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    C1S complement C1s [ Homo sapiens (human) ]

    Gene ID: 716, updated on 10-Dec-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
    mouse all
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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
    • 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
      UniProtKB/TrEMBL
      A8K2N0, B3KNX0
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P09871.1 GenPept UniProtKB/Swiss-Prot:P09871

    Gene LinkOut

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