UniProtKB - P13671 (CO6_HUMAN)
Complement component C6
C6
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.
GO - Biological processi
- complement activation Source: ComplexPortal
- complement activation, classical pathway Source: UniProtKB-KW
- cytolysis Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- in utero embryonic development Source: Ensembl
- positive regulation of immune response Source: ComplexPortal
Keywordsi
Biological process | Complement pathway, Cytolysis, Immunity, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | P13671 |
Reactomei | R-HSA-166665, Terminal pathway of complement R-HSA-977606, Regulation of Complement cascade |
SignaLinki | P13671 |
SIGNORi | P13671 |
Protein family/group databases
TCDBi | 1.C.39.3.3, the membrane attack complex/perforin (macpf) family |
Names & Taxonomyi
Protein namesi | Recommended name: Complement component C6 |
Gene namesi | Name:C6 |
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
HGNCi | HGNC:1339, C6 |
MIMi | 217050, gene |
neXtProti | NX_P13671 |
VEuPathDBi | HostDB:ENSG00000039537 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
Plasma Membrane
- membrane attack complex Source: UniProtKB
- plasma membrane Source: ComplexPortal
Keywords - Cellular componenti
Membrane attack complex, SecretedPathology & Biotechi
Involvement in diseasei
Complement component 6 deficiency (C6D)1 Publication
Organism-specific databases
DisGeNETi | 729 |
MalaCardsi | C6 |
MIMi | 612446, phenotype |
OpenTargetsi | ENSG00000039537 |
Orphaneti | 169150, Immunodeficiency due to a late component of complement deficiency |
PharmGKBi | PA25921 |
Miscellaneous databases
Pharosi | P13671, Tbio |
Genetic variation databases
BioMutai | C6 |
DMDMi | 146345396 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | 1 PublicationAdd BLAST | 21 | |
ChainiPRO_0000023579 | 22 – 934 | Complement component C6Add BLAST | 913 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 22 ↔ 61 | |||
Disulfide bondi | 24 ↔ 65 | |||
Glycosylationi | 29 | C-linked (Man) tryptophan1 Publication | 1 | |
Glycosylationi | 32 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Disulfide bondi | 35 ↔ 73 | |||
Glycosylationi | 38 | O-linked (Fuc...) threonine1 Publication | 1 | |
Disulfide bondi | 39 ↔ 78 | |||
Disulfide bondi | 82 ↔ 117 | |||
Glycosylationi | 90 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Disulfide bondi | 93 ↔ 127 | |||
Disulfide bondi | 96 ↔ 133 | |||
Disulfide bondi | 140 ↔ 151 | |||
Disulfide bondi | 146 ↔ 164 | |||
Disulfide bondi | 158 ↔ 173 | |||
Disulfide bondi | 180 ↔ 218 | |||
Glycosylationi | 324 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 392 | O-linked (Fuc...) threonine1 Publication | 1 | |
Disulfide bondi | 399 ↔ 420 | |||
Disulfide bondi | 499 ↔ 623 | |||
Disulfide bondi | 521 ↔ 570 | |||
Disulfide bondi | 523 ↔ 539 | |||
Disulfide bondi | 526 ↔ 541 | |||
Disulfide bondi | 543 ↔ 552 | |||
Glycosylationi | 568 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Glycosylationi | 571 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Glycosylationi | 574 | C-linked (Man) tryptophan; partial1 Publication | 1 | |
Disulfide bondi | 577 ↔ 611 | |||
Disulfide bondi | 589 ↔ 601 | |||
Disulfide bondi | 644 ↔ 686 | |||
Disulfide bondi | 672 ↔ 699 | |||
Disulfide bondi | 704 ↔ 746 | |||
Disulfide bondi | 732 ↔ 761 | |||
Disulfide bondi | 773 ↔ 823 | |||
Disulfide bondi | 784 ↔ 801 | |||
Disulfide bondi | 786 ↔ 837 | |||
Disulfide bondi | 793 ↔ 816 | |||
Glycosylationi | 855 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 862 ↔ 873 | |||
Disulfide bondi | 867 ↔ 919 | |||
Disulfide bondi | 880 ↔ 897 | |||
Disulfide bondi | 882 ↔ 932 | |||
Disulfide bondi | 888 ↔ 912 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | P13671 |
jPOSTi | P13671 |
MassIVEi | P13671 |
PaxDbi | P13671 |
PeptideAtlasi | P13671 |
PRIDEi | P13671 |
ProteomicsDBi | 52956 |
PTM databases
CarbonylDBi | P13671 |
GlyConnecti | 791, 7 N-Linked glycans (4 sites) |
GlyGeni | P13671, 12 sites, 7 N-linked glycans (4 sites) |
iPTMneti | P13671 |
PhosphoSitePlusi | P13671 |
Expressioni
Gene expression databases
Bgeei | ENSG00000039537, Expressed in liver and 136 other tissues |
ExpressionAtlasi | P13671, baseline and differential |
Genevisiblei | P13671, HS |
Organism-specific databases
HPAi | ENSG00000039537, 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 12-14 copies of the pore-forming subunit C9.
1 PublicationBinary interactionsi
P13671
With | #Exp. | IntAct |
---|---|---|
NCK1 [P16333] | 2 | EBI-1753221,EBI-389883 |
Protein-protein interaction databases
BioGRIDi | 107190, 11 interactors |
ComplexPortali | CPX-6159, Membrane attack complex CPX-677, C5b6 complement complex |
IntActi | P13671, 10 interactors |
STRINGi | 9606.ENSP00000263413 |
Miscellaneous databases
RNActi | P13671, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P13671 |
SMRi | P13671 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 22 – 79 | TSP type-1 1PROSITE-ProRule annotationAdd BLAST | 58 | |
Domaini | 81 – 134 | TSP type-1 2PROSITE-ProRule annotationAdd BLAST | 54 | |
Domaini | 138 – 175 | LDL-receptor class APROSITE-ProRule annotationAdd BLAST | 38 | |
Domaini | 176 – 522 | MACPFPROSITE-ProRule annotationAdd BLAST | 347 | |
Domaini | 523 – 553 | EGF-likeAdd BLAST | 31 | |
Domaini | 565 – 612 | TSP type-1 3PROSITE-ProRule annotationAdd BLAST | 48 | |
Domaini | 642 – 701 | Sushi 1PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 702 – 763 | Sushi 2PROSITE-ProRule annotationAdd BLAST | 62 | |
Domaini | 780 – 839 | Kazal-like 1PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 876 – 934 | Kazal-like 2PROSITE-ProRule annotationAdd BLAST | 59 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 611 – 688 | CCP 1Add BLAST | 78 | |
Regioni | 642 – 934 | C5b-binding domainAdd BLAST | 293 | |
Regioni | 689 – 765 | CCP 2Add BLAST | 77 | |
Regioni | 766 – 840 | Factor I module (FIM) 1Add BLAST | 75 | |
Regioni | 858 – 934 | Factor I module (FIM) 2Add BLAST | 77 |
Sequence similaritiesi
Keywords - Domaini
EGF-like domain, Repeat, Signal, SushiPhylogenomic databases
eggNOGi | ENOG502QPIM, Eukaryota |
GeneTreei | ENSGT00940000156814 |
HOGENOMi | CLU_014082_0_0_1 |
InParanoidi | P13671 |
OMAi | FRPCIPS |
OrthoDBi | 100680at2759 |
PhylomeDBi | P13671 |
TreeFami | TF330498 |
Family and domain databases
CDDi | cd00033, CCP, 2 hits cd00112, LDLa, 1 hit |
Gene3Di | 2.20.100.10, 3 hits 4.10.400.10, 1 hit |
InterProi | View protein in InterPro IPR003884, FacI_MAC IPR002350, Kazal_dom IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR002172, LDrepeatLR_classA_rpt IPR001862, MAC_perforin IPR020864, MACPF IPR020863, MACPF_CS IPR035976, Sushi/SCR/CCP_sf IPR000436, Sushi_SCR_CCP_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 1 hit PF01823, MACPF, 1 hit PF00084, Sushi, 2 hits PF00090, TSP_1, 3 hits |
PRINTSi | PR00764, COMPLEMENTC9 |
SMARTi | View protein in SMART SM00032, CCP, 2 hits SM00057, FIMAC, 2 hits SM00192, LDLa, 1 hit SM00457, MACPF, 1 hit SM00209, TSP1, 3 hits |
SUPFAMi | SSF57424, SSF57424, 1 hit SSF57535, SSF57535, 2 hits SSF82895, SSF82895, 3 hits |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS51465, KAZAL_2, 2 hits PS01209, LDLRA_1, 1 hit PS50068, LDLRA_2, 1 hit PS00279, MACPF_1, 1 hit PS51412, MACPF_2, 1 hit PS50923, SUSHI, 2 hits PS50092, TSP1, 3 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MARRSVLYFI LLNALINKGQ ACFCDHYAWT QWTSCSKTCN SGTQSRHRQI
60 70 80 90 100
VVDKYYQENF CEQICSKQET RECNWQRCPI NCLLGDFGPW SDCDPCIEKQ
110 120 130 140 150
SKVRSVLRPS QFGGQPCTAP LVAFQPCIPS KLCKIEEADC KNKFRCDSGR
160 170 180 190 200
CIARKLECNG ENDCGDNSDE RDCGRTKAVC TRKYNPIPSV QLMGNGFHFL
210 220 230 240 250
AGEPRGEVLD NSFTGGICKT VKSSRTSNPY RVPANLENVG FEVQTAEDDL
260 270 280 290 300
KTDFYKDLTS LGHNENQQGS FSSQGGSSFS VPIFYSSKRS ENINHNSAFK
310 320 330 340 350
QAIQASHKKD SSFIRIHKVM KVLNFTTKAK DLHLSDVFLK ALNHLPLEYN
360 370 380 390 400
SALYSRIFDD FGTHYFTSGS LGGVYDLLYQ FSSEELKNSG LTEEEAKHCV
410 420 430 440 450
RIETKKRVLF AKKTKVEHRC TTNKLSEKHE GSFIQGAEKS ISLIRGGRSE
460 470 480 490 500
YGAALAWEKG SSGLEEKTFS EWLESVKENP AVIDFELAPI VDLVRNIPCA
510 520 530 540 550
VTKRNNLRKA LQEYAAKFDP CQCAPCPNNG RPTLSGTECL CVCQSGTYGE
560 570 580 590 600
NCEKQSPDYK SNAVDGQWGC WSSWSTCDAT YKRSRTRECN NPAPQRGGKR
610 620 630 640 650
CEGEKRQEED CTFSIMENNG QPCINDDEEM KEVDLPEIEA DSGCPQPVPP
660 670 680 690 700
ENGFIRNEKQ LYLVGEDVEI SCLTGFETVG YQYFRCLPDG TWRQGDVECQ
710 720 730 740 750
RTECIKPVVQ EVLTITPFQR LYRIGESIEL TCPKGFVVAG PSRYTCQGNS
760 770 780 790 800
WTPPISNSLT CEKDTLTKLK GHCQLGQKQS GSECICMSPE EDCSHHSEDL
810 820 830 840 850
CVFDTDSNDY FTSPACKFLA EKCLNNQQLH FLHIGSCQDG RQLEWGLERT
860 870 880 890 900
RLSSNSTKKE SCGYDTCYDW EKCSASTSKC VCLLPPQCFK GGNQLYCVKM
910 920 930
GSSTSEKTLN ICEVGTIRCA NRKMEILHPG KCLA
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JC72 | C9JC72_HUMAN | Complement component C6 | C6 | 133 | Annotation score: | ||
C9JX36 | C9JX36_HUMAN | Complement component C6 | C6 | 31 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 567 | Q → H in BAD02321 (Ref. 4) Curated | 1 | |
Sequence conflicti | 616 | M → I in BAD02321 (Ref. 4) Curated | 1 | |
Sequence conflicti | 934 | A → T in BAD02321 (Ref. 4) Curated | 1 |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_006056 | 119 | A → E in allotype C6 A. 5 PublicationsCorresponds to variant dbSNP:rs1801033EnsemblClinVar. | 1 | |
Natural variantiVAR_027647 | 397 | K → E. Corresponds to variant dbSNP:rs6896011EnsemblClinVar. | 1 | |
Natural variantiVAR_027648 | 470 | S → F. Corresponds to variant dbSNP:rs10462014Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05064 mRNA Translation: AAA51860.1 J05024 mRNA Translation: AAA59668.1 X72177 Genomic DNA Translation: CAA50994.1 AB126592 mRNA Translation: BAD02321.1 AC008863 Genomic DNA No translation available. AC091871 Genomic DNA No translation available. BC035723 mRNA Translation: AAH35723.1 J04506 mRNA Translation: AAB59433.1 |
CCDSi | CCDS3936.1 |
PIRi | A34372 |
RefSeqi | NP_000056.2, NM_000065.3 NP_001108603.2, NM_001115131.2 |
Genome annotation databases
Ensembli | ENST00000263413.7; ENSP00000263413.3; ENSG00000039537.14 ENST00000337836.10; ENSP00000338861.5; ENSG00000039537.14 |
GeneIDi | 729 |
KEGGi | hsa:729 |
MANE-Selecti | ENST00000337836.10; ENSP00000338861.5; NM_000065.5; NP_000056.2 |
UCSCi | uc003jmk.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
C6base C6 mutation db |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05064 mRNA Translation: AAA51860.1 J05024 mRNA Translation: AAA59668.1 X72177 Genomic DNA Translation: CAA50994.1 AB126592 mRNA Translation: BAD02321.1 AC008863 Genomic DNA No translation available. AC091871 Genomic DNA No translation available. BC035723 mRNA Translation: AAH35723.1 J04506 mRNA Translation: AAB59433.1 |
CCDSi | CCDS3936.1 |
PIRi | A34372 |
RefSeqi | NP_000056.2, NM_000065.3 NP_001108603.2, NM_001115131.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3T5O | X-ray | 2.87 | A | 22-934 | [»] | |
4A5W | X-ray | 3.50 | B | 22-934 | [»] | |
4E0S | X-ray | 4.21 | B | 22-934 | [»] | |
6H03 | electron microscopy | 5.60 | B | 22-934 | [»] | |
6H04 | electron microscopy | 5.60 | B | 22-934 | [»] | |
7NYC | electron microscopy | 3.50 | B | 22-934 | [»] | |
7NYD | electron microscopy | 3.30 | B | 22-934 | [»] | |
AlphaFoldDBi | P13671 | |||||
SMRi | P13671 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107190, 11 interactors |
ComplexPortali | CPX-6159, Membrane attack complex CPX-677, C5b6 complement complex |
IntActi | P13671, 10 interactors |
STRINGi | 9606.ENSP00000263413 |
Protein family/group databases
TCDBi | 1.C.39.3.3, the membrane attack complex/perforin (macpf) family |
PTM databases
CarbonylDBi | P13671 |
GlyConnecti | 791, 7 N-Linked glycans (4 sites) |
GlyGeni | P13671, 12 sites, 7 N-linked glycans (4 sites) |
iPTMneti | P13671 |
PhosphoSitePlusi | P13671 |
Genetic variation databases
BioMutai | C6 |
DMDMi | 146345396 |
Proteomic databases
EPDi | P13671 |
jPOSTi | P13671 |
MassIVEi | P13671 |
PaxDbi | P13671 |
PeptideAtlasi | P13671 |
PRIDEi | P13671 |
ProteomicsDBi | 52956 |
Protocols and materials databases
ABCDi | P13671, 9 sequenced antibodies |
Antibodypediai | 10692, 304 antibodies from 33 providers |
DNASUi | 729 |
Genome annotation databases
Ensembli | ENST00000263413.7; ENSP00000263413.3; ENSG00000039537.14 ENST00000337836.10; ENSP00000338861.5; ENSG00000039537.14 |
GeneIDi | 729 |
KEGGi | hsa:729 |
MANE-Selecti | ENST00000337836.10; ENSP00000338861.5; NM_000065.5; NP_000056.2 |
UCSCi | uc003jmk.4, human |
Organism-specific databases
CTDi | 729 |
DisGeNETi | 729 |
GeneCardsi | C6 |
HGNCi | HGNC:1339, C6 |
HPAi | ENSG00000039537, Tissue enriched (liver) |
MalaCardsi | C6 |
MIMi | 217050, gene 612446, phenotype |
neXtProti | NX_P13671 |
OpenTargetsi | ENSG00000039537 |
Orphaneti | 169150, Immunodeficiency due to a late component of complement deficiency |
PharmGKBi | PA25921 |
VEuPathDBi | HostDB:ENSG00000039537 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QPIM, Eukaryota |
GeneTreei | ENSGT00940000156814 |
HOGENOMi | CLU_014082_0_0_1 |
InParanoidi | P13671 |
OMAi | FRPCIPS |
OrthoDBi | 100680at2759 |
PhylomeDBi | P13671 |
TreeFami | TF330498 |
Enzyme and pathway databases
PathwayCommonsi | P13671 |
Reactomei | R-HSA-166665, Terminal pathway of complement R-HSA-977606, Regulation of Complement cascade |
SignaLinki | P13671 |
SIGNORi | P13671 |
Miscellaneous databases
BioGRID-ORCSi | 729, 9 hits in 1068 CRISPR screens |
ChiTaRSi | C6, human |
GeneWikii | Complement_component_6 |
GenomeRNAii | 729 |
Pharosi | P13671, Tbio |
PROi | PR:P13671 |
RNActi | P13671, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000039537, Expressed in liver and 136 other tissues |
ExpressionAtlasi | P13671, baseline and differential |
Genevisiblei | P13671, HS |
Family and domain databases
CDDi | cd00033, CCP, 2 hits cd00112, LDLa, 1 hit |
Gene3Di | 2.20.100.10, 3 hits 4.10.400.10, 1 hit |
InterProi | View protein in InterPro IPR003884, FacI_MAC IPR002350, Kazal_dom IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR002172, LDrepeatLR_classA_rpt IPR001862, MAC_perforin IPR020864, MACPF IPR020863, MACPF_CS IPR035976, Sushi/SCR/CCP_sf IPR000436, Sushi_SCR_CCP_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 1 hit PF01823, MACPF, 1 hit PF00084, Sushi, 2 hits PF00090, TSP_1, 3 hits |
PRINTSi | PR00764, COMPLEMENTC9 |
SMARTi | View protein in SMART SM00032, CCP, 2 hits SM00057, FIMAC, 2 hits SM00192, LDLa, 1 hit SM00457, MACPF, 1 hit SM00209, TSP1, 3 hits |
SUPFAMi | SSF57424, SSF57424, 1 hit SSF57535, SSF57535, 2 hits SSF82895, SSF82895, 3 hits |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 1 hit PS51465, KAZAL_2, 2 hits PS01209, LDLRA_1, 1 hit PS50068, LDLRA_2, 1 hit PS00279, MACPF_1, 1 hit PS51412, MACPF_2, 1 hit PS50923, SUSHI, 2 hits PS50092, TSP1, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | CO6_HUMAN | |
Accessioni | P13671Primary (citable) accession number: P13671 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | May 1, 2007 | |
Last modified: | May 25, 2022 | |
This is version 211 of the entry and version 3 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 entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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