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C5 complement C5 [ Homo sapiens (human) ]

Gene ID: 727, updated on 22-Jan-2020

Summary

Official Symbol
C5provided by HGNC
Official Full Name
complement C5provided by HGNC
Primary source
HGNC:HGNC:1331
See related
Ensembl:ENSG00000106804 MIM:120900
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

Genomic context

Location:
9q33.2
Exon count:
43
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (120952335..121074865, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (123714613..123812554, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene CRISPRi-validated cis-regulatory element chr9.2278 Neighboring gene PHD finger protein 19 Neighboring gene TNF receptor associated factor 1 Neighboring gene C5 3' UTR overlapping transcript 1 Neighboring gene centriolin Neighboring gene RAB14, member RAS oncogene family Neighboring gene gelsolin

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Eculizumab, poor response to
MedGen: C3810402 OMIM: 615749 GeneReviews: Not available
Compare labs
Leiner disease
MedGen: C0343047 OMIM: 609536 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

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

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ17816, FLJ17822, MGC142298

Gene Ontology Provided by GOA

Function Evidence Code Pubs
chemokine activity TAS
Traceable Author Statement
more info
PubMed 
endopeptidase inhibitor activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor binding TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
activation of MAPK activity TAS
Traceable Author Statement
more info
PubMed 
cell chemotaxis IEA
Inferred from Electronic Annotation
more info
 
cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
chemotaxis TAS
Traceable Author Statement
more info
PubMed 
complement activation, alternative pathway IEA
Inferred from Electronic Annotation
more info
 
complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
 
cytolysis IEA
Inferred from Electronic Annotation
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
negative regulation of macrophage chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of angiogenesis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of chemokine secretion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of vascular endothelial growth factor production IDA
Inferred from Direct Assay
more info
PubMed 
regulation of complement activation TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space TAS
Traceable Author Statement
more info
PubMed 
membrane attack complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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)

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_007364.1 RefSeqGene

    Range
    5001..102942
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_28

mRNA and Protein(s)

  1. NM_001317163.2NP_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
    UniProtKB/Swiss-Prot
    P01031
    UniProtKB/TrEMBL
    Q59GS8
    Conserved Domains (8) summary
    cd00017
    Location:688756
    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:9991306
    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:15331682
    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:778865
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:132225
    A2M_N; MG2 domain
    pfam07677
    Location:14271515
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10571307
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:478616
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
  2. NM_001317164.2NP_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:682750
    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:772854
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:126219
    A2M_N; MG2 domain
    pfam07703
    Location:472610
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
  3. NM_001735.3NP_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
    Related
    ENSP00000223642.1, ENST00000223642.3
    Conserved Domains (8) summary
    cd00017
    Location:682750
    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:9931300
    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:15271676
    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:772859
    A2M; Alpha-2-macroglobulin family
    pfam01835
    Location:126219
    A2M_N; MG2 domain
    pfam07677
    Location:14211509
    A2M_recep; A-macroglobulin receptor
    pfam07678
    Location:10511301
    A2M_comp; A-macroglobulin complement component
    pfam07703
    Location:472610
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p13 Primary Assembly

    Range
    120952335..121074865 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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