C6

Protein identityUniProt · HPA

UniProt accession

P13671

Gene

C6

Ensembl

ENSG00000039537

Chromosome

5

Canonical length

934 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

Canonical amino-acid sequenceUniProt

934 residues, UniProt reviewed canonical sequence.

>P13671|C6
     1  MARRSVLYFI LLNALINKGQ ACFCDHYAWT QWTSCSKTCN SGTQSRHRQI VVDKYYQENF
    61  CEQICSKQET RECNWQRCPI NCLLGDFGPW SDCDPCIEKQ SKVRSVLRPS QFGGQPCTAP
   121  LVAFQPCIPS KLCKIEEADC KNKFRCDSGR CIARKLECNG ENDCGDNSDE RDCGRTKAVC
   181  TRKYNPIPSV QLMGNGFHFL AGEPRGEVLD NSFTGGICKT VKSSRTSNPY RVPANLENVG
   241  FEVQTAEDDL KTDFYKDLTS LGHNENQQGS FSSQGGSSFS VPIFYSSKRS ENINHNSAFK
   301  QAIQASHKKD SSFIRIHKVM KVLNFTTKAK DLHLSDVFLK ALNHLPLEYN SALYSRIFDD
   361  FGTHYFTSGS LGGVYDLLYQ FSSEELKNSG LTEEEAKHCV RIETKKRVLF AKKTKVEHRC
   421  TTNKLSEKHE GSFIQGAEKS ISLIRGGRSE YGAALAWEKG SSGLEEKTFS EWLESVKENP
   481  AVIDFELAPI VDLVRNIPCA VTKRNNLRKA LQEYAAKFDP CQCAPCPNNG RPTLSGTECL
   541  CVCQSGTYGE NCEKQSPDYK SNAVDGQWGC WSSWSTCDAT YKRSRTRECN NPAPQRGGKR
   601  CEGEKRQEED CTFSIMENNG QPCINDDEEM KEVDLPEIEA DSGCPQPVPP ENGFIRNEKQ
   661  LYLVGEDVEI SCLTGFETVG YQYFRCLPDG TWRQGDVECQ RTECIKPVVQ EVLTITPFQR
   721  LYRIGESIEL TCPKGFVVAG PSRYTCQGNS WTPPISNSLT CEKDTLTKLK GHCQLGQKQS
   781  GSECICMSPE EDCSHHSEDL CVFDTDSNDY FTSPACKFLA EKCLNNQQLH FLHIGSCQDG
   841  RQLEWGLERT RLSSNSTKKE SCGYDTCYDW EKCSASTSKC VCLLPPQCFK GGNQLYCVKM
   901  GSSTSEKTLN ICEVGTIRCA NRKMEILHPG KCLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C6 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

2

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

588 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C6.

Disease | AllUniProt

Conditions C6 is implicated in, by any mechanism.

• Complement component 6 deficiency (C6D) MIM:612446

Disease | GeneticClinVar

64 pathogenic / likely-pathogenic of 627 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Complement component 6 deficiency
• C6-related disorder
• Immunodeficiency due to a late component of complement deficiency
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on C6 was assayed in.

• rheumatoid arthritis B cell

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)

0.99

gnomAD pLI

0

gnomAD missense Z

-0.88

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• complement activation
• complement activation, classical pathway
• complement activation, GZMK pathway
• in utero embryonic development
• killing of cells of another organism
• positive regulation of activation of membrane attack complex
• positive regulation of angiogenesis
• positive regulation of immune response
• transmembrane transport

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Thrombospondin type-1 (TSP1) repeat
• Membrane attack complex component/perforin/complement C9
• Low-density lipoprotein (LDL) receptor class A repeat
• Kazal domain
• Factor I / membrane attack complex
• Membrane attack complex component/perforin domain, conserved site
• Membrane attack complex component/perforin (MACPF) domain
• Low-density lipoprotein (LDL) receptor class A, conserved site
• Sushi/SCR/CCP superfamily
• LDL receptor-like superfamily
• Thrombospondin type-1 repeat superfamily
• Complement components C8A/B/C6, EGF-like domain
• Low-density lipoprotein receptor domain class A
• Sushi repeat (SCR repeat)
• Thrombospondin type 1 domain
• MAC/Perforin domain
• Complement components C8A/B/C6, EGF-like domain
• Complement component C6, KAZAL domain
• Complement component C6, KAZAL domain

KeywordsUniProt

• Complement pathway
• Cytolysis
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Immunity
• Innate immunity
• Membrane
• Membrane attack complex
• Repeat
• Secreted
• Signal
• Sushi
• Target cell membrane
• Target membrane
• Transmembrane
• Transmembrane beta strand

InteractionsUniProt · HPA

Protein binding partners of C6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• C5