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Protein

Complement component C6

Gene

C6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

GO - Biological processi

Keywordsi

Biological processComplement pathway, Cytolysis, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-166665 Terminal pathway of complement
R-HSA-977606 Regulation of Complement cascade

Protein family/group databases

TCDBi1.C.39.3.3 the membrane attack complex/perforin (macpf) family

Names & Taxonomyi

Protein namesi
Recommended name:
Complement component C6
Gene namesi
Name:C6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000039537.13
HGNCiHGNC:1339 C6
MIMi217050 gene
neXtProtiNX_P13671

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane attack complex, Secreted

Pathology & Biotechi

Involvement in diseasei

Complement component 6 deficiency (C6D)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.
See also OMIM:612446

Organism-specific databases

DisGeNETi729
MalaCardsiC6
MIMi612446 phenotype
OpenTargetsiENSG00000039537
Orphaneti169150 Immunodeficiency due to a late component of complements deficiency
PharmGKBiPA25921

Polymorphism and mutation databases

DMDMi146345396

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 211 PublicationAdd BLAST21
ChainiPRO_000002357922 – 934Complement component C6Add BLAST913

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi22 ↔ 61
Disulfide bondi24 ↔ 65
Glycosylationi29C-linked (Man) tryptophan1 Publication1
Glycosylationi32C-linked (Man) tryptophan; partial1 Publication1
Disulfide bondi35 ↔ 73
Glycosylationi38O-linked (Fuc...) threonine1 Publication1
Disulfide bondi39 ↔ 78
Disulfide bondi82 ↔ 117
Glycosylationi90C-linked (Man) tryptophan; partial1 Publication1
Disulfide bondi93 ↔ 127
Disulfide bondi96 ↔ 133
Disulfide bondi140 ↔ 151
Disulfide bondi146 ↔ 164
Disulfide bondi158 ↔ 173
Disulfide bondi180 ↔ 218
Glycosylationi324N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi392O-linked (Fuc...) threonine1 Publication1
Disulfide bondi399 ↔ 420
Disulfide bondi499 ↔ 623
Disulfide bondi521 ↔ 570
Disulfide bondi523 ↔ 539
Disulfide bondi526 ↔ 541
Disulfide bondi543 ↔ 552
Glycosylationi568C-linked (Man) tryptophan; partial1 Publication1
Glycosylationi571C-linked (Man) tryptophan; partial1 Publication1
Glycosylationi574C-linked (Man) tryptophan; partial1 Publication1
Disulfide bondi577 ↔ 611
Disulfide bondi589 ↔ 601
Disulfide bondi644 ↔ 686
Disulfide bondi672 ↔ 699
Disulfide bondi704 ↔ 746
Disulfide bondi732 ↔ 761
Disulfide bondi773 ↔ 823
Disulfide bondi784 ↔ 801
Disulfide bondi786 ↔ 837
Disulfide bondi793 ↔ 816
Glycosylationi855N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi862 ↔ 873
Disulfide bondi867 ↔ 919
Disulfide bondi880 ↔ 897
Disulfide bondi882 ↔ 932
Disulfide bondi888 ↔ 912

Post-translational modificationi

All cysteine residues are assumed to be cross-linked to one another. Individual modules containing an even number of conserved cysteine residues are supposed to have disulfide linkages only within the same module.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP13671
PaxDbiP13671
PeptideAtlasiP13671
PRIDEiP13671
ProteomicsDBi52956

PTM databases

CarbonylDBiP13671
GlyConnecti791
iPTMnetiP13671
PhosphoSitePlusiP13671

Expressioni

Gene expression databases

BgeeiENSG00000039537 Expressed in 117 organ(s), highest expression level in liver
CleanExiHS_C6
ExpressionAtlasiP13671 baseline and differential
GenevisibleiP13671 HS

Organism-specific databases

HPAiCAB069427
HPA043823

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 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK1P163332EBI-1753221,EBI-389883

Protein-protein interaction databases

BioGridi107190, 8 interactors
IntActiP13671, 5 interactors
STRINGi9606.ENSP00000263413

Structurei

Secondary structure

1934
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP13671
SMRiP13671
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 79TSP type-1 1PROSITE-ProRule annotationAdd BLAST58
Domaini81 – 134TSP type-1 2PROSITE-ProRule annotationAdd BLAST54
Domaini138 – 175LDL-receptor class APROSITE-ProRule annotationAdd BLAST38
Domaini176 – 522MACPFPROSITE-ProRule annotationAdd BLAST347
Domaini523 – 553EGF-likeAdd BLAST31
Domaini565 – 612TSP type-1 3PROSITE-ProRule annotationAdd BLAST48
Domaini642 – 701Sushi 1PROSITE-ProRule annotationAdd BLAST60
Domaini702 – 763Sushi 2PROSITE-ProRule annotationAdd BLAST62
Domaini780 – 839Kazal-like 1PROSITE-ProRule annotationAdd BLAST60
Domaini876 – 934Kazal-like 2PROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni611 – 688CCP 1Add BLAST78
Regioni642 – 934C5b-binding domainAdd BLAST293
Regioni689 – 765CCP 2Add BLAST77
Regioni766 – 840Factor I module (FIM) 1Add BLAST75
Regioni858 – 934Factor I module (FIM) 2Add BLAST77

Sequence similaritiesi

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

Keywords - Domaini

EGF-like domain, Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiENOG410IDXP Eukaryota
ENOG410YJ70 LUCA
GeneTreeiENSGT00550000074478
HOGENOMiHOG000111865
HOVERGENiHBG005366
InParanoidiP13671
KOiK03995
OMAiCKNKFRC
OrthoDBiEOG091G07LK
PhylomeDBiP13671
TreeFamiTF330498

Family and domain databases

CDDicd00033 CCP, 2 hits
cd00112 LDLa, 1 hit
Gene3Di2.20.100.10, 3 hits
InterProiView protein in InterPro
IPR037563 Complement_C6
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
PANTHERiPTHR19325:SF23 PTHR19325:SF23, 1 hit
PfamiView protein in Pfam
PF00057 Ldl_recept_a, 1 hit
PF01823 MACPF, 1 hit
PF00084 Sushi, 2 hits
PF00090 TSP_1, 3 hits
PRINTSiPR00764 COMPLEMENTC9
SMARTiView protein in SMART
SM00032 CCP, 2 hits
SM00057 FIMAC, 2 hits
SM00192 LDLa, 1 hit
SM00457 MACPF, 1 hit
SM00209 TSP1, 3 hits
SUPFAMiSSF57424 SSF57424, 1 hit
SSF57535 SSF57535, 2 hits
SSF82895 SSF82895, 3 hits
PROSITEiView 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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P13671-1 [UniParc]FASTAAdd to basket
« Hide
        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
Length:934
Mass (Da):104,786
Last modified:May 1, 2007 - v3
Checksum:iA88F4BED7CC349D3
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JC72C9JC72_HUMAN
Complement component C6
C6
133Annotation score:
C9JX36C9JX36_HUMAN
Complement component C6
C6
31Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti567Q → H in BAD02321 (Ref. 4) Curated1
Sequence conflicti616M → I in BAD02321 (Ref. 4) Curated1
Sequence conflicti934A → T in BAD02321 (Ref. 4) Curated1

Polymorphismi

The sequence shown is that of allotype C6 B.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_006056119A → E in allotype C6 A. 5 PublicationsCorresponds to variant dbSNP:rs1801033EnsemblClinVar.1
Natural variantiVAR_027647397K → E. Corresponds to variant dbSNP:rs6896011Ensembl.1
Natural variantiVAR_027648470S → 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
CCDSiCCDS3936.1
PIRiA34372
RefSeqiNP_000056.2, NM_000065.3
NP_001108603.2, NM_001115131.2
UniGeneiHs.481992

Genome annotation databases

EnsembliENST00000263413; ENSP00000263413; ENSG00000039537
ENST00000337836; ENSP00000338861; ENSG00000039537
GeneIDi729
KEGGihsa:729
UCSCiuc003jmk.4 human

Keywords - Coding sequence diversityi

Polymorphism

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
CCDSiCCDS3936.1
PIRiA34372
RefSeqiNP_000056.2, NM_000065.3
NP_001108603.2, NM_001115131.2
UniGeneiHs.481992

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3T5OX-ray2.87A22-934[»]
4A5WX-ray3.50B22-934[»]
4E0SX-ray4.21B22-934[»]
ProteinModelPortaliP13671
SMRiP13671
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107190, 8 interactors
IntActiP13671, 5 interactors
STRINGi9606.ENSP00000263413

Protein family/group databases

TCDBi1.C.39.3.3 the membrane attack complex/perforin (macpf) family

PTM databases

CarbonylDBiP13671
GlyConnecti791
iPTMnetiP13671
PhosphoSitePlusiP13671

Polymorphism and mutation databases

DMDMi146345396

Proteomic databases

EPDiP13671
PaxDbiP13671
PeptideAtlasiP13671
PRIDEiP13671
ProteomicsDBi52956

Protocols and materials databases

DNASUi729
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263413; ENSP00000263413; ENSG00000039537
ENST00000337836; ENSP00000338861; ENSG00000039537
GeneIDi729
KEGGihsa:729
UCSCiuc003jmk.4 human

Organism-specific databases

CTDi729
DisGeNETi729
EuPathDBiHostDB:ENSG00000039537.13
GeneCardsiC6
H-InvDBiHIX0024838
HGNCiHGNC:1339 C6
HPAiCAB069427
HPA043823
MalaCardsiC6
MIMi217050 gene
612446 phenotype
neXtProtiNX_P13671
OpenTargetsiENSG00000039537
Orphaneti169150 Immunodeficiency due to a late component of complements deficiency
PharmGKBiPA25921
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IDXP Eukaryota
ENOG410YJ70 LUCA
GeneTreeiENSGT00550000074478
HOGENOMiHOG000111865
HOVERGENiHBG005366
InParanoidiP13671
KOiK03995
OMAiCKNKFRC
OrthoDBiEOG091G07LK
PhylomeDBiP13671
TreeFamiTF330498

Enzyme and pathway databases

ReactomeiR-HSA-166665 Terminal pathway of complement
R-HSA-977606 Regulation of Complement cascade

Miscellaneous databases

ChiTaRSiC6 human
GeneWikiiComplement_component_6
GenomeRNAii729
PROiPR:P13671
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000039537 Expressed in 117 organ(s), highest expression level in liver
CleanExiHS_C6
ExpressionAtlasiP13671 baseline and differential
GenevisibleiP13671 HS

Family and domain databases

CDDicd00033 CCP, 2 hits
cd00112 LDLa, 1 hit
Gene3Di2.20.100.10, 3 hits
InterProiView protein in InterPro
IPR037563 Complement_C6
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
PANTHERiPTHR19325:SF23 PTHR19325:SF23, 1 hit
PfamiView protein in Pfam
PF00057 Ldl_recept_a, 1 hit
PF01823 MACPF, 1 hit
PF00084 Sushi, 2 hits
PF00090 TSP_1, 3 hits
PRINTSiPR00764 COMPLEMENTC9
SMARTiView protein in SMART
SM00032 CCP, 2 hits
SM00057 FIMAC, 2 hits
SM00192 LDLa, 1 hit
SM00457 MACPF, 1 hit
SM00209 TSP1, 3 hits
SUPFAMiSSF57424 SSF57424, 1 hit
SSF57535 SSF57535, 2 hits
SSF82895 SSF82895, 3 hits
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiCO6_HUMAN
AccessioniPrimary (citable) accession number: P13671
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: May 1, 2007
Last modified: September 12, 2018
This is version 191 of the entry and version 3 of the sequence. See 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

3D-structure, 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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