C4B (complement C4B (Chido blood group))

Gene

• Entrez ID: 721
• Gene name: Complement C4B (Chido blood group)
• Gene symbol: C4B
• Synonyms: C4B1, C4B12, C4B2, C4B3, C4B5, C4BD, C4B_2, C4F, CH, CO4, CPAMD3
• Chromosome: 6
• Chromosome location: 6p21.33
• Summary: This gene encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, May 2020]

Transcription factors

Transcription factor	Regulation	Reference
SP1	Unknown	9574539

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001848	Function	Complement binding	IDA	2395880
GO:0004866	Function	Endopeptidase inhibitor activity	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005615	Component	Extracellular space	IDA	2395880
GO:0005886	Component	Plasma membrane	TAS
GO:0006954	Process	Inflammatory response	IEA
GO:0006956	Process	Complement activation	IBA	21873635
GO:0006956	Process	Complement activation	IGI	19302245
GO:0006956	Process	Complement activation	TAS
GO:0006958	Process	Complement activation, classical pathway	IEA
GO:0008228	Process	Opsonization	TAS	22333221
GO:0010951	Process	Negative regulation of endopeptidase activity	IEA
GO:0030246	Function	Carbohydrate binding	IDA	2395880
GO:0030424	Component	Axon	IEA
GO:0030425	Component	Dendrite	IEA
GO:0030449	Process	Regulation of complement activation	TAS
GO:0032490	Process	Detection of molecule of bacterial origin	IDA	22333221
GO:0044216	Component	Other organism cell	IDA	22333221
GO:0045087	Process	Innate immune response	IEA
GO:0045202	Component	Synapse	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:2000427	Process	Positive regulation of apoptotic cell clearance	IGI	19302245

Other IDs

• MIM: 120820
• HGNC: 1324
• e!Ensembl: ENSG00000224389

Protein

• UniProt ID: P0C0L4
• Protein name: Complement C4-A (Acidic complement C4) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2) [Cleaved into: Complement C4 beta chain; Complement C4-A alpha chain; C4a anaphylatoxin; C4b-A; C4d-A; Complement C4 gamma chain]
• Protein function: Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.; Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
• PDB: 1HZF, 4FXG, 4FXK, 4XAM, 5JPM, 5JPN, 5JTW
• UniProt ID: P0C0L5
• Protein name: Complement C4-B (Basic complement C4) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 3) [Cleaved into: Complement C4 beta chain; Complement C4-B alpha chain; C4a anaphylatoxin; C4b-B; C4d-B; Complement C4 gamma chain]
• Protein function: Non-enzymatic component of the C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.; Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
• PDB: 4XAM, 6YSQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01835	MG2	140 → 233	MG2 domain	Domain
  PF17791	MG3	235 → 323	Macroglobulin domain MG3	Domain
  PF17789	MG4	369 → 461	Macroglobulin domain MG4	Domain
  PF07703	A2M_BRD	473 → 611	Alpha-2-macroglobulin bait region domain	Domain
  PF01821	ANATO	702 → 736	Anaphylotoxin-like domain	Domain
  PF00207	A2M	781 → 869	Alpha-2-macroglobulin family	Family
  PF07678	TED_complement	982 → 1315	A-macroglobulin TED domain	Domain
  PF07677	A2M_recep	1481 → 1570	A-macroglobulin receptor binding domain	Domain
  PF01759	NTR	1615 → 1725	UNC-6/NTR/C345C module	Domain

• Sequence:

  MRLLWGLIWASSFFTLSLQKPRLLLFSPSVVHLGVPLSVGVQLQDVPRGQVVKGSVFLRN
  PSRNNVPCSPKVDFTLSSERDFALLSLQVPLKDAKSCGLHQLLRGPEVQLVAHSPWLKDS
  LSRTTNIQGINLLFSSRRGHLFLQTDQPIYNPGQRVRYRVFALDQKMRPSTDTITVMVEN
  SHGLRVRKKEVYMPSSIFQDDFVIPDISEPGTWKISARFSDGLESNSSTQFEVKKYVLPN
  FEVKITPGKPYILTVPGHLDEMQLDIQARYIYGKPVQGVAYVRFGLLDEDGKKTFFRGLE
  SQTKLVNGQSHISLSKAEFQDALEKLNMGITDLQGLRLYVAAAIIESPGGEMEEAELTSW
  YFVSSPFSLDLSKTKRHLVPGAPFLLQALVREMSGSPASGIPVKVSATVSSPGSVPEVQD
  IQQNTDGSGQVSIPIIIPQTISELQLSVSAGSPHPAIARLTVAAPPSGGPGFLSIERPDS
  RPPRVGDTLNLNLRAVGSGATFSHYYYMILSRGQIVFMNREPKRTLTSVSVFVDHHLAPS
  FYFVAFYYHGDHPVANSLRVDVQAGACEGKLELSVDGAKQYRNGESVKLHLETDSLALVA
  LGALDTALYAAGSKSHKPLNMGKVFEAMNSYDLGCGPGGGDSALQVFQAAGLAFSDGDQW
  TLSRKRLSCPKEKTTRKKRNVNFQKAINEKLGQYASPTAKRCCQDGVTRLPMMRSCEQRA
  ARVQQPDCREPFLSCCQFAESLRKKSRDKGQAGLQRALEILQEEDLIDEDDIPVRSFFPE
  NWLWRVETVDRFQILTLWLPDSLTTWEIHGLSLSKTKGLCVATPVQLRVFREFHLHLRLP
  MSVRRFEQLELRPVLYNYLDKNLTVSVHVSPVEGLCLAGGGGLAQQVLVPAGSARPVAFS
  VVPTAATAVSLKVVARGSFEFPVGDAVSKVLQIEKEGAIHREELVYELNPLDHRGRTLEI
  PGNSDPNMIPDGDFNSYVRVTASDPLDTLGSEGALSPGGVASLLRLPRGCGEQTMIYLAP
  TLAASRYLDKTEQWSTLPPETKDHAVDLIQKGYMRIQQFRKADGSYAAWLSRGSSTWLTA
  FVLKVLSLAQEQVGGSPEKLQETSNWLLSQQQADGSFQDLSPVIHRSMQGGLVGNDETVA
  LTAFVTIALHHGLAVFQDEGAEPLKQRVEASISKASSFLGEKASAGLLGAHAAAITAYAL
  TLTKAPADLRGVAHNNLMAMAQETGDNLYWGSVTGSQSNAVSPTPAPRNPSDPMPQAPAL
  WIETTAYALLHLLLHEGKAEMADQAAAWLTRQGSFQGGFRSTQDTVIALDALSAYWIASH
  TTEERGLNVTLSSTGRNGFKSHALQLNNRQIRGLEEELQFSLGSKINVKVGGNSKGTLKV
  LRTYNVLDMKNTTCQDLQIEVTVKGHVEYTMEANEDYEDYEYDELPAKDDPDAPLQPVTP
  LQLFEGRRNRRRREAPKVVEEQESRVHYTVCIWRNGKVGLSGMAIADVTLLSGFHALRAD
  LEKLTSLSDRYVSHFETEGPHVLLYFDSVPTSRECVGFEAVQEVPVGLVQPASATLYDYY
  NPERRCSVFYGAPSKSRLLATLCSAEVCQCAEGKCPRQRRALERGLQDEDGYRMKFACYY
  PRVEYGFQVKVLREDSRAAFRLFETKITQVLHFTKDVKAAANQMRNFLVRASCRLRLEPG
  KEYLIMGLDGATYDLEGHPQYLLDSNSWIEEMPSERLCRSTRQRAACAQLNDFLQEYGTQ
  GCQV

• Sequence length: 1744