UniProt functional annotation for P09871



	UniProt functional annotation for P09871

UniProt code: P09871.

Organism: Homo sapiens (Human).

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

Function: C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.

Catalytic activity: Reaction=Cleavage of Arg-|-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase.; EC=3.4.21.42; Evidence={ECO:0000269|PubMed:11527969};

Activity regulation: Inhibited by SERPING1. {ECO:0000269|PubMed:11527969}.

Biophysicochemical properties: Kinetic parameters: KM=12.3 uM for complement component C2 (at 37 degrees Celsius) {ECO:0000269|PubMed:11527969}; KM=1.9 uM for complement component C4 (at 37 degrees Celsius) {ECO:0000269|PubMed:11527969}; Note=Less efficient than MASP2 in C4 cleavage.;

Subunit: C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain. {ECO:0000269|PubMed:2007122}.

Ptm: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. {ECO:0000269|PubMed:2141278}.

Disease: Complement component C1s deficiency (C1SD) [MIM:613783]: A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. {ECO:0000269|PubMed:11390518}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2) [MIM:617174]: A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD2 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:27745832}. Note=The disease is caused by variants affecting the gene represented in this entry.

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

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:		C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.


Catalytic activity:		Reaction=Cleavage of Arg-\|-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-\|-Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase.; EC=3.4.21.42; Evidence={ECO:0000269\|PubMed:11527969};
Activity regulation:		Inhibited by SERPING1. {ECO:0000269\|PubMed:11527969}.
Biophysicochemical properties:		Kinetic parameters: KM=12.3 uM for complement component C2 (at 37 degrees Celsius) {ECO:0000269\|PubMed:11527969}; KM=1.9 uM for complement component C4 (at 37 degrees Celsius) {ECO:0000269\|PubMed:11527969}; Note=Less efficient than MASP2 in C4 cleavage.;
Subunit:		C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain. {ECO:0000269\|PubMed:2007122}.
Ptm:		The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. {ECO:0000269\|PubMed:2141278}.
Disease:		Complement component C1s deficiency (C1SD) [MIM:613783]: A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis. {ECO:0000269\|PubMed:11390518}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2) [MIM:617174]: A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD2 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269\|PubMed:27745832}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1 family. {ECO:0000255\|PROSITE- ProRule:PRU00274}.