P07357 (CO8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Complement component C8 alpha chain

Alternative name(s):
Complement component 8 subunit alpha

Gene names

Name:

C8A

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	584 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. C8A inserts into the target membrane, but does not form pores by itself. Ref.6 Ref.10
Subunit structure	Heterotrimer of 3 chains: alpha, beta and gamma. The alpha and gamma chains are disulfide bonded. 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. Ref.6
Subcellular location	Secreted. Cell membrane; Multi-pass membrane protein. Note: Secreted as soluble protein. Inserts into the cell membrane of target cells.
Involvement in disease	Complement component 8 deficiency, 1 (C8D1) [MIM:613790]: 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 1 LDL-receptor class A domain. Contains 1 MACPF domain. Contains 2 TSP type-1 domains.

Ontologies

Keywords
Biological process	Complement alternate pathway Complement pathway Cytolysis Immunity Innate immunity
Cellular component	Cell membrane Membrane Membrane attack complex Secreted
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane beta strand
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation Inferred from direct assay PubMed 12413696. Source: MGI 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 space Traceable author statement PubMed 6771072. Source: ProtInc membrane attack complex Inferred from direct assay PubMed 12413696. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 30

10

Potential

PRO_0000023585

Chain

31 – 584

554

Complement component C8 alpha chain

PRO_0000023586

Regions

Domain

38 – 91

54

TSP type-1 1

Domain

94 – 132

39

LDL-receptor class A

Domain

135 – 498

364

MACPF

Domain

499 – 529

31

EGF-like

Domain

539 – 583

45

TSP type-1 2

Sites

Site

43

1

Not glycosylated

Amino acid modifications

Glycosylation

44

1

C-linked (Man) Ref.7

Glycosylation

437

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

542

1

C-linked (Man) Ref.7

Glycosylation

545

1

C-linked (Man) Ref.7

Glycosylation

548

1

C-linked (Man) Ref.7

Disulfide bond

39 ↔ 74

By similarity

Disulfide bond

50 ↔ 53

By similarity

Disulfide bond

84 ↔ 90

By similarity

Disulfide bond

96 ↔ 108

By similarity

Disulfide bond

102 ↔ 121

By similarity

Disulfide bond

115 ↔ 130

By similarity

Disulfide bond

140 ↔ 177

Ref.11

Disulfide bond

194

Interchain (with C-60 in C8-gamma chain) Ref.11

Disulfide bond

375 ↔ 399

Ref.11

Natural variations

Natural variant

93

1

Q → K in allele C8A*B. Ref.5 Ref.13
Corresponds to variant rs652785 [ dbSNP | Ensembl ].

VAR_011889

Natural variant

407

1

T → I.
Corresponds to variant rs706479 [ dbSNP | Ensembl ].

VAR_011890

Natural variant

458

1

D → N.
Corresponds to variant rs17114555 [ dbSNP | Ensembl ].

VAR_033800

Natural variant

485

1

R → L.
Corresponds to variant rs1620075 [ dbSNP | Ensembl ].

VAR_011891

Natural variant

561

1

E → Q.
Corresponds to variant rs1342440 [ dbSNP | Ensembl ].

VAR_011892

Natural variant

575

1

P → L.
Corresponds to variant rs17300936 [ dbSNP | Ensembl ].

VAR_033801

Experimental info

Sequence conflict

575

1

P → S in AAA82124. Ref.3

Secondary structure

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584

Helix Strand Turn

Details...

Turn

52 – 54

3

Beta strand

56 – 60

5

Beta strand

63 – 65

3

Beta strand

78 – 83

6

Beta strand

97 – 101

5

Beta strand

103 – 105

3

Helix

111 – 113

3

Beta strand

116 – 118

3

Beta strand

121 – 123

3

Beta strand

127 – 129

3

Beta strand

140 – 143

4

Helix

149 – 152

4

Beta strand

154 – 157

4

Turn

158 – 161

4

Beta strand

162 – 168

7

Beta strand

179 – 182

4

Turn

183 – 186

4

Beta strand

188 – 191

4

Turn

192 – 195

4

Beta strand

196 – 199

4

Helix

201 – 203

3

Beta strand

204 – 207

4

Beta strand

212 – 217

6

Beta strand

226 – 232

7

Helix

233 – 243

11

Beta strand

246 – 252

7

Beta strand

260 – 266

7

Helix

273 – 280

8

Beta strand

287 – 303

17

Beta strand

305 – 308

4

Helix

312 – 319

8

Helix

327 – 337

11

Beta strand

339 – 358

20

Helix

359 – 365

7

Helix

369 – 379

11

Helix

398 – 402

5

Helix

408 – 413

6

Beta strand

416 – 421

6

Helix

443 – 449

7

Turn

450 – 452

3

Beta strand

455 – 463

9

Helix

464 – 470

7

Helix

477 – 491

15

Helix

496 – 498

3

Turn

503 – 505

3

Beta strand

508 – 511

4

Beta strand

514 – 517

4

Beta strand

525 – 527

3

Beta strand

552 – 554

3

Beta strand

556 – 559

4

Beta strand

578 – 582

5

Sequences

	Sequence		Length	Mass (Da)
	P07357 [UniParc]. Last modified February 1, 1995. Version 2. Checksum: 9F61DDA51D2F3BBA	FASTA	584	65,163
	10 20 30 40 50 60 MFAVVFFILS LMTCQPGVTA QEKVNQRVRR AATPAAVTCQ LSNWSEWTDC FPCQDKKYRH 70 80 90 100 110 120 RSLLQPNKFG GTICSGDIWD QASCSSSTTC VRQAQCGQDF QCKETGRCLK RHLVCNGDQD 130 140 150 160 170 180 CLDGSDEDDC EDVRAIDEDC SQYEPIPGSQ KAALGYNILT QEDAQSVYDA SYYGGQCETV 190 200 210 220 230 240 YNGEWRELRY DSTCERLYYG DDEKYFRKPY NFLKYHFEAL ADTGISSEFY DNANDLLSKV 250 260 270 280 290 300 KKDKSDSFGV TIGIGPAGSP LLVGVGVSHS QDTSFLNELN KYNEKKFIFT RIFTKVQTAH 310 320 330 340 350 360 FKMRKDDIML DEGMLQSLME LPDQYNYGMY AKFINDYGTH YITSGSMGGI YEYILVIDKA 370 380 390 400 410 420 KMESLGITSR DITTCFGGSL GIQYEDKINV GGGLSGDHCK KFGGGKTERA RKAMAVEDII 430 440 450 460 470 480 SRVRGGSSGW SGGLAQNRST ITYRSWGRSL KYNPVVIDFE MQPIHEVLRH TSLGPLEAKR 490 500 510 520 530 540 QNLRRALDQY LMEFNACRCG PCFNNGVPIL EGTSCRCQCR LGSLGAACEQ TQTEGAKADG 550 560 570 580 SWSCWSSWSV CRAGIQERRR ECDNPAPQNG GASCPGRKVQ TQAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementary DNA and derived amino acid sequence of the alpha subunit of human complement protein C8: evidence for the existence of a separate alpha subunit messenger RNA." Rao A.G., Howard O.M.Z., Ng S.C., Whitehead A.S., Colten H.R., Sodetz J.M. Biochemistry 26:3556-3564(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	Sodetz J.M. Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 467-479.
[3]	"Genomic organization of human complement protein C8 alpha and further examination of its linkage to C8 beta." Michelotti G.A., Snider J.V., Sodetz J.M. Hum. Genet. 95:513-518(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 LYS-93.
[6]	"The eighth component of human complement. Purification and physicochemical characterization of its unusual subunit structure." Steckel E.W., York R.G., Monahan J.B., Sodetz J.M. J. Biol. Chem. 255:11997-12005(1980) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT.
[7]	"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-44; TRP-542; TRP-545 AND TRP-548.
[8]	"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-437, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-437, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense." Hadders M.A., Beringer D.X., Gros P. Science 317:1552-1554(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 133-492, FUNCTION.
[11]	"Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit." Slade D.J., Lovelace L.L., Chruszcz M., Minor W., Lebioda L., Sodetz J.M. J. Mol. Biol. 379:331-342(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 133-492 IN COMPLEX WITH C8G, INTERCHAIN DISULFIDE BOND.
[12]	"Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: implications for C8gamma ligand binding." Lovelace L.L., Chiswell B., Slade D.J., Sodetz J.M., Lebioda L. Mol. Immunol. 45:750-756(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 188-198 IN COMPLEX WITH C8G.
[13]	"The eighth component of human complement: molecular basis of C8A (C81) polymorphism." Zhang L., Rittner C., Sodetz J.M., Schneider P.M., Kaufmann T. Hum. Genet. 96:281-284(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT C8A*B LYS-93.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16974 mRNA. Translation: AAA52200.1.
U08006 , U07996, U07997, U07998, U07999, U08000, U08001, U08002, U08003, U08004, U08005 Genomic DNA. Translation: AAA82124.1.
AL121998 Genomic DNA. Translation: CAI19172.1.
BC132911 mRNA. Translation: AAI32912.1.
BC132913 mRNA. Translation: AAI32914.1.

IPI

IPI00011252.

PIR

C8HUA. I37213.

RefSeq

NP_000553.1. NM_000562.2.

UniGene

Hs.93210.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QOS	X-ray	1.81	A	188-198	[»]
2QQH	X-ray	2.50	A	133-492	[»]
2RD7	X-ray	2.15	A	133-492	[»]
3OJY	X-ray	2.51	A	31-584	[»]

ProteinModelPortal

P07357.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1125N.

STRING

9606.ENSP00000354458.

Protein family/group databases

TCDB

1.C.39.3.1. membrane attack complex/perforin (MACPF) family.

PTM databases

PhosphoSite

P07357.

Polymorphism databases

DMDM

729167.

Proteomic databases

PaxDb

P07357.

PRIDE

P07357.

Protocols and materials databases

DNASU

731.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361249; ENSP00000354458; ENSG00000157131.

GeneID

731.

KEGG

hsa:731.

UCSC

uc001cyo.2. human.

Organism-specific databases

CTD

731.

GeneCards

GC01P057237.

HGNC

HGNC:1352. C8A.

MIM

120950. gene.
613790. phenotype.

neXtProt

NX_P07357.

Orphanet

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

PharmGKB

PA25951.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG48024.

HOGENOM

HOG000231146.

HOVERGEN

HBG005368.

InParanoid

P07357.

KO

K03997.

OMA

CFPCQDK.

OrthoDB

EOG40ZQXD.

PhylomeDB

P07357.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P07357.

CleanEx

HS_C8A.

Genevestigator

P07357.

GermOnline

ENSG00000157131. Homo sapiens.

Family and domain databases

Gene3D

4.10.400.10. 1 hit.

InterPro

IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]

Pfam

PF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]

PRINTS

PR00764. COMPLEMENTC9.

SMART

SM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]

SUPFAM

SSF57424. LDL_rcpt_classA_cys-rich. 1 hit.
SSF82895. TSP1. 2 hits.

PROSITE

PS00022. EGF_1. 1 hit.
PS01186. EGF_2. False negative.
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.
PS50092. TSP1. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

C8A. human.

EvolutionaryTrace

P07357.

GenomeRNAi

731.

NextBio

2976.

SOURCE

Search...

Entry information

Entry name

CO8A_HUMAN

Accession

Primary (citable) accession number: P07357
Secondary accession number(s): A2RUI4 , A2RUI5, Q13668, Q9H130

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 147 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.