CFB

Protein identityUniProt · HPA

UniProt accession

P00751

Gene

CFB

Ensembl

ENSG00000243649

Chromosome

6

Canonical length

764 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted secreted proteins

Subcellular location

Endoplasmic reticulum,Vesicles,Cell Junctions

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

764 residues, UniProt reviewed canonical sequence.

>P00751|CFB
     1  MGSNLSPQLC LMPFILGLLS GGVTTTPWSL ARPQGSCSLE GVEIKGGSFR LLQEGQALEY
    61  VCPSGFYPYP VQTRTCRSTG SWSTLKTQDQ KTVRKAECRA IHCPRPHDFE NGEYWPRSPY
   121  YNVSDEISFH CYDGYTLRGS ANRTCQVNGR WSGQTAICDN GAGYCSNPGI PIGTRKVGSQ
   181  YRLEDSVTYH CSRGLTLRGS QRRTCQEGGS WSGTEPSCQD SFMYDTPQEV AEAFLSSLTE
   241  TIEGVDAEDG HGPGEQQKRK IVLDPSGSMN IYLVLDGSDS IGASNFTGAK KCLVNLIEKV
   301  ASYGVKPRYG LVTYATYPKI WVKVSEADSS NADWVTKQLN EINYEDHKLK SGTNTKKALQ
   361  AVYSMMSWPD DVPPEGWNRT RHVIILMTDG LHNMGGDPIT VIDEIRDLLY IGKDRKNPRE
   421  DYLDVYVFGV GPLVNQVNIN ALASKKDNEQ HVFKVKDMEN LEDVFYQMID ESQSLSLCGM
   481  VWEHRKGTDY HKQPWQAKIS VIRPSKGHES CMGAVVSEYF VLTAAHCFTV DDKEHSIKVS
   541  VGGEKRDLEI EVVLFHPNYN INGKKEAGIP EFYDYDVALI KLKNKLKYGQ TIRPICLPCT
   601  EGTTRALRLP PTTTCQQQKE ELLPAQDIKA LFVSEEEKKL TRKEVYIKNG DKKGSCERDA
   661  QYAPGYDKVK DISEVVTPRF LCTGGVSPYA DPNTCRGDSG GPLIVHKRSR FIQVGVISWG
   721  VVDVCKNQKR QKQVPAHARD FHINLFQVLP WLKEKLQDED LGFL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CFB 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)

0.27

Highest tissue expression

2,371 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CFB.

Disease | AllUniProt

Conditions CFB is implicated in, by any mechanism.

• Macular degeneration, age-related, 14 (ARMD14) MIM:615489
• Hemolytic uremic syndrome, atypical, 4 (AHUS4) MIM:612924
• Complement factor B deficiency (CFBD) MIM:615561

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 651 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Atypical hemolytic-uremic syndrome
• Atypical hemolytic-uremic syndrome with B factor anomaly
• CFB-related disorder
• Complement factor b deficiency

Disease | ImmuneIEDB

Conditions an epitope on CFB was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for CFB 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)

0.52

gnomAD pLI

0

gnomAD missense Z

1.48

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• complement activation
• complement activation, alternative pathway
• proteolysis
• response to bacterium

Molecular functions

• complement binding
• serine-type endopeptidase activity

Cellular components

• blood microparticle
• cell surface
• extracellular exosome
• extracellular region
• extracellular space
• plasma membrane
• symbiont cell surface

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• von Willebrand factor, type A
• Peptidase S1, PA clan
• Complement B/C2
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Sushi/SCR/CCP superfamily
• von Willebrand factor A-like domain superfamily
• Sushi repeat (SCR repeat)
• Trypsin
• von Willebrand factor type A domain
• Complement factor B

KeywordsUniProt

• Age-related macular degeneration
• Cleavage on pair of basic residues
• Complement alternate pathway
• Disulfide bond
• Glycation
• Glycoprotein
• Hemolytic uremic syndrome
• Hydrolase
• Immunity
• Innate immunity
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Sushi
• Zymogen

InteractionsUniProt · HPA

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

• CFP