CO8A_MOUSE
ID CO8A_MOUSE Reviewed; 587 AA.
AC Q8K182; Q8CHJ9; Q8CHK1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Complement component C8 alpha chain;
DE AltName: Full=Complement component 8 subunit alpha;
DE Flags: Precursor;
GN Name=C8a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS VAL-468; ARG-477 AND
RP 574-GLY--CYS-587 DELINS ASP-GLN-HIS-GLY-GLY-ASP-PHE.
RC STRAIN=BALB/cJ, DBA/2J, and Mae/Stm; TISSUE=Liver;
RA Tanaka S., Kikkawa Y., Hosonuma M.I., Koike S., Yonekawa H.;
RT "Two mouse strains with complementary mutations on the 8th complement.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Constituent of the membrane attack complex (MAC) that plays a
CC key role in the innate and adaptive immune response by forming pores in
CC the plasma membrane of target cells. C8A inserts into the target
CC membrane, but does not form pores by itself (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterotrimer of 3 chains: alpha, beta and gamma. The alpha and
CC gamma chains are disulfide bonded. Component of the membrane attack
CC complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5
CC into C5a and C5b. C5b sequentially binds C6, C7, C8 and multiple copies
CC of the pore-forming subunit C9 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Note=Secreted
CC as soluble protein. Inserts into the cell membrane of target cells (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC {ECO:0000305}.
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DR EMBL; AB077295; BAC41360.1; -; mRNA.
DR EMBL; AB077296; BAC41361.1; -; mRNA.
DR EMBL; AB077298; BAC41363.1; -; mRNA.
DR EMBL; BC027748; AAH27748.1; -; mRNA.
DR CCDS; CCDS18415.1; -.
DR RefSeq; NP_666260.1; NM_146148.2.
DR AlphaFoldDB; Q8K182; -.
DR SMR; Q8K182; -.
DR BioGRID; 230969; 4.
DR ComplexPortal; CPX-6202; Membrane attack complex.
DR STRING; 10090.ENSMUSP00000067541; -.
DR GlyGen; Q8K182; 5 sites.
DR iPTMnet; Q8K182; -.
DR PhosphoSitePlus; Q8K182; -.
DR SwissPalm; Q8K182; -.
DR CPTAC; non-CPTAC-3570; -.
DR MaxQB; Q8K182; -.
DR PaxDb; Q8K182; -.
DR PeptideAtlas; Q8K182; -.
DR PRIDE; Q8K182; -.
DR ProteomicsDB; 283547; -.
DR Antibodypedia; 19367; 58 antibodies from 18 providers.
DR DNASU; 230558; -.
DR Ensembl; ENSMUST00000064873; ENSMUSP00000067541; ENSMUSG00000035031.
DR GeneID; 230558; -.
DR KEGG; mmu:230558; -.
DR UCSC; uc008tya.2; mouse.
DR CTD; 731; -.
DR MGI; MGI:2668347; C8a.
DR VEuPathDB; HostDB:ENSMUSG00000035031; -.
DR eggNOG; ENOG502QT87; Eukaryota.
DR GeneTree; ENSGT00940000160126; -.
DR HOGENOM; CLU_032453_1_0_1; -.
DR InParanoid; Q8K182; -.
DR OMA; EQYDFGM; -.
DR OrthoDB; 787014at2759; -.
DR PhylomeDB; Q8K182; -.
DR TreeFam; TF330498; -.
DR Reactome; R-MMU-166665; Terminal pathway of complement.
DR Reactome; R-MMU-977606; Regulation of Complement cascade.
DR BioGRID-ORCS; 230558; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q8K182; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8K182; protein.
DR Bgee; ENSMUSG00000035031; Expressed in left lobe of liver and 22 other tissues.
DR ExpressionAtlas; Q8K182; baseline and differential.
DR Genevisible; Q8K182; MM.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005579; C:membrane attack complex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0001848; F:complement binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0006956; P:complement activation; ISO:MGI.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0050778; P:positive regulation of immune response; IC:ComplexPortal.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR037565; Complement_C8_alpha.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR001862; MAC_perforin.
DR InterPro; IPR020864; MACPF.
DR InterPro; IPR020863; MACPF_CS.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR45742:SF1; PTHR45742:SF1; 1.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR Pfam; PF01823; MACPF; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR00764; COMPLEMENTC9.
DR SMART; SM00192; LDLa; 1.
DR SMART; SM00457; MACPF; 1.
DR SMART; SM00209; TSP1; 2.
DR SUPFAM; SSF57424; SSF57424; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 1.
DR PROSITE; PS00279; MACPF_1; 1.
DR PROSITE; PS51412; MACPF_2; 1.
DR PROSITE; PS50092; TSP1; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Complement alternate pathway; Complement pathway; Cytolysis;
KW Disulfide bond; EGF-like domain; Glycoprotein; Immunity; Innate immunity;
KW Membrane; Membrane attack complex; Reference proteome; Repeat; Secreted;
KW Signal; Transmembrane; Transmembrane beta strand.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..30
FT /evidence="ECO:0000255"
FT /id="PRO_0000023587"
FT CHAIN 31..587
FT /note="Complement component C8 alpha chain"
FT /id="PRO_0000023588"
FT DOMAIN 38..91
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 94..132
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 136..498
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
FT DOMAIN 499..529
FT /note="EGF-like"
FT DOMAIN 542..586
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT CARBOHYD 44
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P07357"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P07357"
FT CARBOHYD 548
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P07357"
FT CARBOHYD 551
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000250|UniProtKB:P07357"
FT DISULFID 39..74
FT /evidence="ECO:0000250"
FT DISULFID 50..53
FT /evidence="ECO:0000250"
FT DISULFID 84..90
FT /evidence="ECO:0000250"
FT DISULFID 96..108
FT /evidence="ECO:0000250"
FT DISULFID 102..121
FT /evidence="ECO:0000250"
FT DISULFID 115..130
FT /evidence="ECO:0000250"
FT DISULFID 140..177
FT /evidence="ECO:0000250"
FT DISULFID 194
FT /note="Interchain (with C-60 in C8-gamma chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 375..399
FT /evidence="ECO:0000250"
FT VARIANT 263
FT /note="I -> V (in strain: Mae/Stm)"
FT VARIANT 468
FT /note="L -> V (in strain: BALB/c)"
FT VARIANT 469
FT /note="R -> Q (in strain: Mae/Stm)"
FT VARIANT 477
FT /note="E -> R (in strain: BALB/c; requires 2 nucleotide
FT substitutions)"
FT VARIANT 574..587
FT /note="GTPCLGRNLQTQAC -> DQHGGDF (in strain: BALB/c)"
SQ SEQUENCE 587 AA; 66080 MW; EEC529469F380A75 CRC64;
MFVVAFFGLS LVAWHPGVTA QEKVNQRVTR AVTPQAVSCQ LSDWYKWTDC FPCQDKKYRY
RSLLQPSKFG GTICSGDIWD EASCDSPTPC LRQAQCGQDF QCRETGRCLK RHLVCNGDND
CLDGSDESDC EDVRVTEDDC HQYEPIPGSE RAALGYNILT QEEAQSVYDA KYYGGQCETV
YNGDWRKLRY DPTCERLYYG EDEKYFRKPY NFLKYHFEAL ADTSISSEFY DDANDLFFHI
KNGKSHSAGV TVGVAPVKSP VSIEVTGSGS KASSFLNKLN KYNEKRYGFM RVSTKIQTAQ
FKMRRNNIVL DEGMLQSLME LPEQFNYGMY AKFINDYGTH YITSGTMGGI YEYVMVLDKE
KMKTEGTTVD EVQKCIGGGI GIGIKDSTIE GVGISGEFCE NSGDGDRDIR KKITGVEDII
SRVQGGSSVW GSVLTHNSSA ITYQSWGRSL KYNPVVIDFE MQPIYQLLRH TNLGPLETKR
QNLRRALDQY LMEFNACRCG PCFNNGEPIL DGTNCRCQCS MGRQGLACER TVIEGLKDFK
AAGHWSCWSS WSECRGGSQE RRRQCNNPPP KNGGTPCLGR NLQTQAC
