C4BPB_HUMAN
ID C4BPB_HUMAN Reviewed; 252 AA.
AC P20851; A5JYP8; D3DT81; Q5VVR0; Q9BS25;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=C4b-binding protein beta chain;
DE Flags: Precursor;
GN Name=C4BPB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8325877; DOI=10.1016/s0021-9258(18)82432-2;
RA Hillarp A., Pardo-Manuel F., Ruiz R., de Cordoba S., Dahlback B.;
RT "The human C4b-binding protein beta-chain gene.";
RL J. Biol. Chem. 268:15017-15023(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2300577; DOI=10.1073/pnas.87.3.1183;
RA Hillarp A., Dahlback B.;
RT "Cloning of cDNA coding for the beta chain of human complement component
RT C4b-binding protein: sequence homology with the alpha chain.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:1183-1187(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-102.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
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., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skeletal muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-64; ASN-71 AND ASN-98.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-64 AND ASN-98.
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., Moore R.J.,
RA 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 [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98.
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 multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Controls the classical pathway of complement activation. It
CC binds as a cofactor to C3b/C4b inactivator (C3bINA), which then
CC hydrolyzes the complement fragment C4b. It also accelerates the
CC degradation of the C4bC2a complex (C3 convertase) by dissociating the
CC complement fragment C2a. It also interacts with anticoagulant protein S
CC and with serum amyloid P component. The beta chain binds protein S.
CC -!- SUBUNIT: Disulfide-linked complex of alpha and beta chains of 3
CC possible sorts: a 570 kDa complex of 7 alpha chains and 1 beta chain, a
CC 530 kDa homoheptamer of alpha chains or a 500 kDa complex of 6 alpha
CC chains and 1 beta chain. The central body of the alpha chain homomer
CC supports tentacles, each with the binding site for C4b at the end.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P20851-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P20851-2; Sequence=VSP_022594;
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/c4bpb/";
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; L11244; AAA35615.1; -; mRNA.
DR EMBL; L11245; AAA35616.1; -; mRNA.
DR EMBL; M29964; AAB59520.1; -; mRNA.
DR EMBL; EF613556; ABQ52216.1; -; Genomic_DNA.
DR EMBL; AL445493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93504.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93506.1; -; Genomic_DNA.
DR EMBL; BC005378; AAH05378.1; -; mRNA.
DR CCDS; CCDS1476.1; -. [P20851-1]
DR CCDS; CCDS31005.1; -. [P20851-2]
DR PIR; A47107; A34877.
DR RefSeq; NP_000707.1; NM_000716.3. [P20851-1]
DR RefSeq; NP_001017364.1; NM_001017364.1. [P20851-2]
DR RefSeq; NP_001017365.1; NM_001017365.2. [P20851-1]
DR RefSeq; NP_001017366.1; NM_001017366.2. [P20851-2]
DR RefSeq; NP_001017367.1; NM_001017367.1. [P20851-1]
DR RefSeq; XP_005273311.1; XM_005273254.4. [P20851-1]
DR AlphaFoldDB; P20851; -.
DR SMR; P20851; -.
DR BioGRID; 107186; 35.
DR IntAct; P20851; 13.
DR STRING; 9606.ENSP00000243611; -.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR GlyConnect; 1052; 8 N-Linked glycans (5 sites).
DR GlyGen; P20851; 7 sites, 13 N-linked glycans (5 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P20851; -.
DR PhosphoSitePlus; P20851; -.
DR BioMuta; C4BPB; -.
DR DMDM; 115213; -.
DR jPOST; P20851; -.
DR MassIVE; P20851; -.
DR MaxQB; P20851; -.
DR PaxDb; P20851; -.
DR PeptideAtlas; P20851; -.
DR PRIDE; P20851; -.
DR ProteomicsDB; 53819; -. [P20851-1]
DR ProteomicsDB; 53820; -. [P20851-2]
DR Antibodypedia; 20697; 294 antibodies from 27 providers.
DR DNASU; 725; -.
DR Ensembl; ENST00000243611.9; ENSP00000243611.5; ENSG00000123843.13. [P20851-1]
DR Ensembl; ENST00000367076.7; ENSP00000356043.3; ENSG00000123843.13. [P20851-2]
DR Ensembl; ENST00000367078.8; ENSP00000356045.3; ENSG00000123843.13. [P20851-1]
DR Ensembl; ENST00000391923.1; ENSP00000375790.1; ENSG00000123843.13. [P20851-1]
DR GeneID; 725; -.
DR KEGG; hsa:725; -.
DR MANE-Select; ENST00000367078.8; ENSP00000356045.3; NM_001017365.3; NP_001017365.1.
DR UCSC; uc001hfj.4; human. [P20851-1]
DR CTD; 725; -.
DR DisGeNET; 725; -.
DR GeneCards; C4BPB; -.
DR HGNC; HGNC:1328; C4BPB.
DR HPA; ENSG00000123843; Tissue enriched (liver).
DR MIM; 120831; gene.
DR neXtProt; NX_P20851; -.
DR OpenTargets; ENSG00000123843; -.
DR PharmGKB; PA25908; -.
DR VEuPathDB; HostDB:ENSG00000123843; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000163065; -.
DR HOGENOM; CLU_093877_0_0_1; -.
DR InParanoid; P20851; -.
DR OMA; FKCNDHY; -.
DR OrthoDB; 1110574at2759; -.
DR PhylomeDB; P20851; -.
DR TreeFam; TF342864; -.
DR PathwayCommons; P20851; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P20851; -.
DR BioGRID-ORCS; 725; 9 hits in 1058 CRISPR screens.
DR GenomeRNAi; 725; -.
DR Pharos; P20851; Tbio.
DR PRO; PR:P20851; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P20851; protein.
DR Bgee; ENSG00000123843; Expressed in right lobe of liver and 114 other tissues.
DR ExpressionAtlas; P20851; baseline and differential.
DR Genevisible; P20851; HS.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045959; P:negative regulation of complement activation, classical pathway; IDA:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:BHF-UCL.
DR GO; GO:1903027; P:regulation of opsonization; IDA:BHF-UCL.
DR GO; GO:0009609; P:response to symbiotic bacterium; IDA:BHF-UCL.
DR CDD; cd00033; CCP; 3.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00084; Sushi; 3.
DR SMART; SM00032; CCP; 3.
DR SUPFAM; SSF57535; SSF57535; 3.
DR PROSITE; PS50923; SUSHI; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Complement pathway; Disulfide bond; Glycoprotein;
KW Immunity; Innate immunity; Reference proteome; Repeat; Secreted; Signal;
KW Sushi.
FT SIGNAL 1..17
FT CHAIN 18..252
FT /note="C4b-binding protein beta chain"
FT /id="PRO_0000005892"
FT DOMAIN 21..78
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 79..136
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 137..193
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 49..76
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 81..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 107..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 139..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 165..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 202
FT /note="Interchain (with alpha chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 216
FT /note="Interchain (with alpha chain)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT VAR_SEQ 20
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022594"
FT VARIANT 102
FT /note="K -> Q (in dbSNP:rs56258224)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_038734"
FT VARIANT 198
FT /note="P -> S (in dbSNP:rs1803226)"
FT /id="VAR_012039"
SQ SEQUENCE 252 AA; 28357 MW; 0F6CC64067C5E2E7 CRC64;
MFFWCACCLM VAWRVSASDA EHCPELPPVD NSIFVAKEVE GQILGTYVCI KGYHLVGKKT
LFCNASKEWD NTTTECRLGH CPDPVLVNGE FSSSGPVNVS DKITFMCNDH YILKGSNRSQ
CLEDHTWAPP FPICKSRDCD PPGNPVHGYF EGNNFTLGST ISYYCEDRYY LVGVQEQQCV
DGEWSSALPV CKLIQEAPKP ECEKALLAFQ ESKNLCEAME NFMQQLKESG MTMEELKYSL
ELKKAELKAK LL
