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P02748 (CO9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement component C9

Cleaved into the following 2 chains:

  1. Complement component C9a
  2. Complement component C9b
Gene names
Name:C9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length559 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Secreted. Cell membrane; Multi-pass membrane protein. Note: Secreted as soluble monomer. Oligomerizes at target membranes, forming a pre-pore. A conformation change then leads to the formation of a 100 Angstrom diameter pore.

Tissue specificity

Plasma.

Post-translational modification

Thrombin cleaves factor C9 to produce C9a and C9b.

Phosphorylation sites are present in the extracellular medium.

Involvement in disease

Complement component 9 deficiency (C9D) [MIM:613825]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the complement C6/C7/C8/C9 family.

Contains 1 EGF-like domain.

Contains 1 LDL-receptor class A domain.

Contains 1 MACPF domain.

Contains 1 TSP type-1 domain.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.3
Chain22 – 559538Complement component C9
PRO_0000023602
Chain22 – 265244Complement component C9a
PRO_0000023603
Chain266 – 559294Complement component C9b
PRO_0000023604

Regions

Transmembrane314 – 33017Beta stranded; Potential
Transmembrane335 – 35420Beta stranded; Potential
Domain42 – 9554TSP type-1
Domain99 – 13638LDL-receptor class A
Domain138 – 509372MACPF
Domain510 – 54031EGF-like

Sites

Site265 – 2662Cleavage; by thrombin

Amino acid modifications

Glycosylation481C-linked (Man) Ref.8
Glycosylation511C-linked (Man); partial Ref.8
Glycosylation2771N-linked (GlcNAc...) Ref.6 Ref.10 Ref.12
Glycosylation4151N-linked (GlcNAc...) (complex) Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Disulfide bond43 ↔ 78 Ref.7
Disulfide bond54 ↔ 57 Ref.7
Disulfide bond88 ↔ 94 Ref.7
Disulfide bond101 ↔ 112 Ref.7
Disulfide bond107 ↔ 125 Ref.7
Disulfide bond119 ↔ 134 Ref.7
Disulfide bond142 ↔ 181 Ref.7
Disulfide bond254 ↔ 255 Ref.7
Disulfide bond380 ↔ 405 Ref.7
Disulfide bond510 ↔ 526 Ref.7
Disulfide bond513 ↔ 528 Ref.7
Disulfide bond530 ↔ 539 Ref.7

Natural variations

Natural variant51R → W.
Corresponds to variant rs700233 [ dbSNP | Ensembl ].
VAR_022024
Natural variant1191C → G in C9D. Ref.5
VAR_012648
Natural variant1271D → Y.
Corresponds to variant rs696763 [ dbSNP | Ensembl ].
VAR_050481
Natural variant2031I → V.
Corresponds to variant rs13361416 [ dbSNP | Ensembl ].
VAR_027651
Natural variant2791T → S.
Corresponds to variant rs34625111 [ dbSNP | Ensembl ].
VAR_033802
Natural variant4271S → T.
Corresponds to variant rs34421659 [ dbSNP | Ensembl ].
VAR_061503

Experimental info

Sequence conflict431C → R in AAA51889. Ref.3
Sequence conflict3141Missing in AAA51889. Ref.3
Sequence conflict4171T → P in AAA51889. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P02748 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: 7403F6AD77B3ECE1

FASTA55963,173
        10         20         30         40         50         60 
MSACRSFAVA ICILEISILT AQYTTSYDPE LTESSGSASH IDCRMSPWSE WSQCDPCLRQ 

        70         80         90        100        110        120 
MFRSRSIEVF GQFNGKRCTD AVGDRRQCVP TEPCEDAEDD CGNDFQCSTG RCIKMRLRCN 

       130        140        150        160        170        180 
GDNDCGDFSD EDDCESEPRP PCRDRVVEES ELARTAGYGI NILGMDPLST PFDNEFYNGL 

       190        200        210        220        230        240 
CNRDRDGNTL TYYRRPWNVA SLIYETKGEK NFRTEHYEEQ IEAFKSIIQE KTSNFNAAIS 

       250        260        270        280        290        300 
LKFTPTETNK AEQCCEETAS SISLHGKGSF RFSYSKNETY QLFLSYSSKK EKMFLHVKGE 

       310        320        330        340        350        360 
IHLGRFVMRN RDVVLTTTFV DDIKALPTTY EKGEYFAFLE TYGTHYSSSG SLGGLYELIY 

       370        380        390        400        410        420 
VLDKASMKRK GVELKDIKRC LGYHLDVSLA FSEISVGAEF NKDDCVKRGE GRAVNITSEN 

       430        440        450        460        470        480 
LIDDVVSLIR GGTRKYAFEL KEKLLRGTVI DVTDFVNWAS SINDAPVLIS QKLSPIYNLV 

       490        500        510        520        530        540 
PVKMKNAHLK KQNLERAIED YINEFSVRKC HTCQNGGTVI LMDGKCLCAC PFKFEGIACE 

       550 
ISKQKISEGL PALEFPNEK 

« Hide

References

« Hide 'large scale' references
[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]"Heterogeneity in the genetic basis of human complement C9 deficiency."
Witzel-Schloemp K., Hobart M.J., Fernie B.A., Orren A., Wuerzner R., Rittner C., Kaufmann T., Schneider P.M.
Immunogenetics 48:144-147(1998) [PubMed] [Europe PMC] [Abstract]
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]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-415.
[14]"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).
+Additional computationally mapped references.

Web resources

C9base

C9 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X02176 mRNA. Translation: CAA26117.1.
BC020721 mRNA. Translation: AAH20721.1.
K02766 mRNA. Translation: AAA51889.1.
J02833 Genomic DNA. Translation: AAA51890.1.
Y08545 expand/collapse EMBL AC list , Y08546, Y08547, Y08548, Y08549, Y08550, Y08551, Y08552, Y08553, Y08554 Genomic DNA. Translation: CAA69849.1.
PIRC9HU. A59363.
RefSeqNP_001728.1. NM_001737.3.
UniGeneHs.654443.

3D structure databases

ProteinModelPortalP02748.
SMRP02748. Positions 36-540.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107196. 3 interactions.
DIPDIP-1124N.
MINTMINT-2800316.
STRING9606.ENSP00000263408.

PTM databases

PhosphoSiteP02748.

Polymorphism databases

DMDM1352108.

Proteomic databases

PaxDbP02748.
PeptideAtlasP02748.
PRIDEP02748.

Protocols and materials databases

DNASU735.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263408; ENSP00000263408; ENSG00000113600.
GeneID735.
KEGGhsa:735.
UCSCuc003jlv.4. human.

Organism-specific databases

CTD735.
GeneCardsGC05M039320.
HGNCHGNC:1358. C9.
HPACAB002151.
HPA029577.
MIM120940. gene.
613825. phenotype.
neXtProtNX_P02748.
Orphanet169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBPA25968.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46204.
HOGENOMHOG000111869.
HOVERGENHBG106792.
InParanoidP02748.
KOK04000.
OMAPWNVASL.
OrthoDBEOG7D85W9.
PhylomeDBP02748.
TreeFamTF330498.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP02748.
BgeeP02748.
CleanExHS_C9.
GenevestigatorP02748.

Family and domain databases

Gene3D4.10.400.10. 1 hit.
InterProIPR009030. 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]
PfamPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSPR00764. COMPLEMENTC9.
SMARTSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMSSF57184. SSF57184. 2 hits.
SSF57424. SSF57424. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEPS00022. 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]
ProtoNetSearch...

Other

GenomeRNAi735.
NextBio2992.
PROP02748.
SOURCESearch...

Entry information

Entry nameCO9_HUMAN
AccessionPrimary (citable) accession number: P02748
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM