UniProtKB - P02748 (CO9_HUMAN)
Protein
Complement component C9
Gene
C9
Organism
Homo sapiens (Human)
Status
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 (PubMed:9634479, PubMed:9212048, PubMed:26841934). C9 is the pore-forming subunit of the MAC (PubMed:4055801, PubMed:26841934, PubMed:30111885).5 Publications
GO - Biological processi
- cell killing Source: UniProtKB
- complement activation, alternative pathway Source: UniProtKB-KW
- complement activation, classical pathway Source: UniProtKB-KW
- cytolysis Source: UniProtKB-KW
- protein homooligomerization Source: UniProtKB
- regulation of complement activation Source: Reactome
Keywordsi
Biological process | Complement alternate pathway, Complement pathway, Cytolysis, Immunity, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | P02748 |
Reactomei | R-HSA-166665, Terminal pathway of complement R-HSA-977606, Regulation of Complement cascade |
Names & Taxonomyi
Protein namesi | Recommended name: Complement component C9Cleaved into the following 2 chains: |
Gene namesi | Name:C9 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000113600.10 |
HGNCi | HGNC:1358, C9 |
MIMi | 120940, gene |
neXtProti | NX_P02748 |
Subcellular locationi
Extracellular region or secreted
- Secreted 5 Publications
Other locations
- Target cell membrane 3 Publications; Multi-pass membrane protein 1 Publication
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.4 Publications
Extracellular region or secreted
- blood microparticle Source: UniProtKB
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Plasma Membrane
- membrane attack complex Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- other organism cell membrane Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 314 – 330 | Beta strandedSequence analysisAdd BLAST | 17 | |
Transmembranei | 335 – 354 | Beta strandedSequence analysisAdd BLAST | 20 |
Keywords - Cellular componenti
Membrane, Membrane attack complex, Secreted, Target cell membrane, Target membranePathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_012648 | 119 | C → G in C9D. 1 PublicationCorresponds to variant dbSNP:rs121909593EnsemblClinVar. | 1 |
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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070940 | 167 | P → S in ARMD15. 1 PublicationCorresponds to variant dbSNP:rs34882957EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 283 | F → C: Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-427. 1 Publication | 1 | |
Mutagenesisi | 426 | V → C: Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-283. 1 Publication | 1 |
Keywords - Diseasei
Age-related macular degeneration, Disease mutationOrganism-specific databases
DisGeNETi | 735 |
MalaCardsi | C9 |
MIMi | 613825, phenotype 615591, phenotype |
OpenTargetsi | ENSG00000113600 |
Orphaneti | 169150, Immunodeficiency due to a late component of complement deficiency 279, NON RARE IN EUROPE: Age-related macular degeneration |
PharmGKBi | PA25968 |
Miscellaneous databases
Pharosi | P02748, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4295693 |
DrugBanki | DB09130, Copper |
Polymorphism and mutation databases
BioMutai | C9 |
DMDMi | 1352108 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | 1 PublicationAdd BLAST | 21 | |
ChainiPRO_0000023602 | 22 – 559 | Complement component C9Add BLAST | 538 | |
ChainiPRO_0000023603 | 22 – 265 | Complement component C9aAdd BLAST | 244 | |
ChainiPRO_0000023604 | 266 – 559 | Complement component C9bAdd BLAST | 294 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 43 ↔ 78 | Combined sources2 Publications | ||
Glycosylationi | 48 | C-linked (Man) tryptophan1 Publication | 1 | |
Glycosylationi | 51 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Disulfide bondi | 54 ↔ 88 | Combined sources1 Publication | ||
Disulfide bondi | 57 ↔ 94 | Combined sources1 Publication | ||
Disulfide bondi | 101 ↔ 112 | Combined sources2 Publications | ||
Disulfide bondi | 107 ↔ 125 | Combined sources2 Publications | ||
Disulfide bondi | 119 ↔ 134 | Combined sources2 Publications | ||
Disulfide bondi | 142 ↔ 181 | Combined sources2 Publications | ||
Glycosylationi | 277 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Glycosylationi | 415 | N-linked (GlcNAc...) (complex) asparagine6 Publications | 1 | |
Disulfide bondi | 510 ↔ 526 | Combined sources2 Publications | ||
Disulfide bondi | 513 ↔ 528 | Combined sources2 Publications | ||
Disulfide bondi | 530 ↔ 539 | Combined sources2 Publications |
Post-translational modificationi
Thrombin cleaves factor C9 to produce C9a and C9b.1 Publication
Phosphorylation sites are present in the extracellular medium.
Initially, positions and connectivity of disulfide bonds were based on peptide sequencing done for the human protein (PubMed:8603752). The crystal structures for the human and mouse proteins corrected the positions and connectivities of the disulfide bonds (PubMed:30111885). The distance between Cys-57 and Cys-94 in the monomeric mouse protein precludes formation of a disulfide bond, contrary to what is seen in the structure of the human polymeric form of the protein (Probable).1 Publication2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 265 – 266 | Cleavage; by thrombin | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
CPTACi | non-CPTAC-1110 non-CPTAC-1111 non-CPTAC-2656 |
jPOSTi | P02748 |
MassIVEi | P02748 |
MaxQBi | P02748 |
PaxDbi | P02748 |
PeptideAtlasi | P02748 |
PRIDEi | P02748 |
ProteomicsDBi | 51564 |
PTM databases
GlyConnecti | 1150, 8 N-Linked glycans (2 sites) |
GlyGeni | P02748, 10 sites, 2 N-linked glycans (2 sites), 3 O-linked glycans (4 sites) |
iPTMneti | P02748 |
PhosphoSitePlusi | P02748 |
Expressioni
Tissue specificityi
Plasma (at protein level).5 Publications
Gene expression databases
Bgeei | ENSG00000113600, Expressed in liver and 81 other tissues |
Genevisiblei | P02748, HS |
Organism-specific databases
HPAi | ENSG00000113600, Tissue enriched (liver) |
Interactioni
Subunit structurei
Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9 (PubMed:22832194). About 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes (PubMed:26841934, PubMed:30111885).
3 PublicationsProtein-protein interaction databases
BioGRIDi | 107196, 6 interactors |
DIPi | DIP-1124N |
ELMi | P02748 |
IntActi | P02748, 4 interactors |
STRINGi | 9606.ENSP00000263408 |
Miscellaneous databases
RNActi | P02748, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 42 – 95 | TSP type-1PROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 99 – 136 | LDL-receptor class APROSITE-ProRule annotationAdd BLAST | 38 | |
Domaini | 138 – 509 | MACPFPROSITE-ProRule annotationAdd BLAST | 372 | |
Domaini | 510 – 540 | EGF-likeAdd BLAST | 31 |
Sequence similaritiesi
Belongs to the complement C6/C7/C8/C9 family.Curated
Keywords - Domaini
EGF-like domain, Signal, Transmembrane, Transmembrane beta strandPhylogenomic databases
eggNOGi | ENOG502QWHM, Eukaryota |
GeneTreei | ENSGT00940000159777 |
HOGENOMi | CLU_032453_2_0_1 |
InParanoidi | P02748 |
OMAi | WASSIND |
OrthoDBi | 787014at2759 |
PhylomeDBi | P02748 |
TreeFami | TF330498 |
Family and domain databases
CDDi | cd00112, LDLa, 1 hit |
Gene3Di | 2.20.100.10, 1 hit 4.10.400.10, 1 hit |
InterProi | View protein in InterPro IPR037567, Complement_C9 IPR009030, Growth_fac_rcpt_cys_sf IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR002172, LDrepeatLR_classA_rpt IPR001862, MAC_perforin IPR020864, MACPF IPR020863, MACPF_CS IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
PANTHERi | PTHR45742:SF3, PTHR45742:SF3, 1 hit |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 1 hit PF01823, MACPF, 1 hit PF00090, TSP_1, 1 hit |
PRINTSi | PR00764, COMPLEMENTC9 |
SMARTi | View protein in SMART SM00192, LDLa, 1 hit SM00457, MACPF, 1 hit SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF57424, SSF57424, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS00022, 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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P02748-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 43 | C → R in AAA51889 (PubMed:6095282).Curated | 1 | |
Sequence conflicti | 314 | Missing in AAA51889 (PubMed:6095282).Curated | 1 | |
Sequence conflicti | 417 | T → P in AAA51889 (PubMed:6095282).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022024 | 5 | R → W. Corresponds to variant dbSNP:rs700233EnsemblClinVar. | 1 | |
Natural variantiVAR_012648 | 119 | C → G in C9D. 1 PublicationCorresponds to variant dbSNP:rs121909593EnsemblClinVar. | 1 | |
Natural variantiVAR_050481 | 127 | D → Y. Corresponds to variant dbSNP:rs696763EnsemblClinVar. | 1 | |
Natural variantiVAR_070940 | 167 | P → S in ARMD15. 1 PublicationCorresponds to variant dbSNP:rs34882957EnsemblClinVar. | 1 | |
Natural variantiVAR_027651 | 203 | I → V. Corresponds to variant dbSNP:rs13361416Ensembl. | 1 | |
Natural variantiVAR_033802 | 279 | T → S. Corresponds to variant dbSNP:rs34625111EnsemblClinVar. | 1 | |
Natural variantiVAR_061503 | 427 | S → T. Corresponds to variant dbSNP:rs34421659EnsemblClinVar. | 1 |
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 |
CCDSi | CCDS3929.1 |
PIRi | A59363, C9HU |
RefSeqi | NP_001728.1, NM_001737.4 |
Genome annotation databases
Ensembli | ENST00000263408; ENSP00000263408; ENSG00000113600 |
GeneIDi | 735 |
KEGGi | hsa:735 |
UCSCi | uc003jlv.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS3929.1 |
PIRi | A59363, C9HU |
RefSeqi | NP_001728.1, NM_001737.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5FMW | electron microscopy | 6.70 | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V | 39-544 | [»] | |
6DLW | electron microscopy | 3.90 | A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V | 22-559 | [»] | |
6H03 | electron microscopy | 5.60 | G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X | 22-559 | [»] | |
6H04 | electron microscopy | 5.60 | G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X | 22-559 | [»] | |
SMRi | P02748 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107196, 6 interactors |
DIPi | DIP-1124N |
ELMi | P02748 |
IntActi | P02748, 4 interactors |
STRINGi | 9606.ENSP00000263408 |
Chemistry databases
ChEMBLi | CHEMBL4295693 |
DrugBanki | DB09130, Copper |
PTM databases
GlyConnecti | 1150, 8 N-Linked glycans (2 sites) |
GlyGeni | P02748, 10 sites, 2 N-linked glycans (2 sites), 3 O-linked glycans (4 sites) |
iPTMneti | P02748 |
PhosphoSitePlusi | P02748 |
Polymorphism and mutation databases
BioMutai | C9 |
DMDMi | 1352108 |
Proteomic databases
CPTACi | non-CPTAC-1110 non-CPTAC-1111 non-CPTAC-2656 |
jPOSTi | P02748 |
MassIVEi | P02748 |
MaxQBi | P02748 |
PaxDbi | P02748 |
PeptideAtlasi | P02748 |
PRIDEi | P02748 |
ProteomicsDBi | 51564 |
Protocols and materials databases
Antibodypediai | 3685, 509 antibodies |
DNASUi | 735 |
Genome annotation databases
Ensembli | ENST00000263408; ENSP00000263408; ENSG00000113600 |
GeneIDi | 735 |
KEGGi | hsa:735 |
UCSCi | uc003jlv.5, human |
Organism-specific databases
CTDi | 735 |
DisGeNETi | 735 |
EuPathDBi | HostDB:ENSG00000113600.10 |
GeneCardsi | C9 |
HGNCi | HGNC:1358, C9 |
HPAi | ENSG00000113600, Tissue enriched (liver) |
MalaCardsi | C9 |
MIMi | 120940, gene 613825, phenotype 615591, phenotype |
neXtProti | NX_P02748 |
OpenTargetsi | ENSG00000113600 |
Orphaneti | 169150, Immunodeficiency due to a late component of complement deficiency 279, NON RARE IN EUROPE: Age-related macular degeneration |
PharmGKBi | PA25968 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QWHM, Eukaryota |
GeneTreei | ENSGT00940000159777 |
HOGENOMi | CLU_032453_2_0_1 |
InParanoidi | P02748 |
OMAi | WASSIND |
OrthoDBi | 787014at2759 |
PhylomeDBi | P02748 |
TreeFami | TF330498 |
Enzyme and pathway databases
PathwayCommonsi | P02748 |
Reactomei | R-HSA-166665, Terminal pathway of complement R-HSA-977606, Regulation of Complement cascade |
Miscellaneous databases
BioGRID-ORCSi | 735, 3 hits in 839 CRISPR screens |
ChiTaRSi | C9, human |
GenomeRNAii | 735 |
Pharosi | P02748, Tbio |
PROi | PR:P02748 |
RNActi | P02748, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113600, Expressed in liver and 81 other tissues |
Genevisiblei | P02748, HS |
Family and domain databases
CDDi | cd00112, LDLa, 1 hit |
Gene3Di | 2.20.100.10, 1 hit 4.10.400.10, 1 hit |
InterProi | View protein in InterPro IPR037567, Complement_C9 IPR009030, Growth_fac_rcpt_cys_sf IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR002172, LDrepeatLR_classA_rpt IPR001862, MAC_perforin IPR020864, MACPF IPR020863, MACPF_CS IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
PANTHERi | PTHR45742:SF3, PTHR45742:SF3, 1 hit |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 1 hit PF01823, MACPF, 1 hit PF00090, TSP_1, 1 hit |
PRINTSi | PR00764, COMPLEMENTC9 |
SMARTi | View protein in SMART SM00192, LDLa, 1 hit SM00457, MACPF, 1 hit SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF57424, SSF57424, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS00022, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CO9_HUMAN | |
Accessioni | P02748Primary (citable) accession number: P02748 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | February 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 207 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations