ID CO8G_HUMAN Reviewed; 202 AA.
AC P07360; Q14CT8; Q14CU0; Q5SQ07;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 24-JAN-2024, entry version 218.
DE RecName: Full=Complement component C8 gamma chain;
DE Flags: Precursor;
GN Name=C8G;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, PYROGLUTAMATE
RP FORMATION AT GLN-21, AND VARIANT GLY-118.
RX PubMed=3676249; DOI=10.1021/bi00391a003;
RA Ng S.C., Rao A.G., Howard O.M.Z., Sodetz J.M.;
RT "The eighth component of human complement: evidence that it is an
RT oligomeric serum protein assembled from products of three different
RT genes.";
RL Biochemistry 26:5229-5233(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-118.
RC TISSUE=Liver;
RX PubMed=2447883; DOI=10.1016/0006-291x(87)90431-1;
RA Haefliger J.-A., Jenne D.E., Stanley K.K., Tschopp J.;
RT "Structural homology of human complement component C8 gamma and plasma
RT protein HC: identity of the cysteine bond pattern.";
RL Biochem. Biophys. Res. Commun. 149:750-754(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-118.
RC TISSUE=Blood;
RX PubMed=8172891; DOI=10.1021/bi00183a020;
RA Kaufman K.M., Sodetz J.M.;
RT "Genomic structure of the human complement protein C8 gamma: homology to
RT the lipocalin gene family.";
RL Biochemistry 33:5162-5166(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-118.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-118 AND ASN-124.
RC TISSUE=Colon;
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 [7]
RP SIMILARITY TO LIPOCALINS.
RX PubMed=2446620; DOI=10.1016/0006-291x(87)91636-6;
RA Hunt L.T., Elzanowski A., Barker W.C.;
RT "The homology of complement factor C8 gamma chain and alpha-1-
RT microglobulin.";
RL Biochem. Biophys. Res. Commun. 149:282-288(1987).
RN [8]
RP DISULFIDE BONDS, RETINOL-BINDING, AND 3D-STRUCTURE MODELING.
RX PubMed=1707134; DOI=10.1016/0161-5890(91)90095-2;
RA Haefliger J.-A., Peitsch M.C., Jenne D.E., Tschopp J.;
RT "Structural and functional characterization of complement C8 gamma, a
RT member of the lipocalin protein family.";
RL Mol. Immunol. 28:123-131(1991).
RN [9]
RP REVIEW.
RX PubMed=11058761; DOI=10.1016/s0167-4838(00)00155-2;
RA Schreck S.F., Parker C., Plumb M.E., Sodetz J.M.;
RT "Human complement protein C8 gamma.";
RL Biochim. Biophys. Acta 1482:199-208(2000).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 21-202, AND DISULFIDE BOND.
RX PubMed=12033936; DOI=10.1021/bi025696i;
RA Ortlund E., Parker C.L., Schreck S.F., Ginell S., Minor W., Sodetz J.M.,
RA Lebioda L.;
RT "Crystal structure of human complement protein C8gamma at 1.2 A resolution
RT reveals a lipocalin fold and a distinct ligand binding site.";
RL Biochemistry 41:7030-7037(2002).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 21-202, AND DISULFIDE BOND.
RX PubMed=17452033; DOI=10.1016/j.bbapap.2007.03.004;
RA Chiswell B., Lovelace L.L., Brannen C., Ortlund E.A., Lebioda L.,
RA Sodetz J.M.;
RT "Structural features of the ligand binding site on human complement protein
RT C8gamma: a member of the lipocalin family.";
RL Biochim. Biophys. Acta 1774:637-644(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 30-202, AND DISULFIDE BOND.
RX PubMed=17692377; DOI=10.1016/j.molimm.2007.06.359;
RA Lovelace L.L., Chiswell B., Slade D.J., Sodetz J.M., Lebioda L.;
RT "Crystal structure of complement protein C8gamma in complex with a peptide
RT containing the C8gamma binding site on C8alpha: implications for C8gamma
RT ligand binding.";
RL Mol. Immunol. 45:750-756(2008).
CC -!- FUNCTION: C8 is a constituent of the membrane attack complex. C8 binds
CC to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and
CC acts as a catalyst in the polymerization of C9. The gamma subunit seems
CC to be able to bind retinol.
CC -!- SUBUNIT: C8 is composed of three chains: alpha, beta and gamma. The
CC alpha and gamma chains are disulfide bonded.
CC -!- INTERACTION:
CC P07360; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-9021652, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M17263; AAA51888.1; -; mRNA.
DR EMBL; M17999; AAA51863.1; -; mRNA.
DR EMBL; X06465; CAA29773.1; -; mRNA.
DR EMBL; U08198; AAA18482.1; -; Genomic_DNA.
DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88316.1; -; Genomic_DNA.
DR EMBL; BC113624; AAI13625.1; -; mRNA.
DR EMBL; BC113626; AAI13627.1; -; mRNA.
DR CCDS; CCDS7017.1; -.
DR PIR; A27487; C8HUG.
DR RefSeq; NP_000597.2; NM_000606.2.
DR PDB; 1IW2; X-ray; 1.90 A; A=21-202.
DR PDB; 1LF7; X-ray; 1.20 A; A=21-202.
DR PDB; 2OVA; X-ray; 1.50 A; A=21-202.
DR PDB; 2OVD; X-ray; 1.80 A; A=21-202.
DR PDB; 2OVE; X-ray; 2.00 A; A=21-202.
DR PDB; 2QOS; X-ray; 1.81 A; C=30-202.
DR PDB; 2RD7; X-ray; 2.15 A; C=21-202.
DR PDB; 3OJY; X-ray; 2.51 A; C=21-202.
DR PDB; 6H03; EM; 5.60 A; E=21-202.
DR PDB; 6H04; EM; 5.60 A; E=21-202.
DR PDB; 7NYC; EM; 3.50 A; F=21-202.
DR PDB; 7NYD; EM; 3.30 A; F=21-202.
DR PDB; 8B0F; EM; 3.00 A; F=1-202.
DR PDB; 8B0G; EM; 3.30 A; F=1-202.
DR PDB; 8B0H; EM; 3.30 A; F=1-202.
DR PDBsum; 1IW2; -.
DR PDBsum; 1LF7; -.
DR PDBsum; 2OVA; -.
DR PDBsum; 2OVD; -.
DR PDBsum; 2OVE; -.
DR PDBsum; 2QOS; -.
DR PDBsum; 2RD7; -.
DR PDBsum; 3OJY; -.
DR PDBsum; 6H03; -.
DR PDBsum; 6H04; -.
DR PDBsum; 7NYC; -.
DR PDBsum; 7NYD; -.
DR PDBsum; 8B0F; -.
DR PDBsum; 8B0G; -.
DR PDBsum; 8B0H; -.
DR AlphaFoldDB; P07360; -.
DR EMDB; EMD-0106; -.
DR EMDB; EMD-0107; -.
DR EMDB; EMD-12649; -.
DR EMDB; EMD-12650; -.
DR EMDB; EMD-12651; -.
DR EMDB; EMD-15779; -.
DR EMDB; EMD-15780; -.
DR EMDB; EMD-15781; -.
DR EMDB; EMD-3289; -.
DR SMR; P07360; -.
DR BioGRID; 107194; 11.
DR ComplexPortal; CPX-6159; Membrane attack complex.
DR IntAct; P07360; 7.
DR STRING; 9606.ENSP00000360697; -.
DR DrugBank; DB04272; Citric acid.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR iPTMnet; P07360; -.
DR PhosphoSitePlus; P07360; -.
DR BioMuta; C8G; -.
DR jPOST; P07360; -.
DR MassIVE; P07360; -.
DR PaxDb; 9606-ENSP00000224181; -.
DR PeptideAtlas; P07360; -.
DR ProteomicsDB; 52000; -.
DR Antibodypedia; 18835; 91 antibodies from 20 providers.
DR DNASU; 733; -.
DR Ensembl; ENST00000371634.7; ENSP00000360697.3; ENSG00000176919.13.
DR GeneID; 733; -.
DR KEGG; hsa:733; -.
DR MANE-Select; ENST00000371634.7; ENSP00000360697.3; NM_000606.3; NP_000597.2.
DR UCSC; uc004cka.3; human.
DR AGR; HGNC:1354; -.
DR CTD; 733; -.
DR DisGeNET; 733; -.
DR GeneCards; C8G; -.
DR HGNC; HGNC:1354; C8G.
DR HPA; ENSG00000176919; Tissue enriched (liver).
DR MalaCards; C8G; -.
DR MIM; 120930; gene.
DR neXtProt; NX_P07360; -.
DR OpenTargets; ENSG00000176919; -.
DR Orphanet; 169150; Immunodeficiency due to a late component of complement deficiency.
DR PharmGKB; PA25953; -.
DR VEuPathDB; HostDB:ENSG00000176919; -.
DR eggNOG; ENOG502S0KX; Eukaryota.
DR GeneTree; ENSGT00440000034309; -.
DR HOGENOM; CLU_094061_0_0_1; -.
DR InParanoid; P07360; -.
DR OMA; LMCVCLW; -.
DR OrthoDB; 5319720at2759; -.
DR PhylomeDB; P07360; -.
DR TreeFam; TF336103; -.
DR PathwayCommons; P07360; -.
DR Reactome; R-HSA-166665; Terminal pathway of complement.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P07360; -.
DR SIGNOR; P07360; -.
DR BioGRID-ORCS; 733; 27 hits in 1145 CRISPR screens.
DR EvolutionaryTrace; P07360; -.
DR GenomeRNAi; 733; -.
DR Pharos; P07360; Tbio.
DR PRO; PR:P07360; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P07360; Protein.
DR Bgee; ENSG00000176919; Expressed in right lobe of liver and 94 other cell types or tissues.
DR ExpressionAtlas; P07360; baseline and differential.
DR Genevisible; P07360; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005579; C:membrane attack complex; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; NAS:ComplexPortal.
DR GO; GO:0001848; F:complement binding; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0019841; F:retinol binding; IEA:UniProtKB-KW.
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:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR GO; GO:0050778; P:positive regulation of immune response; NAS:ComplexPortal.
DR CDD; cd19417; lipocalin_C8gamma; 1.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR002968; A1-microglobln.
DR InterPro; IPR043245; C8G.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR022272; Lipocalin_CS.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR PANTHER; PTHR47304; COMPLEMENT COMPONENT C8 GAMMA CHAIN; 1.
DR PANTHER; PTHR47304:SF1; COMPLEMENT COMPONENT C8 GAMMA CHAIN; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR PRINTS; PR01215; A1MCGLOBULIN.
DR PRINTS; PR00179; LIPOCALIN.
DR SUPFAM; SSF50814; Lipocalins; 1.
DR PROSITE; PS00213; LIPOCALIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complement alternate pathway; Complement pathway; Cytolysis;
KW Direct protein sequencing; Disulfide bond; Immunity; Innate immunity;
KW Membrane attack complex; Pyrrolidone carboxylic acid; Reference proteome;
KW Retinol-binding; Secreted; Signal.
FT SIGNAL 1..20
FT CHAIN 21..202
FT /note="Complement component C8 gamma chain"
FT /id="PRO_0000017881"
FT MOD_RES 21
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:3676249"
FT DISULFID 60
FT /note="Interchain (with C-194 in C8-alpha chain)"
FT DISULFID 96..188
FT VARIANT 69
FT /note="R -> Q (in dbSNP:rs17614)"
FT /id="VAR_014668"
FT VARIANT 118
FT /note="D -> G (in dbSNP:rs7850844)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2447883, ECO:0000269|PubMed:3676249,
FT ECO:0000269|PubMed:8172891, ECO:0000269|Ref.5"
FT /id="VAR_044319"
FT VARIANT 124
FT /note="H -> N (in dbSNP:rs17613)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_014669"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:1LF7"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1LF7"
FT HELIX 61..66
FT /evidence="ECO:0007829|PDB:2QOS"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:2QOS"
FT STRAND 73..80
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 83..92
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 95..105
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 123..130
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 132..142
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 145..156
FT /evidence="ECO:0007829|PDB:1LF7"
FT HELIX 159..171
FT /evidence="ECO:0007829|PDB:1LF7"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:1LF7"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1LF7"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:1LF7"
SQ SEQUENCE 202 AA; 22277 MW; 4E4F73140E607FFE CRC64;
MLPPGTATLL TLLLAAGSLG QKPQRPRRPA SPISTIQPKA NFDAQQFAGT WLLVAVGSAC
RFLQEQGHRA EATTLHVAPQ GTAMAVSTFR KLDGICWQVR QLYGDTGVLG RFLLQARDAR
GAVHVVVAET DYQSFAVLYL ERAGQLSVKL YARSLPVSDS VLSGFEQRVQ EAHLTEDQIF
YFPKYGFCEA ADQFHVLDEV RR
//
