\|PubMed:16503113}.
Subcellular location:		[Isoform 4]: Secreted {ECO:0000269\|PubMed:16503113}.
Subcellular location:		[Isoform 5]: Secreted {ECO:0000269\|PubMed:16503113}.
Subcellular location:		[Isoform 6]: Cell membrane {ECO:0000305\|PubMed:16503113}; Lipid-anchor, GPI-anchor {ECO:0000305\|PubMed:16503113}.
Subcellular location:		[Isoform 7]: Cell membrane {ECO:0000305\|PubMed:16503113}; Lipid-anchor, GPI-anchor {ECO:0000305\|PubMed:16503113}.
Tissue specificity:		Expressed on the plasma membranes of all cell types that are in intimate contact with plasma complement proteins. It is also found on the surfaces of epithelial cells lining extracellular compartments, and variants of the molecule are present in body fluids and in extracellular matrix.
Domain:		The first Sushi domain (SCR1) is not necessary for function. SCR2 and SCR4 provide the proper conformation for the active site on SCR3 (By similarity). {ECO:0000250}.
Ptm:		The Ser/Thr-rich domain is heavily O-glycosylated. {ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:26207632}.
Polymorphism:		Responsible for the Cromer blood group system (CROM) [MIM:613793]. It consists of at least 8 high-incidence (Cr(a), Tc(a), Dr(a), Es(a), WES(b), UMC, IFC and GUTI) and three low-incidence (Tc(b), Tc(c) and WES(a)) antigens that reside on DAF. In the Cromer phenotypes Dr(a-) and Inab there is reduced or absent expression of DAF, respectively. In the case of the Dr(a-) phenotype, a single nucleotide substitution within exon 5 accounts for two changes: a simple amino acid substitution, Leu-199 that is the basis of the antigenic variation, and an alternative splicing event that underlies the decreased expression of DAF in this phenotype. The Inab phenotype is a very rare one in which the red blood cells lack all Cromer system antigens. The red blood cells of individuals with Inab phenotype have a deficiency of DAF, but these individuals are not known to have any associated hematologic or other abnormalities (PubMed:12675719). {ECO:0000269\|PubMed:12675719}.
Disease:		Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) [MIM:226300]: An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a. {ECO:0000269\|PubMed:28657829, ECO:0000269\|PubMed:28657861}. Note=The disease is caused by variants affecting the gene represented in this entry. CHAPLE is caused by biallelic mutations in the CD55 gene.
Miscellaneous:		[Isoform 6]: Includes partial sequence of the intron 7. {ECO:0000305}.
Miscellaneous:		[Isoform 7]: Includes full sequence of the intron 7. {ECO:0000305}.
Similarity:		Belongs to the receptors of complement activation (RCA) family. {ECO:0000305}.