C5 complement C5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: C5provided by HGNC
Official Full Name: complement C5provided by HGNC
Primary source: HGNC:HGNC:1331
See related: Ensembl:ENSG00000106804 MIM:120900; AllianceGenome:HGNC:1331
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: C5D; C5a; C5b; ECLZB; CPAMD4
Summary: This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]
Expression: Biased expression in liver (RPKM 85.9) and lung (RPKM 3.7) See more
Orthologs: mouse all
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Genomic context

Location:: 9q33.2

Exon count:: 43

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (120952335..121074865, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (133148474..133270972, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (123714613..123837143, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Complement Component C5a and Fungal Pathogen Induce Diverse Responses through Crosstalk between Transient Receptor Potential Channel (TRPs) Subtypes in Human Conjunctival Epithelial Cells.
Title: Complement Component C5a and Fungal Pathogen Induce Diverse Responses through Crosstalk between Transient Receptor Potential Channel (TRPs) Subtypes in Human Conjunctival Epithelial Cells.
Complement decay-accelerating factor inhibits inflammation-induced myopia development.
Title: Complement decay-accelerating factor inhibits inflammation-induced myopia development.
Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children.
Title: Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children.
Differential contributions of the C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients.
Title: Differential contributions of the C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients.
A Transcriptome Array-Based Approach to Link SGLT-2 and Intrarenal Complement C5 Synthesis in Diabetic Nephropathy.
Title: A Transcriptome Array-Based Approach to Link SGLT-2 and Intrarenal Complement C5 Synthesis in Diabetic Nephropathy.
Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.
Title: Dual inhibition of complement C5 and CD14 attenuates inflammation in a cord blood model.
Regulation of murine contact sensitivity to urushiol components by serum factors.
Title: Regulation of murine contact sensitivity to urushiol components by serum factors.
C5a elevation in convalescents from severe COVID-19 is not associated with early complement activation markers C3bBbP or C4d.
Title: C5a elevation in convalescents from severe COVID-19 is not associated with early complement activation markers C3bBbP or C4d.
Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women.
Title: Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women.
C5 and SRGAP3 Polymorphisms Are Linked to Paediatric Allergic Asthma in the Italian Population.
Title: C5 and SRGAP3 Polymorphisms Are Linked to Paediatric Allergic Asthma in the Italian Population.

Submit: New GeneRIF Correction See all GeneRIFs (181)

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 5 deficiency MedGen: C0343047 OMIM: 609536 GeneReviews: Not available	Compare labs
Eculizumab, poor response to MedGen: C3810402 OMIM: 615749 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	A synthetic peptide covering positions 233-251 of the HIV-1 gp120 protein binds to complement proteins C3, C4, C5, C9, and properdin	PubMed
	env	Complement proteins C4, C3d, C5b-9, and properdin bind to HIV-1 gp120-coated CD4+ T cells of healthy individuals when incubated in autologous serum	PubMed
Vif	vif	HIV-1 Vif downregulates the expression of complement component 5 (C5) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G29157 (e-PCR)
- UniSTS:19739

WI-12734 (e-PCR)
- UniSTS:72236

SHGC-52622 (e-PCR)
- UniSTS:70213

D9S2050 (e-PCR)
- UniSTS:19110

C5_001 (e-PCR)
- UniSTS:275883

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chemokine activity	TAS Traceable Author Statement more info	PubMed
enables endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cell chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in complement activation, alternative pathway	IEA Inferred from Electronic Annotation more info
involved_in complement activation, classical pathway	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in killing of cells of another organism	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of macrophage chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of vascular endothelial growth factor production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	TAS Traceable Author Statement more info	PubMed
part_of membrane attack complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: complement C5

Names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4; C5a anaphylatoxin; anaphylatoxin C5a analog; complement component 5; prepro-C5

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_007364.1 RefSeqGene

Range

5001..102942

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_28

mRNA and Protein(s)

NM_001317163.2 → NP_001304092.1 complement C5 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2). This isoform (2) lacks a predicted signal peptide compared to isoform 1.

Source sequence(s)

AB209031, BC113738, CB250401

Consensus CDS

CCDS94473.1

UniProtKB/TrEMBL

A0A8Q3SID6

Related

ENSP00000512521.1, ENST00000696281.1

Conserved Domains (8) summary

cd00017
Location:688 → 756

ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...

cd02896
Location:999 → 1306

complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...

cd03582
Location:1533 → 1682

NTR_complement_C5; NTR/C345C domain, complement C5 subfamily; The NTR domain found in complement C5 is also known as C345C because it occurs at the C-terminus of complement C3, C4 and C5. Complement C5 is activated by C5 convertase, which itself is a complex between C3b ...

pfam00207
Location:778 → 865

A2M; Alpha-2-macroglobulin family

pfam01835
Location:132 → 225

A2M_N; MG2 domain

pfam07677
Location:1427 → 1515

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1057 → 1307

A2M_comp; A-macroglobulin complement component

pfam07703
Location:478 → 616

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
NM_001317164.2 → NP_001304093.1 complement C5 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' and 3' UTRs, lacks a portion of the 5' and 3' coding regions, and initiates translation at an alternate start site compared to variant 2. The encoded isoform (3) has shorter and distinct N- and C-termini compared to isoform 2. This isoform (3) may undergo proteolytic processing similar to isoform (1).

Source sequence(s)

AC006430, AK310774

Conserved Domains (4) summary

cd00017
Location:682 → 750

ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...

pfam00207
Location:772 → 854

A2M; Alpha-2-macroglobulin family

pfam01835
Location:126 → 219

A2M_N; MG2 domain

pfam07703
Location:472 → 610

A2M_N_2; Alpha-2-macroglobulin family N-terminal region
NM_001735.3 → NP_001726.2 complement C5 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001726.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start site compared to variant 2. The encoded isoform (1) has a shorter and unique N-terminus compared to isoform 2.

Source sequence(s)

AV682721, BC022299, BG533927, M57729, M65134, T82068

Consensus CDS

CCDS6826.1

UniProtKB/Swiss-Prot

P01031, Q14CJ0, Q27I61

Related

ENSP00000223642.1, ENST00000223642.3

Conserved Domains (10) summary

cd00017
Location:682 → 750

ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...

cd02896
Location:993 → 1300

complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...

cd03582
Location:1527 → 1676

NTR_complement_C5; NTR/C345C domain, complement C5 subfamily; The NTR domain found in complement C5 is also known as C345C because it occurs at the C-terminus of complement C3, C4 and C5. Complement C5 is activated by C5 convertase, which itself is a complex between C3b ...

pfam00207
Location:772 → 859

A2M; Alpha-2-macroglobulin family

pfam01835
Location:126 → 219

A2M_N; MG2 domain

pfam07677
Location:1421 → 1509

A2M_recep; A-macroglobulin receptor

pfam07703
Location:467 → 610

A2M_N_2; Alpha-2-macroglobulin family N-terminal region

pfam17789
Location:354 → 457

MG4; Macroglobulin domain MG4

pfam17790
Location:20 → 120

MG1; Macroglobulin domain MG1

pfam17791
Location:221 → 301

MG3; Macroglobulin domain MG3