P0C0L4
uniprot
P0C0L4
canonical
activity_regulation
ACTIVITY REGULATION: [Complement C4b-A]: Specifically inhibited by nanobody hC4Nb8, inhibiting the classical complement pathway (PubMed:32769120). Specifically inhibited by NbB5, NbE11 and NbH9 nanobodies, and to a lesser extent by NbH11 and NbE3 nanobodies (PubMed:35428691). {ECO:0000269|PubMed:32769120, ECO:0000269|PubMed:35428691}.
uniprot
proteins
amino_acid_sequence
MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLRNPSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLKDSLSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMVENSHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPNFEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLESQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAELTSWYFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVPEVQDIQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPDSRPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPSFYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVALGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAGLAFSDGDQWTLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTRLPMMRSCEQRAARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLIDEDDIPVRSFFPENWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLPMSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFSVVPTAAAAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNPLDHRGRTLEIPGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASLLRLPRGCGEQTMIYLAPTLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRKADGSYAAWLSRDSSTWLTAFVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQDPCPVLDRSMQGGLVGNDETVALTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKANSFLGEKASAGLLGAHAAAITAYALTLTKAPVDLLGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNPSDPMPQAPALWIETTAYALLHLLLHEGKAEMADQASAWLTRQGSFQGGFRSTQDTVIALDALSAYWIASHTTEERGLNVTLSSTGRNGFKSHALQLNNRQIRGLEEELQFSLGSKINVKVGGNSKGTLKVLRTYNVLDMKNTTCQDLQIEVTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTPLQLFEGRRNRRRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRADLEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYYNPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYYPRVEYGFQVKVLREDSRAAFRLFETKITQVLHFTKDVKAAANQMRNFLVRASCRLRLEPGKEYLIMGLDGATYDLEGHPQYLLDSNSWIEEMPSERLCRSTRQRAACAQLNDFLQEYGTQGCQV
uniprot
proteins
disease_involvement
DISEASE: Complement component 4A deficiency (C4AD) [MIM:614380]: A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. {ECO:0000269|PubMed:8473511}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:10092831, ECO:0000269|PubMed:17503323}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.
uniprot
proteins
function
FUNCTION: Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. {ECO:0000269|PubMed:12878586, ECO:0000269|PubMed:18204047, ECO:0000269|PubMed:22691502, ECO:0000269|PubMed:22949645, ECO:0000269|PubMed:2395880, ECO:0000269|PubMed:32769120, ECO:0000269|PubMed:35428691, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:8538770}.; FUNCTION: [Complement C4b-A]: Non-enzymatic component of C3 and C5 convertases (PubMed:8538770). Generated following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway), it covalently attaches to the surface of pathogens, where it acts as an opsonin that marks the surface of antigens for removal (PubMed:27738201, PubMed:8538770). It then recruits the serine protease complement C2b to form the C3 and C5 convertases, which cleave and activate C3 and C5, respectively, the next components of the complement pathways (PubMed:12878586, PubMed:18204047, PubMed:2387864, PubMed:6906228). Complement C4b-A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while complement C4b-B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens (PubMed:8538770). {ECO:0000269|PubMed:12878586, ECO:0000269|PubMed:18204047, ECO:0000269|PubMed:2387864, ECO:0000269|PubMed:27738201, ECO:0000269|PubMed:6906228, ECO:0000269|PubMed:8538770}.; FUNCTION: [C4a anaphylatoxin]: Putative humoral mediator released following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway) (PubMed:6167582). While it is strongly similar to anaphylatoxins, its role is unclear (PubMed:25659340). Was reported to act as a mediator of local inflammatory process; however these effects were probably due to contamination with C3a and/C5a anaphylatoxins in biological assays (PubMed:25659340). {ECO:0000269|PubMed:6167582, ECO:0000303|PubMed:25659340}.
uniprot
proteins
mass_dalton
192785
uniprot
proteins
post_translational_modification
PTM: Prior to secretion, the single-chain precursor is enzymatically cleaved by plasminogen (PLG) to yield non-identical chains alpha, beta and gamma (PubMed:76991). During activation of the complement systems, the alpha chain is cleaved into C4a and C4b by different proteases depending on the complement pathway: C4b stays linked to the beta and gamma chains, while C4a is released in the plasma (PubMed:11527969, PubMed:16169853, PubMed:22949645, PubMed:467643, PubMed:6319179, PubMed:9422791). The alpha chain is cleaved by C1S to generate C4a and C4b following activation by the classical complement system (PubMed:11527969, PubMed:16169853, PubMed:22949645, PubMed:467643, PubMed:6319179, PubMed:9422791). The alpha chain is cleaved to generate C4a and C4b by MASP2 following activation by the lectin complement system (PubMed:11527969, PubMed:22691502, PubMed:22949645). The alpha chain is cleaved by GZMK to generate C4a and C4b following activation by the GZMK complement system (PubMed:39914456, PubMed:39814882). Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase (PubMed:3696167). The proteolytic cleavages often are incomplete so that many structural forms can be found in plasma (PubMed:3696167). {ECO:0000269|PubMed:11527969, ECO:0000269|PubMed:16169853, ECO:0000269|PubMed:22691502, ECO:0000269|PubMed:22949645, ECO:0000269|PubMed:3696167, ECO:0000269|PubMed:39814882, ECO:0000269|PubMed:39914456, ECO:0000269|PubMed:467643, ECO:0000269|PubMed:6319179, ECO:0000269|PubMed:76991, ECO:0000269|PubMed:9422791}.; PTM: [Complement C4b-A]: Upon activation, the internal thioester bond reacts with carbohydrate antigens on the target surface to form amide or ester bonds, leading to covalent association with the surface of pathogens. {ECO:0000269|PubMed:8538770}.; PTM: [Complement C4b-A]: Ser-1236 of complement C4b interacts with complement C3b via a thioester linkage. {ECO:0000269|PubMed:1740458, ECO:0000269|PubMed:2387864}.; PTM: N- and O-glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:23234360}.
uniprot
proteins
pubmed
10092831
uniprot
proteins
pubmed
11367523
uniprot
proteins
pubmed
11527969
uniprot
proteins
pubmed
12367531
uniprot
proteins
pubmed
12754519
uniprot
proteins
pubmed
12878586
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14760718
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1573268
uniprot
proteins
pubmed
16169853
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
1699796
uniprot
proteins
pubmed
1740458
uniprot
proteins
pubmed
17503323
uniprot
proteins
pubmed
18204047
uniprot
proteins
pubmed
18780401
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19838169
uniprot
proteins
pubmed
1988494
uniprot
proteins
pubmed
22691502
uniprot
proteins
pubmed
22949645
uniprot
proteins
pubmed
23234360
uniprot
proteins
pubmed
2387864
uniprot
proteins
pubmed
2395880
uniprot
proteins
pubmed
2431902
uniprot
proteins
pubmed
25659340
uniprot
proteins
pubmed
25911760
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
26814963
uniprot
proteins
pubmed
27252379
uniprot
proteins
pubmed
27599733
uniprot
proteins
pubmed
27738201
uniprot
proteins
pubmed
31147461
uniprot
proteins
pubmed
32769120
uniprot
proteins
pubmed
35428691
uniprot
proteins
pubmed
3696167
uniprot
proteins
pubmed
3838531
uniprot
proteins
pubmed
3874204
uniprot
proteins
pubmed
3944109
uniprot
proteins
pubmed
39814882
uniprot
proteins
pubmed
39914456
uniprot
proteins
pubmed
4424566
uniprot
proteins
pubmed
467643
uniprot
proteins
pubmed
6167582
uniprot
proteins
pubmed
6319179
uniprot
proteins
pubmed
6546707
uniprot
proteins
pubmed
6572000
uniprot
proteins
pubmed
6577433
uniprot
proteins
pubmed
6832377
uniprot
proteins
pubmed
6906228
uniprot
proteins
pubmed
6950384
uniprot
proteins
pubmed
6978711
uniprot
proteins
pubmed
76991
uniprot
proteins
pubmed
8012361
uniprot
proteins
pubmed
8473511
uniprot
proteins
pubmed
8538770
uniprot
proteins
pubmed
9422791
uniprot
proteins
pubmed
9759862
uniprot
proteins
sequence_length
1744
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:6167582, ECO:0000269|PubMed:8538770}. Synapse {ECO:0000269|PubMed:26814963}. Cell projection, axon {ECO:0000269|PubMed:26814963}. Cell projection, dendrite {ECO:0000269|PubMed:26814963}.; SUBCELLULAR LOCATION: [C4a anaphylatoxin]: Secreted {ECO:0000269|PubMed:6167582}.; SUBCELLULAR LOCATION: [Complement C4b-A]: Secreted {ECO:0000269|PubMed:8538770}. Cell surface {ECO:0000269|PubMed:8538770}. Note=Covalently associated with the surface of pathogens: the internal thioester bond reacts with carbohydrate antigens on the target surface to form amide or ester bonds. {ECO:0000269|PubMed:8538770}.
uniprot
proteins