C5

Protein identityUniProt · HPA

UniProt accession

P01031

Gene

C5

Ensembl

ENSG00000106804

Chromosome

9

Canonical length

1676 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1676 residues, UniProt reviewed canonical sequence.

>P01031|C5
     1  MGLLGILCFL IFLGKTWGQE QTYVISAPKI FRVGASENIV IQVYGYTEAF DATISIKSYP
    61  DKKFSYSSGH VHLSSENKFQ NSAILTIQPK QLPGGQNPVS YVYLEVVSKH FSKSKRMPIT
   121  YDNGFLFIHT DKPVYTPDQS VKVRVYSLND DLKPAKRETV LTFIDPEGSE VDMVEEIDHI
   181  GIISFPDFKI PSNPRYGMWT IKAKYKEDFS TTGTAYFEVK EYVLPHFSVS IEPEYNFIGY
   241  KNFKNFEITI KARYFYNKVV TEADVYITFG IREDLKDDQK EMMQTAMQNT MLINGIAQVT
   301  FDSETAVKEL SYYSLEDLNN KYLYIAVTVI ESTGGFSEEA EIPGIKYVLS PYKLNLVATP
   361  LFLKPGIPYP IKVQVKDSLD QLVGGVPVTL NAQTIDVNQE TSDLDPSKSV TRVDDGVASF
   421  VLNLPSGVTV LEFNVKTDAP DLPEENQARE GYRAIAYSSL SQSYLYIDWT DNHKALLVGE
   481  HLNIIVTPKS PYIDKITHYN YLILSKGKII HFGTREKFSD ASYQSINIPV TQNMVPSSRL
   541  LVYYIVTGEQ TAELVSDSVW LNIEEKCGNQ LQVHLSPDAD AYSPGQTVSL NMATGMDSWV
   601  ALAAVDSAVY GVQRGAKKPL ERVFQFLEKS DLGCGAGGGL NNANVFHLAG LTFLTNANAD
   661  DSQENDEPCK EILRPRRTLQ KKIEEIAAKY KHSVVKKCCY DGACVNNDET CEQRAARISL
   721  GPRCIKAFTE CCVVASQLRA NISHKDMQLG RLHMKTLLPV SKPEIRSYFP ESWLWEVHLV
   781  PRRKQLQFAL PDSLTTWEIQ GVGISNTGIC VADTVKAKVF KDVFLEMNIP YSVVRGEQIQ
   841  LKGTVYNYRT SGMQFCVKMS AVEGICTSES PVIDHQGTKS SKCVRQKVEG SSSHLVTFTV
   901  LPLEIGLHNI NFSLETWFGK EILVKTLRVV PEGVKRESYS GVTLDPRGIY GTISRRKEFP
   961  YRIPLDLVPK TEIKRILSVK GLLVGEILSA VLSQEGINIL THLPKGSAEA ELMSVVPVFY
  1021  VFHYLETGNH WNIFHSDPLI EKQKLKKKLK EGMLSIMSYR NADYSYSVWK GGSASTWLTA
  1081  FALRVLGQVN KYVEQNQNSI CNSLLWLVEN YQLDNGSFKE NSQYQPIKLQ GTLPVEAREN
  1141  SLYLTAFTVI GIRKAFDICP LVKIDTALIK ADNFLLENTL PAQSTFTLAI SAYALSLGDK
  1201  THPQFRSIVS ALKREALVKG NPPIYRFWKD NLQHKDSSVP NTGTARMVET TAYALLTSLN
  1261  LKDINYVNPV IKWLSEEQRY GGGFYSTQDT INAIEGLTEY SLLVKQLRLS MDIDVSYKHK
  1321  GALHNYKMTD KNFLGRPVEV LLNDDLIVST GFGSGLATVH VTTVVHKTST SEEVCSFYLK
  1381  IDTQDIEASH YRGYGNSDYK RIVACASYKP SREESSSGSS HAVMDISLPT GISANEEDLK
  1441  ALVEGVDQLF TDYQIKDGHV ILQLNSIPSS DFLCVRFRIF ELFEVGFLSP ATFTVYEYHR
  1501  PDKQCTMFYS TSNIKIQKVC EGAACKCVEA DCGQMQEELD LTISAETRKQ TACKPEIAYA
  1561  YKVSITSITV ENVFVKYKAT LLDIYKTGEA VAEKDSEITF IKKVTCTNAE LVKGRQYLIM
  1621  GKEALQIKYN FSFRYIYPLD SLTWIEYWPR DTTCSSCQAF LANLDEFAED IFLNGC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

419 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C5.

Disease | AllUniProt

Conditions C5 is implicated in, by any mechanism.

• Complement component 5 deficiency (C5D) MIM:609536

Disease | GeneticClinVar

54 pathogenic / likely-pathogenic of 918 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Complement component 5 deficiency
• Eculizumab, poor response to
• C5-related disorder
• Lathosterolosis

Disease | ImmuneIEDB

Conditions an epitope on C5 was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for C5 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.7

gnomAD pLI

0

gnomAD missense Z

1.47

DepMap mean gene effect

-0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• chemotaxis
• complement activation, alternative pathway
• complement activation, classical pathway
• complement activation, GZMK pathway
• G protein-coupled receptor signaling pathway
• inflammatory response
• killing of cells of another organism
• negative regulation of macrophage chemotaxis
• positive regulation of chemokine production
• positive regulation of vascular endothelial growth factor production

Molecular functions

• chemokine activity
• endopeptidase inhibitor activity
• signaling receptor binding

Cellular components

• extracellular exosome
• extracellular region
• extracellular space
• membrane attack complex
• other organism cell membrane

Protein domainsUniProt · Pfam · InterPro

• Anaphylatoxin/fibulin
• Netrin domain
• Alpha-2-macroglobulin
• Anaphylatoxin, complement system domain
• Macroglobulin domain
• Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid
• Tissue inhibitor of metalloproteinases-like, OB-fold
• Alpha-macroglobulin, receptor-binding
• Alpha-2-macroglobulin, bait region domain
• Alpha-macroglobulin-like, TED domain
• Immunoglobulin-like fold
• Anaphylatoxin, complement system
• Netrin module, non-TIMP type
• Alpha-macroglobulin, receptor-binding domain superfamily
• Macroglobulin domain MG4
• Complement C3/4/5, macroglobulin domain MG1
• Macroglobulin domain MG3
• Alpha-2-macroglobulin/Complement system
• Alpha-2-macroglobulin family
• UNC-6/NTR/C345C module
• Anaphylotoxin-like domain
• MG2 domain
• A-macroglobulin receptor binding domain
• A-macroglobulin TED domain
• Alpha-2-macroglobulin bait region domain
• Macroglobulin domain MG4
• Macroglobulin domain MG1
• Macroglobulin domain MG3
• Complement component 5, CUB domain
• Complement component 5, CUB domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Complement alternate pathway
• Complement pathway
• Cytolysis
• Disulfide bond
• Glycoprotein
• Immunity
• Inflammatory response
• Innate immunity
• Membrane
• Membrane attack complex
• Secreted
• Signal
• Target cell membrane
• Target membrane

InteractionsUniProt · HPA

Protein binding partners of C5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• C6