Full text data of C1QC
C1QC
(C1QG)
[Confidence: low (only semi-automatic identification from reviews)]
Complement C1q subcomponent subunit C; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Complement C1q subcomponent subunit C; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02747
ID C1QC_HUMAN Reviewed; 245 AA.
AC P02747; Q7Z502; Q96DL2; Q96H05;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Complement C1q subcomponent subunit C;
DE Flags: Precursor;
GN Name=C1QC; Synonyms=C1QG;
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 [GENOMIC DNA].
RC TISSUE=Monocyte;
RX PubMed=1706597;
RA Sellar G.C., Blake D.J., Reid K.B.M.;
RT "Characterization and organization of the genes encoding the A-, B-
RT and C-chains of human complement subcomponent C1q. The complete
RT derived amino acid sequence of human C1q.";
RL Biochem. J. 274:481-490(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dai F.Y., Yu L., Wan Y.Z., Zhang H.L., Huang J., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homology to murine
RT C1q C-chain mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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].
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 MRNA].
RC TISSUE=Brain;
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 [6]
RP PROTEIN SEQUENCE OF 29-122.
RX PubMed=486087;
RA Reid K.B.M.;
RT "Complete amino acid sequences of the three collagen-like regions
RT present in subcomponent C1q of the first component of human
RT complement.";
RL Biochem. J. 179:367-371(1979).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 117-245.
RX PubMed=12960167; DOI=10.1074/jbc.M307764200;
RA Gaboriaud C., Juanhuix J., Gruez A., Lacroix M., Darnault C.,
RA Pignol D., Verger D., Fontecilla-Camps J.-C., Arlaud G.J.;
RT "The crystal structure of the globular head of complement protein C1q
RT provides a basis for its versatile recognition properties.";
RL J. Biol. Chem. 278:46974-46982(2003).
RN [8]
RP REVIEW ON C1Q DEFICIENCY.
RX PubMed=9777412;
RA Petry F.;
RT "Molecular basis of hereditary C1q deficiency.";
RL Immunobiology 199:286-294(1998).
RN [9]
RP VARIANT C1QD ARG-34.
RX PubMed=8630118; DOI=10.1002/art.1780390419;
RA Slingsby J.H., Norsworthy P., Pearce G., Vaishnaw A.K., Issler H.,
RA Morley B.J., Walport M.J.;
RT "Homozygous hereditary C1q deficiency and systemic lupus
RT erythematosus. A new family and the molecular basis of C1q deficiency
RT in three families.";
RL Arthritis Rheum. 39:663-670(1996).
CC -!- FUNCTION: C1q associates with the proenzymes C1r and C1s to yield
CC C1, the first component of the serum complement system. The
CC collagen-like regions of C1q interact with the Ca(2+)-dependent
CC C1r(2)C1s(2) proenzyme complex, and efficient activation of C1
CC takes place on interaction of the globular heads of C1q with the
CC Fc regions of IgG or IgM antibody present in immune complexes.
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, R
CC and S in the molar ration of 1:2:2. C1q subcomponent is composed
CC of nine subunits, six of which are disulfide-linked dimers of the
CC A and B chains, and three of which are disulfide-linked dimers of
CC the C chain.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: O-linked glycans consist of Glc-Gal disaccharides bound to
CC the oxygen atom of post-translationally added hydroxyl groups.
CC -!- DISEASE: Complement component C1q deficiency (C1QD) [MIM:613652]:
CC A disorder caused by impaired activation of the complement
CC classical pathway. It generally leads to severe immune complex
CC disease with features of systemic lupus erythematosus and
CC glomerulonephritis. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 C1q domain.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- WEB RESOURCE: Name=C1QGbase; Note=C1QC mutation db;
CC URL="http://bioinf.uta.fi/C1QGbase/";
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DR EMBL; AF087892; AAP97191.1; -; mRNA.
DR EMBL; AK057792; BAB71575.1; -; mRNA.
DR EMBL; AL158086; CAI22894.1; -; Genomic_DNA.
DR EMBL; BC009016; AAH09016.1; -; mRNA.
DR PIR; S14351; C1HUQC.
DR RefSeq; NP_001107573.1; NM_001114101.1.
DR RefSeq; NP_758957.2; NM_172369.3.
DR UniGene; Hs.467753; -.
DR PDB; 1PK6; X-ray; 1.85 A; C=117-245.
DR PDB; 2JG8; X-ray; 2.05 A; C/F=115-245.
DR PDB; 2JG9; X-ray; 1.90 A; C/F=115-245.
DR PDB; 2WNU; X-ray; 2.30 A; C/F=115-245.
DR PDB; 2WNV; X-ray; 1.25 A; C/F=115-245.
DR PDBsum; 1PK6; -.
DR PDBsum; 2JG8; -.
DR PDBsum; 2JG9; -.
DR PDBsum; 2WNU; -.
DR PDBsum; 2WNV; -.
DR ProteinModelPortal; P02747; -.
DR SMR; P02747; 77-103, 117-245.
DR IntAct; P02747; 2.
DR MINT; MINT-6630018; -.
DR STRING; 9606.ENSP00000363768; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00092; Alefacept.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00095; Efalizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00081; Tositumomab.
DR DrugBank; DB00072; Trastuzumab.
DR DMDM; 20178281; -.
DR PaxDb; P02747; -.
DR PeptideAtlas; P02747; -.
DR PRIDE; P02747; -.
DR DNASU; 714; -.
DR Ensembl; ENST00000374637; ENSP00000363768; ENSG00000159189.
DR Ensembl; ENST00000374639; ENSP00000363770; ENSG00000159189.
DR Ensembl; ENST00000374640; ENSP00000363771; ENSG00000159189.
DR GeneID; 714; -.
DR KEGG; hsa:714; -.
DR UCSC; uc001bga.4; human.
DR CTD; 714; -.
DR GeneCards; GC01P022970; -.
DR HGNC; HGNC:1245; C1QC.
DR HPA; CAB009828; -.
DR HPA; HPA001471; -.
DR MIM; 120575; gene.
DR MIM; 613652; phenotype.
DR neXtProt; NX_P02747; -.
DR Orphanet; 169147; Immunodeficiency due to an early component of complement deficiency.
DR PharmGKB; PA25626; -.
DR eggNOG; NOG115796; -.
DR HOGENOM; HOG000085653; -.
DR HOVERGEN; HBG108220; -.
DR InParanoid; P02747; -.
DR KO; K03988; -.
DR OMA; QTANLCV; -.
DR OrthoDB; EOG70ZZPW; -.
DR PhylomeDB; P02747; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; C1QC; human.
DR EvolutionaryTrace; P02747; -.
DR GenomeRNAi; 714; -.
DR NextBio; 2902; -.
DR PMAP-CutDB; P02747; -.
DR PRO; PR:P02747; -.
DR Bgee; P02747; -.
DR CleanEx; HS_C1QC; -.
DR Genevestigator; P02747; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:BHF-UCL.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; IDA:BHF-UCL.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 1.
DR Pfam; PF01391; Collagen; 2.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Collagen; Complement pathway; Complete proteome;
KW Direct protein sequencing; Disease mutation; Disulfide bond;
KW Glycoprotein; Hydroxylation; Immunity; Innate immunity;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 28
FT CHAIN 29 245 Complement C1q subcomponent subunit C.
FT /FTId=PRO_0000003524.
FT DOMAIN 31 112 Collagen-like.
FT DOMAIN 115 245 C1q.
FT MOD_RES 36 36 4-hydroxyproline.
FT MOD_RES 39 39 4-hydroxyproline.
FT MOD_RES 42 42 4-hydroxyproline.
FT MOD_RES 45 45 4-hydroxyproline.
FT MOD_RES 54 54 4-hydroxyproline.
FT MOD_RES 57 57 5-hydroxylysine.
FT MOD_RES 63 63 4-hydroxyproline.
FT MOD_RES 75 75 5-hydroxylysine.
FT MOD_RES 81 81 4-hydroxyproline.
FT MOD_RES 93 93 4-hydroxyproline.
FT MOD_RES 96 96 4-hydroxyproline.
FT MOD_RES 99 99 4-hydroxyproline.
FT MOD_RES 105 105 4-hydroxyproline.
FT CARBOHYD 75 75 O-linked (Gal...).
FT DISULFID 32 32 Interchain.
FT VARIANT 34 34 G -> R (in C1QD).
FT /FTId=VAR_008542.
FT CONFLICT 14 14 K -> R (in Ref. 3; BAB71575).
FT CONFLICT 23 23 P -> A (in Ref. 1; no nucleotide entry).
FT CONFLICT 26 27 GQ -> AK (in Ref. 2; AAP97191).
FT CONFLICT 57 57 K -> P (in Ref. 6; AA sequence).
FT CONFLICT 66 66 P -> K (in Ref. 6; AA sequence).
FT CONFLICT 72 72 K -> P (in Ref. 6; AA sequence).
FT CONFLICT 84 84 P -> K (in Ref. 6; AA sequence).
FT CONFLICT 87 87 N -> D (in Ref. 6; AA sequence).
FT CONFLICT 90 90 M -> N (in Ref. 6; AA sequence).
FT CONFLICT 104 104 I -> F (in Ref. 2; AAP97191).
FT CONFLICT 149 149 G -> E (in Ref. 2; AAP97191).
FT CONFLICT 215 215 E -> G (in Ref. 3; BAB71575).
FT HELIX 116 118
FT STRAND 121 125
FT STRAND 142 145
FT TURN 153 155
FT STRAND 157 159
FT STRAND 164 176
FT STRAND 178 184
FT STRAND 187 194
FT STRAND 197 199
FT STRAND 201 211
FT STRAND 216 225
FT STRAND 236 244
SQ SEQUENCE 245 AA; 25774 MW; FA17117EB7ABFC12 CRC64;
MDVGPSSLPH LGLKLLLLLL LLPLRGQANT GCYGIPGMPG LPGAPGKDGY DGLPGPKGEP
GIPAIPGIRG PKGQKGEPGL PGHPGKNGPM GPPGMPGVPG PMGIPGEPGE EGRYKQKFQS
VFTVTRQTHQ PPAPNSLIRF NAVLTNPQGD YDTSTGKFTC KVPGLYYFVY HASHTANLCV
LLYRSGVKVV TFCGHTSKTN QVNSGGVLLR LQVGEEVWLA VNDYYDMVGI QGSDSVFSGF
LLFPD
//
ID C1QC_HUMAN Reviewed; 245 AA.
AC P02747; Q7Z502; Q96DL2; Q96H05;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-APR-2002, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Complement C1q subcomponent subunit C;
DE Flags: Precursor;
GN Name=C1QC; Synonyms=C1QG;
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 [GENOMIC DNA].
RC TISSUE=Monocyte;
RX PubMed=1706597;
RA Sellar G.C., Blake D.J., Reid K.B.M.;
RT "Characterization and organization of the genes encoding the A-, B-
RT and C-chains of human complement subcomponent C1q. The complete
RT derived amino acid sequence of human C1q.";
RL Biochem. J. 274:481-490(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Dai F.Y., Yu L., Wan Y.Z., Zhang H.L., Huang J., Zhao S.Y.;
RT "Cloning and characterization of a novel human cDNA homology to murine
RT C1q C-chain mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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].
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 MRNA].
RC TISSUE=Brain;
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 [6]
RP PROTEIN SEQUENCE OF 29-122.
RX PubMed=486087;
RA Reid K.B.M.;
RT "Complete amino acid sequences of the three collagen-like regions
RT present in subcomponent C1q of the first component of human
RT complement.";
RL Biochem. J. 179:367-371(1979).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 117-245.
RX PubMed=12960167; DOI=10.1074/jbc.M307764200;
RA Gaboriaud C., Juanhuix J., Gruez A., Lacroix M., Darnault C.,
RA Pignol D., Verger D., Fontecilla-Camps J.-C., Arlaud G.J.;
RT "The crystal structure of the globular head of complement protein C1q
RT provides a basis for its versatile recognition properties.";
RL J. Biol. Chem. 278:46974-46982(2003).
RN [8]
RP REVIEW ON C1Q DEFICIENCY.
RX PubMed=9777412;
RA Petry F.;
RT "Molecular basis of hereditary C1q deficiency.";
RL Immunobiology 199:286-294(1998).
RN [9]
RP VARIANT C1QD ARG-34.
RX PubMed=8630118; DOI=10.1002/art.1780390419;
RA Slingsby J.H., Norsworthy P., Pearce G., Vaishnaw A.K., Issler H.,
RA Morley B.J., Walport M.J.;
RT "Homozygous hereditary C1q deficiency and systemic lupus
RT erythematosus. A new family and the molecular basis of C1q deficiency
RT in three families.";
RL Arthritis Rheum. 39:663-670(1996).
CC -!- FUNCTION: C1q associates with the proenzymes C1r and C1s to yield
CC C1, the first component of the serum complement system. The
CC collagen-like regions of C1q interact with the Ca(2+)-dependent
CC C1r(2)C1s(2) proenzyme complex, and efficient activation of C1
CC takes place on interaction of the globular heads of C1q with the
CC Fc regions of IgG or IgM antibody present in immune complexes.
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, R
CC and S in the molar ration of 1:2:2. C1q subcomponent is composed
CC of nine subunits, six of which are disulfide-linked dimers of the
CC A and B chains, and three of which are disulfide-linked dimers of
CC the C chain.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: O-linked glycans consist of Glc-Gal disaccharides bound to
CC the oxygen atom of post-translationally added hydroxyl groups.
CC -!- DISEASE: Complement component C1q deficiency (C1QD) [MIM:613652]:
CC A disorder caused by impaired activation of the complement
CC classical pathway. It generally leads to severe immune complex
CC disease with features of systemic lupus erythematosus and
CC glomerulonephritis. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 C1q domain.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- WEB RESOURCE: Name=C1QGbase; Note=C1QC mutation db;
CC URL="http://bioinf.uta.fi/C1QGbase/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF087892; AAP97191.1; -; mRNA.
DR EMBL; AK057792; BAB71575.1; -; mRNA.
DR EMBL; AL158086; CAI22894.1; -; Genomic_DNA.
DR EMBL; BC009016; AAH09016.1; -; mRNA.
DR PIR; S14351; C1HUQC.
DR RefSeq; NP_001107573.1; NM_001114101.1.
DR RefSeq; NP_758957.2; NM_172369.3.
DR UniGene; Hs.467753; -.
DR PDB; 1PK6; X-ray; 1.85 A; C=117-245.
DR PDB; 2JG8; X-ray; 2.05 A; C/F=115-245.
DR PDB; 2JG9; X-ray; 1.90 A; C/F=115-245.
DR PDB; 2WNU; X-ray; 2.30 A; C/F=115-245.
DR PDB; 2WNV; X-ray; 1.25 A; C/F=115-245.
DR PDBsum; 1PK6; -.
DR PDBsum; 2JG8; -.
DR PDBsum; 2JG9; -.
DR PDBsum; 2WNU; -.
DR PDBsum; 2WNV; -.
DR ProteinModelPortal; P02747; -.
DR SMR; P02747; 77-103, 117-245.
DR IntAct; P02747; 2.
DR MINT; MINT-6630018; -.
DR STRING; 9606.ENSP00000363768; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00092; Alefacept.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00095; Efalizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00081; Tositumomab.
DR DrugBank; DB00072; Trastuzumab.
DR DMDM; 20178281; -.
DR PaxDb; P02747; -.
DR PeptideAtlas; P02747; -.
DR PRIDE; P02747; -.
DR DNASU; 714; -.
DR Ensembl; ENST00000374637; ENSP00000363768; ENSG00000159189.
DR Ensembl; ENST00000374639; ENSP00000363770; ENSG00000159189.
DR Ensembl; ENST00000374640; ENSP00000363771; ENSG00000159189.
DR GeneID; 714; -.
DR KEGG; hsa:714; -.
DR UCSC; uc001bga.4; human.
DR CTD; 714; -.
DR GeneCards; GC01P022970; -.
DR HGNC; HGNC:1245; C1QC.
DR HPA; CAB009828; -.
DR HPA; HPA001471; -.
DR MIM; 120575; gene.
DR MIM; 613652; phenotype.
DR neXtProt; NX_P02747; -.
DR Orphanet; 169147; Immunodeficiency due to an early component of complement deficiency.
DR PharmGKB; PA25626; -.
DR eggNOG; NOG115796; -.
DR HOGENOM; HOG000085653; -.
DR HOVERGEN; HBG108220; -.
DR InParanoid; P02747; -.
DR KO; K03988; -.
DR OMA; QTANLCV; -.
DR OrthoDB; EOG70ZZPW; -.
DR PhylomeDB; P02747; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; C1QC; human.
DR EvolutionaryTrace; P02747; -.
DR GenomeRNAi; 714; -.
DR NextBio; 2902; -.
DR PMAP-CutDB; P02747; -.
DR PRO; PR:P02747; -.
DR Bgee; P02747; -.
DR CleanEx; HS_C1QC; -.
DR Genevestigator; P02747; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:BHF-UCL.
DR GO; GO:0045650; P:negative regulation of macrophage differentiation; IDA:BHF-UCL.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 1.
DR Pfam; PF01391; Collagen; 2.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Collagen; Complement pathway; Complete proteome;
KW Direct protein sequencing; Disease mutation; Disulfide bond;
KW Glycoprotein; Hydroxylation; Immunity; Innate immunity;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 28
FT CHAIN 29 245 Complement C1q subcomponent subunit C.
FT /FTId=PRO_0000003524.
FT DOMAIN 31 112 Collagen-like.
FT DOMAIN 115 245 C1q.
FT MOD_RES 36 36 4-hydroxyproline.
FT MOD_RES 39 39 4-hydroxyproline.
FT MOD_RES 42 42 4-hydroxyproline.
FT MOD_RES 45 45 4-hydroxyproline.
FT MOD_RES 54 54 4-hydroxyproline.
FT MOD_RES 57 57 5-hydroxylysine.
FT MOD_RES 63 63 4-hydroxyproline.
FT MOD_RES 75 75 5-hydroxylysine.
FT MOD_RES 81 81 4-hydroxyproline.
FT MOD_RES 93 93 4-hydroxyproline.
FT MOD_RES 96 96 4-hydroxyproline.
FT MOD_RES 99 99 4-hydroxyproline.
FT MOD_RES 105 105 4-hydroxyproline.
FT CARBOHYD 75 75 O-linked (Gal...).
FT DISULFID 32 32 Interchain.
FT VARIANT 34 34 G -> R (in C1QD).
FT /FTId=VAR_008542.
FT CONFLICT 14 14 K -> R (in Ref. 3; BAB71575).
FT CONFLICT 23 23 P -> A (in Ref. 1; no nucleotide entry).
FT CONFLICT 26 27 GQ -> AK (in Ref. 2; AAP97191).
FT CONFLICT 57 57 K -> P (in Ref. 6; AA sequence).
FT CONFLICT 66 66 P -> K (in Ref. 6; AA sequence).
FT CONFLICT 72 72 K -> P (in Ref. 6; AA sequence).
FT CONFLICT 84 84 P -> K (in Ref. 6; AA sequence).
FT CONFLICT 87 87 N -> D (in Ref. 6; AA sequence).
FT CONFLICT 90 90 M -> N (in Ref. 6; AA sequence).
FT CONFLICT 104 104 I -> F (in Ref. 2; AAP97191).
FT CONFLICT 149 149 G -> E (in Ref. 2; AAP97191).
FT CONFLICT 215 215 E -> G (in Ref. 3; BAB71575).
FT HELIX 116 118
FT STRAND 121 125
FT STRAND 142 145
FT TURN 153 155
FT STRAND 157 159
FT STRAND 164 176
FT STRAND 178 184
FT STRAND 187 194
FT STRAND 197 199
FT STRAND 201 211
FT STRAND 216 225
FT STRAND 236 244
SQ SEQUENCE 245 AA; 25774 MW; FA17117EB7ABFC12 CRC64;
MDVGPSSLPH LGLKLLLLLL LLPLRGQANT GCYGIPGMPG LPGAPGKDGY DGLPGPKGEP
GIPAIPGIRG PKGQKGEPGL PGHPGKNGPM GPPGMPGVPG PMGIPGEPGE EGRYKQKFQS
VFTVTRQTHQ PPAPNSLIRF NAVLTNPQGD YDTSTGKFTC KVPGLYYFVY HASHTANLCV
LLYRSGVKVV TFCGHTSKTN QVNSGGVLLR LQVGEEVWLA VNDYYDMVGI QGSDSVFSGF
LLFPD
//
MIM
120575
*RECORD*
*FIELD* NO
120575
*FIELD* TI
*120575 COMPLEMENT COMPONENT 1, q SUBCOMPONENT, C CHAIN; C1QC
;;COMPLEMENT COMPONENT C1q, C CHAIN;;
read moreCOMPLEMENT COMPONENT 1, q SUBCOMPONENT, GAMMA POLYPEPTIDE; C1QG
*FIELD* TX
CLONING
C1q, the first subcomponent of C1, has a complicated 18-chain structure:
6 A, 6 B, and 6 C chains. Each chain has a stretch of about 80 amino
acids with the collagenous triplet Gly-X-Y where X and Y can include
hydroxyproline and hydroxylysine. The A (120550), B (120570), and C
chains combine to form 6 heteromeric triple helices in the collagenous
regions of the chains (Sellar et al., 1991).
MAPPING
Sellar et al. (1991) found that the genes encoding the A, B, and C
chains of human C1q are aligned, 5-prime to 3-prime, in the same
orientation in the order A-C-B on a 24-kb stretch of DNA on chromosome
1p. A and C are separated by 4 kb and B and C are separated by 11 kb.
Hybridization of cDNA probes to a hybrid cell line containing the
derived X chromosome from an X;1(q21.2;p34) translocation described in a
female patient with Duchenne muscular dystrophy (Lindenbaum et al.,
1979; Boyd et al., 1988) showed that the A and B genes are located in
the region 1p36.3-p34.1 (Sellar et al., 1992).
GENE STRUCTURE
The A- (120550), B- (120570), and C-chain C1q genes are approximately
2.5, 2.6, and 3.2 kb long, respectively, and each contains 1 intron
located within a codon for a glycine residue found halfway along the
collagen-like region present in each chain. These glycine residues are
located just before the point where the triple-helical portions of the
C1q molecule appear to bend when viewed by electron microscopy. Southern
blot analysis showed that there is only one gene per chain.
MOLECULAR GENETICS
In patients with C1q deficiency (613652), Slingsby et al. (1996)
identified homozygous mutations in the C1QC gene
(120575.0001-120575.0003).
*FIELD* AV
.0001
C1Q DEFICIENCY
C1QC, 1-BP DEL, 43C
In a patient with C1q deficiency (613652), Slingsby et al. (1996)
identified a homozygous deletion of a C nucleotide at position 43 of the
C1QC gene, resulting in a frameshift with a premature stop codon
in-frame at position 108.
.0002
C1Q DEFICIENCY
C1QC, 41C-T
In a patient with C1q deficiency (613652), Slingsby et al. (1996)
identified homozygosity for a C-to-T transition at position 41 of the C
chain, resulting in a premature stop codon. The patient had no
detectable C1q protein.
.0003
C1Q DEFICIENCY
C1QC, 6G-A
In patients from 2 racially distinct groups, Slingsby et al. (1996) and
Kirschfink et al. (1993) described the same homozygous point mutation as
the cause of dysfunctional C1q deficiency (613652): a G-to-A transition
at position 6 of the C chain.
*FIELD* RF
1. Boyd, Y.; Cockburn, D.; Holt, S.; Munro, E.; van Ommen, G. J.;
Gillard, B.; Affara, N.; Ferguson-Smith, M.; Craig, I.: Mapping of
12 translocation breakpoints in the Xp21 region with respect to the
locus for Duchenne muscular dystrophy. Cytogenet. Cell Genet. 48:
28-34, 1988.
2. Kirschfink, M.; Petry, F.; Khirwadkar, K.; Wigand, R.; Kaltwasser,
J. P.; Loos, M.: Complete functional C1q deficiency associated with
systemic lupus erythematosus (SLE). Clin. Exp. Immun. 94: 267-272,
1993.
3. Lindenbaum, R. H.; Clarke, G.; Patel, C.; Moncrieff, M.; Hughes,
J. T.: Muscular dystrophy in an X;1 translocation female suggests
that Duchenne locus is on X chromosome short arm. J. Med. Genet. 16:
389-392, 1979.
4. Sellar, G. C.; Blake, D. J.; Reid, K. B.: Characterization and
organization of the genes encoding the A-, B- and C-chains of human
complement subcomponent C1q: the complete derived amino acid sequence
of human C1q. Biochem. J. 274: 481-490, 1991.
5. Sellar, G. C.; Cockburn, D.; Reid, K. B. M.: Localization of the
gene cluster encoding the A, B, and C chains of human C1q to 1p34.1-1p36.3. Immunogenetics 35:
214-216, 1992.
6. Slingsby, J. H.; Norsworthy, P.; Pearce, G.; Vaishnaw, A. K.; Issler,
H.; Morley, B. J.; Walport, M. J.: Homozygous hereditary C1q deficiency
and systemic lupus erythematosus: a new family and the molecular basis
of C1q deficiency in three families. Arthritis Rheum. 39: 663-670,
1996.
*FIELD* CD
Victor A. McKusick: 9/9/1991
*FIELD* ED
terry: 02/18/2011
carol: 2/17/2011
carol: 2/16/2011
carol: 4/21/1999
terry: 5/29/1998
jamie: 11/22/1996
terry: 11/14/1996
terry: 11/11/1996
jason: 6/17/1994
carol: 10/13/1992
carol: 5/12/1992
supermim: 3/16/1992
carol: 9/9/1991
*RECORD*
*FIELD* NO
120575
*FIELD* TI
*120575 COMPLEMENT COMPONENT 1, q SUBCOMPONENT, C CHAIN; C1QC
;;COMPLEMENT COMPONENT C1q, C CHAIN;;
read moreCOMPLEMENT COMPONENT 1, q SUBCOMPONENT, GAMMA POLYPEPTIDE; C1QG
*FIELD* TX
CLONING
C1q, the first subcomponent of C1, has a complicated 18-chain structure:
6 A, 6 B, and 6 C chains. Each chain has a stretch of about 80 amino
acids with the collagenous triplet Gly-X-Y where X and Y can include
hydroxyproline and hydroxylysine. The A (120550), B (120570), and C
chains combine to form 6 heteromeric triple helices in the collagenous
regions of the chains (Sellar et al., 1991).
MAPPING
Sellar et al. (1991) found that the genes encoding the A, B, and C
chains of human C1q are aligned, 5-prime to 3-prime, in the same
orientation in the order A-C-B on a 24-kb stretch of DNA on chromosome
1p. A and C are separated by 4 kb and B and C are separated by 11 kb.
Hybridization of cDNA probes to a hybrid cell line containing the
derived X chromosome from an X;1(q21.2;p34) translocation described in a
female patient with Duchenne muscular dystrophy (Lindenbaum et al.,
1979; Boyd et al., 1988) showed that the A and B genes are located in
the region 1p36.3-p34.1 (Sellar et al., 1992).
GENE STRUCTURE
The A- (120550), B- (120570), and C-chain C1q genes are approximately
2.5, 2.6, and 3.2 kb long, respectively, and each contains 1 intron
located within a codon for a glycine residue found halfway along the
collagen-like region present in each chain. These glycine residues are
located just before the point where the triple-helical portions of the
C1q molecule appear to bend when viewed by electron microscopy. Southern
blot analysis showed that there is only one gene per chain.
MOLECULAR GENETICS
In patients with C1q deficiency (613652), Slingsby et al. (1996)
identified homozygous mutations in the C1QC gene
(120575.0001-120575.0003).
*FIELD* AV
.0001
C1Q DEFICIENCY
C1QC, 1-BP DEL, 43C
In a patient with C1q deficiency (613652), Slingsby et al. (1996)
identified a homozygous deletion of a C nucleotide at position 43 of the
C1QC gene, resulting in a frameshift with a premature stop codon
in-frame at position 108.
.0002
C1Q DEFICIENCY
C1QC, 41C-T
In a patient with C1q deficiency (613652), Slingsby et al. (1996)
identified homozygosity for a C-to-T transition at position 41 of the C
chain, resulting in a premature stop codon. The patient had no
detectable C1q protein.
.0003
C1Q DEFICIENCY
C1QC, 6G-A
In patients from 2 racially distinct groups, Slingsby et al. (1996) and
Kirschfink et al. (1993) described the same homozygous point mutation as
the cause of dysfunctional C1q deficiency (613652): a G-to-A transition
at position 6 of the C chain.
*FIELD* RF
1. Boyd, Y.; Cockburn, D.; Holt, S.; Munro, E.; van Ommen, G. J.;
Gillard, B.; Affara, N.; Ferguson-Smith, M.; Craig, I.: Mapping of
12 translocation breakpoints in the Xp21 region with respect to the
locus for Duchenne muscular dystrophy. Cytogenet. Cell Genet. 48:
28-34, 1988.
2. Kirschfink, M.; Petry, F.; Khirwadkar, K.; Wigand, R.; Kaltwasser,
J. P.; Loos, M.: Complete functional C1q deficiency associated with
systemic lupus erythematosus (SLE). Clin. Exp. Immun. 94: 267-272,
1993.
3. Lindenbaum, R. H.; Clarke, G.; Patel, C.; Moncrieff, M.; Hughes,
J. T.: Muscular dystrophy in an X;1 translocation female suggests
that Duchenne locus is on X chromosome short arm. J. Med. Genet. 16:
389-392, 1979.
4. Sellar, G. C.; Blake, D. J.; Reid, K. B.: Characterization and
organization of the genes encoding the A-, B- and C-chains of human
complement subcomponent C1q: the complete derived amino acid sequence
of human C1q. Biochem. J. 274: 481-490, 1991.
5. Sellar, G. C.; Cockburn, D.; Reid, K. B. M.: Localization of the
gene cluster encoding the A, B, and C chains of human C1q to 1p34.1-1p36.3. Immunogenetics 35:
214-216, 1992.
6. Slingsby, J. H.; Norsworthy, P.; Pearce, G.; Vaishnaw, A. K.; Issler,
H.; Morley, B. J.; Walport, M. J.: Homozygous hereditary C1q deficiency
and systemic lupus erythematosus: a new family and the molecular basis
of C1q deficiency in three families. Arthritis Rheum. 39: 663-670,
1996.
*FIELD* CD
Victor A. McKusick: 9/9/1991
*FIELD* ED
terry: 02/18/2011
carol: 2/17/2011
carol: 2/16/2011
carol: 4/21/1999
terry: 5/29/1998
jamie: 11/22/1996
terry: 11/14/1996
terry: 11/11/1996
jason: 6/17/1994
carol: 10/13/1992
carol: 5/12/1992
supermim: 3/16/1992
carol: 9/9/1991
MIM
613652
*RECORD*
*FIELD* NO
613652
*FIELD* TI
#613652 C1q DEFICIENCY; C1QD
*FIELD* TX
A number sign (#) is used with this entry because C1q deficiency can be
read morecaused by homozygous mutation in the C1QA (120550), C1QB (120570), or
C1QC (120575) gene, all of which are located on chromosome 1p36.
DESCRIPTION
C1q deficiency is a rare autosomal recessive disorder associated with
recurrent skin lesions, chronic infections, systemic lupus erythematosis
(SLE; see 152700) or SLE-like diseases. It has also been associated with
mesangial proliferative glomerulonephritis. C1q deficiency presents in 2
different forms, absent C1q protein or presence of a dysfunctional
molecule (summary by Topaloglu et al., 1996).
CLINICAL FEATURES
Thompson et al. (1980) reported C1q deficiency in a 4-year-old son of
first-cousin Pakistani parents, who presented with a lupus-like illness
and later developed glomerulonephritis. A younger sister, as yet
clinically unaffected, had the same complement profile and a younger
brother had half-normal functional C1 levels. The heterozygous status of
both parents, the younger brother, and an older sister was suggested by
the presence of double lines on immunochemical analysis of serum from
these persons using anti-C1q antiserum; one line showed a reaction of
identity with the abnormal C1q of the proband, whereas the other showed
a reaction of identity with normal C1q.
Hannema et al. (1984) found deficiency of C1q in 2 sisters and a
brother. In these persons a dysfunctional C1q molecule was characterized
by low molecular weight and antigenic deficiency. In the 2 sisters a
systemic lupus erythematosus-like disease began at ages 20 and 23,
respectively, resulting in death of 1 of them. All 3 sibs suffered from
glomerulonephritis during childhood. The brother was apparently healthy
but showed membranous glomerulopathy, stage 1, on renal biopsy.
Topaloglu et al. (1996) described 2 sibs with C1q deficiency. Both
presented with a photosensitive rash and during follow-up 1 developed
SLE with proteinuria in the nephrotic range. The other sib had
microscopic hematuria with a history of macroscopic hematuria. Renal
biopsies revealed mesangioproliferative glomerulonephritis in 1 and IgA
nephropathy in the other. Antibody response to hepatitis B vaccine was
normal in affected and unaffected members of the family.
Topaloglu et al. (1996) stated that of the 34 reported patients with C1q
deficiency, all but one had SLE or an SLE-like illness.
MOLECULAR GENETICS
The first molecular lesion in C1q deficiency was reported by McAdam et
al. (1988). A homozygous G-to-A transition at nucleotide 150 in the C1QB
gene (120570.0001) resulted in a premature stop codon.
In 2 sibs with C1q deficiency, Topaloglu et al. (1996) identified
homozygosity for a C-T transition in codon 186 of the C1QA gene
(120550.0001) that resulted in a gln-to-stop (Q186X) substitution. The
mutation was present in heterozygous state in both parents and in 2
unaffected sibs. Topaloglu et al. (1996) stated that the same mutation
had been described in an affected member of a Slovakian family with C1q
deficiency by Petry et al. (1995).
Petry et al. (1997) identified homozygosity for the Q186X mutation in
affected members of 3 Turkish families. In 1 family, an asymptomatic
sister of the proband was also found to be homozygous for the mutation.
Petry et al. (1997) hypothesized that this defective allele is present
in the population of southeast Europe and Turkey.
In patients with C1q deficiency, Slingsby et al. (1996) identified
homozygous mutations in the C1QC gene (120575.0001-120575.0003).
- Reviews
Rother (1986) gave a summary of reported deficiencies of components of
complement. Many examples of deficiencies of C1q were listed, most of
them associated with systemic lupus erythematosus or glomerulonephritis.
ANIMAL MODEL
The complement system plays a paradoxical role in development and
expression of autoimmunity in humans. The activation of complement in
SLE contributes to tissue injury. In contrast, inherited deficiency of
classic pathway components, particularly C1q, is probably associated
with development of SLE. This leads to the hypothesis that a physiologic
action of the early part of the classic pathway protects against
development of SLE and implies that C1q may play a key role in this
respect. Botto et al. (1998) generated C1q-deficient (C1qa -/-) mice by
gene targeting and monitored them for 8 months. C1qa -/- mice had
increased mortality and higher titers of autoantibodies, compared with
strain-matched controls. Of the C1qa -/- mice, 25% had
glomerulonephritis with immune deposits and multiple apoptotic cell
bodies. Among mice without glomerulonephritis, there were significantly
greater numbers of glomerular apoptotic bodies in C1q-deficient mice
compared with controls. The phenotype associated with C1q deficiency was
modified by background genes. These findings are compatible with the
hypothesis that C1q deficiency causes autoimmunity by impairment of the
clearance of apoptotic cells.
Garlanda et al. (2002) found that C1q-deficient mice were highly
susceptible to invasive pulmonary aspergillus infection, which could be
reversed by administration of pentraxin-3 (PTX3; 602492).
*FIELD* RF
1. Botto, M.; Dell'Agnola, C.; Bygrave, A. E.; Thompson, E. M.; Cook,
H. T.; Petry, F.; Loos, M.; Pandolfi, P. P.; Walport, M. J.: Homozygous
C1q deficiency causes glomerulonephritis associated with multiple
apoptotic bodies. Nature Genet. 19: 56-59, 1998.
2. Garlanda, C.; Hirsch, E.; Bozza, S.; Salustri, A.; De Acetis, M.;
Nota, R.; Maccagno, A.; Riva, F.; Bottazzi, B.; Peri, G.; Doni, A.;
Vago, L.; Botto, M.; De Santis, R.; Carminati, P.; Siracusa, G.; Altruda,
F.; Vecchi, A.; Romani, L.; Mantovani, A.: Non-redundant role of
the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:
182-186, 2002.
3. Hannema, A. J.; Kluin-Nelemans, J. C.; Hack, C. E.; Eerenberg-Belmer,
A. J. M.; Mallee, C.; van Helden, H. P. T.: SLE like syndrome and
functional deficiency of C1q in members of a large family. Clin.
Exp. Immun. 55: 106-114, 1984.
4. McAdam, R. A.; Goundis, D.; Reid, K. B. M.: A homozygous point
mutation results in a stop codon in the C1q B-chain of a C1q-deficient
individual. Immunogenetics 27: 259-264, 1988.
5. Petry, F.; Berkel, A. I.; Loos, M.: Multiple identification of
a particular type of hereditary C1q deficiency in the Turkish population:
review of the cases and additional genetic and functional analysis. Hum.
Genet. 100: 51-56, 1997.
6. Petry, F.; Le, D. T.; Kirschfink, M.; Loos, M.: Non-sense and
missense mutations in the structural genes of complement component
C1qA and C chains are linked with two different types of complete
selective C1q deficiencies. J. Immun. 155: 4735-4738, 1995.
7. Rother, K.: Hereditary deficiencies in man: summary of reported
deficiencies. Prog. Allergy 39: 202-211, 1986.
8. Slingsby, J. H.; Norsworthy, P.; Pearce, G.; Vaishnaw, A. K.; Issler,
H.; Morley, B. J.; Walport, M. J.: Homozygous hereditary C1q deficiency
and systemic lupus erythematosus: a new family and the molecular basis
of C1q deficiency in three families. Arthritis Rheum. 39: 663-670,
1996.
9. Thompson, R. A.; Haeney, M.; Reid, K. B. M.; Davis, J. G.; White,
R. H.; Cameron, A. H.: A genetic defect of the C1q subcomponent of
complement associated with childhood (immune complex) nephritis. New
Eng. J. Med. 303: 22-24, 1980.
10. Topaloglu, R.; Bakkaloglu, A.; Slingsby, J. H.; Mihatsch, M. J.;
Pascual, M.; Norsworthy, P.; Morley, B. J.; Saatci, U.; Schifferli,
J. A.; Walport, M. J.: Molecular basis of hereditary C1q deficiency
associated with SLE and IgA nephropathy in a Turkish family. Kidney
Int. 50: 635-642, 1996.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Mesangial proliferative glomerulonephritis (in some patients)
IMMUNOLOGY:
Systemic lupus erythematosis (in some patients);
Autoimmune disease;
C1q deficiency;
C1q molecule present, but dysfunctional
MOLECULAR BASIS:
Caused by mutation in the complement component 1, q subcomponent,
A chain gene (C1QA, 120550.0001);
Caused by mutation in the complement component 1, q subcomponent,
B chain gene (C1QB, 120570.0001);
Caused by mutation in the complement component 1, q subcomponent,
C chain gene (C1QC, 120575.0001)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CD
Carol A. Bocchini: 11/19/2010
*FIELD* ED
carol: 04/27/2012
terry: 3/27/2012
carol: 4/22/2011
terry: 2/18/2011
carol: 2/17/2011
*RECORD*
*FIELD* NO
613652
*FIELD* TI
#613652 C1q DEFICIENCY; C1QD
*FIELD* TX
A number sign (#) is used with this entry because C1q deficiency can be
read morecaused by homozygous mutation in the C1QA (120550), C1QB (120570), or
C1QC (120575) gene, all of which are located on chromosome 1p36.
DESCRIPTION
C1q deficiency is a rare autosomal recessive disorder associated with
recurrent skin lesions, chronic infections, systemic lupus erythematosis
(SLE; see 152700) or SLE-like diseases. It has also been associated with
mesangial proliferative glomerulonephritis. C1q deficiency presents in 2
different forms, absent C1q protein or presence of a dysfunctional
molecule (summary by Topaloglu et al., 1996).
CLINICAL FEATURES
Thompson et al. (1980) reported C1q deficiency in a 4-year-old son of
first-cousin Pakistani parents, who presented with a lupus-like illness
and later developed glomerulonephritis. A younger sister, as yet
clinically unaffected, had the same complement profile and a younger
brother had half-normal functional C1 levels. The heterozygous status of
both parents, the younger brother, and an older sister was suggested by
the presence of double lines on immunochemical analysis of serum from
these persons using anti-C1q antiserum; one line showed a reaction of
identity with the abnormal C1q of the proband, whereas the other showed
a reaction of identity with normal C1q.
Hannema et al. (1984) found deficiency of C1q in 2 sisters and a
brother. In these persons a dysfunctional C1q molecule was characterized
by low molecular weight and antigenic deficiency. In the 2 sisters a
systemic lupus erythematosus-like disease began at ages 20 and 23,
respectively, resulting in death of 1 of them. All 3 sibs suffered from
glomerulonephritis during childhood. The brother was apparently healthy
but showed membranous glomerulopathy, stage 1, on renal biopsy.
Topaloglu et al. (1996) described 2 sibs with C1q deficiency. Both
presented with a photosensitive rash and during follow-up 1 developed
SLE with proteinuria in the nephrotic range. The other sib had
microscopic hematuria with a history of macroscopic hematuria. Renal
biopsies revealed mesangioproliferative glomerulonephritis in 1 and IgA
nephropathy in the other. Antibody response to hepatitis B vaccine was
normal in affected and unaffected members of the family.
Topaloglu et al. (1996) stated that of the 34 reported patients with C1q
deficiency, all but one had SLE or an SLE-like illness.
MOLECULAR GENETICS
The first molecular lesion in C1q deficiency was reported by McAdam et
al. (1988). A homozygous G-to-A transition at nucleotide 150 in the C1QB
gene (120570.0001) resulted in a premature stop codon.
In 2 sibs with C1q deficiency, Topaloglu et al. (1996) identified
homozygosity for a C-T transition in codon 186 of the C1QA gene
(120550.0001) that resulted in a gln-to-stop (Q186X) substitution. The
mutation was present in heterozygous state in both parents and in 2
unaffected sibs. Topaloglu et al. (1996) stated that the same mutation
had been described in an affected member of a Slovakian family with C1q
deficiency by Petry et al. (1995).
Petry et al. (1997) identified homozygosity for the Q186X mutation in
affected members of 3 Turkish families. In 1 family, an asymptomatic
sister of the proband was also found to be homozygous for the mutation.
Petry et al. (1997) hypothesized that this defective allele is present
in the population of southeast Europe and Turkey.
In patients with C1q deficiency, Slingsby et al. (1996) identified
homozygous mutations in the C1QC gene (120575.0001-120575.0003).
- Reviews
Rother (1986) gave a summary of reported deficiencies of components of
complement. Many examples of deficiencies of C1q were listed, most of
them associated with systemic lupus erythematosus or glomerulonephritis.
ANIMAL MODEL
The complement system plays a paradoxical role in development and
expression of autoimmunity in humans. The activation of complement in
SLE contributes to tissue injury. In contrast, inherited deficiency of
classic pathway components, particularly C1q, is probably associated
with development of SLE. This leads to the hypothesis that a physiologic
action of the early part of the classic pathway protects against
development of SLE and implies that C1q may play a key role in this
respect. Botto et al. (1998) generated C1q-deficient (C1qa -/-) mice by
gene targeting and monitored them for 8 months. C1qa -/- mice had
increased mortality and higher titers of autoantibodies, compared with
strain-matched controls. Of the C1qa -/- mice, 25% had
glomerulonephritis with immune deposits and multiple apoptotic cell
bodies. Among mice without glomerulonephritis, there were significantly
greater numbers of glomerular apoptotic bodies in C1q-deficient mice
compared with controls. The phenotype associated with C1q deficiency was
modified by background genes. These findings are compatible with the
hypothesis that C1q deficiency causes autoimmunity by impairment of the
clearance of apoptotic cells.
Garlanda et al. (2002) found that C1q-deficient mice were highly
susceptible to invasive pulmonary aspergillus infection, which could be
reversed by administration of pentraxin-3 (PTX3; 602492).
*FIELD* RF
1. Botto, M.; Dell'Agnola, C.; Bygrave, A. E.; Thompson, E. M.; Cook,
H. T.; Petry, F.; Loos, M.; Pandolfi, P. P.; Walport, M. J.: Homozygous
C1q deficiency causes glomerulonephritis associated with multiple
apoptotic bodies. Nature Genet. 19: 56-59, 1998.
2. Garlanda, C.; Hirsch, E.; Bozza, S.; Salustri, A.; De Acetis, M.;
Nota, R.; Maccagno, A.; Riva, F.; Bottazzi, B.; Peri, G.; Doni, A.;
Vago, L.; Botto, M.; De Santis, R.; Carminati, P.; Siracusa, G.; Altruda,
F.; Vecchi, A.; Romani, L.; Mantovani, A.: Non-redundant role of
the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:
182-186, 2002.
3. Hannema, A. J.; Kluin-Nelemans, J. C.; Hack, C. E.; Eerenberg-Belmer,
A. J. M.; Mallee, C.; van Helden, H. P. T.: SLE like syndrome and
functional deficiency of C1q in members of a large family. Clin.
Exp. Immun. 55: 106-114, 1984.
4. McAdam, R. A.; Goundis, D.; Reid, K. B. M.: A homozygous point
mutation results in a stop codon in the C1q B-chain of a C1q-deficient
individual. Immunogenetics 27: 259-264, 1988.
5. Petry, F.; Berkel, A. I.; Loos, M.: Multiple identification of
a particular type of hereditary C1q deficiency in the Turkish population:
review of the cases and additional genetic and functional analysis. Hum.
Genet. 100: 51-56, 1997.
6. Petry, F.; Le, D. T.; Kirschfink, M.; Loos, M.: Non-sense and
missense mutations in the structural genes of complement component
C1qA and C chains are linked with two different types of complete
selective C1q deficiencies. J. Immun. 155: 4735-4738, 1995.
7. Rother, K.: Hereditary deficiencies in man: summary of reported
deficiencies. Prog. Allergy 39: 202-211, 1986.
8. Slingsby, J. H.; Norsworthy, P.; Pearce, G.; Vaishnaw, A. K.; Issler,
H.; Morley, B. J.; Walport, M. J.: Homozygous hereditary C1q deficiency
and systemic lupus erythematosus: a new family and the molecular basis
of C1q deficiency in three families. Arthritis Rheum. 39: 663-670,
1996.
9. Thompson, R. A.; Haeney, M.; Reid, K. B. M.; Davis, J. G.; White,
R. H.; Cameron, A. H.: A genetic defect of the C1q subcomponent of
complement associated with childhood (immune complex) nephritis. New
Eng. J. Med. 303: 22-24, 1980.
10. Topaloglu, R.; Bakkaloglu, A.; Slingsby, J. H.; Mihatsch, M. J.;
Pascual, M.; Norsworthy, P.; Morley, B. J.; Saatci, U.; Schifferli,
J. A.; Walport, M. J.: Molecular basis of hereditary C1q deficiency
associated with SLE and IgA nephropathy in a Turkish family. Kidney
Int. 50: 635-642, 1996.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GENITOURINARY:
[Kidneys];
Mesangial proliferative glomerulonephritis (in some patients)
IMMUNOLOGY:
Systemic lupus erythematosis (in some patients);
Autoimmune disease;
C1q deficiency;
C1q molecule present, but dysfunctional
MOLECULAR BASIS:
Caused by mutation in the complement component 1, q subcomponent,
A chain gene (C1QA, 120550.0001);
Caused by mutation in the complement component 1, q subcomponent,
B chain gene (C1QB, 120570.0001);
Caused by mutation in the complement component 1, q subcomponent,
C chain gene (C1QC, 120575.0001)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CD
Carol A. Bocchini: 11/19/2010
*FIELD* ED
carol: 04/27/2012
terry: 3/27/2012
carol: 4/22/2011
terry: 2/18/2011
carol: 2/17/2011