P09871 · C1S_HUMAN
- ProteinComplement C1s subcomponent
- GeneC1S
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids688 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. Cleaves also IGFBP5 and thereby inhibits the trophic effects of IGF1.
Catalytic activity
Activity regulation
Inhibited by SERPING1.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
12.3 μM | complement component C2 | 37 | ||||
1.9 μM | complement component C4 | 37 |
Less efficient than MASP2 in C4 cleavage.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 60 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 68 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 113 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 131 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 132 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 134 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 149 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 150 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 153 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Active site | 475 | Charge relay system | ||||
Sequence: H | ||||||
Active site | 529 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 632 | Charge relay system | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | blood microparticle | |
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Molecular Function | calcium ion binding | |
Molecular Function | identical protein binding | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | complement activation, classical pathway | |
Biological Process | innate immune response | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameComplement C1s subcomponent
- EC number
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP09871
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Involvement in disease
Complement component C1s deficiency (C1SD)
- Note
- DescriptionA 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.
- See alsoMIM:613783
Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2)
- Note
- DescriptionA 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.
- See alsoMIM:617174
Natural variants in EDSPD2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_077120 | 294 | C>R | in EDSPD2; dbSNP:rs886040975 | |
VAR_077121 | 316 | missing | in EDSPD2; uncertain significance |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_033643 | 119 | in dbSNP:rs12146727 | |||
Sequence: R → H | ||||||
Natural variant | VAR_077120 | 294 | in EDSPD2; dbSNP:rs886040975 | |||
Sequence: C → R | ||||||
Natural variant | VAR_077121 | 316 | in EDSPD2; uncertain significance | |||
Sequence: Missing | ||||||
Natural variant | VAR_033644 | 327 | in dbSNP:rs2239170 | |||
Sequence: V → L | ||||||
Natural variant | VAR_014565 | 383 | in dbSNP:rs20573 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,010 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, modified residue, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-15 | |||||
Sequence: MWCIVLFSLLAWVYA | ||||||
Chain | PRO_0000027587 | 16-437 | Complement C1s subcomponent heavy chain | |||
Sequence: EPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKCVPVCGVPREPFEEKQR | ||||||
Chain | PRO_0000027586 | 16-688 | Complement C1s subcomponent | |||
Sequence: EPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKCVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQENSTPRED | ||||||
Disulfide bond | 65↔83 | |||||
Sequence: CAYDSVQIISGDTEEGRLC | ||||||
Disulfide bond | 135↔147 | |||||
Sequence: CTDFVDVPCSHFC | ||||||
Disulfide bond | 143↔156 | |||||
Sequence: CSHFCNNFIGGYFC | ||||||
Modified residue | 149 | (3R)-3-hydroxyasparagine | ||||
Sequence: N | ||||||
Disulfide bond | 158↔171 | |||||
Sequence: CPPEYFLHDDMKNC | ||||||
Glycosylation | 174 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 175↔202 | |||||
Sequence: CSGDVFTALIGEIASPNYPKPYPENSRC | ||||||
Disulfide bond | 234↔251 | |||||
Sequence: CLDSLVFVAGDRQFGPYC | ||||||
Disulfide bond | 294↔341 | |||||
Sequence: CPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTC | ||||||
Disulfide bond | 321↔354 | |||||
Sequence: CLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKC | ||||||
Disulfide bond | 359↔403 | |||||
Sequence: CGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHC | ||||||
Disulfide bond | 386↔421 | |||||
Sequence: CEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKC | ||||||
Glycosylation | 406 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 425↔549 | Interchain (between heavy and light chains) | ||||
Sequence: CGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPIC | ||||||
Chain | PRO_0000027588 | 438-688 | Complement C1s subcomponent light chain | |||
Sequence: IIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQENSTPRED | ||||||
Disulfide bond | 595↔618 | |||||
Sequence: CKEVKVEKPTADAEAYVFTPNMIC | ||||||
Disulfide bond | 628↔659 | |||||
Sequence: CKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQC |
Post-translational modification
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P09871 | C1R P00736 | 7 | EBI-2810045, EBI-3926504 | |
BINARY | P09871 | C1S P09871 | 2 | EBI-2810045, EBI-2810045 | |
BINARY | P09871 | C2 P06681 | 3 | EBI-2810045, EBI-2835920 | |
BINARY | P09871 | CREB3 O43889-2 | 3 | EBI-2810045, EBI-625022 | |
BINARY | P09871 | REEP4 Q9H6H4 | 3 | EBI-2810045, EBI-7545592 | |
BINARY | P09871 | SERPING1 P05155 | 5 | EBI-2810045, EBI-1223454 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 16-130 | CUB 1 | ||||
Sequence: EPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVAT | ||||||
Domain | 131-172 | EGF-like; calcium-binding | ||||
Sequence: DINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCG | ||||||
Domain | 175-290 | CUB 2 | ||||
Sequence: CSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGD | ||||||
Domain | 292-356 | Sushi 1 | ||||
Sequence: MPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQP | ||||||
Domain | 357-423 | Sushi 2 | ||||
Sequence: VDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPKCVP | ||||||
Domain | 438-680 | Peptidase S1 | ||||
Sequence: IIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQ |
Sequence similarities
Belongs to the peptidase S1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length688
- Mass (Da)76,684
- Last updated1989-07-01 v1
- Checksum85522647A4C47205
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 294 | in Ref. 8; AA sequence | ||||
Sequence: C → K | ||||||
Sequence conflict | 513 | in Ref. 7 | ||||
Sequence: G → GG | ||||||
Sequence conflict | 573 | in Ref. 9; AA sequence | ||||
Sequence: T → A | ||||||
Sequence conflict | 645-646 | in Ref. 9; AA sequence | ||||
Sequence: TK → GR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X06596 EMBL· GenBank· DDBJ | CAA29817.1 EMBL· GenBank· DDBJ | mRNA | ||
M18767 EMBL· GenBank· DDBJ | AAA51853.1 EMBL· GenBank· DDBJ | mRNA | ||
J04080 EMBL· GenBank· DDBJ | AAA51852.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471116 EMBL· GenBank· DDBJ | EAW88689.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471116 EMBL· GenBank· DDBJ | EAW88690.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC056903 EMBL· GenBank· DDBJ | AAH56903.1 EMBL· GenBank· DDBJ | mRNA | ||
AB009076 EMBL· GenBank· DDBJ | BAA86864.1 EMBL· GenBank· DDBJ | Genomic DNA |