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    C5 complement C5 [ Homo sapiens (human) ]

    Gene ID: 727, updated on 3-Nov-2024

    Summary

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    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

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    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

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. A second stimulus required for enhanced antifungal activity of human neutrophils in blood is provided by anaphylatoxin C5a. HĂĽnniger K, et al. J Immunol, 2015 Feb 1. PMID 25539819
    2. Structure of human desArg-C5a. Cook WJ, et al. Acta Crystallogr D Biol Crystallogr, 2010 Feb. PMID 20124699
    3. Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus. Laursen NS, et al. Proc Natl Acad Sci U S A, 2010 Feb 23. PMID 20133685, Free PMC Article
    4. Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis. Kourtzelis I, et al. Blood, 2010 Jul 29. PMID 20424189, Free PMC Article
    5. Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials. Smith PK, et al. J Thorac Cardiovasc Surg, 2011 Jul. PMID 20880552

    See all (290) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. Complement decay-accelerating factor inhibits inflammation-induced myopia development.
      Title: Complement decay-accelerating factor inhibits inflammation-induced myopia development.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Regulation of murine contact sensitivity to urushiol components by serum factors.
      Title: Regulation of murine contact sensitivity to urushiol components by serum factors.
    8. 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.
    9. 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.
    10. 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
    		not available
    Eculizumab, poor response to
    MedGen: C3810402 OMIM: 615749 GeneReviews: Not available
    		not available

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    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

    • 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 
    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 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

    1. NG_007364.1 RefSeqGene

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

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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

    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)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P01031.4 GenPept UniProtKB/Swiss-Prot:P01031

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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