P13671 (CO6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement component C6

Gene names

Name:

C6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	934 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 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.
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	Defects in C6 are the cause of 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.
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.

Ontologies

Keywords
Biological process	Complement pathway Cytolysis Immunity Innate immunity
Cellular component	Membrane attack complex Secreted
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Repeat Signal Sushi
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	complement activation, classical pathway Inferred from electronic annotation. Source: UniProtKB-KW cytolysis Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome
Cellular component	membrane attack complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1753221,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.1
	Chain	22 – 934	913	Complement component C6		PRO_0000023579
Regions
	Domain	22 – 79	58	TSP type-1 1
	Domain	81 – 134	54	TSP type-1 2
	Domain	138 – 175	38	LDL-receptor class A
	Domain	176 – 522	347	MACPF
	Domain	523 – 553	31	EGF-like
	Domain	565 – 612	48	TSP type-1 3
	Domain	642 – 701	60	Sushi 1
	Domain	702 – 763	62	Sushi 2
	Domain	780 – 839	60	Kazal-like 1
	Domain	876 – 934	59	Kazal-like 2
	Region	642 – 934	293	C5b-binding domain
	Region	766 – 840	75	Complement control factor I module 1
	Region	858 – 934	77	Complement control factor I module 2
Amino acid modifications
	Modified residue	278	1	Phosphoserine Ref.11
	Glycosylation	29	1	C-linked (Man) Ref.9
	Glycosylation	32	1	C-linked (Man); partial Ref.9
	Glycosylation	90	1	C-linked (Man); partial Ref.9
	Glycosylation	324	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	568	1	C-linked (Man); partial Ref.9
	Glycosylation	571	1	C-linked (Man); partial Ref.9
	Glycosylation	574	1	C-linked (Man); partial Ref.9
	Glycosylation	855	1	N-linked (GlcNAc...) Ref.10
	Disulfide bond	24 ↔ 65		By similarity
	Disulfide bond	35 ↔ 39		By similarity
	Disulfide bond	73 ↔ 78		By similarity
	Disulfide bond	82 ↔ 117		By similarity
	Disulfide bond	93 ↔ 96		By similarity
	Disulfide bond	127 ↔ 133		By similarity
	Disulfide bond	140 ↔ 151		By similarity
	Disulfide bond	146 ↔ 164		By similarity
	Disulfide bond	158 ↔ 173		By similarity
	Disulfide bond	399 ↔ 420		By similarity
	Disulfide bond	523 ↔ 539		By similarity
	Disulfide bond	526 ↔ 541		By similarity
	Disulfide bond	543 ↔ 552		By similarity
	Disulfide bond	644 ↔ 686		By similarity
	Disulfide bond	672 ↔ 699		By similarity
	Disulfide bond	704 ↔ 746		By similarity
	Disulfide bond	732 ↔ 761		By similarity
	Disulfide bond	773 ↔ 823		Ref.8
	Disulfide bond	784 ↔ 801		Ref.8
	Disulfide bond	786 ↔ 837		Ref.8
	Disulfide bond	793 ↔ 816		Ref.8
	Disulfide bond	862 ↔ 873		Ref.8
	Disulfide bond	867 ↔ 919		Ref.8
	Disulfide bond	880 ↔ 897		Ref.8
	Disulfide bond	882 ↔ 932		Ref.8
	Disulfide bond	888 ↔ 912		Ref.8
Natural variations
	Natural variant	119	1	A → E in allotype C6 A. Ref.2 Ref.3 Ref.6 Ref.7 Ref.12 Corresponds to variant rs1801033 [ dbSNP | Ensembl ].		VAR_006056
	Natural variant	397	1	K → E. Corresponds to variant rs6896011 [ dbSNP | Ensembl ].		VAR_027647
	Natural variant	470	1	S → F. Corresponds to variant rs10462014 [ dbSNP | Ensembl ].		VAR_027648
Experimental info
	Sequence conflict	567	1	Q → H in BAD02321. Ref.4
	Sequence conflict	616	1	M → I in BAD02321. Ref.4
	Sequence conflict	934	1	A → T in BAD02321. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P13671 [UniParc]. Last modified May 1, 2007. Version 3. Checksum: A88F4BED7CC349D3	FASTA	934	104,786
	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

References

	« Hide 'large scale' referencesShow '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: 2808363] [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: 2789218] [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: 8512929] [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. , 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: 15372022] [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: 15489334] [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: 2468158] [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: 9366265] [Abstract] Cited for: DISULFIDE BONDS IN COMPLEMENT CONTROL FACTOR 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: 10551839] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-324 AND ASN-855, MASS SPECTROMETRY. Tissue: Plasma.
[11]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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: 8101442] [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: 15565285] [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.
IPI	IPI00879709.
PIR	A34372.
RefSeq	NP_000056.2. NM_000065.2. NP_001108603.2. NM_001115131.1.
UniGene	Hs.481992.
3D structure databases
ProteinModelPortal	P13671.
SMR	P13671. Positions 25-613, 642-758.
ModBase	Search...
Protein-protein interaction databases
IntAct	P13671. 5 interactions.
MINT	MINT-7241404.
STRING	P13671.
Polymorphism databases
DMDM	146345396.
Proteomic databases
PRIDE	P13671.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263413; ENSP00000263413; ENSG00000039537. ENST00000337836; ENSP00000338861; ENSG00000039537.
GeneID	729.
KEGG	hsa:729.
UCSC	uc003jmk.2. human.
Organism-specific databases
CTD	729.
GeneCards	GC05M041178.
H-InvDB	HIX0024838.
HGNC	HGNC:1339. C6.
HPA	HPA043823.
MIM	217050. gene. 612446. phenotype.
neXtProt	NX_P13671.
Orphanet	169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKB	PA25921.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04585.
GeneTree	ENSGT00550000074478.
HOGENOM	HBG445244.
HOVERGEN	HBG005366.
InParanoid	P13671.
OMA	VYDLLYQ.
OrthoDB	EOG4QRH3K.
PhylomeDB	P13671.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P13671.
Bgee	P13671.
CleanEx	HS_C6.
Genevestigator	P13671.
GermOnline	ENSG00000039537. Homo sapiens.
Family and domain databases
InterPro	IPR016060. Complement_control_module. IPR003884. FacI_MAC. IPR023415. LDLR_class-A_CS. IPR002172. LDrepeatLR_classA_rpt. IPR001862. MAC_perforin. IPR020864. MACPF. IPR020863. MACPF_CS. IPR002350. Prot_inh_Kazal. IPR011497. Prot_Inh_Kazal_2. IPR000436. Sushi_SCR_CCP. IPR000884. Thrombospondin_1_rpt. [Graphical view]
Gene3D	G3DSA:2.10.70.10. Complement_control_module. 2 hits. G3DSA:4.10.400.10. LDL_rcpt_classA_cys-rich. 1 hit.
KO	K03995.
Pfam	PF07648. 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]
PRINTS	PR00764. COMPLEMENTC9.
SMART	SM00032. 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]
SUPFAM	SSF57535. Complement_control_module. 2 hits. SSF57424. LDL_rcpt_classA_cys-rich. 1 hit. SSF82895. TSP1. 3 hits.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. False negative. PS50026. EGF_3. False negative. 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]
ProtoNet	Search...
Other
NextBio	2968.
SOURCE	Search...

Entry information

Entry name

CO6_HUMAN

Accession

Primary (citable) accession number: P13671

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	May 1, 2007
Last modified:	January 25, 2012
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.