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CFH

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.
Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins

Predicted location

Secreted

Single cell type specificity

Group enriched (Hepatocytes, Fibroblasts, Leydig cells)

Immune cell specificity

Immune cell enhanced (MAIT T-cell)

Cell line specificity

Cell line enhanced (HHSteC, HSkMC, hTERT-RPE1, RT4)

Interaction

Homodimer (PubMed:18005991, PubMed:19505476). Forms also homooligomers (PubMed:19505476). Interacts with complement protein C3b; this interaction inhibits complement activation (PubMed:16601698, PubMed:19503104, PubMed:20378178, PubMed:21285368, PubMed:28671664). Interacts with complement protein C3d (PubMed:20378178, PubMed:21285368, PubMed:29190743). Interacts with CR3/ITGAM; this interaction mediates adhesion of neutrophils to pathogens leading to pathogen clearance (PubMed:9558116, PubMed:20008295). Interacts with complement factor I (PubMed:28671664). (Microbial infection) Interacts with West nile virus non-structural protein 1 (NS1); this interaction leads to the degradation of C3. (Microbial infection) Interacts with Neisseria meningitidis protein fHbp. (Microbial infection) Interacts with Borrelia burgdorferi outer surface protein E/OspE; this interaction recruits complement regulator factor H onto the bacterial surface to evade complement-mediated cell lysis. (Microbial infection) Interacts with Streptococcus pneumoniae protein virulence factor choline-binding protein A/CbpAN; this interaction enables Streptococcus pneumoniae to evade surveillance by human complement system. (Microbial infection) Interacts with Staphylococcus aureus surface protein serine-aspartate repeat protein E/SdrE; this interaction sequesters CFH on the surface of S. aureus for complement evasion. (Microbial infection) Interacts with Staphylococcus aureus protein Sbi; this interaction inhibits the complement activation of the alternative pathway. [Isoform 1]: (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits CFH onto the merozoite surface preventing complement-mediated cell lysis (PubMed:26700768). The interaction does not affect CFH activity (PubMed:26700768). [Isoform 2]: (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits FHL-1 isoform onto the merozoite surface preventing complement-mediated cell lysis (PubMed:26700768). The interaction does not affect FHL-1 isoform activity (PubMed:26700768).

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