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Protein

Complement component C9

Gene

C9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C9 is the pore-forming subunit of the MAC.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei265 – 2662Cleavage; by thrombin

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Complement alternate pathway, Complement pathway, Cytolysis, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_118707. Regulation of Complement cascade.
REACT_8028. Terminal pathway of complement.

Names & Taxonomyi

Protein namesi
Recommended name:
Complement component C9
Cleaved into the following 2 chains:
Gene namesi
Name:C9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:1358. C9.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei314 – 33017Beta strandedSequence AnalysisAdd
BLAST
Transmembranei335 – 35420Beta strandedSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • integral component of plasma membrane Source: ProtInc
  • membrane attack complex Source: UniProtKB-KW
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Membrane attack complex, Secreted

Pathology & Biotechi

Involvement in diseasei

Complement component 9 deficiency (C9D)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may develop dermatomyositis.

See also OMIM:613825
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti119 – 1191C → G in C9D. 1 Publication
VAR_012648
Macular degeneration, age-related, 15 (ARMD15)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.

See also OMIM:615591
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti167 – 1671P → S in ARMD15. 1 Publication
VAR_070940

Keywords - Diseasei

Age-related macular degeneration, Disease mutation

Organism-specific databases

MIMi613825. phenotype.
615591. phenotype.
Orphaneti279. Age-related macular degeneration.
169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBiPA25968.

Polymorphism and mutation databases

BioMutaiC9.
DMDMi1352108.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 21211 PublicationAdd
BLAST
Chaini22 – 559538Complement component C9PRO_0000023602Add
BLAST
Chaini22 – 265244Complement component C9aPRO_0000023603Add
BLAST
Chaini266 – 559294Complement component C9bPRO_0000023604Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi43 ↔ 781 Publication
Glycosylationi48 – 481C-linked (Man)
Glycosylationi51 – 511C-linked (Man); partial
Disulfide bondi54 ↔ 571 Publication
Disulfide bondi88 ↔ 941 Publication
Disulfide bondi101 ↔ 1121 Publication
Disulfide bondi107 ↔ 1251 Publication
Disulfide bondi119 ↔ 1341 Publication
Disulfide bondi142 ↔ 1811 Publication
Disulfide bondi254 ↔ 2551 Publication
Glycosylationi277 – 2771N-linked (GlcNAc...)3 Publications
Disulfide bondi380 ↔ 4051 Publication
Glycosylationi415 – 4151N-linked (GlcNAc...) (complex)6 Publications
Disulfide bondi510 ↔ 5261 Publication
Disulfide bondi513 ↔ 5281 Publication
Disulfide bondi530 ↔ 5391 Publication

Post-translational modificationi

Thrombin cleaves factor C9 to produce C9a and C9b.
Phosphorylation sites are present in the extracellular medium.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP02748.
PaxDbiP02748.
PeptideAtlasiP02748.
PRIDEiP02748.

PTM databases

PhosphoSiteiP02748.

Expressioni

Tissue specificityi

Plasma.

Gene expression databases

BgeeiP02748.
CleanExiHS_C9.
GenevisibleiP02748. HS.

Organism-specific databases

HPAiCAB002151.
HPA029577.

Interactioni

Subunit structurei

Component of the membrane attack complex (MAC). MAC assembly is initiated by protelytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9.

Protein-protein interaction databases

BioGridi107196. 4 interactions.
DIPiDIP-1124N.
MINTiMINT-2800316.
STRINGi9606.ENSP00000263408.

Structurei

3D structure databases

ProteinModelPortaliP02748.
SMRiP02748. Positions 36-540.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 9554TSP type-1PROSITE-ProRule annotationAdd
BLAST
Domaini99 – 13638LDL-receptor class APROSITE-ProRule annotationAdd
BLAST
Domaini138 – 509372MACPFPROSITE-ProRule annotationAdd
BLAST
Domaini510 – 54031EGF-likeAdd
BLAST

Sequence similaritiesi

Belongs to the complement C6/C7/C8/C9 family.Curated
Contains 1 EGF-like domain.Curated
Contains 1 LDL-receptor class A domain.PROSITE-ProRule annotation
Contains 1 MACPF domain.PROSITE-ProRule annotation
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane beta strand

Phylogenomic databases

eggNOGiNOG46204.
GeneTreeiENSGT00550000074478.
HOGENOMiHOG000111869.
HOVERGENiHBG106792.
InParanoidiP02748.
KOiK04000.
OMAiSKNETYQ.
OrthoDBiEOG7D85W9.
PhylomeDBiP02748.
TreeFamiTF330498.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_N_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSiPR00764. COMPLEMENTC9.
SMARTiSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.
SSF57424. SSF57424. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02748-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSACRSFAVA ICILEISILT AQYTTSYDPE LTESSGSASH IDCRMSPWSE
60 70 80 90 100
WSQCDPCLRQ MFRSRSIEVF GQFNGKRCTD AVGDRRQCVP TEPCEDAEDD
110 120 130 140 150
CGNDFQCSTG RCIKMRLRCN GDNDCGDFSD EDDCESEPRP PCRDRVVEES
160 170 180 190 200
ELARTAGYGI NILGMDPLST PFDNEFYNGL CNRDRDGNTL TYYRRPWNVA
210 220 230 240 250
SLIYETKGEK NFRTEHYEEQ IEAFKSIIQE KTSNFNAAIS LKFTPTETNK
260 270 280 290 300
AEQCCEETAS SISLHGKGSF RFSYSKNETY QLFLSYSSKK EKMFLHVKGE
310 320 330 340 350
IHLGRFVMRN RDVVLTTTFV DDIKALPTTY EKGEYFAFLE TYGTHYSSSG
360 370 380 390 400
SLGGLYELIY VLDKASMKRK GVELKDIKRC LGYHLDVSLA FSEISVGAEF
410 420 430 440 450
NKDDCVKRGE GRAVNITSEN LIDDVVSLIR GGTRKYAFEL KEKLLRGTVI
460 470 480 490 500
DVTDFVNWAS SINDAPVLIS QKLSPIYNLV PVKMKNAHLK KQNLERAIED
510 520 530 540 550
YINEFSVRKC HTCQNGGTVI LMDGKCLCAC PFKFEGIACE ISKQKISEGL

PALEFPNEK
Length:559
Mass (Da):63,173
Last modified:February 1, 1996 - v2
Checksum:i7403F6AD77B3ECE1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti43 – 431C → R in AAA51889 (PubMed:6095282).Curated
Sequence conflicti314 – 3141Missing in AAA51889 (PubMed:6095282).Curated
Sequence conflicti417 – 4171T → P in AAA51889 (PubMed:6095282).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti5 – 51R → W.
Corresponds to variant rs700233 [ dbSNP | Ensembl ].
VAR_022024
Natural varianti119 – 1191C → G in C9D. 1 Publication
VAR_012648
Natural varianti127 – 1271D → Y.
Corresponds to variant rs696763 [ dbSNP | Ensembl ].
VAR_050481
Natural varianti167 – 1671P → S in ARMD15. 1 Publication
VAR_070940
Natural varianti203 – 2031I → V.
Corresponds to variant rs13361416 [ dbSNP | Ensembl ].
VAR_027651
Natural varianti279 – 2791T → S.
Corresponds to variant rs34625111 [ dbSNP | Ensembl ].
VAR_033802
Natural varianti427 – 4271S → T.
Corresponds to variant rs34421659 [ dbSNP | Ensembl ].
VAR_061503

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02176 mRNA. Translation: CAA26117.1.
BC020721 mRNA. Translation: AAH20721.1.
K02766 mRNA. Translation: AAA51889.1.
J02833 Genomic DNA. Translation: AAA51890.1.
Y08545
, Y08546, Y08547, Y08548, Y08549, Y08550, Y08551, Y08552, Y08553, Y08554 Genomic DNA. Translation: CAA69849.1.
CCDSiCCDS3929.1.
PIRiA59363. C9HU.
RefSeqiNP_001728.1. NM_001737.3.
UniGeneiHs.654443.

Genome annotation databases

EnsembliENST00000263408; ENSP00000263408; ENSG00000113600.
GeneIDi735.
KEGGihsa:735.
UCSCiuc003jlv.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

C9base

C9 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02176 mRNA. Translation: CAA26117.1.
BC020721 mRNA. Translation: AAH20721.1.
K02766 mRNA. Translation: AAA51889.1.
J02833 Genomic DNA. Translation: AAA51890.1.
Y08545
, Y08546, Y08547, Y08548, Y08549, Y08550, Y08551, Y08552, Y08553, Y08554 Genomic DNA. Translation: CAA69849.1.
CCDSiCCDS3929.1.
PIRiA59363. C9HU.
RefSeqiNP_001728.1. NM_001737.3.
UniGeneiHs.654443.

3D structure databases

ProteinModelPortaliP02748.
SMRiP02748. Positions 36-540.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107196. 4 interactions.
DIPiDIP-1124N.
MINTiMINT-2800316.
STRINGi9606.ENSP00000263408.

PTM databases

PhosphoSiteiP02748.

Polymorphism and mutation databases

BioMutaiC9.
DMDMi1352108.

Proteomic databases

MaxQBiP02748.
PaxDbiP02748.
PeptideAtlasiP02748.
PRIDEiP02748.

Protocols and materials databases

DNASUi735.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263408; ENSP00000263408; ENSG00000113600.
GeneIDi735.
KEGGihsa:735.
UCSCiuc003jlv.4. human.

Organism-specific databases

CTDi735.
GeneCardsiGC05M039320.
HGNCiHGNC:1358. C9.
HPAiCAB002151.
HPA029577.
MIMi120940. gene.
613825. phenotype.
615591. phenotype.
neXtProtiNX_P02748.
Orphaneti279. Age-related macular degeneration.
169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBiPA25968.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG46204.
GeneTreeiENSGT00550000074478.
HOGENOMiHOG000111869.
HOVERGENiHBG106792.
InParanoidiP02748.
KOiK04000.
OMAiSKNETYQ.
OrthoDBiEOG7D85W9.
PhylomeDBiP02748.
TreeFamiTF330498.

Enzyme and pathway databases

ReactomeiREACT_118707. Regulation of Complement cascade.
REACT_8028. Terminal pathway of complement.

Miscellaneous databases

ChiTaRSiC9. human.
GenomeRNAii735.
NextBioi2992.
PROiP02748.
SOURCEiSearch...

Gene expression databases

BgeeiP02748.
CleanExiHS_C9.
GenevisibleiP02748. HS.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_N_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSiPR00764. COMPLEMENTC9.
SMARTiSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.
SSF57424. SSF57424. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
PS00279. MACPF_1. 1 hit.
PS51412. MACPF_2. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The sequence and topology of human complement component C9."
    Stanley K.K., Kocher H.-P., Luzio J.P., Jackson P., Tschopp J.
    EMBO J. 4:375-382(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.
  3. "Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9."
    Discipio R.G., Gehring M.R., Podack E.R., Kan C.C., Hugli T.E., Fey G.H.
    Proc. Natl. Acad. Sci. U.S.A. 81:7298-7302(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-559, PROTEIN SEQUENCE OF N-TERMINUS.
  4. "Relationships between the gene and protein structure in human complement component C9."
    Marazziti D., Eggertsen G., Fey G.H., Stanley K.K.
    Biochemistry 27:6529-6534(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 62-159.
  5. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-559, VARIANT C9D GLY-119.
  6. "The architecture of complement component C9 and poly(C9)."
    DiScipio R.G., Hugli T.E.
    J. Biol. Chem. 260:14802-14809(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE, ELECTRON MICROSCOPY, GLYCOSYLATION AT ASN-277 AND ASN-415.
  7. "Identification of disulfide bonds in the ninth component (C9) of human complement."
    Lengweiler S., Schaller J., Rickli E.E.
    FEBS Lett. 380:8-12(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  8. "The four terminal components of the complement system are C-mannosylated on multiple tryptophan residues."
    Hofsteenge J., Blommers M., Hess D., Furmanek A., Miroshnichenko O.
    J. Biol. Chem. 274:32786-32794(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT TRP-48 AND TRP-51.
  9. "Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
    Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
    Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-415.
    Tissue: Plasma.
  10. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
    Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
    J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-277 AND ASN-415.
    Tissue: Plasma.
  11. "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
    Lewandrowski U., Moebius J., Walter U., Sickmann A.
    Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-415.
    Tissue: Platelet.
  12. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-277 AND ASN-415.
    Tissue: Liver.
  13. Cited for: GLYCOSYLATION AT ASN-415.
  14. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  15. "Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin."
    Peitsch M.C., Amiguet P., Guy R., Brunner J., Maizel J.V. Jr., Tschopp J.
    Mol. Immunol. 27:589-602(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING OF MEMBRANE-SPANNING DOMAIN (MSB).
  16. Cited for: VARIANT ARMD15 SER-167.

Entry informationi

Entry nameiCO9_HUMAN
AccessioniPrimary (citable) accession number: P02748
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 165 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.