C5 (complement C5)

Gene

• Entrez ID: 727
• Gene name: Complement C5
• Gene symbol: C5
• Synonyms: C5D, C5a, C5b, CPAMD4, ECLZB
• Chromosome: 9
• Chromosome location: 9q33.2
• Summary: This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs56040400	C>T	Affects	Genic downstream transcript variant, missense variant, coding sequence variant
rs121909587	G>A	Pathogenic	Coding sequence variant, stop gained, intron variant
rs121909588	G>A	Pathogenic	Coding sequence variant, stop gained, genic downstream transcript variant
rs373359894	G>A,T	Affects	Missense variant, genic downstream transcript variant, coding sequence variant
rs587776846	T>C	Pathogenic	Missense variant, coding sequence variant
rs1554718962	C>-	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016535	hsa-miR-193b-3p	Microarray	20304954
MIRT047564	hsa-miR-10a-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000187	Process	Activation of MAPK activity	TAS	7649993
GO:0001701	Process	In utero embryonic development	IEA
GO:0004866	Function	Endopeptidase inhibitor activity	IEA
GO:0005102	Function	Signaling receptor binding	TAS	9590258, 10820279
GO:0005515	Function	Protein binding	IPI	19528535, 21217642, 25416956, 32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005579	Component	Membrane attack complex	IDA	22832194
GO:0005615	Component	Extracellular space	TAS	9218605
GO:0006935	Process	Chemotaxis	TAS	10820279
GO:0006954	Process	Inflammatory response	IEA
GO:0006957	Process	Complement activation, alternative pathway	IEA
GO:0006958	Process	Complement activation, classical pathway	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	10820279
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0008009	Function	Chemokine activity	TAS	10820279
GO:0010575	Process	Positive regulation of vascular endothelial growth factor production	IDA	14566334, 16452172
GO:0010760	Process	Negative regulation of macrophage chemotaxis	IDA	14566334
GO:0010951	Process	Negative regulation of endopeptidase activity	IEA
GO:0019835	Process	Cytolysis	IEA
GO:0030449	Process	Regulation of complement activation	TAS
GO:0032722	Process	Positive regulation of chemokine production	IDA	14566334
GO:0045766	Process	Positive regulation of angiogenesis	IEA
GO:0060326	Process	Cell chemotaxis	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145

Other IDs

• MIM: 120900
• HGNC: 1331
• e!Ensembl: ENSG00000106804

Protein

• UniProt ID: P01031
• Protein name: Complement C5 (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4) [Cleaved into: Complement C5 beta chain; Complement C5 alpha chain; C5a anaphylatoxin; Complement C5 alpha' chain]
• Protein function: Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.; Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes (PubMed:8182049). C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.
• PDB: 1CFA, 1KJS, 1XWE, 3CU7, 3HQA, 3HQB, 3KLS, 3KM9, 3PRX, 3PVM, 4A5W, 4E0S, 4P39, 4UU9, 5B4P, 5B71, 5HCC, 5HCD, 5HCE, 5I5K, 6H03, 6H04, 6RPT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17790	MG1	20 → 120	Macroglobulin domain MG1	Domain
  PF01835	MG2	125 → 219	MG2 domain	Domain
  PF17791	MG3	221 → 309	Macroglobulin domain MG3	Domain
  PF17789	MG4	354 → 457	Macroglobulin domain MG4	Domain
  PF07703	A2M_BRD	467 → 612	Alpha-2-macroglobulin bait region domain	Domain
  PF01821	ANATO	698 → 732	Anaphylotoxin-like domain	Domain
  PF00207	A2M	772 → 859	Alpha-2-macroglobulin family	Family
  PF07678	TED_complement	977 → 1300	A-macroglobulin TED domain	Domain
  PF07677	A2M_recep	1419 → 1509	A-macroglobulin receptor binding domain	Domain
  PF01759	NTR	1550 → 1660	UNC-6/NTR/C345C module	Domain

• Sequence:

  MGLLGILCFLIFLGKTWGQEQTYVISAPKIFRVGASENIVIQVYGYTEAFDATISIKSYP
  DKKFSYSSGHVHLSSENKFQNSAILTIQPKQLPGGQNPVSYVYLEVVSKHFSKSKRMPIT
  YDNGFLFIHTDKPVYTPDQSVKVRVYSLNDDLKPAKRETVLTFIDPEGSEVDMVEEIDHI
  GIISFPDFKIPSNPRYGMWTIKAKYKEDFSTTGTAYFEVKEYVLPHFSVSIEPEYNFIGY
  KNFKNFEITIKARYFYNKVVTEADVYITFGIREDLKDDQKEMMQTAMQNTMLINGIAQVT
  FDSETAVKELSYYSLEDLNNKYLYIAVTVIESTGGFSEEAEIPGIKYVLSPYKLNLVATP
  LFLKPGIPYPIKVQVKDSLDQLVGGVPVTLNAQTIDVNQETSDLDPSKSVTRVDDGVASF
  VLNLPSGVTVLEFNVKTDAPDLPEENQAREGYRAIAYSSLSQSYLYIDWTDNHKALLVGE
  HLNIIVTPKSPYIDKITHYNYLILSKGKIIHFGTREKFSDASYQSINIPVTQNMVPSSRL
  LVYYIVTGEQTAELVSDSVWLNIEEKCGNQLQVHLSPDADAYSPGQTVSLNMATGMDSWV
  ALAAVDSAVYGVQRGAKKPLERVFQFLEKSDLGCGAGGGLNNANVFHLAGLTFLTNANAD
  DSQENDEPCKEILRPRRTLQKKIEEIAAKYKHSVVKKCCYDGACVNNDETCEQRAARISL
  GPRCIKAFTECCVVASQLRANISHKDMQLGRLHMKTLLPVSKPEIRSYFPESWLWEVHLV
  PRRKQLQFALPDSLTTWEIQGVGISNTGICVADTVKAKVFKDVFLEMNIPYSVVRGEQIQ
  LKGTVYNYRTSGMQFCVKMSAVEGICTSESPVIDHQGTKSSKCVRQKVEGSSSHLVTFTV
  LPLEIGLHNINFSLETWFGKEILVKTLRVVPEGVKRESYSGVTLDPRGIYGTISRRKEFP
  YRIPLDLVPKTEIKRILSVKGLLVGEILSAVLSQEGINILTHLPKGSAEAELMSVVPVFY
  VFHYLETGNHWNIFHSDPLIEKQKLKKKLKEGMLSIMSYRNADYSYSVWKGGSASTWLTA
  FALRVLGQVNKYVEQNQNSICNSLLWLVENYQLDNGSFKENSQYQPIKLQGTLPVEAREN
  SLYLTAFTVIGIRKAFDICPLVKIDTALIKADNFLLENTLPAQSTFTLAISAYALSLGDK
  THPQFRSIVSALKREALVKGNPPIYRFWKDNLQHKDSSVPNTGTARMVETTAYALLTSLN
  LKDINYVNPVIKWLSEEQRYGGGFYSTQDTINAIEGLTEYSLLVKQLRLSMDIDVSYKHK
  GALHNYKMTDKNFLGRPVEVLLNDDLIVSTGFGSGLATVHVTTVVHKTSTSEEVCSFYLK
  IDTQDIEASHYRGYGNSDYKRIVACASYKPSREESSSGSSHAVMDISLPTGISANEEDLK
  ALVEGVDQLFTDYQIKDGHVILQLNSIPSSDFLCVRFRIFELFEVGFLSPATFTVYEYHR
  PDKQCTMFYSTSNIKIQKVCEGAACKCVEADCGQMQEELDLTISAETRKQTACKPEIAYA
  YKVSITSITVENVFVKYKATLLDIYKTGEAVAEKDSEITFIKKVTCTNAELVKGRQYLIM
  GKEALQIKYNFSFRYIYPLDSLTWIEYWPRDTTCSSCQAFLANLDEFAEDIFLNGC

• Sequence length: 1676