UniProt functional annotation for P58335



	UniProt functional annotation for P58335

UniProt code: P58335.

Organism: Homo sapiens (Human).

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

Function: Necessary for cellular interactions with laminin and the extracellular matrix. {ECO:0000269|PubMed:11683410, ECO:0000269|PubMed:12973667}.

Function: (Microbial infection) Receptor for the protective antigen (PA) of B.anthracis (PubMed:12700348, PubMed:15243628, PubMed:15326297). Binding of PA leads to heptamerization of the receptor-PA complex (PubMed:12700348, PubMed:15243628, PubMed:15326297). Upon binding of the PA of B.anthracis, the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway (PubMed:12551953, PubMed:15337774). In the endosomal membrane, at pH under 7, the complex then rearranges and forms a pore allowing the other components of anthrax toxin to escape to the cytoplasm (PubMed:12551953, PubMed:15337774). {ECO:0000269|PubMed:12551953, ECO:0000269|PubMed:12700348, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:15337774}.

Subunit: Binds laminin, and possibly also collagen type IV. {ECO:0000269|PubMed:11683410}.

Subunit: (Microbial infection) Interacts (via VWFA domain) with the protective antigen (PA) of B.anthracis. {ECO:0000269|PubMed:12551953, ECO:0000269|PubMed:12700348, ECO:0000269|PubMed:15243628, ECO:0000269|PubMed:15326297, ECO:0000269|PubMed:15337774}.

Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:12700348}; Single-pass type I membrane protein {ECO:0000255}. Note=Expressed at the cell surface. {ECO:0000269|PubMed:12700348}.

Subcellular location: [Isoform 2]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:11683410}; Single-pass type I membrane protein {ECO:0000255}. Note=Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane. {ECO:0000269|PubMed:11683410}.

Subcellular location: [Isoform 3]: Secreted {ECO:0000305}.

Tissue specificity: Expressed in prostate, thymus, ovary, testis, pancreas, colon, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, skeletal muscle, small intestine and spleen. {ECO:0000269|PubMed:14508707}.

Disease: Hyaline fibromatosis syndrome (HFS) [MIM:228600]: An autosomal recessive syndrome characterized by abnormal growth of hyalinized fibrous tissue usually affecting subcutaneous regions on the scalp, ears, neck, face, hands, and feet. The lesions appear as pearly papules or fleshy nodules. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Disease severity is variable. Some individuals manifest symptoms in infancy and have additional visceral or systemic involvement. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to early death. Surviving children may suffer from severely reduced mobility due to joint contractures. Other patients have later onset of a milder disorder affecting only the face and digits. {ECO:0000269|PubMed:12973667, ECO:0000269|PubMed:14508707, ECO:0000269|PubMed:15725249}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.

Similarity: Belongs to the ATR family. {ECO:0000305}.

Sequence caution: Sequence=AAY40907.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAB70976.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD93150.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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:		Necessary for cellular interactions with laminin and the extracellular matrix. {ECO:0000269\|PubMed:11683410, ECO:0000269\|PubMed:12973667}.



Function:		(Microbial infection) Receptor for the protective antigen (PA) of B.anthracis (PubMed:12700348, PubMed:15243628, PubMed:15326297). Binding of PA leads to heptamerization of the receptor-PA complex (PubMed:12700348, PubMed:15243628, PubMed:15326297). Upon binding of the PA of B.anthracis, the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway (PubMed:12551953, PubMed:15337774). In the endosomal membrane, at pH under 7, the complex then rearranges and forms a pore allowing the other components of anthrax toxin to escape to the cytoplasm (PubMed:12551953, PubMed:15337774). {ECO:0000269\|PubMed:12551953, ECO:0000269\|PubMed:12700348, ECO:0000269\|PubMed:15243628, ECO:0000269\|PubMed:15326297, ECO:0000269\|PubMed:15337774}.


Subunit:		Binds laminin, and possibly also collagen type IV. {ECO:0000269\|PubMed:11683410}.
Subunit:		(Microbial infection) Interacts (via VWFA domain) with the protective antigen (PA) of B.anthracis. {ECO:0000269\|PubMed:12551953, ECO:0000269\|PubMed:12700348, ECO:0000269\|PubMed:15243628, ECO:0000269\|PubMed:15326297, ECO:0000269\|PubMed:15337774}.
Subcellular location:		[Isoform 1]: Cell membrane {ECO:0000269\|PubMed:12700348}; Single-pass type I membrane protein {ECO:0000255}. Note=Expressed at the cell surface. {ECO:0000269\|PubMed:12700348}.
Subcellular location:		[Isoform 2]: Endoplasmic reticulum membrane {ECO:0000269\|PubMed:11683410}; Single-pass type I membrane protein {ECO:0000255}. Note=Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane. {ECO:0000269\|PubMed:11683410}.
Subcellular location:		[Isoform 3]: Secreted {ECO:0000305}.
Tissue specificity:		Expressed in prostate, thymus, ovary, testis, pancreas, colon, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, skeletal muscle, small intestine and spleen. {ECO:0000269\|PubMed:14508707}.
Disease:		Hyaline fibromatosis syndrome (HFS) [MIM:228600]: An autosomal recessive syndrome characterized by abnormal growth of hyalinized fibrous tissue usually affecting subcutaneous regions on the scalp, ears, neck, face, hands, and feet. The lesions appear as pearly papules or fleshy nodules. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Disease severity is variable. Some individuals manifest symptoms in infancy and have additional visceral or systemic involvement. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to early death. Surviving children may suffer from severely reduced mobility due to joint contractures. Other patients have later onset of a milder disorder affecting only the face and digits. {ECO:0000269\|PubMed:12973667, ECO:0000269\|PubMed:14508707, ECO:0000269\|PubMed:15725249}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.
Similarity:		Belongs to the ATR family. {ECO:0000305}.
Sequence caution:		Sequence=AAY40907.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAB70976.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD93150.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};