ID C1QB_HUMAN Reviewed; 253 AA. AC P02746; Q5T959; Q96H17; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 15-JUN-2010, sequence version 3. DT 27-MAR-2024, entry version 228. DE RecName: Full=Complement C1q subcomponent subunit B; DE Flags: Precursor; GN Name=C1QB; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [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., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., 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., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., 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., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., 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 [2] 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-253. RX PubMed=3000358; DOI=10.1042/bj2310729; RA Reid K.B.M.; RT "Molecular cloning and characterization of the complementary DNA and gene RT coding for the B-chain of subcomponent C1q of the human complement RT system."; RL Biochem. J. 231:729-735(1985). RN [4] RP PROTEIN SEQUENCE OF 28-195, GLYCOSYLATION, PYROGLUTAMATE FORMATION AT RP GLN-28, DISULFIDE BOND, AND HYDROXYLATION. RX PubMed=708376; DOI=10.1042/bj1730863; RA Reid K.B.M., Thompson E.O.P.; RT "Amino acid sequence of the N-terminal 108 amino acid residues of the B RT chain of subcomponent C1q of the first component of human complement."; RL Biochem. J. 173:863-868(1978). RN [5] RP PROTEIN SEQUENCE OF 28-135, AND HYDROXYLATION AT PRO-35; PRO-38; PRO-41; RP PRO-53; PRO-56; LYS-59; LYS-62; PRO-65; LYS-77; PRO-83; PRO-86; LYS-92; RP LYS-98; PRO-101; PRO-104; PRO-107 AND LYS-110. RX PubMed=486087; DOI=10.1042/bj1790367; RA Reid K.B.M.; RT "Complete amino acid sequences of the three collagen-like regions present RT in subcomponent C1q of the first component of human complement."; RL Biochem. J. 179:367-371(1979). RN [6] RP PROTEIN SEQUENCE OF 136-253. RX PubMed=6981411; DOI=10.1042/bj2030559; RA Reid K.B.M., Gagnon J., Frampton J.; RT "Completion of the amino acid sequences of the A and B chains of RT subcomponent C1q of the first component of human complement."; RL Biochem. J. 203:559-569(1982). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-253. RC TISSUE=Liver; RX PubMed=6208566; DOI=10.1098/rstb.1984.0095; RA Reid K.B.M., Bentley D.R., Wood K.J.; RT "Cloning and characterization of the complementary DNA for the B chain of RT normal human serum C1q."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 306:345-354(1984). RN [8] RP INTERACTION WITH IMMUNOGLOBULIN MU. RX PubMed=12847249; DOI=10.4049/jimmunol.171.2.812; RA Kishore U., Gupta S.K., Perdikoulis M.V., Kojouharova M.S., Urban B.C., RA Reid K.B.; RT "Modular organization of the carboxyl-terminal, globular head region of RT human C1q A, B, and C chains."; RL J. Immunol. 171:812-820(2003). RN [9] RP INTERACTION WITH IMMUNOGLOBULINS. RX PubMed=19006321; DOI=10.1021/bi801131h; RA Gadjeva M.G., Rouseva M.M., Zlatarova A.S., Reid K.B., Kishore U., RA Kojouharova M.S.; RT "Interaction of human C1q with IgG and IgM: revisited."; RL Biochemistry 47:13093-13102(2008). RN [10] RP GLYCOSYLATION ON HYDROXYLYSINES. RX PubMed=6286235; DOI=10.1016/s0174-173x(81)80015-5; RA Yonemasu K., Shinkai H., Sasaki T.; RT "Comparable content of hydroxylysine-linked glycosides in subcomponents C1q RT of the first component of human, bovine and mouse complement."; RL Coll. Relat. Res. 1:385-390(1981). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 119-250. RX PubMed=12960167; DOI=10.1074/jbc.m307764200; RA Gaboriaud C., Juanhuix J., Gruez A., Lacroix M., Darnault C., Pignol D., RA 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 [12] RP REVIEW ON C1Q DEFICIENCY. RX PubMed=9777412; DOI=10.1016/s0171-2985(98)80033-8; RA Petry F.; RT "Molecular basis of hereditary C1q deficiency."; RL Immunobiology 199:286-294(1998). RN [13] RP VARIANT C1QD2 ASP-42. RX PubMed=9476130; DOI=10.1016/s0162-3109(97)00065-9; RA Petry F., Hauptmann G., Goetz J., Grosshans E., Loos M.; RT "Molecular basis of a new type of C1q-deficiency associated with a non- RT functional low molecular weight (LMW) C1q: parallels and differences to RT other known genetic C1q-defects."; RL Immunopharmacology 38:189-201(1997). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] THR-123. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: C1q associates with the proenzymes C1r and C1s to yield C1, CC the first component of the serum complement system. The collagen-like CC regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) CC proenzyme complex, and efficient activation of C1 takes place on CC interaction of the globular heads of C1q with the Fc regions of IgG or CC IgM antibody present in immune complexes. CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, c1r and CC C1s in the molar ration of 1:2:2. C1q subcomponent is composed of nine CC subunits, six of which are disulfide-linked dimers of the A and B CC chains, and three of which are disulfide-linked dimers of the C chain. CC Antigen-bound IgM (via the Fc region) interacts with the globular CC domains of C1q component of the complement system, all three modules CC C1QA, C1QB and C1QC being involved in IgM binding; this interaction is CC multivalent. It initiates the classical complement pathway CC (PubMed:12847249, PubMed:19006321). {ECO:0000269|PubMed:12847249, CC ECO:0000269|PubMed:19006321, ECO:0000269|PubMed:708376}. CC -!- INTERACTION: CC P02746; P02745: C1QA; NbExp=5; IntAct=EBI-2813376, EBI-1220209; CC P02746; PRO_0000018590 [Q07021]: C1QBP; NbExp=4; IntAct=EBI-2813376, EBI-14032968; CC P02746; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-2813376, EBI-947187; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- PTM: Hydroxylated on lysine and proline residues. Hydroxylated lysine CC residues can be glycosylated. Human C1Q contains up to 68.3 CC hydroxylysine-galactosylglucose residues and up to 2.5 hydroxylysine- CC galactose per molecule. Total percentage hydroxylysine residues CC glycosylated is 86.4%. {ECO:0000269|PubMed:486087, CC ECO:0000269|PubMed:6286235, ECO:0000269|PubMed:708376}. CC -!- DISEASE: C1q deficiency 2 (C1QD2) [MIM:620321]: An autosomal recessive CC disorder caused by impaired activation of the complement classical CC pathway. It generally leads to severe immune complex disease CC characterized by recurrent skin lesions, chronic infections, an CC increased risk of systemic lupus erythematosus, and glomerulonephritis. CC {ECO:0000269|PubMed:9476130}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=C1QBbase; Note=C1QB mutation db; CC URL="http://structure.bmc.lu.se/idbase/C1QBbase/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL158086; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008983; AAH08983.1; -; mRNA. DR EMBL; X03084; CAA26880.1; -; mRNA. DR EMBL; M36278; AAC41692.1; -; mRNA. DR PIR; B23422; C1HUQB. DR RefSeq; NP_000482.3; NM_000491.4. DR RefSeq; XP_011540361.1; XM_011542059.2. DR PDB; 1PK6; X-ray; 1.85 A; B=119-250. DR PDB; 2JG8; X-ray; 2.05 A; B/E=118-253. DR PDB; 2JG9; X-ray; 1.90 A; B/E=118-253. DR PDB; 2WNU; X-ray; 2.30 A; B/E=118-253. DR PDB; 2WNV; X-ray; 1.25 A; B/E=118-253. DR PDB; 5HKJ; X-ray; 1.35 A; A=117-253. DR PDB; 5HZF; X-ray; 1.55 A; A=117-253. DR PDB; 6FCZ; EM; 10.00 A; B=119-250. DR PDB; 6Z6V; X-ray; 2.19 A; B/E=119-253. DR PDBsum; 1PK6; -. DR PDBsum; 2JG8; -. DR PDBsum; 2JG9; -. DR PDBsum; 2WNU; -. DR PDBsum; 2WNV; -. DR PDBsum; 5HKJ; -. DR PDBsum; 5HZF; -. DR PDBsum; 6FCZ; -. DR PDBsum; 6Z6V; -. DR AlphaFoldDB; P02746; -. DR EMDB; EMD-4232; -. DR SASBDB; P02746; -. DR SMR; P02746; -. DR BioGRID; 107174; 98. DR ComplexPortal; CPX-1919; Complement component C1q complex. DR CORUM; P02746; -. DR IntAct; P02746; 20. DR MINT; P02746; -. DR STRING; 9606.ENSP00000313967; -. DR DrugBank; DB00112; Bevacizumab. DR DrugBank; DB00002; Cetuximab. DR DrugBank; DB00111; Daclizumab. DR DrugBank; DB00005; Etanercept. DR DrugBank; DB00110; Palivizumab. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR iPTMnet; P02746; -. DR PhosphoSitePlus; P02746; -. DR BioMuta; C1QB; -. DR DMDM; 298286922; -. DR CPTAC; non-CPTAC-1101; -. DR jPOST; P02746; -. DR MassIVE; P02746; -. DR PaxDb; 9606-ENSP00000313967; -. DR PeptideAtlas; P02746; -. DR ProteomicsDB; 51562; -. DR DNASU; 713; -. DR GeneID; 713; -. DR KEGG; hsa:713; -. DR UCSC; uc001bgd.3; human. DR AGR; HGNC:1242; -. DR CTD; 713; -. DR DisGeNET; 713; -. DR GeneCards; C1QB; -. DR HGNC; HGNC:1242; C1QB. DR MalaCards; C1QB; -. DR MIM; 120570; gene. DR MIM; 620321; phenotype. DR neXtProt; NX_P02746; -. DR Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency. DR PharmGKB; PA25623; -. DR eggNOG; ENOG502RYR2; Eukaryota. DR InParanoid; P02746; -. DR OrthoDB; 3683851at2759; -. DR PhylomeDB; P02746; -. DR TreeFam; TF329591; -. DR PathwayCommons; P02746; -. DR Reactome; R-HSA-166663; Initial triggering of complement. DR Reactome; R-HSA-173623; Classical antibody-mediated complement activation. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P02746; -. DR SIGNOR; P02746; -. DR BioGRID-ORCS; 713; 11 hits in 1154 CRISPR screens. DR ChiTaRS; C1QB; human. DR EvolutionaryTrace; P02746; -. DR GenomeRNAi; 713; -. DR Pharos; P02746; Tbio. DR PRO; PR:P02746; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P02746; Protein. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005602; C:complement component C1 complex; TAS:ProtInc. DR GO; GO:0062167; C:complement component C1q complex; IPI:ComplexPortal. DR GO; GO:0005576; C:extracellular region; IDA:ComplexPortal. DR GO; GO:0098794; C:postsynapse; ISS:ARUK-UCL. DR GO; GO:0045202; C:synapse; ISS:ARUK-UCL. DR GO; GO:0006956; P:complement activation; TAS:ProtInc. DR GO; GO:0006958; P:complement activation, classical pathway; IDA:ComplexPortal. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0098883; P:synapse pruning; ISS:ARUK-UCL. DR Gene3D; 2.60.120.40; -; 1. DR InterPro; IPR001073; C1q_dom. DR InterPro; IPR008160; Collagen. DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom. DR PANTHER; PTHR15427:SF18; COMPLEMENT C1Q SUBCOMPONENT SUBUNIT B; 1. DR PANTHER; PTHR15427; EMILIN ELASTIN MICROFIBRIL INTERFACE-LOCATED PROTEIN ELASTIN MICROFIBRIL INTERFACER; 1. DR Pfam; PF00386; C1q; 1. DR Pfam; PF01391; Collagen; 2. DR PRINTS; PR00007; COMPLEMNTC1Q. DR SMART; SM00110; C1Q; 1. DR SUPFAM; SSF49842; TNF-like; 1. DR PROSITE; PS50871; C1Q; 1. DR Genevisible; P02746; HS. PE 1: Evidence at protein level; KW 3D-structure; Collagen; Complement pathway; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Hydroxylation; Immunity; KW Innate immunity; Pyrrolidone carboxylic acid; Reference proteome; Repeat; KW Secreted; Signal. FT SIGNAL 1..27 FT /evidence="ECO:0000269|PubMed:486087, FT ECO:0000269|PubMed:708376" FT CHAIN 28..253 FT /note="Complement C1q subcomponent subunit B" FT /id="PRO_0000003521" FT DOMAIN 37..86 FT /note="Collagen-like 1" FT DOMAIN 60..114 FT /note="Collagen-like 2" FT DOMAIN 117..253 FT /note="C1q" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368" FT REGION 38..115 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 28 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|PubMed:708376" FT MOD_RES 35 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 38 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 41 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 53 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 56 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 59 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 62 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 65 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 77 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 83 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 86 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 92 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 98 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 101 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 104 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 107 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:486087" FT MOD_RES 110 FT /note="5-hydroxylysine" FT /evidence="ECO:0000269|PubMed:486087" FT DISULFID 31 FT /note="Interchain (with C-26 in chain A)" FT /evidence="ECO:0000269|PubMed:708376" FT VARIANT 42 FT /note="G -> D (in C1QD2)" FT /evidence="ECO:0000269|PubMed:9476130" FT /id="VAR_008541" FT VARIANT 123 FT /note="A -> T (in a breast cancer sample; somatic mutation; FT dbSNP:rs776292843)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035551" FT CONFLICT 28 FT /note="Q -> E (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 85 FT /note="N -> D (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 100 FT /note="G -> P (in Ref. 4; AA sequence and 5; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:5HKJ" FT STRAND 123..127 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 144..149 FT /evidence="ECO:0007829|PDB:2WNV" FT TURN 155..157 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:1PK6" FT STRAND 166..178 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 180..190 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 192..199 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 206..216 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 221..230 FT /evidence="ECO:0007829|PDB:2WNV" FT STRAND 241..249 FT /evidence="ECO:0007829|PDB:2WNV" SQ SEQUENCE 253 AA; 26722 MW; D80C753C0D430EDC CRC64; MMMKIPWGSI PVLMLLLLLG LIDISQAQLS CTGPPAIPGI PGIPGTPGPD GQPGTPGIKG EKGLPGLAGD HGEFGEKGDP GIPGNPGKVG PKGPMGPKGG PGAPGAPGPK GESGDYKATQ KIAFSATRTI NVPLRRDQTI RFDHVITNMN NNYEPRSGKF TCKVPGLYYF TYHASSRGNL CVNLMRGRER AQKVVTFCDY AYNTFQVTTG GMVLKLEQGE NVFLQATDKN SLLGMEGANS IFSGFLLFPD MEA //