Complement Factor H

Complement factor H, also known as H factor 1, and CFH, is a sialic acid containing glycoprotein that plays an integral role in the regulation of the complement-mediated immune system that is involved in microbial defense, immune complex processing, and programmed cell death. Factor H protects host cells from injury resulting from unrestrained complement activation. CFH regulates complement activation on self cells by possessing both cofactor activity for the Factor I mediated C3b cleavage, and decay accelerating activity against the alternative pathway C3 convertase, C3bBb. CFH protects self cells from complement activation but not bacteria/viruses. Due to the central role that CFH plays in the regulation of complement, there are many clinical implications arrising from aberrant CFH activity. Mutations in the Factor H gene are associated with severe and diverse diseases including the rare renal disorders hemolytic uremic syndrome (HUS) and membranoproliferative glomerulonephritis (MPGN) also termed dense deposit disease (DDD), membranoproliferative glomuleronephritis type II or dense deposit disease, as well as the more frequent retinal disease age related macular degeneration (AMD). In addition to its complement regulatory activities, factor H has multiple physiological activities and 1) acts as an extracellular matrix component, 2) binds to cellular receptors of the integrin type, and 3) interacts with a wide selection of ligands, such as the C-reactive protein, thrombospondin, bone sialoprotein, osteopontin, and heparin.

Complement Factor H Related Areas

Immunology>>Innate Immunity>>Complement System>>Complement Factor H/CFH

Complement Factor H Alternative Names

Complement Factor H, CFH, RP1-177P10.1, AHUS1, ARMD4, ARMS1, CFHL3, FH, FHL1, HF, HF1, HF2, HUS, MGC88246 [Homo sapiens]

Complement Factor H, Cfh, Mud-1, NOM, Sas-1, Sas1 [Mus musculus]

Summaries for Complement Factor H

Entrez Gene summary for Complement Factor H:

This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized

OMIM - description for Complement Factor H:

Complement factor H (CFH), originally known as beta-1H globulin, is a serum glycoprotein that regulates the function of the alternative complement pathway in fluid phase and on cellular surfaces. It binds to C3b (see C3, 120700), accelerates the decay of the alternative pathway convertase C3bBb, and also acts as a cofactor for complement factor I (CFI; 217030), another C3b inhibitor

Wikipedia summary for Complement Factor H:

Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at a concentration of 500–800 micrograms per milliliter). Its principal function is to regulate the Alternative Pathway of the complement system, ensuring that the complement system is directed towards pathogens and does not damage host tissue. Factor H regulates complement activation on self cells by possessing both cofactor activity for the Factor I mediated C3b cleavage, and decay accelerating activity against the alternative pathway C3 convertase, C3bBb. Factor H protects self cells from complement activation but not bacteria/viruses, in that it binds to glycosaminoglycans (GAGs) that are present on host cells but not pathogen cell surfaces.

Human Complement Factor H Protein General Information

 

• Protein names: Recommended name: Complement factor H-related protein 1 Short name=FHR-1
• Sequence length: 330 AA.
• Domain: Repeat Signal Sushi
• Sequence similarities: Contains 5 Sushi (CCP/SCR) domains.
• Post-translational modification: modification N-glycosylated. Two forms are observed; one with a single side chain and the other with two.
• Subcellular location: Secreted.
• Tissue specificity: Expressed by the liver and secreted in plasma.

General information above from UniProt

Function for Complement Factor H Protein

UniProtKB:

Might be involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism.

Genatlas:

• Complement Factor H is involved in the regulation of complement activation and protection of cellular surfaces from complement activation (restricting this innate defense mechanism to microbial infections)
• an adhesion ligand for human neutrophils but not for eosinophils
• Complement Factor H is one essential complement inhibitor that binds to the acute phase reactant C-reactive protein
• Complement Factor H acts as a cofactor with factor I also known as C3b inactivator
• It regulates the activity of C3 convertases, such as C4b2a

Homology for human Complement Factor H

• ortholog to cfh, Danio rerio
• ortholog to Cfh, Rattus norvegicus
• ortholog to Cfh, Mus musculus
• ortholog to CFH, Pan trogloytes

Phenotype Information for Complement Factor H

• Gene/Locus: HF1, CFH, HUS, ARMD4, AHUS1
• Phenotype: Basal laminar drusen Complement factor H deficiency {Hemolytic uremic syndrome, atypical, susceptibility to, 1} {Macular degeneration, age-related, 4}

Phenotype Information for Complement Factor H from OMIM (Online Mendelian Inheritance in Man)