C1S complement C1s [Homo sapiens (human)] - Gene

Summary

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

Location:: 12p13.31

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (7060718..7071032)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (7074188..7084511)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (7168022..7178336)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

STS-T93284 (e-PCR)
- UniSTS:16451

RH17587 (e-PCR)
- UniSTS:63348

C1S_1475 (e-PCR)
- UniSTS:280469

GDB:181601 (e-PCR)
- UniSTS:155308

G61997 (e-PCR)
- UniSTS:139216

D12S2020 (e-PCR)
- UniSTS:25808

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 more info	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

EC 3.4.21.42

NP_001725.1

EC 3.4.21.42

NP_958850.1

EC 3.4.21.42

XP_054229092.1

EC 3.4.21.42

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

NG_011694.1 RefSeqGene

Range

5001..15357

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_25

mRNA and Protein(s)

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
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
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