P10643 (CO7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement component C7

Gene names

Name:

C7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	843 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. C7 serves as a membrane anchor.
Subunit structure	Monomer or dimer; as a C5b-7 complex it can also form multimeric rosettes. 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	C7 has 28 disulfide bridges. O- and C-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Ref.4 Ref.7
Involvement in disease	Complement component 7 deficiency (C7D) [MIM:610102]: 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. Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the complement C6/C7/C8/C9 family. Contains 1 EGF-like domain. Contains 1 LDL-receptor class A domain. Contains 1 MACPF domain. Contains 2 Sushi (CCP/SCR) domains. Contains 2 TSP type-1 domains.

Ontologies

Keywords
Biological process	Complement alternate pathway Complement pathway Cytolysis Immunity Innate immunity
Cellular component	Membrane attack complex Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	EGF-like domain Repeat Signal Sushi
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation Traceable author statement Ref.1. Source: ProtInc complement activation, alternative pathway Inferred from electronic annotation. Source: UniProtKB-KW 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	extracellular region Traceable author statement. Source: Reactome membrane attack complex Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Chain

23 – 843

821

Complement component C7

PRO_0000023583

Regions

Domain

27 – 80

54

TSP type-1 1

Domain

83 – 121

39

LDL-receptor class A

Domain

124 – 456

333

MACPF

Domain

457 – 487

31

EGF-like

Domain

500 – 549

50

TSP type-1 2

Domain

569 – 628

60

Sushi 1

Domain

629 – 690

62

Sushi 2

Region

545 – 615

71

CCP 1

Region

616 – 693

78

CCP 2

Region

695 – 770

76

Factor I module (FIM) 1

Region

771 – 843

73

Factor I module (FIM) 2

Amino acid modifications

Glycosylation

36

1

C-linked (Man) Ref.4

Glycosylation

202

1

N-linked (GlcNAc...) Ref.5 Ref.6

Glycosylation

503

1

C-linked (Man); partial Ref.4

Glycosylation

506

1

C-linked (Man); partial Ref.4

Glycosylation

509

1

C-linked (Man); partial Ref.4

Glycosylation

696

1

O-linked (GalNAc...) Ref.7

Glycosylation

754

1

N-linked (GlcNAc...) Ref.6

Disulfide bond

85 ↔ 96

By similarity

Disulfide bond

91 ↔ 109

By similarity

Disulfide bond

103 ↔ 119

By similarity

Disulfide bond

128 ↔ 165

By similarity

Disulfide bond

337 ↔ 353

Ref.8

Disulfide bond

571 ↔ 613

By similarity

Disulfide bond

599 ↔ 626

By similarity

Disulfide bond

631 ↔ 673

By similarity

Disulfide bond

659 ↔ 688

By similarity

Disulfide bond

702 ↔ 713

Ref.8

Disulfide bond

715 ↔ 750

Ref.8

Disulfide bond

721 ↔ 743

Ref.8

Disulfide bond

728 ↔ 763

Ref.8

Disulfide bond

773 ↔ 782

Ref.8

Disulfide bond

776 ↔ 789

Ref.8

Disulfide bond

791 ↔ 825

Ref.8

Disulfide bond

797 ↔ 818

Ref.8

Disulfide bond

805 ↔ 838

Ref.8

Natural variations

Natural variant

128

1

C → R.
Corresponds to variant rs2271708 [ dbSNP | Ensembl ].

VAR_050480

Natural variant

220

1

R → Q in C7D. Ref.11

VAR_012643

Natural variant

379

1

G → R in C7D. Ref.10

VAR_012644

Natural variant

389

1

S → T Polymorphism confirmed at protein level. Ref.3 Ref.12
Corresponds to variant rs1063499 [ dbSNP | Ensembl ].

VAR_033798

Natural variant

420

1

K → Q.
Corresponds to variant rs3792646 [ dbSNP | Ensembl ].

VAR_022023

Natural variant

521

1

R → S in C7D. Ref.9

VAR_012645

Natural variant

587

1

T → P Polymorphism confirmed at protein level. Ref.1 Ref.12
Corresponds to variant rs13157656 [ dbSNP | Ensembl ].

VAR_033799

Natural variant

682

1

E → Q in C7D. Ref.11

VAR_012646

Natural variant

687

1

R → H in C7D. Ref.11

VAR_012647

Experimental info

Sequence conflict

152

1

R → V in CAA60121. Ref.3

Sequence conflict

821 – 822

2

GA → AL Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

.

.

.

843

Helix Strand Turn

Details...

Beta strand

706 – 709

4

Beta strand

712 – 715

4

Helix

718 – 720

3

Beta strand

726 – 731

6

Turn

732 – 734

3

Beta strand

737 – 741

5

Helix

742 – 750

9

Beta strand

755 – 757

3

Beta strand

766 – 769

4

Beta strand

778 – 782

5

Beta strand

784 – 791

8

Helix

794 – 796

3

Beta strand

803 – 808

6

Beta strand

811 – 816

6

Helix

817 – 826

10

Beta strand

831 – 836

6

Sequences

	Sequence		Length	Mass (Da)
	P10643 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: DBD5D7C92DF71FA5	FASTA	843	93,518
	10 20 30 40 50 60 MKVISLFILV GFIGEFQSFS SASSPVNCQW DFYAPWSECN GCTKTQTRRR SVAVYGQYGG 70 80 90 100 110 120 QPCVGNAFET QSCEPTRGCP TEEGCGERFR CFSGQCISKS LVCNGDSDCD EDSADEDRCE 130 140 150 160 170 180 DSERRPSCDI DKPPPNIELT GNGYNELTGQ FRNRVINTKS FGGQCRKVFS GDGKDFYRLS 190 200 210 220 230 240 GNVLSYTFQV KINNDFNYEF YNSTWSYVKH TSTEHTSSSR KRSFFRSSSS SSRSYTSHTN 250 260 270 280 290 300 EIHKGKSYQL LVVENTVEVA QFINNNPEFL QLAEPFWKEL SHLPSLYDYS AYRRLIDQYG 310 320 330 340 350 360 THYLQSGSLG GEYRVLFYVD SEKLKQNDFN SVEEKKCKSS GWHFVVKFSS HGCKELENAL 370 380 390 400 410 420 KAASGTQNNV LRGEPFIRGG GAGFISGLSY LELDNPAGNK RRYSAWAESV TNLPQVIKQK 430 440 450 460 470 480 LTPLYELVKE VPCASVKKLY LKWALEEYLD EFDPCHCRPC QNGGLATVEG THCLCHCKPY 490 500 510 520 530 540 TFGAACEQGV LVGNQAGGVD GGWSCWSSWS PCVQGKKTRS RECNNPPPSG GGRSCVGETT 550 560 570 580 590 600 ESTQCEDEEL EHLRLLEPHC FPLSLVPTEF CPSPPALKDG FVQDEGTMFP VGKNVVYTCN 610 620 630 640 650 660 EGYSLIGNPV ARCGEDLRWL VGEMHCQKIA CVLPVLMDGI QSHPQKPFYT VGEKVTVSCS 670 680 690 700 710 720 GGMSLEGPSA FLCGSSLKWS PEMKNARCVQ KENPLTQAVP KCQRWEKLQN SRCVCKMPYE 730 740 750 760 770 780 CGPSLDVCAQ DERSKRILPL TVCKMHVLHC QGRNYTLTGR DSCTLPASAE KACGACPLWG 790 800 810 820 830 840 KCDAESSKCV CREASECEEE GFSICVEVNG KEQTMSECEA GALRCRGQSI SVTSIRPCAA ETQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The structure of human complement component C7 and the C5b-7 complex." Discipio R.G., Chakravari D.N., Mueller-Eberhard H.J., Fey G.H. J. Biol. Chem. 263:549-560(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT PRO-587.
[2]	"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]. Tissue: PNS.
[3]	"Structure of the human C7 gene and comparison with the C6, C8A, C8B and C9 genes." Hobart M.J., Fernie B.A., DiScipio R.G. J. Immunol. 154:5188-5194(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-822, VARIANT THR-389.
[4]	"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-36; TRP-503; TRP-506 AND TRP-509.
[5]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-202, MASS SPECTROMETRY. Tissue: Plasma.
[6]	"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-202 AND ASN-754, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-696, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[8]	"Solution structure of factor I-like modules from complement C7 reveals a pair of follistatin domains in compact pseudosymmetric arrangement." Phelan M.M., Thai C.-T., Soares D.C., Ogata R.T., Barlow P.N., Bramham J. J. Biol. Chem. 284:19637-19649(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 693-843, DISULFIDE BONDS.
[9]	"Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies." Fernie B.A., Wurzner R., Orren A., Morgan B.P., Potter P.C., Platonov A.E., Vershinina I.V., Shipulin G.A., Lachmann P.J., Hobart M.J. J. Immunol. 157:3648-3657(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT C7D SER-521.
[10]	"Molecular bases of C7 deficiency: three different defects." Fernie B.A., Orren A., Sheehan G., Schlesinger M., Hobart M.J. J. Immunol. 159:1019-1026(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT C7D ARG-379.
[11]	"Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes." Fernie B.A., Hobart M.J. Hum. Genet. 103:513-519(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS C7D GLN-220; GLN-682 AND HIS-687.
[12]	"Quantitative detection of single amino acid polymorphisms by targeted proteomics." Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X., Zeng R., Wu J.R. J. Mol. Cell Biol. 3:309-315(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-389 AND PRO-587, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

C7base

C7 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03507 mRNA. Translation: AAA51861.1.
BC063851 mRNA. Translation: AAH63851.1.
X86328 , X86329, X86330, X86331, X86332, X86333, X86334, X86335, X86336, X86337, X86338, X86339, X86340, X86341, X86342, X86343, X86344 Genomic DNA. Translation: CAA60121.1.

IPI

IPI00296608.

PIR

A27340.

RefSeq

NP_000578.2. NM_000587.2.

UniGene

Hs.78065.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WCY	NMR	-	A	693-843	[»]

ProteinModelPortal

P10643.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10643. 1 interaction.

MINT

MINT-7032139.

STRING

9606.ENSP00000322061.

PTM databases

PhosphoSite

P10643.

Polymorphism databases

DMDM

61252057.

Proteomic databases

PaxDb

P10643.

PRIDE

P10643.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000313164; ENSP00000322061; ENSG00000112936.

GeneID

730.

KEGG

hsa:730.

UCSC

uc003jmh.3. human.

Organism-specific databases

CTD

730.

GeneCards

GC05P040909.

HGNC

HGNC:1346. C7.

HPA

HPA001465.

MIM

217070. gene.
610102. phenotype.

neXtProt

NX_P10643.

Orphanet

169150. Immunodeficiency due to a late component of complements deficiency.

PharmGKB

PA25941.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG145238.

HOGENOM

HOG000111868.

HOVERGEN

HBG005367.

InParanoid

P10643.

KO

K03996.

OMA

GERFRCF.

OrthoDB

EOG4NS3B1.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P10643.

CleanEx

HS_C7.

Genevestigator

P10643.

GermOnline

ENSG00000112936. Homo sapiens.

Family and domain databases

Gene3D

4.10.400.10. 1 hit.

InterPro

IPR003884. FacI_MAC.
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]

Pfam

PF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00084. Sushi. 2 hits.
PF00090. TSP_1. 2 hits.
[Graphical view]

PRINTS

PR00764. COMPLEMENTC9.

SMART

SM00032. CCP. 2 hits.
SM00057. FIMAC. 2 hits.
SM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]

SUPFAM

SSF57535. Complement_control_module. 2 hits.
SSF82895. TSP1. 2 hits.

PROSITE

PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. False negative.
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. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

C7. human.

EvolutionaryTrace

P10643.

GenomeRNAi

730.

NextBio

2972.

SOURCE

Search...

Entry information

Entry name

CO7_HUMAN

Accession

Primary (citable) accession number: P10643
Secondary accession number(s): Q6P3T5, Q92489

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 145 of the entry and version 2 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.