C8A
entrez
731
canonical
uniprot
P07357
canonical
ensembl
ENSG00000157131
resolver
ensp
ENSP00000354458
resolver
ensp
ENSP00000788828
resolver
ensp
ENSP00000788832
resolver
enst
ENST00000361249
resolver
genesymbol
C8A
resolver
hgnc
HGNC:1352
resolver
uniprot
A2RUI4
resolver
uniprot
A2RUI5
resolver
uniprot
Q13668
resolver
uniprot
Q9H130
resolver
uniprot_entry
CO8A_HUMAN
resolver
uniprot_sec
A2RUI4
resolver
uniprot_sec
A2RUI5
resolver
uniprot_sec
Q13668
resolver
uniprot_sec
Q9H130
resolver
activity_regulation
ACTIVITY REGULATION: Membrane attack complex (MAC) assembly is inhibited by CD59, thereby protecting self-cells from damage during complement activation (PubMed:36797260). CD59 acts by binding to the beta-haipins of C8 (C8A and C8B), forming an intermolecular beta-sheet that prevents incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (PubMed:36797260). MAC assembly is also inhibited by clusterin (CLU) chaperones that inhibit polymerization of C9 (PubMed:34667172). {ECO:0000269|PubMed:34667172, ECO:0000269|PubMed:36797260}.
uniprot
proteins
amino_acid_sequence
MFAVVFFILSLMTCQPGVTAQEKVNQRVRRAATPAAVTCQLSNWSEWTDCFPCQDKKYRHRSLLQPNKFGGTICSGDIWDQASCSSSTTCVRQAQCGQDFQCKETGRCLKRHLVCNGDQDCLDGSDEDDCEDVRAIDEDCSQYEPIPGSQKAALGYNILTQEDAQSVYDASYYGGQCETVYNGEWRELRYDSTCERLYYGDDEKYFRKPYNFLKYHFEALADTGISSEFYDNANDLLSKVKKDKSDSFGVTIGIGPAGSPLLVGVGVSHSQDTSFLNELNKYNEKKFIFTRIFTKVQTAHFKMRKDDIMLDEGMLQSLMELPDQYNYGMYAKFINDYGTHYITSGSMGGIYEYILVIDKAKMESLGITSRDITTCFGGSLGIQYEDKINVGGGLSGDHCKKFGGGKTERARKAMAVEDIISRVRGGSSGWSGGLAQNRSTITYRSWGRSLKYNPVVIDFEMQPIHEVLRHTSLGPLEAKRQNLRRALDQYLMEFNACRCGPCFNNGVPILEGTSCRCQCRLGSLGAACEQTQTEGAKADGSWSCWSSWSVCRAGIQERRRECDNPAPQNGGASCPGRKVQTQAC
uniprot
proteins
disease_involvement
DISEASE: Complement component 8 deficiency, 1 (C8D1) [MIM:613790]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. {ECO:0000269|PubMed:9759902}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:17872444, PubMed:22832194, PubMed:26841837, PubMed:27052168, PubMed:30552328, PubMed:7440581). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:17872444, PubMed:30552328, PubMed:39914456, PubMed:39814882, PubMed:7440581). The complement pathways consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:17872444, PubMed:30552328, PubMed:7440581). C8A, together with C8B and C8G, inserts into the target membrane, but does not form pores by itself (PubMed:17872444, PubMed:30552328). During MAC assembly, associates with C5b, C6 and C7 to form the C5b8 intermediate complex that inserts into the target membrane and traverses the bilayer increasing membrane rigidity (PubMed:30552328, PubMed:6833260). {ECO:0000269|PubMed:17872444, ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841837, ECO:0000269|PubMed:27052168, ECO:0000269|PubMed:30552328, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:6833260, ECO:0000269|PubMed:7440581}.
uniprot
proteins
mass_dalton
65163
uniprot
proteins
protein_family
Complement C6/C7/C8/C9 family
uniprot
proteins
pubmed
10551839
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17692377
uniprot
proteins
pubmed
17872444
uniprot
proteins
pubmed
18440555
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
21454577
uniprot
proteins
pubmed
22832194
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26841837
uniprot
proteins
pubmed
27052168
uniprot
proteins
pubmed
2820471
uniprot
proteins
pubmed
30552328
uniprot
proteins
pubmed
31061395
uniprot
proteins
pubmed
34667172
uniprot
proteins
pubmed
36797260
uniprot
proteins
pubmed
39814882
uniprot
proteins
pubmed
39914456
uniprot
proteins
pubmed
6833260
uniprot
proteins
pubmed
7440581
uniprot
proteins
pubmed
7649542
uniprot
proteins
pubmed
7759071
uniprot
proteins
pubmed
9759902
uniprot
proteins
sequence_length
584
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2820471}. Target cell membrane {ECO:0000269|PubMed:30552328}; Multi-pass membrane protein {ECO:0000269|PubMed:30552328, ECO:0000269|PubMed:31061395}. Note=Secreted as soluble protein (PubMed:2820471). Inserts into the cell membrane of target cells (PubMed:30552328, PubMed:31061395). {ECO:0000269|PubMed:2820471, ECO:0000269|PubMed:30552328, ECO:0000269|PubMed:31061395}.
uniprot
proteins
transmembrane_region
TRANSMEM 248..256; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H04"; TRANSMEM 259..266; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H04"; TRANSMEM 377..384; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H04"; TRANSMEM 390..395; /note="Beta stranded"; /evidence="ECO:0000269|PubMed:30552328, ECO:0007744|PDB:6H04
uniprot
proteins