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P07357 (CO8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Complement component C8 alpha chain
Alternative name(s):
Complement component 8 subunit alpha
Gene names
Name:C8A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length584 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. 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Propeptide21 – 3010 Potential
PRO_0000023585
Chain31 – 584554Complement component C8 alpha chain
PRO_0000023586

Regions

Domain38 – 9154TSP type-1 1
Domain94 – 13239LDL-receptor class A
Domain135 – 498364MACPF
Domain499 – 52931EGF-like
Domain539 – 58345TSP type-1 2

Sites

Site431Not glycosylated

Amino acid modifications

Glycosylation441C-linked (Man) Ref.7
Glycosylation4371N-linked (GlcNAc...) Ref.8 Ref.9
Glycosylation5421C-linked (Man) Ref.7
Glycosylation5451C-linked (Man) Ref.7
Glycosylation5481C-linked (Man) Ref.7
Disulfide bond39 ↔ 74 By similarity
Disulfide bond50 ↔ 53 By similarity
Disulfide bond84 ↔ 90 By similarity
Disulfide bond96 ↔ 108 By similarity
Disulfide bond102 ↔ 121 By similarity
Disulfide bond115 ↔ 130 By similarity
Disulfide bond140 ↔ 177 Ref.11
Disulfide bond194Interchain (with C-60 in C8-gamma chain) Ref.11
Disulfide bond375 ↔ 399 Ref.11

Natural variations

Natural variant931Q → K in allele C8A*B. Ref.5 Ref.13
Corresponds to variant rs652785 [ dbSNP | Ensembl ].
VAR_011889
Natural variant4071T → I.
Corresponds to variant rs706479 [ dbSNP | Ensembl ].
VAR_011890
Natural variant4581D → N.
Corresponds to variant rs17114555 [ dbSNP | Ensembl ].
VAR_033800
Natural variant4851R → L.
Corresponds to variant rs1620075 [ dbSNP | Ensembl ].
VAR_011891
Natural variant5611E → Q.
Corresponds to variant rs1342440 [ dbSNP | Ensembl ].
VAR_011892
Natural variant5751P → L.
Corresponds to variant rs17300936 [ dbSNP | Ensembl ].
VAR_033801

Experimental info

Sequence conflict5751P → S in AAA82124. Ref.3

Secondary structure

............................................................................................. 584
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07357 [UniParc].

Last modified February 1, 1995. Version 2.
Checksum: 9F61DDA51D2F3BBA

FASTA58465,163
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
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.
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 expand/collapse EMBL AC list , 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.
PIRC8HUA. I37213.
RefSeqNP_000553.1. NM_000562.2.
UniGeneHs.93210.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QOSX-ray1.81A188-198[»]
2QQHX-ray2.50A133-492[»]
2RD7X-ray2.15A133-492[»]
3OJYX-ray2.51A31-584[»]
ProteinModelPortalP07357.
SMRP07357. Positions 32-582.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107192. 2 interactions.
DIPDIP-1125N.
STRING9606.ENSP00000354458.

Protein family/group databases

TCDB1.C.39.3.1. the membrane attack complex/perforin (macpf) family.

PTM databases

PhosphoSiteP07357.

Polymorphism databases

DMDM729167.

Proteomic databases

PaxDbP07357.
PRIDEP07357.

Protocols and materials databases

DNASU731.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361249; ENSP00000354458; ENSG00000157131.
GeneID731.
KEGGhsa:731.
UCSCuc001cyo.2. human.

Organism-specific databases

CTD731.
GeneCardsGC01P057237.
HGNCHGNC:1352. C8A.
MIM120950. gene.
613790. phenotype.
neXtProtNX_P07357.
Orphanet169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBPA25951.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG48024.
HOGENOMHOG000231146.
HOVERGENHBG005368.
InParanoidP07357.
KOK03997.
OMAFMRIFTK.
OrthoDBEOG7CRTPG.
PhylomeDBP07357.
TreeFamTF330498.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP07357.
CleanExHS_C8A.
GenevestigatorP07357.

Family and domain databases

Gene3D4.10.400.10. 1 hit.
InterProIPR009030. Growth_fac_rcpt_N_dom.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSPR00764. COMPLEMENTC9.
SMARTSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 3 hits.
SSF82895. SSF82895. 2 hits.
PROSITEPS00022. EGF_1. 1 hit.
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]
ProtoNetSearch...

Other

ChiTaRSC8A. human.
EvolutionaryTraceP07357.
GenomeRNAi731.
NextBio2976.
PROP07357.
SOURCESearch...

Entry information

Entry nameCO8A_HUMAN
AccessionPrimary (citable) accession number: P07357
Secondary accession number(s): A2RUI4 expand/collapse secondary AC list , A2RUI5, Q13668, Q9H130
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 156 of the entry and version 2 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 1

Human chromosome 1: entries, gene names and cross-references to MIM