Property Summary

NCBI Gene PubMed Count 57
PubMed Score 918.86
PubTator Score 483.75

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count
cystic fibrosis 1670
Disease Target Count P-value
lung carcinoma 2844 3.4e-24
juvenile dermatomyositis 1189 7.6e-16
pituitary cancer 1972 6.4e-12
Duchenne muscular dystrophy 602 3.3e-09
ovarian cancer 8491 4.8e-08
malignant mesothelioma 3163 8.5e-08
limb girdle muscular dystrophy 2A 156 6.3e-07
lung cancer 4473 7.5e-06
posterior fossa group A ependymoma 1511 1.0e-05
ulcerative colitis 2087 1.1e-05
acute quadriplegic myopathy 1157 1.5e-05
pilocytic astrocytoma 3086 1.6e-05
pancreatic cancer 2300 8.8e-05
primary pancreatic ductal adenocarcinoma 1271 1.8e-04
head and neck cancer and chronic obstructive pulmonary disease 237 5.5e-04
non-small cell lung cancer 2798 6.0e-04
psoriasis 6685 6.9e-04
intraductal papillary-mucinous carcinoma (IPMC) 2988 1.5e-03
invasive ductal carcinoma 2950 1.8e-03
diabetes mellitus 1663 1.8e-03
medulloblastoma, large-cell 6234 2.0e-03
dermatomyositis 966 2.2e-03
glioblastoma 5572 3.6e-03
subependymal giant cell astrocytoma 2287 3.7e-03
Becker muscular dystrophy 187 3.9e-03
intraductal papillary-mucinous adenoma (IPMA) 2956 4.0e-03
primary Sjogren syndrome 788 4.1e-03
autosomal dominant Emery-Dreifuss muscular dystrophy 499 4.1e-03
gastric carcinoma 832 5.2e-03
sonic hedgehog group medulloblastoma 1482 8.9e-03
intraductal papillary-mucinous neoplasm (IPMN) 3289 9.2e-03
colon cancer 1475 9.6e-03
pediatric high grade glioma 2712 1.2e-02
adrenocortical carcinoma 1427 1.4e-02
chronic kidney disease 90 1.7e-02
Atopic dermatitis 944 2.3e-02
esophageal adenocarcinoma 737 3.5e-02
Disease Target Count Z-score Confidence
Ehlers-Danlos syndrome 42 0.0 4.0

Expression

  Differential Expression (38)

Disease log2 FC p
malignant mesothelioma -1.900 8.5e-08
esophageal adenocarcinoma 1.400 3.5e-02
psoriasis 1.400 6.9e-04
glioblastoma 2.300 3.6e-03
posterior fossa group A ependymoma 3.000 1.0e-05
cystic fibrosis 2.300 7.6e-03
medulloblastoma, large-cell -1.200 2.0e-03
Duchenne muscular dystrophy 1.913 3.3e-09
limb girdle muscular dystrophy 2A 1.679 6.3e-07
autosomal dominant Emery-Dreifuss muscul... 1.426 4.1e-03
Becker muscular dystrophy 1.111 3.9e-03
juvenile dermatomyositis 2.232 7.6e-16
acute quadriplegic myopathy 1.610 1.5e-05
Atopic dermatitis -1.900 2.3e-02
adrenocortical carcinoma -1.399 1.4e-02
chronic kidney disease 1.600 1.7e-02
primary pancreatic ductal adenocarcinoma 1.815 1.8e-04
non-small cell lung cancer 1.323 6.0e-04
intraductal papillary-mucinous adenoma (... -2.600 4.0e-03
intraductal papillary-mucinous carcinoma... -3.200 1.5e-03
intraductal papillary-mucinous neoplasm ... -3.500 9.2e-03
lung cancer -2.500 7.5e-06
colon cancer -1.200 9.6e-03
diabetes mellitus -1.500 1.8e-03
pediatric high grade glioma 1.800 1.2e-02
pilocytic astrocytoma 2.300 1.6e-05
sonic hedgehog group medulloblastoma 1.600 8.9e-03
primary Sjogren syndrome 2.100 4.1e-03
subependymal giant cell astrocytoma 2.514 3.7e-03
lung carcinoma -3.200 3.4e-24
gastric carcinoma 1.600 5.2e-03
invasive ductal carcinoma -1.400 1.8e-03
ulcerative colitis 2.900 1.1e-05
ovarian cancer -3.600 4.8e-08
pituitary cancer -3.600 6.4e-12
pancreatic cancer 1.900 8.8e-05
dermatomyositis 2.000 2.2e-03
head and neck cancer and chronic obstruc... 1.200 5.5e-04

MLP Assay (3)

AID Type Active / Inconclusive / Inactive Description
538 screening 102 / 0 / 62035 Complement factor C1s
787 confirmatory 23 / 1 / 160 Complement factor C1s IC50 from mixture screen
829 confirmatory 0 / 0 / 21 Complement C1s ELISA

Gene RIF (15)

PMID Text
26231209 C1q exists as the C1 complex (C1qC1r2C1s2), and C1q binding to ligands activates the C1r/C1s proteases. Incubation of nucleoli with C1 caused degradation of the nucleolar proteins nucleolin and nucleophosmin 1. T
24695853 TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins.
23989031 Data indicate that complement C1s mRNA level was low in ICR-derived glomerulonephritis (ICGN) mice liver as compared with age-matched ICR mice.
23650384 Analysis of its interaction properties by surface plasmon resonance shows that rC1q retains the ability of serum C1q to associate with the C1s-C1r-C1r-C1s tetramer, to recognize physiological C1q ligands such as IgG and pentraxin 3
23592783 A molecular switch governs the interaction between the human complement protease C1s and its substrate, complement C4.
22855709 Four positively charged amino acids on the serine protease domain appear to form a catalytic exosite that is required for efficient cleavage of C4 in the classical pathway of complement.
20592021 These results provide further structural insights into the architecture of the C1 complex, and the interactions between C1r and C1s.
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20406964 Observational study of gene-disease association. (HuGE Navigator)
20008834 Detailed mapping of post-translational modifications and insights into the C1r/C1s binding sites.
19423540 Observational study of gene-disease association. (HuGE Navigator)
19344414 Observational study of gene-disease association. (HuGE Navigator)
18062908 There are splice variants of C1s mRNA transcripts in normal human cells
16169853 full specificity of the enzyme using a randomized phage display library
14674770 Interaction with the prime side residues at the cleavage point in C1s enhances the affinity of the enzyme for complement 2 and complement 4 substrates; these prime subsite residues mediate positive cooperativity in the cleavage of the substrate.

AA Sequence

MWCIVLFSLLAWVYAEPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIELSENCAYDSV      1 - 70
QIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERFTGFAAYYVATDINECTDFVD     71 - 140
VPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVFTALIGEIASPNYPKPYPENSRCEYQIRLEK    141 - 210
GFQVVVTLRREDFDVEAADSAGNCLDSLVFVAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQK    211 - 280
KGWKLRYHGDPMPCPKEDTPNSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNS    281 - 350
KLKCQPVDCGIPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPK    351 - 420
CVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGNREPTMYVGST    421 - 490
SVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVKMGPTVSPICLPGTSSDYNLM    491 - 560
DGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKVEKPTADAEAYVFTPNMICAGGEKGMDSCKG    561 - 630
DSGGAFAVQDPNDKTKFYAAGLVSWGPQCGTYGLYTRVKNYVDWIMKTMQENSTPRED                631 - 688
//

Text Mined References (59)

PMID Year Title
26231209 2015 C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.
24695853 2014 TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23989031 2013 Gene expression analysis detected a low expression level of C1s gene in ICR-derived glomerulonephritis (ICGN) mice.
23650384 2013 Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites.
23592783 2013 A molecular switch governs the interaction between the human complement protease C1s and its substrate, complement C4.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22855709 2012 Identification of a catalytic exosite for complement component C4 on the serine protease domain of C1s.
22516433 2012 Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability.
20592021 2010 Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20008834 2010 Analysis of human C1q by combined bottom-up and top-down mass spectrometry: detailed mapping of post-translational modifications and insights into the C1r/C1s binding sites.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19344414 2009 Risk of non-Hodgkin lymphoma in association with germline variation in complement genes.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
18062908 2008 Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene.
17996945 2008 Revisiting the mechanism of the autoactivation of the complement protease C1r in the C1 complex: structure of the active catalytic region of C1r.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16335952 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.
16169853 2005 Elucidation of the substrate specificity of the C1s protease of the classical complement pathway.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14674770 2003 Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates.
12788922 2003 X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement.
12645945 2003 Biochemical and functional characterization of the interaction between pentraxin 3 and C1q.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11527969 2001 Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2.
11390518 2001 Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases.
11337467 2001 Identification and characterization of the potential promoter regions of 1031 kinds of human genes.
10878362 2000 Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19.
10775260 2000 Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle.
10630213 1999 Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor.
10092586 1999 The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s.
9973493 1999 Molecular basis of human complement C1s deficiency.
9882449 1999 Heparin binding and augmentation of C1 inhibitor activity.
9856483 1998 Selective complement C1s deficiency caused by homozygous four-base deletion in the C1s gene.
9794427 1998 Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates.
9477945 1998 Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
7779774 1995 Structure of the catalytic region of human complement protease C1s: study by chemical cross-linking and three-dimensional homology modeling.
6604523 1983 Structural and circular-dichroism studies on the interaction between human C1-esterase inhibitor and C1s.
6362661 1983 The serine proteinase chain of human complement component C1s. Cyanogen bromide cleavage and N-terminal sequences of the fragments.
3756141 1986 Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization.
3521730 1986 Basic proline-rich proteins from human parotid saliva: complete covalent structures of proteins IB-1 and IB-6.
3500856 1987 Molecular cloning of cDNA for human complement component C1s. The complete amino acid sequence.
3007145 1986 Human complement component C1s. Partial sequence determination of the heavy chain and identification of the peptide bond cleaved during activation.
2834284 1988 Assignment of the complement serine protease genes C1r and C1s to chromosome 12 region 12p13.
2831944 1987 Complete cDNA sequence of human complement Cls and close physical linkage of the homologous genes Cls and Clr.
2553984 1989 Complement genes C1r and C1s feature an intronless serine protease domain closely related to haptoglobin.
2537870 1989 Synthesis and regulation of C1 inhibitor in human skin fibroblasts.
2459702 1988 Human genes for complement components C1r and C1s in a close tail-to-tail arrangement.
2387866 1990 Ca2+ binding properties and Ca2(+)-dependent interactions of the isolated NH2-terminal alpha fragments of human complement proteases C1-r and C1-s.
2372546 1990 NH2-terminal calcium-binding domain of human complement C1s- mediates the interaction of C1r- with C1q.
2141278 1990 Chemical and functional characterization of a fragment of C1-s containing the epidermal growth factor homology region.
2007122 1991 Identification of the disulfide bonds of human complement C1s.
1854725 1991 Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)-dependent interactions of human C1s. Location of the iodination sites.
1533159 1992 Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex.
1249422 1976 Activation of C1r by proteolytic cleavage.
814163 1976 Physicochemical and functional characterization of the C1r subunit of the first complement component.