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Protein

Complement component C8 alpha chain

Gene

C8A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  • complement activation Source: MGI
  • complement activation, alternative pathway Source: UniProtKB-KW
  • complement activation, classical pathway Source: UniProtKB-KW
  • cytolysis Source: UniProtKB-KW
  • immune response Source: ProtInc
  • regulation of complement activation Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Complement alternate pathway, Complement pathway, Cytolysis, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000157131-MONOMER.
ReactomeiR-HSA-166665. Terminal pathway of complement.
R-HSA-977606. Regulation of Complement cascade.

Protein family/group databases

TCDBi1.C.39.3.1. the membrane attack complex/perforin (macpf) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Complement component C8 alpha chain
Alternative name(s):
Complement component 8 subunit alpha
Gene namesi
Name:C8A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:1352. C8A.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: ProtInc
  • membrane Source: ProtInc
  • membrane attack complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Membrane attack complex, Secreted

Pathology & Biotechi

Involvement in diseasei

Complement component 8 deficiency, 1 (C8D1)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
See also OMIM:613790

Organism-specific databases

DisGeNETi731.
MalaCardsiC8A.
MIMi613790. phenotype.
OpenTargetsiENSG00000157131.
Orphaneti169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBiPA25951.

Polymorphism and mutation databases

BioMutaiC8A.
DMDMi729167.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002358521 – 30Sequence analysis10
ChainiPRO_000002358631 – 584Complement component C8 alpha chainAdd BLAST554

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi39 ↔ 74By similarity
Glycosylationi44C-linked (Man)1 Publication1
Disulfide bondi50 ↔ 53By similarity
Disulfide bondi84 ↔ 90By similarity
Disulfide bondi96 ↔ 108By similarity
Disulfide bondi102 ↔ 121By similarity
Disulfide bondi115 ↔ 130By similarity
Disulfide bondi140 ↔ 177
Disulfide bondi194Interchain (with C-60 in C8-gamma chain)
Disulfide bondi375 ↔ 399
Glycosylationi437N-linked (GlcNAc...)2 Publications1
Glycosylationi542C-linked (Man)1 Publication1
Glycosylationi545C-linked (Man)1 Publication1
Glycosylationi548C-linked (Man)1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei43Not glycosylated1

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP07357.
PaxDbiP07357.
PeptideAtlasiP07357.
PRIDEiP07357.

PTM databases

iPTMnetiP07357.
PhosphoSitePlusiP07357.

Expressioni

Gene expression databases

BgeeiENSG00000157131.
CleanExiHS_C8A.
GenevisibleiP07357. HS.

Interactioni

Subunit structurei

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 proteolytic cleavage of C5 into C5a and C5b. C5b sequentially binds C6, C7, C8 and multiple copies of the pore-forming subunit C9.3 Publications

Protein-protein interaction databases

BioGridi107192. 2 interactors.
DIPiDIP-1125N.
STRINGi9606.ENSP00000354458.

Structurei

Secondary structure

1584
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni52 – 54Combined sources3
Beta strandi56 – 60Combined sources5
Beta strandi63 – 65Combined sources3
Beta strandi78 – 83Combined sources6
Beta strandi97 – 101Combined sources5
Beta strandi103 – 105Combined sources3
Helixi111 – 113Combined sources3
Beta strandi116 – 118Combined sources3
Beta strandi121 – 123Combined sources3
Beta strandi127 – 129Combined sources3
Beta strandi140 – 143Combined sources4
Helixi149 – 152Combined sources4
Beta strandi154 – 157Combined sources4
Turni158 – 161Combined sources4
Beta strandi162 – 168Combined sources7
Beta strandi179 – 182Combined sources4
Turni183 – 186Combined sources4
Beta strandi189 – 191Combined sources3
Turni192 – 195Combined sources4
Beta strandi196 – 198Combined sources3
Helixi201 – 203Combined sources3
Beta strandi204 – 207Combined sources4
Beta strandi212 – 217Combined sources6
Beta strandi226 – 232Combined sources7
Helixi233 – 243Combined sources11
Beta strandi246 – 252Combined sources7
Beta strandi260 – 266Combined sources7
Helixi273 – 280Combined sources8
Beta strandi287 – 303Combined sources17
Beta strandi305 – 308Combined sources4
Helixi312 – 319Combined sources8
Helixi327 – 337Combined sources11
Beta strandi339 – 358Combined sources20
Helixi359 – 365Combined sources7
Helixi369 – 379Combined sources11
Helixi398 – 402Combined sources5
Helixi408 – 413Combined sources6
Beta strandi416 – 421Combined sources6
Helixi443 – 449Combined sources7
Turni450 – 452Combined sources3
Beta strandi455 – 463Combined sources9
Helixi464 – 470Combined sources7
Helixi477 – 491Combined sources15
Helixi496 – 498Combined sources3
Turni503 – 505Combined sources3
Beta strandi508 – 511Combined sources4
Beta strandi514 – 517Combined sources4
Beta strandi525 – 527Combined sources3
Beta strandi552 – 554Combined sources3
Beta strandi556 – 559Combined sources4
Beta strandi578 – 582Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QOSX-ray1.81A188-198[»]
2QQHX-ray2.50A133-366[»]
A410-492[»]
2RD7X-ray2.15A133-492[»]
3OJYX-ray2.51A31-584[»]
ProteinModelPortaliP07357.
SMRiP07357.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07357.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 91TSP type-1 1PROSITE-ProRule annotationAdd BLAST54
Domaini94 – 132LDL-receptor class APROSITE-ProRule annotationAdd BLAST39
Domaini135 – 498MACPFPROSITE-ProRule annotationAdd BLAST364
Domaini499 – 529EGF-likeAdd BLAST31
Domaini539 – 583TSP type-1 2PROSITE-ProRule annotationAdd BLAST45

Sequence similaritiesi

Belongs to the complement C6/C7/C8/C9 family.Curated
Contains 1 EGF-like domain.Curated
Contains 1 LDL-receptor class A domain.PROSITE-ProRule annotation
Contains 1 MACPF domain.PROSITE-ProRule annotation
Contains 2 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane beta strand

Phylogenomic databases

eggNOGiENOG410IE8U. Eukaryota.
ENOG410Y5MF. LUCA.
GeneTreeiENSGT00550000074478.
HOGENOMiHOG000231146.
HOVERGENiHBG005368.
InParanoidiP07357.
KOiK03997.
OMAiFMRIFTK.
OrthoDBiEOG091G07LK.
PhylomeDBiP07357.
TreeFamiTF330498.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSiPR00764. COMPLEMENTC9.
SMARTiSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 3 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS00022. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07357-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFAVVFFILS LMTCQPGVTA QEKVNQRVRR AATPAAVTCQ LSNWSEWTDC
60 70 80 90 100
FPCQDKKYRH RSLLQPNKFG GTICSGDIWD QASCSSSTTC VRQAQCGQDF
110 120 130 140 150
QCKETGRCLK RHLVCNGDQD CLDGSDEDDC EDVRAIDEDC SQYEPIPGSQ
160 170 180 190 200
KAALGYNILT QEDAQSVYDA SYYGGQCETV YNGEWRELRY DSTCERLYYG
210 220 230 240 250
DDEKYFRKPY NFLKYHFEAL ADTGISSEFY DNANDLLSKV KKDKSDSFGV
260 270 280 290 300
TIGIGPAGSP LLVGVGVSHS QDTSFLNELN KYNEKKFIFT RIFTKVQTAH
310 320 330 340 350
FKMRKDDIML DEGMLQSLME LPDQYNYGMY AKFINDYGTH YITSGSMGGI
360 370 380 390 400
YEYILVIDKA KMESLGITSR DITTCFGGSL GIQYEDKINV GGGLSGDHCK
410 420 430 440 450
KFGGGKTERA RKAMAVEDII SRVRGGSSGW SGGLAQNRST ITYRSWGRSL
460 470 480 490 500
KYNPVVIDFE MQPIHEVLRH TSLGPLEAKR QNLRRALDQY LMEFNACRCG
510 520 530 540 550
PCFNNGVPIL EGTSCRCQCR LGSLGAACEQ TQTEGAKADG SWSCWSSWSV
560 570 580
CRAGIQERRR ECDNPAPQNG GASCPGRKVQ TQAC
Length:584
Mass (Da):65,163
Last modified:February 1, 1995 - v2
Checksum:i9F61DDA51D2F3BBA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti575P → S in AAA82124 (PubMed:7759071).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01188993Q → K in allele C8A*B. 2 PublicationsCorresponds to variant rs652785dbSNPEnsembl.1
Natural variantiVAR_011890407T → I.Corresponds to variant rs706479dbSNPEnsembl.1
Natural variantiVAR_033800458D → N.Corresponds to variant rs17114555dbSNPEnsembl.1
Natural variantiVAR_011891485R → L.Corresponds to variant rs1620075dbSNPEnsembl.1
Natural variantiVAR_011892561E → Q.Corresponds to variant rs1342440dbSNPEnsembl.1
Natural variantiVAR_033801575P → L.Corresponds to variant rs17300936dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS606.1.
PIRiI37213. C8HUA.
RefSeqiNP_000553.1. NM_000562.2.
UniGeneiHs.93210.

Genome annotation databases

EnsembliENST00000361249; ENSP00000354458; ENSG00000157131.
GeneIDi731.
KEGGihsa:731.
UCSCiuc001cyo.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS606.1.
PIRiI37213. C8HUA.
RefSeqiNP_000553.1. NM_000562.2.
UniGeneiHs.93210.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QOSX-ray1.81A188-198[»]
2QQHX-ray2.50A133-366[»]
A410-492[»]
2RD7X-ray2.15A133-492[»]
3OJYX-ray2.51A31-584[»]
ProteinModelPortaliP07357.
SMRiP07357.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107192. 2 interactors.
DIPiDIP-1125N.
STRINGi9606.ENSP00000354458.

Protein family/group databases

TCDBi1.C.39.3.1. the membrane attack complex/perforin (macpf) family.

PTM databases

iPTMnetiP07357.
PhosphoSitePlusiP07357.

Polymorphism and mutation databases

BioMutaiC8A.
DMDMi729167.

Proteomic databases

MaxQBiP07357.
PaxDbiP07357.
PeptideAtlasiP07357.
PRIDEiP07357.

Protocols and materials databases

DNASUi731.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361249; ENSP00000354458; ENSG00000157131.
GeneIDi731.
KEGGihsa:731.
UCSCiuc001cyo.3. human.

Organism-specific databases

CTDi731.
DisGeNETi731.
GeneCardsiC8A.
HGNCiHGNC:1352. C8A.
MalaCardsiC8A.
MIMi120950. gene.
613790. phenotype.
neXtProtiNX_P07357.
OpenTargetsiENSG00000157131.
Orphaneti169150. Immunodeficiency due to a late component of complements deficiency.
PharmGKBiPA25951.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE8U. Eukaryota.
ENOG410Y5MF. LUCA.
GeneTreeiENSGT00550000074478.
HOGENOMiHOG000231146.
HOVERGENiHBG005368.
InParanoidiP07357.
KOiK03997.
OMAiFMRIFTK.
OrthoDBiEOG091G07LK.
PhylomeDBiP07357.
TreeFamiTF330498.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000157131-MONOMER.
ReactomeiR-HSA-166665. Terminal pathway of complement.
R-HSA-977606. Regulation of Complement cascade.

Miscellaneous databases

ChiTaRSiC8A. human.
EvolutionaryTraceiP07357.
GenomeRNAii731.
PROiP07357.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157131.
CleanExiHS_C8A.
GenevisibleiP07357. HS.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR001862. MAC_perforin.
IPR020864. MACPF.
IPR020863. MACPF_CS.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 1 hit.
PF01823. MACPF. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
PRINTSiPR00764. COMPLEMENTC9.
SMARTiSM00192. LDLa. 1 hit.
SM00457. MACPF. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 3 hits.
SSF82895. SSF82895. 2 hits.
PROSITEiPS00022. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiCO8A_HUMAN
AccessioniPrimary (citable) accession number: P07357
Secondary accession number(s): A2RUI4
, A2RUI5, Q13668, Q9H130
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: February 1, 1995
Last modified: November 30, 2016
This is version 179 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.