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C5 complement C5 [ Homo sapiens (human) ]

Gene ID: 727, updated on 8-Oct-2024

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
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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_000009.12Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory regions 2033 and 13781 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28897 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123618013-123618514 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123618515-123619014 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28898 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20224 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr9:123635243-123635866 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:123635867-123636492 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20227 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20226 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:123638303-123638894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28899 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28900 Neighboring gene cutA divalent cation tolerance like, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28901 Neighboring gene CRISPRi-validated cis-regulatory element chr9.2278 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28902 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28903 Neighboring gene PHD finger protein 19 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28904 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123675790-123676294 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28906 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123687703-123688226 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28909 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20228 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28911 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28912 Neighboring gene TNF receptor associated factor 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:123725569-123725752 Neighboring gene C5 3' UTR overlapping transcript 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28913 Neighboring gene uncharacterized LOC124902261 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28914 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:123836497-123836693 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20230 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28915 Neighboring gene NANOG hESC enhancer GRCh37_chr9:123883693-123884194 Neighboring gene centriolin Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28917 Neighboring gene uncharacterized LOC124902357 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20231 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:123963761-123964260 Neighboring gene RAB14, member RAS oncogene family Neighboring gene gelsolin

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
EBI GWAS Catalog
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
EBI GWAS 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

Clone Names

  • FLJ17816, FLJ17822, MGC142298

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 

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)

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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_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
    Consensus CDS
    CCDS94473.1
    UniProtKB/TrEMBL
    A0A8Q3SID6
    Related
    ENSP00000512521.1, ENST00000696281.1
    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, Q14CJ0, Q27I61
    Related
    ENSP00000223642.1, ENST00000223642.3
    Conserved Domains (10) 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
    pfam07703
    Location:467610
    A2M_N_2; Alpha-2-macroglobulin family N-terminal region
    pfam17789
    Location:354457
    MG4; Macroglobulin domain MG4
    pfam17790
    Location:20120
    MG1; Macroglobulin domain MG1
    pfam17791
    Location:221301
    MG3; Macroglobulin domain MG3

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_000009.12 Reference GRCh38.p14 Primary Assembly

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    133148474..133270972 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)