UniProt functional annotation for P08246



	UniProt functional annotation for P08246

UniProt code: P08246.

Organism: Homo sapiens (Human).

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

Function: Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae (PubMed:10947984). {ECO:0000269|PubMed:10947984, ECO:0000269|PubMed:15140022}.

Catalytic activity: Reaction=Hydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa.; EC=3.4.21.37;

Subunit: Interacts with NOTCH2NL. {ECO:0000269|PubMed:14673143}.

Subcellular location: Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:10947984}. Note=Localized in phagolysosomes following ingestion of E.coli by neutrophils. {ECO:0000269|PubMed:10947984}.

Tissue specificity: Bone marrow cells. Neutrophil (PubMed:10947984). {ECO:0000269|PubMed:10947984}.

Disease: Cyclic haematopoiesis (CH) [MIM:162800]: Autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency. {ECO:0000269|PubMed:10581030, ECO:0000269|PubMed:11001877, ECO:0000269|PubMed:14673143, ECO:0000269|PubMed:14962902, ECO:0000269|PubMed:23463630}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Neutropenia, severe congenital 1, autosomal dominant (SCN1) [MIM:202700]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. {ECO:0000269|PubMed:11001877, ECO:0000269|PubMed:11675333, ECO:0000269|PubMed:12091371, ECO:0000269|PubMed:14962902, ECO:0000269|PubMed:17436313, ECO:0000269|PubMed:18946670, ECO:0000269|PubMed:19036076, ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:19927291, ECO:0000269|PubMed:20220065, ECO:0000269|PubMed:20803142, ECO:0000269|PubMed:21425445, ECO:0000269|PubMed:23463630}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase S1 family. Elastase subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.

Sequence caution: Sequence=CAA29300.1; Type=Erroneous initiation; Note=Truncated 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:		Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (PubMed:15140022). Capable of killing E.coli but not S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli and K.pneumoniae (PubMed:10947984). {ECO:0000269\|PubMed:10947984, ECO:0000269\|PubMed:15140022}.


Catalytic activity:		Reaction=Hydrolysis of proteins, including elastin. Preferential cleavage: Val-\|-Xaa > Ala-\|-Xaa.; EC=3.4.21.37;
Subunit:		Interacts with NOTCH2NL. {ECO:0000269\|PubMed:14673143}.
Subcellular location:		Cytoplasmic vesicle, phagosome {ECO:0000269\|PubMed:10947984}. Note=Localized in phagolysosomes following ingestion of E.coli by neutrophils. {ECO:0000269\|PubMed:10947984}.
Tissue specificity:		Bone marrow cells. Neutrophil (PubMed:10947984). {ECO:0000269\|PubMed:10947984}.
Disease:		Cyclic haematopoiesis (CH) [MIM:162800]: Autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency. {ECO:0000269\|PubMed:10581030, ECO:0000269\|PubMed:11001877, ECO:0000269\|PubMed:14673143, ECO:0000269\|PubMed:14962902, ECO:0000269\|PubMed:23463630}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Neutropenia, severe congenital 1, autosomal dominant (SCN1) [MIM:202700]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. {ECO:0000269\|PubMed:11001877, ECO:0000269\|PubMed:11675333, ECO:0000269\|PubMed:12091371, ECO:0000269\|PubMed:14962902, ECO:0000269\|PubMed:17436313, ECO:0000269\|PubMed:18946670, ECO:0000269\|PubMed:19036076, ECO:0000269\|PubMed:19415009, ECO:0000269\|PubMed:19927291, ECO:0000269\|PubMed:20220065, ECO:0000269\|PubMed:20803142, ECO:0000269\|PubMed:21425445, ECO:0000269\|PubMed:23463630}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1 family. Elastase subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00274}.
Sequence caution:		Sequence=CAA29300.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};