Full text data of C8B
C8B
[Confidence: low (only semi-automatic identification from reviews)]
Complement component C8 beta chain (Complement component 8 subunit beta; Flags: Precursor)
Complement component C8 beta chain (Complement component 8 subunit beta; Flags: Precursor)
UniProt
P07358
ID CO8B_HUMAN Reviewed; 591 AA.
AC P07358; A1L4K7;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 3.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Complement component C8 beta chain;
DE AltName: Full=Complement component 8 subunit beta;
DE Flags: Precursor;
GN Name=C8B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND
RP GLYCOSYLATION.
RC TISSUE=Liver;
RX PubMed=2820472; DOI=10.1021/bi00386a047;
RA Howard O.M.Z., Rao A.G., Sodetz J.M.;
RT "Complementary DNA and derived amino acid sequence of the beta subunit
RT of human complement protein C8: identification of a close structural
RT and ancestral relationship to the alpha subunit and C9.";
RL Biochemistry 26:3565-3570(1987).
RN [2]
RP SEQUENCE REVISION.
RA Sodetz J.M.;
RL Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-117.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 47-591, AND PROTEIN SEQUENCE OF 55-68.
RC TISSUE=Liver;
RX PubMed=3651397; DOI=10.1021/bi00386a045;
RA Haefliger J.-A., Tschopp J., Nardelli D., Wahli W., Kocher H.-P.,
RA Tosi M., Stanley K.K.;
RT "Complementary DNA cloning of complement C8 beta and its sequence
RT homology to C9.";
RL Biochemistry 26:3551-3556(1987).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION, AND SUBUNIT.
RX PubMed=7440581;
RA Steckel E.W., York R.G., Monahan J.B., Sodetz J.M.;
RT "The eighth component of human complement. Purification and
RT physicochemical characterization of its unusual subunit structure.";
RL J. Biol. Chem. 255:11997-12005(1980).
RN [9]
RP GLYCOSYLATION AT TRP-70; TRP-73; TRP-551 AND TRP-554.
RX PubMed=10551839; DOI=10.1074/jbc.274.46.32786;
RA Hofsteenge J., Blommers M., Hess D., Furmanek A., Miroshnichenko O.;
RT "The four terminal components of the complement system are C-
RT mannosylated on multiple tryptophan residues.";
RL J. Biol. Chem. 274:32786-32794(1999).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-243, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-243, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 55-591, PHOSPHORYLATION AT
RP THR-418, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=21454577; DOI=10.1074/jbc.M111.219766;
RA Lovelace L.L., Cooper C.L., Sodetz J.M., Lebioda L.;
RT "Structure of human C8 protein provides mechanistic insight into
RT membrane pore formation by complement.";
RL J. Biol. Chem. 286:17585-17592(2011).
RN [13]
RP VARIANT GLY-117, AND DEFINITION OF ALLOTYPES C8B A AND C8B B.
RX PubMed=8131848; DOI=10.1016/0014-5793(94)80140-1;
RA Dewald G., Hemmer S., Noethen M.M.;
RT "Human complement component C8. Molecular basis of the beta-chain
RT polymorphism.";
RL FEBS Lett. 340:211-215(1994).
CC -!- FUNCTION: Constituent of the membrane attack complex (MAC) that
CC plays a key role in the innate and adaptive immune response by
CC forming pores in the plasma membrane of target cells.
CC -!- SUBUNIT: Heterotrimer of 3 chains: alpha, beta and gamma. The
CC alpha and gamma chains are disulfide bonded. Component of the
CC membrane attack complex (MAC). MAC assembly is initiated by
CC protelytic cleavage of C5 into C5a and C5b. C5b binds sequentially
CC C6, C7, C8 and multiple copies of the pore-forming subunit C9.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: N-glycosylated; contains one or two bound glycans. Not O-
CC glycosylated.
CC -!- POLYMORPHISM: The sequence shown is that of allotype C8B B.
CC -!- DISEASE: Complement component 8 deficiency, 2 (C8D2) [MIM:613789]:
CC A rare defect of the complement classical pathway associated with
CC susceptibility to severe recurrent infections, predominantly by
CC Neisseria gonorrhoeae or Neisseria meningitidis. Note=Disease
CC susceptibility is associated with variations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC -!- SIMILARITY: Contains 1 EGF-like domain.
CC -!- SIMILARITY: Contains 1 LDL-receptor class A domain.
CC -!- SIMILARITY: Contains 1 MACPF domain.
CC -!- SIMILARITY: Contains 2 TSP type-1 domains.
CC -!- WEB RESOURCE: Name=C8Bbase; Note=C8B mutation db;
CC URL="http://bioinf.uta.fi/C8Bbase/";
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DR EMBL; M16973; AAA51862.1; -; mRNA.
DR EMBL; AK313382; BAG36180.1; -; mRNA.
DR EMBL; AL121998; CAC18532.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06641.1; -; Genomic_DNA.
DR EMBL; BC130575; AAI30576.1; -; mRNA.
DR EMBL; X04393; CAA27981.1; -; mRNA.
DR PIR; A43071; C8HUB.
DR RefSeq; NP_000057.2; NM_000066.3.
DR UniGene; Hs.391835; -.
DR PDB; 3OJY; X-ray; 2.51 A; B=55-591.
DR PDBsum; 3OJY; -.
DR ProteinModelPortal; P07358; -.
DR SMR; P07358; 61-590.
DR STRING; 9606.ENSP00000360281; -.
DR PhosphoSite; P07358; -.
DR DMDM; 20141201; -.
DR PaxDb; P07358; -.
DR PeptideAtlas; P07358; -.
DR PRIDE; P07358; -.
DR DNASU; 732; -.
DR Ensembl; ENST00000371237; ENSP00000360281; ENSG00000021852.
DR GeneID; 732; -.
DR KEGG; hsa:732; -.
DR UCSC; uc001cyp.3; human.
DR CTD; 732; -.
DR GeneCards; GC01M057311; -.
DR HGNC; HGNC:1353; C8B.
DR HPA; HPA023694; -.
DR MIM; 120960; gene.
DR MIM; 613789; phenotype.
DR neXtProt; NX_P07358; -.
DR Orphanet; 169150; Immunodeficiency due to a late component of complements deficiency.
DR PharmGKB; PA25952; -.
DR eggNOG; NOG146647; -.
DR HOGENOM; HOG000231146; -.
DR HOVERGEN; HBG106489; -.
DR InParanoid; P07358; -.
DR KO; K03998; -.
DR OrthoDB; EOG7QK0BJ; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; P07358; -.
DR GenomeRNAi; 732; -.
DR NextBio; 2980; -.
DR PRO; PR:P07358; -.
DR ArrayExpress; P07358; -.
DR Bgee; P07358; -.
DR CleanEx; HS_C8B; -.
DR Genevestigator; P07358; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005579; C:membrane attack complex; IEA:UniProtKB-KW.
DR GO; GO:0006956; P:complement activation; TAS:ProtInc.
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:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0030449; P:regulation of complement activation; TAS:Reactome.
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; Thrombospondin_1_rpt.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR Pfam; PF01823; MACPF; 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; 2.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; FALSE_NEG.
DR PROSITE; PS50026; EGF_3; FALSE_NEG.
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 3D-structure; Complement alternate pathway; Complement pathway;
KW Complete proteome; Cytolysis; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Immunity;
KW Innate immunity; Membrane attack complex; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 32 Potential.
FT PROPEP 33 54
FT /FTId=PRO_0000023591.
FT CHAIN 55 591 Complement component C8 beta chain.
FT /FTId=PRO_0000023592.
FT DOMAIN 64 117 TSP type-1 1.
FT DOMAIN 120 157 LDL-receptor class A.
FT DOMAIN 158 504 MACPF.
FT DOMAIN 505 535 EGF-like.
FT DOMAIN 545 591 TSP type-1 2.
FT MOD_RES 418 418 Phosphothreonine.
FT CARBOHYD 70 70 C-linked (Man).
FT CARBOHYD 73 73 C-linked (Man).
FT CARBOHYD 101 101 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 243 243 N-linked (GlcNAc...).
FT CARBOHYD 551 551 C-linked (Man).
FT CARBOHYD 554 554 C-linked (Man).
FT DISULFID 65 100
FT DISULFID 76 110
FT DISULFID 79 116
FT DISULFID 122 133
FT DISULFID 127 146
FT DISULFID 140 155
FT DISULFID 378 403
FT DISULFID 503 550
FT DISULFID 505 521
FT DISULFID 508 523
FT DISULFID 525 534
FT DISULFID 557 590
FT VARIANT 108 108 E -> K (in dbSNP:rs12067507).
FT /FTId=VAR_027649.
FT VARIANT 117 117 R -> G (in allotype C8B A;
FT dbSNP:rs1013579).
FT /FTId=VAR_012642.
FT VARIANT 261 261 P -> L (in dbSNP:rs12085435).
FT /FTId=VAR_027650.
FT TURN 78 81
FT STRAND 82 86
FT STRAND 89 91
FT STRAND 104 109
FT STRAND 123 126
FT TURN 128 130
FT HELIX 136 138
FT STRAND 141 143
FT STRAND 146 149
FT HELIX 172 176
FT STRAND 177 179
FT TURN 181 183
FT STRAND 186 189
FT STRAND 201 205
FT STRAND 208 212
FT STRAND 216 221
FT STRAND 229 236
FT HELIX 237 240
FT TURN 256 258
FT TURN 269 271
FT STRAND 272 275
FT HELIX 276 283
FT STRAND 290 297
FT STRAND 299 306
FT STRAND 308 310
FT HELIX 315 321
FT HELIX 330 340
FT STRAND 342 352
FT STRAND 355 361
FT HELIX 362 365
FT TURN 366 369
FT HELIX 372 378
FT TURN 379 381
FT TURN 404 408
FT HELIX 409 412
FT TURN 413 415
FT STRAND 419 426
FT HELIX 435 439
FT STRAND 441 443
FT HELIX 449 457
FT STRAND 461 469
FT HELIX 470 473
FT TURN 476 478
FT HELIX 482 499
FT HELIX 502 504
FT STRAND 513 517
FT STRAND 520 524
FT HELIX 532 534
FT STRAND 536 541
FT STRAND 557 563
FT STRAND 584 588
SQ SEQUENCE 591 AA; 67047 MW; B01722A6F2E9AFCE CRC64;
MKNSRTWAWR APVELFLLCA ALGCLSLPGS RGERPHSFGS NAVNKSFAKS RQMRSVDVTL
MPIDCELSSW SSWTTCDPCQ KKRYRYAYLL QPSQFHGEPC NFSDKEVEDC VTNRPCRSQV
RCEGFVCAQT GRCVNRRLLC NGDNDCGDQS DEANCRRIYK KCQHEMDQYW GIGSLASGIN
LFTNSFEGPV LDHRYYAGGC SPHYILNTRF RKPYNVESYT PQTQGKYEFI LKEYESYSDF
ERNVTEKMAS KSGFSFGFKI PGIFELGISS QSDRGKHYIR RTKRFSHTKS VFLHARSDLE
VAHYKLKPRS LMLHYEFLQR VKRLPLEYSY GEYRDLFRDF GTHYITEAVL GGIYEYTLVM
NKEAMERGDY TLNNVHACAK NDFKIGGAIE EVYVSLGVSV GKCRGILNEI KDRNKRDTMV
EDLVVLVRGG ASEHITTLAY QELPTADLMQ EWGDAVQYNP AIIKVKVEPL YELVTATDFA
YSSTVRQNMK QALEEFQKEV SSCHCAPCQG NGVPVLKGSR CDCICPVGSQ GLACEVSYRK
NTPIDGKWNC WSNWSSCSGR RKTRQRQCNN PPPQNGGSPC SGPASETLDC S
//
ID CO8B_HUMAN Reviewed; 591 AA.
AC P07358; A1L4K7;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 3.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Complement component C8 beta chain;
DE AltName: Full=Complement component 8 subunit beta;
DE Flags: Precursor;
GN Name=C8B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND
RP GLYCOSYLATION.
RC TISSUE=Liver;
RX PubMed=2820472; DOI=10.1021/bi00386a047;
RA Howard O.M.Z., Rao A.G., Sodetz J.M.;
RT "Complementary DNA and derived amino acid sequence of the beta subunit
RT of human complement protein C8: identification of a close structural
RT and ancestral relationship to the alpha subunit and C9.";
RL Biochemistry 26:3565-3570(1987).
RN [2]
RP SEQUENCE REVISION.
RA Sodetz J.M.;
RL Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-117.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 47-591, AND PROTEIN SEQUENCE OF 55-68.
RC TISSUE=Liver;
RX PubMed=3651397; DOI=10.1021/bi00386a045;
RA Haefliger J.-A., Tschopp J., Nardelli D., Wahli W., Kocher H.-P.,
RA Tosi M., Stanley K.K.;
RT "Complementary DNA cloning of complement C8 beta and its sequence
RT homology to C9.";
RL Biochemistry 26:3551-3556(1987).
RN [8]
RP PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION, AND SUBUNIT.
RX PubMed=7440581;
RA Steckel E.W., York R.G., Monahan J.B., Sodetz J.M.;
RT "The eighth component of human complement. Purification and
RT physicochemical characterization of its unusual subunit structure.";
RL J. Biol. Chem. 255:11997-12005(1980).
RN [9]
RP GLYCOSYLATION AT TRP-70; TRP-73; TRP-551 AND TRP-554.
RX PubMed=10551839; DOI=10.1074/jbc.274.46.32786;
RA Hofsteenge J., Blommers M., Hess D., Furmanek A., Miroshnichenko O.;
RT "The four terminal components of the complement system are C-
RT mannosylated on multiple tryptophan residues.";
RL J. Biol. Chem. 274:32786-32794(1999).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-243, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-243, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 55-591, PHOSPHORYLATION AT
RP THR-418, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=21454577; DOI=10.1074/jbc.M111.219766;
RA Lovelace L.L., Cooper C.L., Sodetz J.M., Lebioda L.;
RT "Structure of human C8 protein provides mechanistic insight into
RT membrane pore formation by complement.";
RL J. Biol. Chem. 286:17585-17592(2011).
RN [13]
RP VARIANT GLY-117, AND DEFINITION OF ALLOTYPES C8B A AND C8B B.
RX PubMed=8131848; DOI=10.1016/0014-5793(94)80140-1;
RA Dewald G., Hemmer S., Noethen M.M.;
RT "Human complement component C8. Molecular basis of the beta-chain
RT polymorphism.";
RL FEBS Lett. 340:211-215(1994).
CC -!- FUNCTION: Constituent of the membrane attack complex (MAC) that
CC plays a key role in the innate and adaptive immune response by
CC forming pores in the plasma membrane of target cells.
CC -!- SUBUNIT: Heterotrimer of 3 chains: alpha, beta and gamma. The
CC alpha and gamma chains are disulfide bonded. Component of the
CC membrane attack complex (MAC). MAC assembly is initiated by
CC protelytic cleavage of C5 into C5a and C5b. C5b binds sequentially
CC C6, C7, C8 and multiple copies of the pore-forming subunit C9.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: N-glycosylated; contains one or two bound glycans. Not O-
CC glycosylated.
CC -!- POLYMORPHISM: The sequence shown is that of allotype C8B B.
CC -!- DISEASE: Complement component 8 deficiency, 2 (C8D2) [MIM:613789]:
CC A rare defect of the complement classical pathway associated with
CC susceptibility to severe recurrent infections, predominantly by
CC Neisseria gonorrhoeae or Neisseria meningitidis. Note=Disease
CC susceptibility is associated with variations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC -!- SIMILARITY: Contains 1 EGF-like domain.
CC -!- SIMILARITY: Contains 1 LDL-receptor class A domain.
CC -!- SIMILARITY: Contains 1 MACPF domain.
CC -!- SIMILARITY: Contains 2 TSP type-1 domains.
CC -!- WEB RESOURCE: Name=C8Bbase; Note=C8B mutation db;
CC URL="http://bioinf.uta.fi/C8Bbase/";
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DR EMBL; M16973; AAA51862.1; -; mRNA.
DR EMBL; AK313382; BAG36180.1; -; mRNA.
DR EMBL; AL121998; CAC18532.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06641.1; -; Genomic_DNA.
DR EMBL; BC130575; AAI30576.1; -; mRNA.
DR EMBL; X04393; CAA27981.1; -; mRNA.
DR PIR; A43071; C8HUB.
DR RefSeq; NP_000057.2; NM_000066.3.
DR UniGene; Hs.391835; -.
DR PDB; 3OJY; X-ray; 2.51 A; B=55-591.
DR PDBsum; 3OJY; -.
DR ProteinModelPortal; P07358; -.
DR SMR; P07358; 61-590.
DR STRING; 9606.ENSP00000360281; -.
DR PhosphoSite; P07358; -.
DR DMDM; 20141201; -.
DR PaxDb; P07358; -.
DR PeptideAtlas; P07358; -.
DR PRIDE; P07358; -.
DR DNASU; 732; -.
DR Ensembl; ENST00000371237; ENSP00000360281; ENSG00000021852.
DR GeneID; 732; -.
DR KEGG; hsa:732; -.
DR UCSC; uc001cyp.3; human.
DR CTD; 732; -.
DR GeneCards; GC01M057311; -.
DR HGNC; HGNC:1353; C8B.
DR HPA; HPA023694; -.
DR MIM; 120960; gene.
DR MIM; 613789; phenotype.
DR neXtProt; NX_P07358; -.
DR Orphanet; 169150; Immunodeficiency due to a late component of complements deficiency.
DR PharmGKB; PA25952; -.
DR eggNOG; NOG146647; -.
DR HOGENOM; HOG000231146; -.
DR HOVERGEN; HBG106489; -.
DR InParanoid; P07358; -.
DR KO; K03998; -.
DR OrthoDB; EOG7QK0BJ; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; P07358; -.
DR GenomeRNAi; 732; -.
DR NextBio; 2980; -.
DR PRO; PR:P07358; -.
DR ArrayExpress; P07358; -.
DR Bgee; P07358; -.
DR CleanEx; HS_C8B; -.
DR Genevestigator; P07358; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005579; C:membrane attack complex; IEA:UniProtKB-KW.
DR GO; GO:0006956; P:complement activation; TAS:ProtInc.
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:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0030449; P:regulation of complement activation; TAS:Reactome.
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; Thrombospondin_1_rpt.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR Pfam; PF01823; MACPF; 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; 2.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; FALSE_NEG.
DR PROSITE; PS50026; EGF_3; FALSE_NEG.
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 3D-structure; Complement alternate pathway; Complement pathway;
KW Complete proteome; Cytolysis; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Immunity;
KW Innate immunity; Membrane attack complex; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 32 Potential.
FT PROPEP 33 54
FT /FTId=PRO_0000023591.
FT CHAIN 55 591 Complement component C8 beta chain.
FT /FTId=PRO_0000023592.
FT DOMAIN 64 117 TSP type-1 1.
FT DOMAIN 120 157 LDL-receptor class A.
FT DOMAIN 158 504 MACPF.
FT DOMAIN 505 535 EGF-like.
FT DOMAIN 545 591 TSP type-1 2.
FT MOD_RES 418 418 Phosphothreonine.
FT CARBOHYD 70 70 C-linked (Man).
FT CARBOHYD 73 73 C-linked (Man).
FT CARBOHYD 101 101 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 243 243 N-linked (GlcNAc...).
FT CARBOHYD 551 551 C-linked (Man).
FT CARBOHYD 554 554 C-linked (Man).
FT DISULFID 65 100
FT DISULFID 76 110
FT DISULFID 79 116
FT DISULFID 122 133
FT DISULFID 127 146
FT DISULFID 140 155
FT DISULFID 378 403
FT DISULFID 503 550
FT DISULFID 505 521
FT DISULFID 508 523
FT DISULFID 525 534
FT DISULFID 557 590
FT VARIANT 108 108 E -> K (in dbSNP:rs12067507).
FT /FTId=VAR_027649.
FT VARIANT 117 117 R -> G (in allotype C8B A;
FT dbSNP:rs1013579).
FT /FTId=VAR_012642.
FT VARIANT 261 261 P -> L (in dbSNP:rs12085435).
FT /FTId=VAR_027650.
FT TURN 78 81
FT STRAND 82 86
FT STRAND 89 91
FT STRAND 104 109
FT STRAND 123 126
FT TURN 128 130
FT HELIX 136 138
FT STRAND 141 143
FT STRAND 146 149
FT HELIX 172 176
FT STRAND 177 179
FT TURN 181 183
FT STRAND 186 189
FT STRAND 201 205
FT STRAND 208 212
FT STRAND 216 221
FT STRAND 229 236
FT HELIX 237 240
FT TURN 256 258
FT TURN 269 271
FT STRAND 272 275
FT HELIX 276 283
FT STRAND 290 297
FT STRAND 299 306
FT STRAND 308 310
FT HELIX 315 321
FT HELIX 330 340
FT STRAND 342 352
FT STRAND 355 361
FT HELIX 362 365
FT TURN 366 369
FT HELIX 372 378
FT TURN 379 381
FT TURN 404 408
FT HELIX 409 412
FT TURN 413 415
FT STRAND 419 426
FT HELIX 435 439
FT STRAND 441 443
FT HELIX 449 457
FT STRAND 461 469
FT HELIX 470 473
FT TURN 476 478
FT HELIX 482 499
FT HELIX 502 504
FT STRAND 513 517
FT STRAND 520 524
FT HELIX 532 534
FT STRAND 536 541
FT STRAND 557 563
FT STRAND 584 588
SQ SEQUENCE 591 AA; 67047 MW; B01722A6F2E9AFCE CRC64;
MKNSRTWAWR APVELFLLCA ALGCLSLPGS RGERPHSFGS NAVNKSFAKS RQMRSVDVTL
MPIDCELSSW SSWTTCDPCQ KKRYRYAYLL QPSQFHGEPC NFSDKEVEDC VTNRPCRSQV
RCEGFVCAQT GRCVNRRLLC NGDNDCGDQS DEANCRRIYK KCQHEMDQYW GIGSLASGIN
LFTNSFEGPV LDHRYYAGGC SPHYILNTRF RKPYNVESYT PQTQGKYEFI LKEYESYSDF
ERNVTEKMAS KSGFSFGFKI PGIFELGISS QSDRGKHYIR RTKRFSHTKS VFLHARSDLE
VAHYKLKPRS LMLHYEFLQR VKRLPLEYSY GEYRDLFRDF GTHYITEAVL GGIYEYTLVM
NKEAMERGDY TLNNVHACAK NDFKIGGAIE EVYVSLGVSV GKCRGILNEI KDRNKRDTMV
EDLVVLVRGG ASEHITTLAY QELPTADLMQ EWGDAVQYNP AIIKVKVEPL YELVTATDFA
YSSTVRQNMK QALEEFQKEV SSCHCAPCQG NGVPVLKGSR CDCICPVGSQ GLACEVSYRK
NTPIDGKWNC WSNWSSCSGR RKTRQRQCNN PPPQNGGSPC SGPASETLDC S
//
MIM
120960
*RECORD*
*FIELD* NO
120960
*FIELD* TI
*120960 COMPLEMENT COMPONENT 8, BETA SUBUNIT; C8B
;;COMPLEMENT COMPONENT C8B;;
C8 BETA
read more*FIELD* TX
DESCRIPTION
The eighth component of complement (C8) belongs to the late-acting
complement proteins (C5-C9) forming the membrane attack complex. C8 is a
serum protein that consists of 3 nonidentical subunits arranged
asymmetrically as a disulfide-linked alpha-gamma dimer (C8A, 120950;
C8G, 120930) and a noncovalently associated beta chain (C8B). Each
component is encoded by a different gene (Ng et al., 1987; Kaufmann et
al., 1993).
GENE STRUCTURE
Herrmann et al. (1989) estimated the size of the C8B gene to be 32 to 36
kb.
By using PCR primers located in the adjacent intron sequences of C8B,
Kaufmann et al. (1993) could amplify all 12 exons of the C8B gene from
genomic DNA. These analyses and the insert sizes of the genomic lambda
clones indicated that the C8B gene has a total size of approximately 40
kb.
MAPPING
The C8A and C8B genes are closely linked on chromosome 1p (Rogde et al.,
1986).
Bahary et al. (1991) mapped the murine homolog of C8B to chromosome 4.
MOLECULAR GENETICS
By direct sequence analysis of all exon-specific PCR products from
normal and C8B-deficient persons, Kaufmann et al. (1993) found a single
C-T change in exon 9 leading to a stop codon (R428X; 120960.0001). An
allele-specific PCR system was designed to detect the normal and the
deficiency allele simultaneously. Using this approach as well as PCR
typing of the TaqI polymorphism located in intron 11, 5 families with 7
C8B-deficient members were investigated. The mutant allele was observed
in all families investigated and could therefore be regarded as a major
cause of C8B deficiency in Caucasians. In 2 C8B-deficient patients, only
1 chromosome carried the C-T change; the molecular nature of the other
allele had not been determined.
In a study of 34 unrelated families with C8B deficiency from the U.S.
and the former U.S.S.R., Saucedo et al. (1995) found that 59 (86%) of 69
null alleles were due to the C-to-T transition in exon 9. An additional
6 null alleles were caused by C-to-T transitions in exons 3 (120960.0003
and 120960.0004) and 6 (120960.0002). Two null alleles were caused by
cytosine deletions in exons 3 (120960.0005) and 5 (120960.0006). Of the
null alleles, 97% were C-to-T transitions in which an arg (64 alleles)
or gln (1 allele) was replaced by a stop codon.
- C8B Mutation Nomenclature
Using current recommendations for mutation nomenclature, Arnold et al.
(2009) numbered nucleotides of the C8B gene starting at the A of the ATG
translational start site of the coding reference sequence GENBANK
NM_000066. They noted that, traditionally, C8B nucleotides had been
numbered starting at the 5-prime end of cDNA clone GENBANK M16973. In
their Table 2, Arnold et al. (2009) provided a comparison of the
recommended mutation nomenclature used by them with the traditional
mutation nomenclature used by others, including Kaufmann et al. (1993),
Saucedo et al. (1995), and Rao et al. (2004), along with the
corresponding protein changes.
*FIELD* AV
.0001
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG428TER
In all 7 affected members of 5 Caucasian families segregating C8
deficiency (613789), Kaufmann et al. (1993) identified a C-to-T
transition in exon 9 of the C8B gene, leading to the creation of a stop
codon; CGA (arg) was changed to TGA (stop) at nucleotide position 1309.
The codon involved was 374, according to Kaufmann (1993), resulting in
an ARG374TER substitution. The authors noted that the mutation occurred
at a CpG dinucleotide. Five patients were homozygous for the mutation;
in 2 the mutation was found on only 1 chromosome and the other mutation
was not identified.
In 2 patients with C8B deficiency from Switzerland and Poland, Rao et
al. (2004) identified compound heterozygosity for the exon 9 C-T
transition and another missense mutation in the C8B gene. The Swiss
patient also had a 298C-T transition in exon 3 (Q91X; 120960.0004), and
the Polish patient also had a 388C-T transition in exon 3 (R121X;
120960.0003).
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 1282C-T rather than 1309C-T. The correct amino acid
substitution is arg428 to ter (R428X).
.0002
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG274TER
In a patient with C8 deficiency (613789), Saucedo et al. (1995)
identified compound heterozygosity for the 1309C-T mutation
(120960.0001) in exon 9 of the C8B gene and an 847C-T transition in exon
6.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 820C-T rather than 847C-T. The resulting amino acid
substitution is arg274 to ter (R274X).
.0003
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG121TER
Saucedo et al. (1995) identified 5 patients in 3 families with C8
deficiency (613789) who had a 388C-T transition in exon 3 of the C8B
gene. The mutation was linked to a polymorphism at nucleotide 376 that
accounts for an acidic allotype. Four of the patients were compound
heterozygous for 388C-T and the 1309C-T mutation (120960.0001), and 1
patient was homozygous for 388C-T.
In a Polish patient with C8B deficiency, Rao et al. (2004) identified
compound heterozygosity for the exon 9 C-T transition and the 388C-T
transition in exon 3 of the C8B gene.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 361C-T rather than 388C-T. The resulting amino acid
substitution is arg121 to ter (R121X).
.0004
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, GLN91TER
Saucedo et al. (1995) identified 4 sibs with C8 deficiency (613789) who
were compound heterozygous for a 298C-T transition in exon 3 of the C8B
gene and the 1309C-T mutation (120960.0001). In a Swiss patient with C8B
deficiency, Rao et al. (2004) identified compound heterozygosity for the
exon 9 C-T transition and a 298C-T transition in exon 3 of the C8B gene.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 271C-T rather than 298C-T. The resulting amino acid
substitution is gln91 to ter (Q121X).
In a British male with recurrent meningococcal disease and C8B
deficiency, Arnold et al. (2009) identified compound heterozygosity for
the 271C-T mutation and a duplication of nucleotides 1047 to 1053
(GGCTGTG) in exon 7 (120960.0007) of the C8B gene.
.0005
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 1-BP DEL, 336C
Saucedo et al. (1995) identified 2 sibs with C8 deficiency (613789) who
were compound heterozygous for 2 frameshift mutations in the C8B gene: a
cytosine deletion at nucleotide 363 in exon 3 and a cytosine deletion at
nucleotide 632 in exon 5 (120960.0006). Both mutations resulted in
premature protein termination.
In their Table 2, Arnold et al. (2009) reported that these cytosine
deletions should be designated as occurring at nucleotides 336 and 605
rather than at nucleotides 363 and 632, respectively.
.0006
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 1-BP DEL, 605C
See 120960.0004, Saucedo et al. (1995), and Arnold et al. (2009).
.0007
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 7-BP DUP, NT1047
In a British male with recurrent meningococcal disease and C8B
deficiency (613789), Arnold et al. (2009) identified a duplication of
nucleotides 1047 to 1053 (GGCTGTG) in exon 7 of the C8B gene. The
mutation introduced a frameshift that resulted in premature termination.
The patient was compound heterozygous for the 271C-T mutation (Q91X;
120960.0004) in C8B.
*FIELD* RF
1. Arnold, D. F.; Roberts, A. G.; Thomas, A.; Ferry, B.; Morgan, B.
P.; Chapel, H.: A novel mutation in a patient with a deficiency of
the eighth component of complement associated with recurrent meningococcal
meningitis. J. Clin. Immun. 29: 691-695, 2009.
2. Bahary, N.; Zorich, G.; Pachter, J. E.; Leibel, R. L.; Friedman,
J. M.: Molecular genetic linkage maps of mouse chromosomes 4 and
6. Genomics 11: 33-47, 1991.
3. Herrmann, D.; Sodetz, J. M.; Rittner, C.; Schneider, P. M.: DNA
polymorphism of the human complement C8B gene: formal genetics and
intragenic localization. Immunogenetics 30: 291-295, 1989.
4. Kaufmann, T.: Personal Communication. Mainz, Germany 7/14/1993.
5. Kaufmann, T.; Hansch, G.; Rittner, C.; Spath, P.; Tedesco, F.;
Schneider, P. M.: Genetic basis of human complement C8-beta deficiency. J.
Immun. 150: 4943-4947, 1993.
6. Kaufmann, T.; Rittner, C.; Schneider, P. M.: The human complement
component C8B gene: structure and phylogenetic relationship. Hum.
Genet. 92: 69-75, 1993.
7. Ng, S. C.; Rao, A. G.; Howard, O. M. Z.; Sodetz, J. M.: The eighth
component of human complement: evidence that it is an oligomeric serum
protein assembled from products of three different genes. Biochemistry 26:
5229-5233, 1987.
8. Rao, L.; Li, Y.; Chen, G.; Zhou, B.; Schneider, P. M.; Zhang, L.
: Further study on heterogeneic basis of complement C8-beta deficiency. Chin.
J. Med. Genet. 21: 10-13, 2004.
9. Rogde, S.; Olaisen, B.; Gedde-Dahl, T., Jr.; Teisberg, P.: The
C8A and C8B loci are closely linked on chromosome 1. Ann. Hum. Genet. 50:
139-144, 1986.
10. Saucedo, L.; Ackermann, L.; Platonov, A. E.; Gewurz, A.; Rakita,
R. M.; Densen, P.: Delineation of additional genetic bases for C8-beta
deficiency: prevalence of null alleles and predominance of C-to-T
transition in their genesis. J. Immun. 155: 5022-5028, 1995.
*FIELD* CN
Paul J. Converse - updated: 7/26/2012
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/27/2012
mgross: 8/1/2012
terry: 7/26/2012
mgross: 3/22/2011
terry: 3/15/2011
carol: 3/2/2011
carol: 3/17/2004
tkritzer: 2/6/2004
carol: 6/22/1999
psherman: 3/12/1999
carol: 7/2/1998
dkim: 6/30/1998
carol: 1/3/1995
mimadm: 6/25/1994
carol: 11/4/1993
carol: 9/2/1993
carol: 6/28/1993
supermim: 3/16/1992
*RECORD*
*FIELD* NO
120960
*FIELD* TI
*120960 COMPLEMENT COMPONENT 8, BETA SUBUNIT; C8B
;;COMPLEMENT COMPONENT C8B;;
C8 BETA
read more*FIELD* TX
DESCRIPTION
The eighth component of complement (C8) belongs to the late-acting
complement proteins (C5-C9) forming the membrane attack complex. C8 is a
serum protein that consists of 3 nonidentical subunits arranged
asymmetrically as a disulfide-linked alpha-gamma dimer (C8A, 120950;
C8G, 120930) and a noncovalently associated beta chain (C8B). Each
component is encoded by a different gene (Ng et al., 1987; Kaufmann et
al., 1993).
GENE STRUCTURE
Herrmann et al. (1989) estimated the size of the C8B gene to be 32 to 36
kb.
By using PCR primers located in the adjacent intron sequences of C8B,
Kaufmann et al. (1993) could amplify all 12 exons of the C8B gene from
genomic DNA. These analyses and the insert sizes of the genomic lambda
clones indicated that the C8B gene has a total size of approximately 40
kb.
MAPPING
The C8A and C8B genes are closely linked on chromosome 1p (Rogde et al.,
1986).
Bahary et al. (1991) mapped the murine homolog of C8B to chromosome 4.
MOLECULAR GENETICS
By direct sequence analysis of all exon-specific PCR products from
normal and C8B-deficient persons, Kaufmann et al. (1993) found a single
C-T change in exon 9 leading to a stop codon (R428X; 120960.0001). An
allele-specific PCR system was designed to detect the normal and the
deficiency allele simultaneously. Using this approach as well as PCR
typing of the TaqI polymorphism located in intron 11, 5 families with 7
C8B-deficient members were investigated. The mutant allele was observed
in all families investigated and could therefore be regarded as a major
cause of C8B deficiency in Caucasians. In 2 C8B-deficient patients, only
1 chromosome carried the C-T change; the molecular nature of the other
allele had not been determined.
In a study of 34 unrelated families with C8B deficiency from the U.S.
and the former U.S.S.R., Saucedo et al. (1995) found that 59 (86%) of 69
null alleles were due to the C-to-T transition in exon 9. An additional
6 null alleles were caused by C-to-T transitions in exons 3 (120960.0003
and 120960.0004) and 6 (120960.0002). Two null alleles were caused by
cytosine deletions in exons 3 (120960.0005) and 5 (120960.0006). Of the
null alleles, 97% were C-to-T transitions in which an arg (64 alleles)
or gln (1 allele) was replaced by a stop codon.
- C8B Mutation Nomenclature
Using current recommendations for mutation nomenclature, Arnold et al.
(2009) numbered nucleotides of the C8B gene starting at the A of the ATG
translational start site of the coding reference sequence GENBANK
NM_000066. They noted that, traditionally, C8B nucleotides had been
numbered starting at the 5-prime end of cDNA clone GENBANK M16973. In
their Table 2, Arnold et al. (2009) provided a comparison of the
recommended mutation nomenclature used by them with the traditional
mutation nomenclature used by others, including Kaufmann et al. (1993),
Saucedo et al. (1995), and Rao et al. (2004), along with the
corresponding protein changes.
*FIELD* AV
.0001
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG428TER
In all 7 affected members of 5 Caucasian families segregating C8
deficiency (613789), Kaufmann et al. (1993) identified a C-to-T
transition in exon 9 of the C8B gene, leading to the creation of a stop
codon; CGA (arg) was changed to TGA (stop) at nucleotide position 1309.
The codon involved was 374, according to Kaufmann (1993), resulting in
an ARG374TER substitution. The authors noted that the mutation occurred
at a CpG dinucleotide. Five patients were homozygous for the mutation;
in 2 the mutation was found on only 1 chromosome and the other mutation
was not identified.
In 2 patients with C8B deficiency from Switzerland and Poland, Rao et
al. (2004) identified compound heterozygosity for the exon 9 C-T
transition and another missense mutation in the C8B gene. The Swiss
patient also had a 298C-T transition in exon 3 (Q91X; 120960.0004), and
the Polish patient also had a 388C-T transition in exon 3 (R121X;
120960.0003).
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 1282C-T rather than 1309C-T. The correct amino acid
substitution is arg428 to ter (R428X).
.0002
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG274TER
In a patient with C8 deficiency (613789), Saucedo et al. (1995)
identified compound heterozygosity for the 1309C-T mutation
(120960.0001) in exon 9 of the C8B gene and an 847C-T transition in exon
6.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 820C-T rather than 847C-T. The resulting amino acid
substitution is arg274 to ter (R274X).
.0003
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, ARG121TER
Saucedo et al. (1995) identified 5 patients in 3 families with C8
deficiency (613789) who had a 388C-T transition in exon 3 of the C8B
gene. The mutation was linked to a polymorphism at nucleotide 376 that
accounts for an acidic allotype. Four of the patients were compound
heterozygous for 388C-T and the 1309C-T mutation (120960.0001), and 1
patient was homozygous for 388C-T.
In a Polish patient with C8B deficiency, Rao et al. (2004) identified
compound heterozygosity for the exon 9 C-T transition and the 388C-T
transition in exon 3 of the C8B gene.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 361C-T rather than 388C-T. The resulting amino acid
substitution is arg121 to ter (R121X).
.0004
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, GLN91TER
Saucedo et al. (1995) identified 4 sibs with C8 deficiency (613789) who
were compound heterozygous for a 298C-T transition in exon 3 of the C8B
gene and the 1309C-T mutation (120960.0001). In a Swiss patient with C8B
deficiency, Rao et al. (2004) identified compound heterozygosity for the
exon 9 C-T transition and a 298C-T transition in exon 3 of the C8B gene.
In their Table 2, Arnold et al. (2009) reported that this mutation
should be designated 271C-T rather than 298C-T. The resulting amino acid
substitution is gln91 to ter (Q121X).
In a British male with recurrent meningococcal disease and C8B
deficiency, Arnold et al. (2009) identified compound heterozygosity for
the 271C-T mutation and a duplication of nucleotides 1047 to 1053
(GGCTGTG) in exon 7 (120960.0007) of the C8B gene.
.0005
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 1-BP DEL, 336C
Saucedo et al. (1995) identified 2 sibs with C8 deficiency (613789) who
were compound heterozygous for 2 frameshift mutations in the C8B gene: a
cytosine deletion at nucleotide 363 in exon 3 and a cytosine deletion at
nucleotide 632 in exon 5 (120960.0006). Both mutations resulted in
premature protein termination.
In their Table 2, Arnold et al. (2009) reported that these cytosine
deletions should be designated as occurring at nucleotides 336 and 605
rather than at nucleotides 363 and 632, respectively.
.0006
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 1-BP DEL, 605C
See 120960.0004, Saucedo et al. (1995), and Arnold et al. (2009).
.0007
COMPLEMENT C8 DEFICIENCY, TYPE II
C8B, 7-BP DUP, NT1047
In a British male with recurrent meningococcal disease and C8B
deficiency (613789), Arnold et al. (2009) identified a duplication of
nucleotides 1047 to 1053 (GGCTGTG) in exon 7 of the C8B gene. The
mutation introduced a frameshift that resulted in premature termination.
The patient was compound heterozygous for the 271C-T mutation (Q91X;
120960.0004) in C8B.
*FIELD* RF
1. Arnold, D. F.; Roberts, A. G.; Thomas, A.; Ferry, B.; Morgan, B.
P.; Chapel, H.: A novel mutation in a patient with a deficiency of
the eighth component of complement associated with recurrent meningococcal
meningitis. J. Clin. Immun. 29: 691-695, 2009.
2. Bahary, N.; Zorich, G.; Pachter, J. E.; Leibel, R. L.; Friedman,
J. M.: Molecular genetic linkage maps of mouse chromosomes 4 and
6. Genomics 11: 33-47, 1991.
3. Herrmann, D.; Sodetz, J. M.; Rittner, C.; Schneider, P. M.: DNA
polymorphism of the human complement C8B gene: formal genetics and
intragenic localization. Immunogenetics 30: 291-295, 1989.
4. Kaufmann, T.: Personal Communication. Mainz, Germany 7/14/1993.
5. Kaufmann, T.; Hansch, G.; Rittner, C.; Spath, P.; Tedesco, F.;
Schneider, P. M.: Genetic basis of human complement C8-beta deficiency. J.
Immun. 150: 4943-4947, 1993.
6. Kaufmann, T.; Rittner, C.; Schneider, P. M.: The human complement
component C8B gene: structure and phylogenetic relationship. Hum.
Genet. 92: 69-75, 1993.
7. Ng, S. C.; Rao, A. G.; Howard, O. M. Z.; Sodetz, J. M.: The eighth
component of human complement: evidence that it is an oligomeric serum
protein assembled from products of three different genes. Biochemistry 26:
5229-5233, 1987.
8. Rao, L.; Li, Y.; Chen, G.; Zhou, B.; Schneider, P. M.; Zhang, L.
: Further study on heterogeneic basis of complement C8-beta deficiency. Chin.
J. Med. Genet. 21: 10-13, 2004.
9. Rogde, S.; Olaisen, B.; Gedde-Dahl, T., Jr.; Teisberg, P.: The
C8A and C8B loci are closely linked on chromosome 1. Ann. Hum. Genet. 50:
139-144, 1986.
10. Saucedo, L.; Ackermann, L.; Platonov, A. E.; Gewurz, A.; Rakita,
R. M.; Densen, P.: Delineation of additional genetic bases for C8-beta
deficiency: prevalence of null alleles and predominance of C-to-T
transition in their genesis. J. Immun. 155: 5022-5028, 1995.
*FIELD* CN
Paul J. Converse - updated: 7/26/2012
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/27/2012
mgross: 8/1/2012
terry: 7/26/2012
mgross: 3/22/2011
terry: 3/15/2011
carol: 3/2/2011
carol: 3/17/2004
tkritzer: 2/6/2004
carol: 6/22/1999
psherman: 3/12/1999
carol: 7/2/1998
dkim: 6/30/1998
carol: 1/3/1995
mimadm: 6/25/1994
carol: 11/4/1993
carol: 9/2/1993
carol: 6/28/1993
supermim: 3/16/1992
MIM
613789
*RECORD*
*FIELD* NO
613789
*FIELD* TI
#613789 COMPLEMENT COMPONENT 8 DEFICIENCY, TYPE II; C8D2
;;C8 DEFICIENCY, TYPE II;;
read moreCOMPLEMENT COMPONENT 8B DEFICIENCY;;
C8 BETA DEFICIENCY;;
C8B DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because complement component 8
deficiency type II (C8B deficiency) is caused by mutation in the C8B
gene (120960) on chromosome 1p32.
DESCRIPTION
Patients with deficiency of C8 suffer from recurrent neisserial
infections, predominantly with meningococcus infection of rare
serotypes. Most such patients are discovered among those having their
first episode of meningitis at ages older than 10 years (Ross and
Densen, 1984).
Two types of inherited C8 deficiency have been reported in man: type I
(613790), in which only C8 alpha (C8A, 120950) and C8 gamma (C8G;
120930) are deficient, and type II, in which only C8 beta is deficient
(Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically
indistinguishable (Ross and Densen, 1984).
CLINICAL FEATURES
Wulffraat et al. (1994) described a family in which a 13-year-old boy
was found to be homozygous for C8B deficiency and to have juvenile
chronic arthritis of 6 months' duration. Antinuclear antibodies,
anti-double-stranded DNA antibodies, and rheumatoid factor were not
detected. The same deficiency was present in the patient's sister, and
both parents were heterozygous. There was no history of meningococcal
disease in the family.
PATHOGENESIS
Activation of the terminal complement components (C5-C9) results in the
assembly of the membrane attack complex. Effective insertion of this
complex into cell membranes is responsible for C-dependent bactericidal
activity, as well as the lysis or death of other cell types. A
deficiency of any of the terminal C components is associated with the
absence of this functional activity, and accounts for the substantially
increased risk of developing meningococcal disease observed in
individuals with such a deficiency (summary by Saucedo et al., 1995).
POPULATION GENETICS
Ross and Densen (1984) stated that C8B deficiency had been reported
exclusively in Caucasians (12 kindreds), and that C8AG deficiency had
been found in 4 Black families, 1 Hispanic family, and no Caucasian
families.
Saucedo et al. (1995) stated that C8B deficiency has been reported
primarily in Caucasians, whereas C8AG deficiency has been reported
predominantly in Blacks and Hispanics.
MAPPING
In a family with deficiency of C8 beta, Pericak-Vance et al. (1982)
found a suggestion of linkage of the disorder to 1p markers: lod score
of 1.44 for UMPK at male theta of 0.14 and female theta of 0.17; lod
score of 1.65 for PGM1 at male theta of 0.0 and female theta of 0.22.
Tanaka et al. (1991) studied deficient activity of the beta subunit of
C8 in mice and demonstrated by linkage studies that this form of C8
deficiency is controlled by a single recessive gene, designated C8b,
located on mouse chromosome 4.
MOLECULAR GENETICS
Raum et al. (1979) used serum from patients with type I deficiency
(which lacks alpha-gamma chains but has normal beta chains) to raise
antisera against beta C8 and to demonstrate polymorphism thereof.
By direct sequence analysis of all exon-specific PCR products from
normal and C8B-deficient persons, Kaufmann et al. (1993) found a single
C-T change in exon 9 leading to a stop codon (120960.0001). An
allele-specific PCR system was designed to detect the normal and the
deficiency allele simultaneously. Using this approach as well as PCR
typing of the TaqI polymorphism located in intron 11, 5 families with 7
C8B-deficient members were investigated. The mutant allele was observed
in all 7 affected members of the families investigated and could
therefore be regarded as a major cause of C8B deficiency in Caucasians.
Five patients were homozygous for the mutation. In the 2 others, only 1
chromosome carried the mutation; the molecular nature of the other
allele had not been determined.
In a study of 34 unrelated families with C8B deficiency from the U.S.
and the former U.S.S.R., Saucedo et al. (1995) found that 59 (86%) of 69
null alleles were due to the C-to-T transition in exon 9. An additional
6 null alleles were caused by C-to-T transitions in exons 3 (120960.0003
and 120960.0004) and 6 (120960.0002). Two null alleles were caused by
cytosine deletions in exons 3 (120960.0005) and 5 (120960.0006). Of the
null alleles, 97% were C-to-T transitions in which an arg (64 alleles)
or gln (1 allele) was replaced by a stop codon.
HISTORY
Tedesco et al. (1983) studied restoration of hemolytic activity in sera
from 7 unrelated persons with C8 deficiency. The sera fell into 2
groups, depending on whether hemolytic activity was restored by addition
of the beta subunit (group 1) or the alpha-gamma subunit (group 2)
purified from normal human C8. A dysfunctional C8 was demonstrated by
antigenic analysis in all 4 sera of group 1. A different dysfunctional
C8 was found in one of the group 2 cases. Chromatographic analysis
demonstrated that the generation of hemolytic activity in the mixture of
2 sera resulted from reconstitution of the C8 molecule rather than the
sequential action of the two C8 subunits. By the technique used by Rogde
et al. (1984), 2 different protein patterns, each with polymorphism,
were demonstrated: A for acidic; B for basic. The B pattern, which was
absent from a serum with known beta-chain deficiency, reflected the
presence of 4 or 5 frequently occurring alleles in the Norwegian
population.
*FIELD* SA
Tedesco et al. (1990)
*FIELD* RF
1. Kaufmann, T.; Hansch, G.; Rittner, C.; Spath, P.; Tedesco, F.;
Schneider, P. M.: Genetic basis of human complement C8-beta deficiency. J.
Immun. 150: 4943-4947, 1993.
2. Marcus, D.; Spira, T. J.; Petersen, B. H.; Raum, D.; Alper, C.
A.: There are two unlinked genetic loci for human C8. (Abstract) Molec.
Immun. 19: 1385 only, 1982.
3. Pericak-Vance, M. A.; Elston, R. C.; Spira, T. J.; Band, J.: Segregation
and linkage analysis of immunochemical C8 levels in a family with
C8 beta-chain deficiency. (Abstract) Am. J. Hum. Genet. 34: 109A
only, 1982.
4. Raum, D.; Spence, M. A.; Balavitch, D.; Tideman, S.; Merritt, A.
D.; Taggart, R. T.; Petersen, B. H.; Day, N. K.; Alper, C. A.: Genetic
control of the eighth component of complement. J. Clin. Invest. 64:
858-865, 1979.
5. Rogde, S.; Mevag, B.; Olaisen, B.; Gedde-Dahl, T., Jr.; Teisberg,
P.: Structural genes for complement factor C8 on chromosome 1. (Abstract) Cytogenet.
Cell Genet. 37: 571 only, 1984.
6. Ross, S. C.; Densen, P.: Complement deficiency states and infection:
epidemiology, pathogenesis and consequences of neisserial and other
infections in an immune deficiency. Medicine 63: 243-273, 1984.
7. Saucedo, L.; Ackermann, L.; Platonov, A. E.; Gewurz, A.; Rakita,
R. M.; Densen, P.: Delineation of additional genetic bases for C8-beta
deficiency: prevalence of null alleles and predominance of C-to-T
transition in their genesis. J. Immun. 155: 5022-5028, 1995.
8. Tanaka, S.; Suzuki, T.; Sakaizumi, M.; Harada, Y.; Matsushima,
Y.; Miyashita, N.; Fukumori, Y.; Inai, S.; Moriwaki, K.; Yonekawa,
H.: Gene responsible for deficient activity of the beta subunit of
C8, the eighth component of complement, is located on mouse chromosome
4. Immunogenetics 33: 18-23, 1991.
9. Tedesco, F.; Densen, P.; Villa, M. A.; Petersen, B. H.; Sirchia,
G.: Two types of dysfunctional eighth component of complement (C8)
molecules in C8 deficiency in man: reconstitution of normal C8 from
the mixture of two abnormal C8 molecules. J. Clin. Invest. 71: 183-191,
1983.
10. Tedesco, F.; Roncelli, L.; Petersen, B. H.; Agnello, V.; Sodetz,
J. M.: Two distinct abnormalities in patients with C8-alpha-gamma
deficiency: low level of C8-beta chain and presence of dysfunctional
C8-alpha-gamma subunit. J. Clin. Invest. 86: 884-888, 1990.
11. Wulffraat, N. M.; Sanders, E. A. M.; Fijen, C. A. P.; Hannema,
A.; Kuis, W.; Zegers, B. J. M.: Deficiency of the beta subunit of
the eighth component of complement presenting as arthritis and exanthem. Arthritis
Rheum. 37: 1704-1706, 1994.
*FIELD* CS
INHERITANCE:
Autosomal recessive
NEUROLOGIC:
[Central nervous system];
Meningitis
IMMUNOLOGY:
C8 deficiency;
Recurrent neisserial infections;
Antigenically defective C8 detected
MOLECULAR BASIS:
Caused by mutation in the complement component-8, beta polypeptide
gene (C8B, 120960.0001)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CN
Paul J. Converse - updated: 7/26/2012
*FIELD* CD
Carol A. Bocchini: 3/2/2011
*FIELD* ED
mgross: 08/01/2012
terry: 7/26/2012
carol: 4/22/2011
terry: 3/3/2011
carol: 3/2/2011
*RECORD*
*FIELD* NO
613789
*FIELD* TI
#613789 COMPLEMENT COMPONENT 8 DEFICIENCY, TYPE II; C8D2
;;C8 DEFICIENCY, TYPE II;;
read moreCOMPLEMENT COMPONENT 8B DEFICIENCY;;
C8 BETA DEFICIENCY;;
C8B DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because complement component 8
deficiency type II (C8B deficiency) is caused by mutation in the C8B
gene (120960) on chromosome 1p32.
DESCRIPTION
Patients with deficiency of C8 suffer from recurrent neisserial
infections, predominantly with meningococcus infection of rare
serotypes. Most such patients are discovered among those having their
first episode of meningitis at ages older than 10 years (Ross and
Densen, 1984).
Two types of inherited C8 deficiency have been reported in man: type I
(613790), in which only C8 alpha (C8A, 120950) and C8 gamma (C8G;
120930) are deficient, and type II, in which only C8 beta is deficient
(Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically
indistinguishable (Ross and Densen, 1984).
CLINICAL FEATURES
Wulffraat et al. (1994) described a family in which a 13-year-old boy
was found to be homozygous for C8B deficiency and to have juvenile
chronic arthritis of 6 months' duration. Antinuclear antibodies,
anti-double-stranded DNA antibodies, and rheumatoid factor were not
detected. The same deficiency was present in the patient's sister, and
both parents were heterozygous. There was no history of meningococcal
disease in the family.
PATHOGENESIS
Activation of the terminal complement components (C5-C9) results in the
assembly of the membrane attack complex. Effective insertion of this
complex into cell membranes is responsible for C-dependent bactericidal
activity, as well as the lysis or death of other cell types. A
deficiency of any of the terminal C components is associated with the
absence of this functional activity, and accounts for the substantially
increased risk of developing meningococcal disease observed in
individuals with such a deficiency (summary by Saucedo et al., 1995).
POPULATION GENETICS
Ross and Densen (1984) stated that C8B deficiency had been reported
exclusively in Caucasians (12 kindreds), and that C8AG deficiency had
been found in 4 Black families, 1 Hispanic family, and no Caucasian
families.
Saucedo et al. (1995) stated that C8B deficiency has been reported
primarily in Caucasians, whereas C8AG deficiency has been reported
predominantly in Blacks and Hispanics.
MAPPING
In a family with deficiency of C8 beta, Pericak-Vance et al. (1982)
found a suggestion of linkage of the disorder to 1p markers: lod score
of 1.44 for UMPK at male theta of 0.14 and female theta of 0.17; lod
score of 1.65 for PGM1 at male theta of 0.0 and female theta of 0.22.
Tanaka et al. (1991) studied deficient activity of the beta subunit of
C8 in mice and demonstrated by linkage studies that this form of C8
deficiency is controlled by a single recessive gene, designated C8b,
located on mouse chromosome 4.
MOLECULAR GENETICS
Raum et al. (1979) used serum from patients with type I deficiency
(which lacks alpha-gamma chains but has normal beta chains) to raise
antisera against beta C8 and to demonstrate polymorphism thereof.
By direct sequence analysis of all exon-specific PCR products from
normal and C8B-deficient persons, Kaufmann et al. (1993) found a single
C-T change in exon 9 leading to a stop codon (120960.0001). An
allele-specific PCR system was designed to detect the normal and the
deficiency allele simultaneously. Using this approach as well as PCR
typing of the TaqI polymorphism located in intron 11, 5 families with 7
C8B-deficient members were investigated. The mutant allele was observed
in all 7 affected members of the families investigated and could
therefore be regarded as a major cause of C8B deficiency in Caucasians.
Five patients were homozygous for the mutation. In the 2 others, only 1
chromosome carried the mutation; the molecular nature of the other
allele had not been determined.
In a study of 34 unrelated families with C8B deficiency from the U.S.
and the former U.S.S.R., Saucedo et al. (1995) found that 59 (86%) of 69
null alleles were due to the C-to-T transition in exon 9. An additional
6 null alleles were caused by C-to-T transitions in exons 3 (120960.0003
and 120960.0004) and 6 (120960.0002). Two null alleles were caused by
cytosine deletions in exons 3 (120960.0005) and 5 (120960.0006). Of the
null alleles, 97% were C-to-T transitions in which an arg (64 alleles)
or gln (1 allele) was replaced by a stop codon.
HISTORY
Tedesco et al. (1983) studied restoration of hemolytic activity in sera
from 7 unrelated persons with C8 deficiency. The sera fell into 2
groups, depending on whether hemolytic activity was restored by addition
of the beta subunit (group 1) or the alpha-gamma subunit (group 2)
purified from normal human C8. A dysfunctional C8 was demonstrated by
antigenic analysis in all 4 sera of group 1. A different dysfunctional
C8 was found in one of the group 2 cases. Chromatographic analysis
demonstrated that the generation of hemolytic activity in the mixture of
2 sera resulted from reconstitution of the C8 molecule rather than the
sequential action of the two C8 subunits. By the technique used by Rogde
et al. (1984), 2 different protein patterns, each with polymorphism,
were demonstrated: A for acidic; B for basic. The B pattern, which was
absent from a serum with known beta-chain deficiency, reflected the
presence of 4 or 5 frequently occurring alleles in the Norwegian
population.
*FIELD* SA
Tedesco et al. (1990)
*FIELD* RF
1. Kaufmann, T.; Hansch, G.; Rittner, C.; Spath, P.; Tedesco, F.;
Schneider, P. M.: Genetic basis of human complement C8-beta deficiency. J.
Immun. 150: 4943-4947, 1993.
2. Marcus, D.; Spira, T. J.; Petersen, B. H.; Raum, D.; Alper, C.
A.: There are two unlinked genetic loci for human C8. (Abstract) Molec.
Immun. 19: 1385 only, 1982.
3. Pericak-Vance, M. A.; Elston, R. C.; Spira, T. J.; Band, J.: Segregation
and linkage analysis of immunochemical C8 levels in a family with
C8 beta-chain deficiency. (Abstract) Am. J. Hum. Genet. 34: 109A
only, 1982.
4. Raum, D.; Spence, M. A.; Balavitch, D.; Tideman, S.; Merritt, A.
D.; Taggart, R. T.; Petersen, B. H.; Day, N. K.; Alper, C. A.: Genetic
control of the eighth component of complement. J. Clin. Invest. 64:
858-865, 1979.
5. Rogde, S.; Mevag, B.; Olaisen, B.; Gedde-Dahl, T., Jr.; Teisberg,
P.: Structural genes for complement factor C8 on chromosome 1. (Abstract) Cytogenet.
Cell Genet. 37: 571 only, 1984.
6. Ross, S. C.; Densen, P.: Complement deficiency states and infection:
epidemiology, pathogenesis and consequences of neisserial and other
infections in an immune deficiency. Medicine 63: 243-273, 1984.
7. Saucedo, L.; Ackermann, L.; Platonov, A. E.; Gewurz, A.; Rakita,
R. M.; Densen, P.: Delineation of additional genetic bases for C8-beta
deficiency: prevalence of null alleles and predominance of C-to-T
transition in their genesis. J. Immun. 155: 5022-5028, 1995.
8. Tanaka, S.; Suzuki, T.; Sakaizumi, M.; Harada, Y.; Matsushima,
Y.; Miyashita, N.; Fukumori, Y.; Inai, S.; Moriwaki, K.; Yonekawa,
H.: Gene responsible for deficient activity of the beta subunit of
C8, the eighth component of complement, is located on mouse chromosome
4. Immunogenetics 33: 18-23, 1991.
9. Tedesco, F.; Densen, P.; Villa, M. A.; Petersen, B. H.; Sirchia,
G.: Two types of dysfunctional eighth component of complement (C8)
molecules in C8 deficiency in man: reconstitution of normal C8 from
the mixture of two abnormal C8 molecules. J. Clin. Invest. 71: 183-191,
1983.
10. Tedesco, F.; Roncelli, L.; Petersen, B. H.; Agnello, V.; Sodetz,
J. M.: Two distinct abnormalities in patients with C8-alpha-gamma
deficiency: low level of C8-beta chain and presence of dysfunctional
C8-alpha-gamma subunit. J. Clin. Invest. 86: 884-888, 1990.
11. Wulffraat, N. M.; Sanders, E. A. M.; Fijen, C. A. P.; Hannema,
A.; Kuis, W.; Zegers, B. J. M.: Deficiency of the beta subunit of
the eighth component of complement presenting as arthritis and exanthem. Arthritis
Rheum. 37: 1704-1706, 1994.
*FIELD* CS
INHERITANCE:
Autosomal recessive
NEUROLOGIC:
[Central nervous system];
Meningitis
IMMUNOLOGY:
C8 deficiency;
Recurrent neisserial infections;
Antigenically defective C8 detected
MOLECULAR BASIS:
Caused by mutation in the complement component-8, beta polypeptide
gene (C8B, 120960.0001)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CN
Paul J. Converse - updated: 7/26/2012
*FIELD* CD
Carol A. Bocchini: 3/2/2011
*FIELD* ED
mgross: 08/01/2012
terry: 7/26/2012
carol: 4/22/2011
terry: 3/3/2011
carol: 3/2/2011