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C1S complement C1s [ Homo sapiens (human) ]

Gene ID: 716, updated on 2-Nov-2024

Summary

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Official Symbol
C1Sprovided by HGNC
Official Full Name
complement C1sprovided by HGNC
Primary source
HGNC:HGNC:1247
See related
Ensembl:ENSG00000182326 MIM:120580; AllianceGenome:HGNC:1247
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EDSPD2
Summary
This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]
Expression
Broad expression in liver (RPKM 683.7), gall bladder (RPKM 363.8) and 18 other tissues See more
Orthologs
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Genomic context

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See C1S in Genome Data Viewer
Location:
12p13.31
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (7060718..7071032)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (7074188..7084511)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (7168022..7178336)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L37 pseudogene 20 Neighboring gene zinc finger protein 655 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7167609-7168110 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7168111-7168610 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:7188509-7189008 Neighboring gene complement C1r Neighboring gene Sharpr-MPRA regulatory region 13442 Neighboring gene complement C1r subcomponent like Neighboring gene MED14-independent group 3 enhancer GRCh37_chr12:7260830-7262029 Neighboring gene C1RL antisense RNA 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The serine proteinase chain of human complement component C1s. Cyanogen bromide cleavage and N-terminal sequences of the fragments. Carter PE, et al. Biochem J, 1983 Dec 1. PMID 6362661, Free PMC Article
  2. Identification of a catalytic exosite for complement component C4 on the serine protease domain of C1s. Duncan RC, et al. J Immunol, 2012 Sep 1. PMID 22855709
  3. Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene. Amano MT, et al. Mol Immunol, 2008 Mar. PMID 18062908
  4. Elucidation of the substrate specificity of the C1s protease of the classical complement pathway. Kerr FK, et al. J Biol Chem, 2005 Nov 25. PMID 16169853
  5. Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates. O'Brien G, et al. Biochemistry, 2003 Dec 23. PMID 14674770

See all (77) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Cytoprotective effects of C1s enzyme in macrophages in atherosclerosis mediated through the LRP5 and Wnt/beta-catenin pathway.
    Title: Cytoprotective effects of C1s enzyme in macrophages in atherosclerosis mediated through the LRP5 and Wnt/β-catenin pathway.
  2. A homozygous loss-of-function C1S mutation is associated with Kikuchi-Fujimoto disease.
    Title: A homozygous loss-of-function C1S mutation is associated with Kikuchi-Fujimoto disease.
  3. Degradation of collagen I by activated C1s in periodontal Ehlers-Danlos Syndrome.
    Title: Degradation of collagen I by activated C1s in periodontal Ehlers-Danlos Syndrome.
  4. C1q binding to surface-bound IgG is stabilized by C1r2s2 proteases.
    Title: C1q binding to surface-bound IgG is stabilized by C1r(2)s(2) proteases.
  5. The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's Disease.
    Title: The Impact of Complement Genes on the Risk of Late-Onset Alzheimer's Disease.
  6. Two Different Missense C1S Mutations, Associated to Periodontal Ehlers-Danlos Syndrome, Lead to Identical Molecular Outcomes.
    Title: Two Different Missense C1S Mutations, Associated to Periodontal Ehlers-Danlos Syndrome, Lead to Identical Molecular Outcomes.
  7. The serine protease domains of C1r and C1s are at the periphery of the C1r2s2 tetramer both when alone or within the nonactivated C1 complex. The C1 complex adopts a conformation incompatible with intramolecular activation of C1. Instead, intermolecular proteolytic activation between neighboring C1 complexes bound to a complement-activating surface occurs. Many structurally unrelated molecular patterns can activate C1.
    Title: Structure and activation of C1, the complex initiating the classical pathway of the complement cascade.
  8. Periodontal Ehlers-Danlos Syndrome in at least the great majority of cases results from specific classes of heterozygous mutations in C1R and C1S.
    Title: Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.
  9. 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
    Title: C1q protein binds to the apoptotic nucleolus and causes C1 protease degradation of nucleolar proteins.
  10. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins.
    Title: TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Complement component C1s deficiency
MedGen: C3151078 OMIM: 613783 GeneReviews: Not available
Compare labs
Ehlers-Danlos syndrome, periodontal type 2
MedGen: C4310681 OMIM: 617174 GeneReviews: Periodontal Ehlers-Danlos Syndrome
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ44757

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables serine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
complement C1s subcomponent
Names
C1 esterase
basic proline-rich peptide IB-1
complement component 1 subcomponent s
complement component 1, s subcomponent
NP_001333779.1
NP_001725.1
NP_958850.1
XP_054229092.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011694.1 RefSeqGene

    Range
    5001..15357
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_25

mRNA and Protein(s)

  1. NM_001346850.2 → NP_001333779.1  complement C1s subcomponent isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1.
    Source sequence(s)
    AM886411, BC056903, DA638990
    Consensus CDS
    CCDS86271.1
    UniProtKB/TrEMBL
    F8WCZ6
    Related
    ENSP00000384171.3, ENST00000402681.7

  2. NM_001734.5 → NP_001725.1  complement C1s subcomponent isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001725.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    BC056903, DA638990, J04080
    Consensus CDS
    CCDS31735.1
    UniProtKB/Swiss-Prot
    D3DUT4, P09871, Q9UCU7, Q9UCU8, Q9UCU9, Q9UCV0, Q9UCV1, Q9UCV2, Q9UCV3, Q9UCV4, Q9UCV5, Q9UM14
    UniProtKB/TrEMBL
    A8K2N0, B3KNX0
    Related
    ENSP00000354057.5, ENST00000360817.10
    Conserved Domains (6) summary
    cd00033
    Location:294 → 355
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    cd00041
    Location:18 → 129
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00190
    Location:438 → 678
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00084
    Location:359 → 421
    Sushi; Sushi repeat (SCR repeat)
    pfam00431
    Location:175 → 287
    CUB; CUB domain
    pfam14670
    Location:143 → 171
    FXa_inhibition; Coagulation Factor Xa inhibitory site

  3. NM_201442.4 → NP_958850.1  complement C1s subcomponent isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_958850.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    BC056903, DA638990
    Consensus CDS
    CCDS31735.1
    UniProtKB/Swiss-Prot
    D3DUT4, P09871, Q9UCU7, Q9UCU8, Q9UCU9, Q9UCV0, Q9UCV1, Q9UCV2, Q9UCV3, Q9UCV4, Q9UCV5, Q9UM14
    UniProtKB/TrEMBL
    A8K2N0, B3KNX0
    Related
    ENSP00000328173.3, ENST00000328916.7
    Conserved Domains (6) summary
    cd00033
    Location:294 → 355
    CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    cd00041
    Location:18 → 129
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00190
    Location:438 → 678
    Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
    pfam00084
    Location:359 → 421
    Sushi; Sushi repeat (SCR repeat)
    pfam00431
    Location:175 → 287
    CUB; CUB domain
    pfam14670
    Location:143 → 171
    FXa_inhibition; Coagulation Factor Xa inhibitory site

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    7060718..7071032
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    7074188..7084511
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054373117.1 → XP_054229092.1  complement C1s subcomponent isoform X1

    UniProtKB/Swiss-Prot
    D3DUT4, P09871, Q9UCU7, Q9UCU8, Q9UCU9, Q9UCV0, Q9UCV1, Q9UCV2, Q9UCV3, Q9UCV4, Q9UCV5, Q9UM14
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P09871.1 GenPept UniProtKB/Swiss-Prot:P09871

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