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P13671 (CO6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement component C6
Gene names
Name:C6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length934 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.

Subunit structure

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. Ref.11

Subcellular location

Secreted.

Post-translational modification

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.

Polymorphism

The sequence shown is that of allotype C6 B.

Involvement in disease

Complement component 6 deficiency (C6D) [MIM:612446]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Sequence similarities

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

Contains 1 EGF-like domain.

Contains 2 Kazal-like domains.

Contains 1 LDL-receptor class A domain.

Contains 1 MACPF domain.

Contains 2 Sushi (CCP/SCR) domains.

Contains 3 TSP type-1 domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCK1P163332EBI-1753221,EBI-389883

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.1
Chain22 – 934913Complement component C6
PRO_0000023579

Regions

Domain22 – 7958TSP type-1 1
Domain81 – 13454TSP type-1 2
Domain138 – 17538LDL-receptor class A
Domain176 – 522347MACPF
Domain523 – 55331EGF-like
Domain565 – 61248TSP type-1 3
Domain642 – 70160Sushi 1
Domain702 – 76362Sushi 2
Domain780 – 83960Kazal-like 1
Domain876 – 93459Kazal-like 2
Region611 – 68878CCP 1
Region642 – 934293C5b-binding domain
Region689 – 76577CCP 2
Region766 – 84075Factor I module (FIM) 1
Region858 – 93477Factor I module (FIM) 2

Amino acid modifications

Glycosylation291C-linked (Man) Ref.9 Ref.11
Glycosylation321C-linked (Man); partial Ref.9 Ref.11
Glycosylation381O-linked (Fuc...) Probable
Glycosylation901C-linked (Man); partial Ref.9
Glycosylation3241N-linked (GlcNAc...) Ref.10 Ref.11
Glycosylation3921O-linked (Fuc...) Probable
Glycosylation5681C-linked (Man); partial Ref.9 Ref.11
Glycosylation5711C-linked (Man); partial Ref.9 Ref.11
Glycosylation5741C-linked (Man); partial Ref.9
Glycosylation8551N-linked (GlcNAc...) Ref.10
Disulfide bond22 ↔ 61 Ref.8 Ref.11
Disulfide bond24 ↔ 65 Ref.8 Ref.11
Disulfide bond35 ↔ 73 Ref.8 Ref.11
Disulfide bond39 ↔ 78 Ref.8 Ref.11
Disulfide bond82 ↔ 117 Ref.8 Ref.11
Disulfide bond93 ↔ 127 Ref.8 Ref.11
Disulfide bond96 ↔ 133 Ref.8 Ref.11
Disulfide bond140 ↔ 151 Ref.8 Ref.11
Disulfide bond146 ↔ 164 Ref.8 Ref.11
Disulfide bond158 ↔ 173 Ref.8 Ref.11
Disulfide bond180 ↔ 218 Ref.8 Ref.11
Disulfide bond399 ↔ 420 Ref.8 Ref.11
Disulfide bond499 ↔ 623 Ref.8 Ref.11
Disulfide bond521 ↔ 570 Ref.8 Ref.11
Disulfide bond523 ↔ 539 Ref.8 Ref.11
Disulfide bond526 ↔ 541 Ref.8 Ref.11
Disulfide bond543 ↔ 552 Ref.8 Ref.11
Disulfide bond577 ↔ 611 Ref.8 Ref.11
Disulfide bond589 ↔ 601 Ref.8 Ref.11
Disulfide bond644 ↔ 686 Ref.8 Ref.11
Disulfide bond672 ↔ 699 Ref.8 Ref.11
Disulfide bond704 ↔ 746 Ref.8 Ref.11
Disulfide bond732 ↔ 761 Ref.8 Ref.11
Disulfide bond773 ↔ 823 Ref.8 Ref.11
Disulfide bond784 ↔ 801 Ref.8 Ref.11
Disulfide bond786 ↔ 837 Ref.8 Ref.11
Disulfide bond793 ↔ 816 Ref.8 Ref.11
Disulfide bond862 ↔ 873 Ref.8 Ref.11
Disulfide bond867 ↔ 919 Ref.8 Ref.11
Disulfide bond880 ↔ 897 Ref.8 Ref.11
Disulfide bond882 ↔ 932 Ref.8 Ref.11
Disulfide bond888 ↔ 912 Ref.8 Ref.11

Natural variations

Natural variant1191A → E in allotype C6 A. Ref.2 Ref.3 Ref.6 Ref.7 Ref.12
Corresponds to variant rs1801033 [ dbSNP | Ensembl ].
VAR_006056
Natural variant3971K → E.
Corresponds to variant rs6896011 [ dbSNP | Ensembl ].
VAR_027647
Natural variant4701S → F.
Corresponds to variant rs10462014 [ dbSNP | Ensembl ].
VAR_027648

Experimental info

Sequence conflict5671Q → H in BAD02321. Ref.4
Sequence conflict6161M → I in BAD02321. Ref.4
Sequence conflict9341A → T in BAD02321. Ref.4

Secondary structure

................................................................................................................................................................................ 934
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13671 [UniParc].

Last modified May 1, 2007. Version 3.
Checksum: A88F4BED7CC349D3

FASTA934104,786
        10         20         30         40         50         60 
MARRSVLYFI LLNALINKGQ ACFCDHYAWT QWTSCSKTCN SGTQSRHRQI VVDKYYQENF 

        70         80         90        100        110        120 
CEQICSKQET RECNWQRCPI NCLLGDFGPW SDCDPCIEKQ SKVRSVLRPS QFGGQPCTAP 

       130        140        150        160        170        180 
LVAFQPCIPS KLCKIEEADC KNKFRCDSGR CIARKLECNG ENDCGDNSDE RDCGRTKAVC 

       190        200        210        220        230        240 
TRKYNPIPSV QLMGNGFHFL AGEPRGEVLD NSFTGGICKT VKSSRTSNPY RVPANLENVG 

       250        260        270        280        290        300 
FEVQTAEDDL KTDFYKDLTS LGHNENQQGS FSSQGGSSFS VPIFYSSKRS ENINHNSAFK 

       310        320        330        340        350        360 
QAIQASHKKD SSFIRIHKVM KVLNFTTKAK DLHLSDVFLK ALNHLPLEYN SALYSRIFDD 

       370        380        390        400        410        420 
FGTHYFTSGS LGGVYDLLYQ FSSEELKNSG LTEEEAKHCV RIETKKRVLF AKKTKVEHRC 

       430        440        450        460        470        480 
TTNKLSEKHE GSFIQGAEKS ISLIRGGRSE YGAALAWEKG SSGLEEKTFS EWLESVKENP 

       490        500        510        520        530        540 
AVIDFELAPI VDLVRNIPCA VTKRNNLRKA LQEYAAKFDP CQCAPCPNNG RPTLSGTECL 

       550        560        570        580        590        600 
CVCQSGTYGE NCEKQSPDYK SNAVDGQWGC WSSWSTCDAT YKRSRTRECN NPAPQRGGKR 

       610        620        630        640        650        660 
CEGEKRQEED CTFSIMENNG QPCINDDEEM KEVDLPEIEA DSGCPQPVPP ENGFIRNEKQ 

       670        680        690        700        710        720 
LYLVGEDVEI SCLTGFETVG YQYFRCLPDG TWRQGDVECQ RTECIKPVVQ EVLTITPFQR 

       730        740        750        760        770        780 
LYRIGESIEL TCPKGFVVAG PSRYTCQGNS WTPPISNSLT CEKDTLTKLK GHCQLGQKQS 

       790        800        810        820        830        840 
GSECICMSPE EDCSHHSEDL CVFDTDSNDY FTSPACKFLA EKCLNNQQLH FLHIGSCQDG 

       850        860        870        880        890        900 
RQLEWGLERT RLSSNSTKKE SCGYDTCYDW EKCSASTSKC VCLLPPQCFK GGNQLYCVKM 

       910        920        930 
GSSTSEKTLN ICEVGTIRCA NRKMEILHPG KCLA 

« Hide

References

« Hide 'large scale' references
[1]"Complete primary structure and functional characterization of the sixth component of the human complement system. Identification of the C5b-binding domain in complement C6."
Haefliger J.-A., Tschopp J., Vial N., Jenne D.E.
J. Biol. Chem. 264:18041-18051(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 22-31 AND 633-640.
[2]"The molecular architecture of human complement component C6."
Discipio R.G., Hugli T.E.
J. Biol. Chem. 264:16197-16206(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-119.
[3]"Structure of the human C6 gene."
Hobart M.J., Fernie B., Discipio R.G.
Biochemistry 32:6198-6205(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-119.
Tissue: Blood.
[4]"Sequence variation in C6 locus."
Soejima M., Koda Y.
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANT GLU-119.
Tissue: Ovary.
[7]"Structural homology of complement protein C6 with other channel-forming proteins of complement."
Chakravarti D.N., Chakravarti B., Parra C.A., Mueller-Eberhard H.J.
Proc. Natl. Acad. Sci. U.S.A. 86:2799-2803(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-491, VARIANT GLU-119.
[8]"Elucidation of the disulfide-bonding pattern in the factor I modules of the sixth component (C6) of human complement."
Lengweiler S., Schaller J., DiScipio R.G., Rickli E.E.
Biochim. Biophys. Acta 1342:13-18(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS IN FACTOR I MODULE 1 REGION.
[9]"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-29; TRP-32; TRP-90; TRP-568; TRP-571 AND TRP-574.
[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-324 AND ASN-855.
Tissue: Plasma.
[11]"Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC)."
Aleshin A.E., Schraufstatter I.U., Stec B., Bankston L.A., Liddington R.C., DiScipio R.G.
J. Biol. Chem. 287:10210-10222(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 22-934, GLYCOSYLATION AT TRP-29; TRP-32; THR-38; ASN-324; THR-392; TRP-568 AND TRP-571, SUBUNIT, DISULFIDE BONDS.
[12]"Polymorphism of human complement component C6: an amino acid substitution (Glu/Ala) within the second thrombospondin repeat differentiates between the two common allotypes C6 A and C6 B."
Dewald G., Nothen M.M., Cichon S.
Biochem. Biophys. Res. Commun. 194:458-464(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALLOTYPE C6 A GLU-119.
[13]"Meningococccal meningitis and complement component 6 deficiency associated with oculocutaneous albinism."
Ikinciogullari A., Tekin M., Dogu F., Reisli I., Tanir G., Yi Z., Garrison N., Brilliant M.H., Babacan E.
Eur. J. Pediatr. 164:177-179(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN COMPLEMENT COMPONENT 6 DEFICIENCY.
+Additional computationally mapped references.

Web resources

C6base

C6 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA34372.
RefSeqNP_000056.2. NM_000065.3.
NP_001108603.2. NM_001115131.2.
UniGeneHs.481992.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3T5OX-ray2.87A22-934[»]
4A5WX-ray3.50B22-934[»]
4E0SX-ray4.21B22-934[»]
ProteinModelPortalP13671.
SMRP13671. Positions 22-934.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107190. 3 interactions.
IntActP13671. 5 interactions.
STRING9606.ENSP00000263413.

Protein family/group databases

TCDB1.C.39.3.3. the membrane attack complex/perforin (macpf) family.

PTM databases

PhosphoSiteP13671.

Polymorphism databases

DMDM146345396.

Proteomic databases

PaxDbP13671.
PRIDEP13671.

Protocols and materials databases

DNASU729.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263413; ENSP00000263413; ENSG00000039537.
ENST00000337836; ENSP00000338861; ENSG00000039537.
GeneID729.
KEGGhsa:729.
UCSCuc003jmk.3. human.

Organism-specific databases

CTD729.
GeneCardsGC05M041178.
H-InvDBHIX0024838.
HGNCHGNC:1339. C6.
HPAHPA043823.
MIM217050. gene.
612446. phenotype.
neXtProtNX_P13671.
Orphanet169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBPA25921.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145238.
HOGENOMHOG000111865.
HOVERGENHBG005366.
InParanoidP13671.
KOK03995.
OMACVCQSGT.
OrthoDBEOG7NPFT9.
PhylomeDBP13671.
TreeFamTF330498.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP13671.
BgeeP13671.
CleanExHS_C6.
GenevestigatorP13671.

Family and domain databases

InterProIPR003884. FacI_MAC.
IPR002350. Kazal_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000436. Sushi_SCR_CCP.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF07648. Kazal_2. 1 hit.
PF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00084. Sushi. 2 hits.
PF00090. TSP_1. 3 hits.
[Graphical view]
PRINTSPR00764. COMPLEMENTC9.
SMARTSM00032. CCP. 2 hits.
SM00057. FIMAC. 2 hits.
SM00280. KAZAL. 1 hit.
SM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 3 hits.
[Graphical view]
SUPFAMSSF57424. SSF57424. 1 hit.
SSF57535. SSF57535. 2 hits.
SSF82895. SSF82895. 3 hits.
PROSITEPS00022. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSC6. human.
GeneWikiComplement_component_6.
GenomeRNAi729.
NextBio2968.
PROP13671.
SOURCESearch...

Entry information

Entry nameCO6_HUMAN
AccessionPrimary (citable) accession number: P13671
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: May 1, 2007
Last modified: March 19, 2014
This is version 155 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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