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   27-MAR-2024, entry version 191.
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; 36.
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   GlyCosmos; P20851; 7 sites, 11 glycans.
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; 9606-ENSP00000243611; -.
DR   PeptideAtlas; P20851; -.
DR   ProteomicsDB; 53819; -. [P20851-1]
DR   ProteomicsDB; 53820; -. [P20851-2]
DR   Antibodypedia; 20697; 317 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   AGR; HGNC:1328; -.
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; ICIKGYH; -.
DR   OrthoDB; 4519459at2759; -.
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; 10 hits in 1147 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 115 other cell types or tissues.
DR   ExpressionAtlas; P20851; baseline and differential.
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   Gene3D; 2.10.70.10; Complement Module, domain 1; 3.
DR   InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR   InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR   PANTHER; PTHR45656:SF4; PROTEIN BETA CHAIN, PUTATIVE-RELATED; 1.
DR   PANTHER; PTHR45656; PROTEIN CBR-CLEC-78; 1.
DR   Pfam; PF00084; Sushi; 3.
DR   SMART; SM00032; CCP; 3.
DR   SUPFAM; SSF57535; Complement control module/SCR domain; 3.
DR   PROSITE; PS50923; SUSHI; 3.
DR   Genevisible; P20851; HS.
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
//