UniProt functional annotation for P53634



	UniProt functional annotation for P53634

UniProt code: P53634.

Organism: Homo sapiens (Human).

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

Function: Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. {ECO:0000269|PubMed:1586157}.

Catalytic activity: Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro.; EC=3.4.14.1;

Cofactor: Name=chloride; Xref=ChEBI:CHEBI:17996; Note=Binds 1 Cl(-) ion per heavy chain.;

Activity regulation: Strongly inhibited by the cysteine peptidase inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N- ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal ion chelators. {ECO:0000269|PubMed:1586157}.

Biophysicochemical properties: pH dependence: High activity at pH 4.5-6.8. {ECO:0000269|PubMed:1586157};

Subunit: Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains. {ECO:0000269|PubMed:11726493, ECO:0000269|PubMed:1586157}.

Subcellular location: Lysosome.

Tissue specificity: Ubiquitous. Highly expressed in lung, kidney and placenta. Detected at intermediate levels in colon, small intestine, spleen and pancreas. {ECO:0000269|PubMed:9092576}.

Induction: Up-regulated in lymphocytes by IL2/interleukin-2. {ECO:0000269|PubMed:9092576}.

Ptm: N-glycosylated. While glycosylation at Asn-53, Asn-119 and Asn-276 is mediated by STT3A-containing complexes, glycosylation at Asn-29 is mediated STT3B-containing complexes. {ECO:0000269|PubMed:11726493, ECO:0000269|PubMed:1586157, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19167329, ECO:0000269|PubMed:9507095}.

Ptm: In approximately 50% of the complexes the exclusion domain is cleaved at position 58 or 61. The two parts of the exclusion domain are held together by a disulfide bond.

Disease: Papillon-Lefevre syndrome (PLS) [MIM:245000]: An autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees. {ECO:0000269|PubMed:10581027, ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:11106356, ECO:0000269|PubMed:11158173, ECO:0000269|PubMed:11180012, ECO:0000269|PubMed:11180601, ECO:0000269|PubMed:11886537, ECO:0000269|PubMed:12112662, ECO:0000269|PubMed:12809647, ECO:0000269|PubMed:14974080, ECO:0000269|PubMed:15108292, ECO:0000269|PubMed:15991336, ECO:0000269|PubMed:25799584}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Haim-Munk syndrome (HMS) [MIM:245010]: An autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis. {ECO:0000269|PubMed:10662807}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Periodontititis, aggressive, 1 (AP1) [MIM:170650]: A disease characterized by severe and protracted gingival infections, generalized or localized, leading to tooth loss. Amounts of microbial deposits are generally inconsistent with the severity of periodontal tissue destruction and the progression of attachment and bone loss may be self arresting. {ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:14974080}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE- ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}.

Sequence caution: Sequence=CAD97897.1; 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:		Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. {ECO:0000269\|PubMed:1586157}.


Catalytic activity:		Reaction=Release of an N-terminal dipeptide, Xaa-Yaa-\|-Zaa-, except when Xaa is Arg or Lys, or Yaa or Zaa is Pro.; EC=3.4.14.1;
Cofactor:		Name=chloride; Xref=ChEBI:CHEBI:17996; Note=Binds 1 Cl(-) ion per heavy chain.;
Activity regulation:		Strongly inhibited by the cysteine peptidase inhibitors mersalyl acid, iodoacetic acid and cystatin. Inhibited by N- ethylmaleimide, Gly-Phe-diazomethane, TLCK, TPCK and, at low pH, by dithiodipyridine. Not inhibited by the serine peptidase inhibitor PMSF, the aminopeptidase inhibitor bestatin, or metal ion chelators. {ECO:0000269\|PubMed:1586157}.
Biophysicochemical properties:		pH dependence: High activity at pH 4.5-6.8. {ECO:0000269\|PubMed:1586157};
Subunit:		Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains. {ECO:0000269\|PubMed:11726493, ECO:0000269\|PubMed:1586157}.
Subcellular location:		Lysosome.
Tissue specificity:		Ubiquitous. Highly expressed in lung, kidney and placenta. Detected at intermediate levels in colon, small intestine, spleen and pancreas. {ECO:0000269\|PubMed:9092576}.
Induction:		Up-regulated in lymphocytes by IL2/interleukin-2. {ECO:0000269\|PubMed:9092576}.
Ptm:		N-glycosylated. While glycosylation at Asn-53, Asn-119 and Asn-276 is mediated by STT3A-containing complexes, glycosylation at Asn-29 is mediated STT3B-containing complexes. {ECO:0000269\|PubMed:11726493, ECO:0000269\|PubMed:1586157, ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:19167329, ECO:0000269\|PubMed:9507095}.
Ptm:		In approximately 50% of the complexes the exclusion domain is cleaved at position 58 or 61. The two parts of the exclusion domain are held together by a disulfide bond.
Disease:		Papillon-Lefevre syndrome (PLS) [MIM:245000]: An autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees. {ECO:0000269\|PubMed:10581027, ECO:0000269\|PubMed:10662808, ECO:0000269\|PubMed:11106356, ECO:0000269\|PubMed:11158173, ECO:0000269\|PubMed:11180012, ECO:0000269\|PubMed:11180601, ECO:0000269\|PubMed:11886537, ECO:0000269\|PubMed:12112662, ECO:0000269\|PubMed:12809647, ECO:0000269\|PubMed:14974080, ECO:0000269\|PubMed:15108292, ECO:0000269\|PubMed:15991336, ECO:0000269\|PubMed:25799584}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Haim-Munk syndrome (HMS) [MIM:245010]: An autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis. {ECO:0000269\|PubMed:10662807}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Periodontititis, aggressive, 1 (AP1) [MIM:170650]: A disease characterized by severe and protracted gingival infections, generalized or localized, leading to tooth loss. Amounts of microbial deposits are generally inconsistent with the severity of periodontal tissue destruction and the progression of attachment and bone loss may be self arresting. {ECO:0000269\|PubMed:10662808, ECO:0000269\|PubMed:14974080}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase C1 family. {ECO:0000255\|PROSITE- ProRule:PRU10088, ECO:0000255\|PROSITE-ProRule:PRU10089, ECO:0000255\|PROSITE-ProRule:PRU10090}.
Sequence caution:		Sequence=CAD97897.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};