Full text data of IFNB1
IFNB1
(IFB, IFNB)
[Confidence: low (only semi-automatic identification from reviews)]
Interferon beta; IFN-beta (Fibroblast interferon; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Interferon beta; IFN-beta (Fibroblast interferon; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P01574
ID IFNB_HUMAN Reviewed; 187 AA.
AC P01574;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Interferon beta;
DE Short=IFN-beta;
DE AltName: Full=Fibroblast interferon;
DE Flags: Precursor;
GN Name=IFNB1; Synonyms=IFB, IFNB;
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].
RX PubMed=6164984; DOI=10.1093/nar/9.5.1045;
RA Lawn R.M., Adelman J., Franke A.E., Houck C.M., Gross M., Najarian R.,
RA Goeddel D.V.;
RT "Human fibroblast interferon gene lacks introns.";
RL Nucleic Acids Res. 9:1045-1052(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16593086; DOI=10.1073/pnas.78.9.5305;
RA Ohno S., Taniguchi T.;
RT "Structure of a chromosomal gene for human interferon beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:5305-5309(1981).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6157601; DOI=10.1016/0378-1119(80)90138-9;
RA Taniguchi T., Ohno S., Fujii-Kuriyama Y., Muramatsu M.;
RT "The nucleotide sequence of human fibroblast interferon cDNA.";
RL Gene 10:11-15(1980).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6157094; DOI=10.1038/285542a0;
RA Derynck R., Content J., Declercq E., Volckaert G., Tavernier J.,
RA Devos R., Fiers W.;
RT "Isolation and structure of a human fibroblast interferon gene.";
RL Nature 285:542-547(1980).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6159580; DOI=10.1093/nar/8.13.2885;
RA Houghton M., Eaton M.A.W., Stewart A.G., Smith J.C., Doel S.M.,
RA Cartlin G.H., Lewis H.M., Patel T.P., Emtage J.S., Carey N.H.,
RA Porter A.G.;
RT "The complete amino acid sequence of human fibroblast interferon as
RT deduced using synthetic oligodeoxyribonucleotide primers of reverse
RT transcriptase.";
RL Nucleic Acids Res. 8:2885-2894(1980).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6159584; DOI=10.1093/nar/8.18.4057;
RA Goeddel D.V., Shepard H.M., Yelverton E., Leung D., Crea R., Sloma A.,
RA Pestka S.;
RT "Synthesis of human fibroblast interferon by E. coli.";
RL Nucleic Acids Res. 8:4057-4074(1980).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2414376;
RA May L.T., Sehgal P.B.;
RT "On the relationship between human interferon alpha 1 and beta 1
RT genes.";
RL J. Interferon Res. 5:521-526(1985).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-68.
RX PubMed=6159597; DOI=10.1093/nar/8.9.1913;
RA Houghton M., Stewart A.G., Doel S.M., Emtage J.S., Eaton M.A.W.,
RA Smith J.C., Patel T.P., Lewis H.M., Porter A.G., Birch J.R.,
RA Cartwright T., Carey N.H.;
RT "The amino-terminal sequence of human fibroblast interferon as deduced
RT from reverse transcripts obtained using synthetic oligonucleotide
RT primers.";
RL Nucleic Acids Res. 8:1913-1931(1980).
RN [10]
RP DISULFIDE BOND.
RX PubMed=6162107; DOI=10.1038/289606a0;
RA Wetzel R.;
RT "Assignment of the disulphide bonds of leukocyte interferon.";
RL Nature 289:606-607(1981).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 71-187 (VARIANT CLONE PF526).
RX PubMed=6171735; DOI=10.1038/294563a0;
RA Shepard H.M., Leung D., Stebbing N., Goeddel D.V.;
RT "A single amino acid change in IFN-beta1 abolishes its antiviral
RT activity.";
RL Nature 294:563-565(1981).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=9342320; DOI=10.1073/pnas.94.22.11813;
RA Karpusas M., Nolte M., Benton C.B., Meier W., Lipscomb W.N., Goelz S.;
RT "The crystal structure of human interferon beta at 2.2-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11813-11818(1997).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-164.
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Has antiviral, antibacterial and anticancer activities.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PHARMACEUTICAL: Available under the names Avonex (Biogen),
CC Betaseron (Berlex) and Rebif (Serono). Used in the treatment of
CC multiple sclerosis (MS). Betaseron is a slightly modified form of
CC IFNB1 with two residue substitutions.
CC -!- SIMILARITY: Belongs to the alpha/beta interferon family.
CC -!- WEB RESOURCE: Name=Avonex; Note=Clinical information on Avonex;
CC URL="http://www.avonex.com/index.xml";
CC -!- WEB RESOURCE: Name=Betaseron; Note=Clinical information on
CC Betaseron;
CC URL="http://www.betaseron.com/home";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; V00534; CAA23795.1; -; Genomic_DNA.
DR EMBL; V00535; CAA23796.1; -; Genomic_DNA.
DR EMBL; V00546; CAA23807.1; -; mRNA.
DR EMBL; V00547; CAA23808.1; -; mRNA.
DR EMBL; M28622; AAA36040.1; -; mRNA.
DR EMBL; BC069314; AAH69314.1; -; mRNA.
DR PIR; A93721; IVHUB1.
DR RefSeq; NP_002167.1; NM_002176.2.
DR UniGene; Hs.93177; -.
DR PDB; 1AU1; X-ray; 2.20 A; A/B=22-187.
DR PDBsum; 1AU1; -.
DR ProteinModelPortal; P01574; -.
DR SMR; P01574; 22-187.
DR DIP; DIP-6018N; -.
DR STRING; 9606.ENSP00000369581; -.
DR DrugBank; DB00060; Interferon beta-1a.
DR DrugBank; DB00068; Interferon beta-1b.
DR Allergome; 9875; Hom s IFN beta.
DR PhosphoSite; P01574; -.
DR DMDM; 124469; -.
DR PaxDb; P01574; -.
DR PRIDE; P01574; -.
DR Ensembl; ENST00000380232; ENSP00000369581; ENSG00000171855.
DR GeneID; 3456; -.
DR KEGG; hsa:3456; -.
DR UCSC; uc003zok.3; human.
DR CTD; 3456; -.
DR GeneCards; GC09M021077; -.
DR HGNC; HGNC:5434; IFNB1.
DR HPA; CAB009386; -.
DR MIM; 147640; gene.
DR neXtProt; NX_P01574; -.
DR PharmGKB; PA29672; -.
DR eggNOG; NOG43895; -.
DR HOGENOM; HOG000230501; -.
DR HOVERGEN; HBG052086; -.
DR InParanoid; P01574; -.
DR KO; K05415; -.
DR OMA; NGRLEYC; -.
DR OrthoDB; EOG7J9VRD; -.
DR PhylomeDB; P01574; -.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P01574; -.
DR EvolutionaryTrace; P01574; -.
DR GeneWiki; IFNB1; -.
DR GenomeRNAi; 3456; -.
DR NextBio; 13618; -.
DR PMAP-CutDB; P01574; -.
DR PRO; PR:P01574; -.
DR ArrayExpress; P01574; -.
DR CleanEx; HS_IFNB1; -.
DR Genevestigator; P01574; -.
DR GO; GO:0005576; C:extracellular region; IC:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005132; F:interferon-alpha/beta receptor binding; NAS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; NAS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:BHF-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
DR GO; GO:0030101; P:natural killer cell activation; NAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; NAS:UniProtKB.
DR GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:UniProtKB.
DR GO; GO:2000552; P:negative regulation of T-helper 2 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; NAS:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL.
DR GO; GO:0032897; P:negative regulation of viral transcription; IDA:BHF-UCL.
DR GO; GO:0045089; P:positive regulation of innate immune response; NAS:UniProtKB.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0045343; P:regulation of MHC class I biosynthetic process; NAS:UniProtKB.
DR GO; GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR012351; 4_helix_cytokine_core.
DR InterPro; IPR000471; Interferon_alpha/beta/delta.
DR InterPro; IPR015588; Interferon_beta.
DR PANTHER; PTHR11691; PTHR11691; 1.
DR PANTHER; PTHR11691:SF7; PTHR11691:SF7; 1.
DR Pfam; PF00143; Interferon; 1.
DR PRINTS; PR00266; INTERFERONAB.
DR SMART; SM00076; IFabd; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00252; INTERFERON_A_B_D; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Complete proteome; Cytokine;
KW Disulfide bond; Glycoprotein; Pharmaceutical; Phosphoprotein;
KW Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 21
FT CHAIN 22 187 Interferon beta.
FT /FTId=PRO_0000016400.
FT MOD_RES 24 24 Phosphotyrosine (By similarity).
FT CARBOHYD 101 101 N-linked (GlcNAc...).
FT DISULFID 52 162
FT VARIANT 162 162 C -> Y (in clone PF526, loss of ability
FT to form the essential disulfide bond,
FT loss of antiviral activity).
FT /FTId=VAR_004016.
FT VARIANT 164 164 W -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036330.
FT HELIX 24 42
FT HELIX 51 55
FT HELIX 63 67
FT HELIX 73 91
FT HELIX 96 98
FT HELIX 102 127
FT TURN 137 139
FT HELIX 140 156
FT TURN 157 159
FT HELIX 161 182
SQ SEQUENCE 187 AA; 22294 MW; 0B013D4087723CEC CRC64;
MTNKCLLQIA LLLCFSTTAL SMSYNLLGFL QRSSNFQCQK LLWQLNGRLE YCLKDRMNFD
IPEEIKQLQQ FQKEDAALTI YEMLQNIFAI FRQDSSSTGW NETIVENLLA NVYHQINHLK
TVLEEKLEKE DFTRGKLMSS LHLKRYYGRI LHYLKAKEYS HCAWTIVRVE ILRNFYFINR
LTGYLRN
//
ID IFNB_HUMAN Reviewed; 187 AA.
AC P01574;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Interferon beta;
DE Short=IFN-beta;
DE AltName: Full=Fibroblast interferon;
DE Flags: Precursor;
GN Name=IFNB1; Synonyms=IFB, IFNB;
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].
RX PubMed=6164984; DOI=10.1093/nar/9.5.1045;
RA Lawn R.M., Adelman J., Franke A.E., Houck C.M., Gross M., Najarian R.,
RA Goeddel D.V.;
RT "Human fibroblast interferon gene lacks introns.";
RL Nucleic Acids Res. 9:1045-1052(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16593086; DOI=10.1073/pnas.78.9.5305;
RA Ohno S., Taniguchi T.;
RT "Structure of a chromosomal gene for human interferon beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:5305-5309(1981).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6157601; DOI=10.1016/0378-1119(80)90138-9;
RA Taniguchi T., Ohno S., Fujii-Kuriyama Y., Muramatsu M.;
RT "The nucleotide sequence of human fibroblast interferon cDNA.";
RL Gene 10:11-15(1980).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6157094; DOI=10.1038/285542a0;
RA Derynck R., Content J., Declercq E., Volckaert G., Tavernier J.,
RA Devos R., Fiers W.;
RT "Isolation and structure of a human fibroblast interferon gene.";
RL Nature 285:542-547(1980).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6159580; DOI=10.1093/nar/8.13.2885;
RA Houghton M., Eaton M.A.W., Stewart A.G., Smith J.C., Doel S.M.,
RA Cartlin G.H., Lewis H.M., Patel T.P., Emtage J.S., Carey N.H.,
RA Porter A.G.;
RT "The complete amino acid sequence of human fibroblast interferon as
RT deduced using synthetic oligodeoxyribonucleotide primers of reverse
RT transcriptase.";
RL Nucleic Acids Res. 8:2885-2894(1980).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6159584; DOI=10.1093/nar/8.18.4057;
RA Goeddel D.V., Shepard H.M., Yelverton E., Leung D., Crea R., Sloma A.,
RA Pestka S.;
RT "Synthesis of human fibroblast interferon by E. coli.";
RL Nucleic Acids Res. 8:4057-4074(1980).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2414376;
RA May L.T., Sehgal P.B.;
RT "On the relationship between human interferon alpha 1 and beta 1
RT genes.";
RL J. Interferon Res. 5:521-526(1985).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-68.
RX PubMed=6159597; DOI=10.1093/nar/8.9.1913;
RA Houghton M., Stewart A.G., Doel S.M., Emtage J.S., Eaton M.A.W.,
RA Smith J.C., Patel T.P., Lewis H.M., Porter A.G., Birch J.R.,
RA Cartwright T., Carey N.H.;
RT "The amino-terminal sequence of human fibroblast interferon as deduced
RT from reverse transcripts obtained using synthetic oligonucleotide
RT primers.";
RL Nucleic Acids Res. 8:1913-1931(1980).
RN [10]
RP DISULFIDE BOND.
RX PubMed=6162107; DOI=10.1038/289606a0;
RA Wetzel R.;
RT "Assignment of the disulphide bonds of leukocyte interferon.";
RL Nature 289:606-607(1981).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 71-187 (VARIANT CLONE PF526).
RX PubMed=6171735; DOI=10.1038/294563a0;
RA Shepard H.M., Leung D., Stebbing N., Goeddel D.V.;
RT "A single amino acid change in IFN-beta1 abolishes its antiviral
RT activity.";
RL Nature 294:563-565(1981).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=9342320; DOI=10.1073/pnas.94.22.11813;
RA Karpusas M., Nolte M., Benton C.B., Meier W., Lipscomb W.N., Goelz S.;
RT "The crystal structure of human interferon beta at 2.2-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11813-11818(1997).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-164.
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Has antiviral, antibacterial and anticancer activities.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PHARMACEUTICAL: Available under the names Avonex (Biogen),
CC Betaseron (Berlex) and Rebif (Serono). Used in the treatment of
CC multiple sclerosis (MS). Betaseron is a slightly modified form of
CC IFNB1 with two residue substitutions.
CC -!- SIMILARITY: Belongs to the alpha/beta interferon family.
CC -!- WEB RESOURCE: Name=Avonex; Note=Clinical information on Avonex;
CC URL="http://www.avonex.com/index.xml";
CC -!- WEB RESOURCE: Name=Betaseron; Note=Clinical information on
CC Betaseron;
CC URL="http://www.betaseron.com/home";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; V00534; CAA23795.1; -; Genomic_DNA.
DR EMBL; V00535; CAA23796.1; -; Genomic_DNA.
DR EMBL; V00546; CAA23807.1; -; mRNA.
DR EMBL; V00547; CAA23808.1; -; mRNA.
DR EMBL; M28622; AAA36040.1; -; mRNA.
DR EMBL; BC069314; AAH69314.1; -; mRNA.
DR PIR; A93721; IVHUB1.
DR RefSeq; NP_002167.1; NM_002176.2.
DR UniGene; Hs.93177; -.
DR PDB; 1AU1; X-ray; 2.20 A; A/B=22-187.
DR PDBsum; 1AU1; -.
DR ProteinModelPortal; P01574; -.
DR SMR; P01574; 22-187.
DR DIP; DIP-6018N; -.
DR STRING; 9606.ENSP00000369581; -.
DR DrugBank; DB00060; Interferon beta-1a.
DR DrugBank; DB00068; Interferon beta-1b.
DR Allergome; 9875; Hom s IFN beta.
DR PhosphoSite; P01574; -.
DR DMDM; 124469; -.
DR PaxDb; P01574; -.
DR PRIDE; P01574; -.
DR Ensembl; ENST00000380232; ENSP00000369581; ENSG00000171855.
DR GeneID; 3456; -.
DR KEGG; hsa:3456; -.
DR UCSC; uc003zok.3; human.
DR CTD; 3456; -.
DR GeneCards; GC09M021077; -.
DR HGNC; HGNC:5434; IFNB1.
DR HPA; CAB009386; -.
DR MIM; 147640; gene.
DR neXtProt; NX_P01574; -.
DR PharmGKB; PA29672; -.
DR eggNOG; NOG43895; -.
DR HOGENOM; HOG000230501; -.
DR HOVERGEN; HBG052086; -.
DR InParanoid; P01574; -.
DR KO; K05415; -.
DR OMA; NGRLEYC; -.
DR OrthoDB; EOG7J9VRD; -.
DR PhylomeDB; P01574; -.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P01574; -.
DR EvolutionaryTrace; P01574; -.
DR GeneWiki; IFNB1; -.
DR GenomeRNAi; 3456; -.
DR NextBio; 13618; -.
DR PMAP-CutDB; P01574; -.
DR PRO; PR:P01574; -.
DR ArrayExpress; P01574; -.
DR CleanEx; HS_IFNB1; -.
DR Genevestigator; P01574; -.
DR GO; GO:0005576; C:extracellular region; IC:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005132; F:interferon-alpha/beta receptor binding; NAS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; NAS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IMP:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:BHF-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
DR GO; GO:0030101; P:natural killer cell activation; NAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; NAS:UniProtKB.
DR GO; GO:0045581; P:negative regulation of T cell differentiation; IDA:UniProtKB.
DR GO; GO:2000552; P:negative regulation of T-helper 2 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; NAS:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL.
DR GO; GO:0032897; P:negative regulation of viral transcription; IDA:BHF-UCL.
DR GO; GO:0045089; P:positive regulation of innate immune response; NAS:UniProtKB.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0045343; P:regulation of MHC class I biosynthetic process; NAS:UniProtKB.
DR GO; GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR012351; 4_helix_cytokine_core.
DR InterPro; IPR000471; Interferon_alpha/beta/delta.
DR InterPro; IPR015588; Interferon_beta.
DR PANTHER; PTHR11691; PTHR11691; 1.
DR PANTHER; PTHR11691:SF7; PTHR11691:SF7; 1.
DR Pfam; PF00143; Interferon; 1.
DR PRINTS; PR00266; INTERFERONAB.
DR SMART; SM00076; IFabd; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00252; INTERFERON_A_B_D; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Complete proteome; Cytokine;
KW Disulfide bond; Glycoprotein; Pharmaceutical; Phosphoprotein;
KW Polymorphism; Reference proteome; Secreted; Signal.
FT SIGNAL 1 21
FT CHAIN 22 187 Interferon beta.
FT /FTId=PRO_0000016400.
FT MOD_RES 24 24 Phosphotyrosine (By similarity).
FT CARBOHYD 101 101 N-linked (GlcNAc...).
FT DISULFID 52 162
FT VARIANT 162 162 C -> Y (in clone PF526, loss of ability
FT to form the essential disulfide bond,
FT loss of antiviral activity).
FT /FTId=VAR_004016.
FT VARIANT 164 164 W -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036330.
FT HELIX 24 42
FT HELIX 51 55
FT HELIX 63 67
FT HELIX 73 91
FT HELIX 96 98
FT HELIX 102 127
FT TURN 137 139
FT HELIX 140 156
FT TURN 157 159
FT HELIX 161 182
SQ SEQUENCE 187 AA; 22294 MW; 0B013D4087723CEC CRC64;
MTNKCLLQIA LLLCFSTTAL SMSYNLLGFL QRSSNFQCQK LLWQLNGRLE YCLKDRMNFD
IPEEIKQLQQ FQKEDAALTI YEMLQNIFAI FRQDSSSTGW NETIVENLLA NVYHQINHLK
TVLEEKLEKE DFTRGKLMSS LHLKRYYGRI LHYLKAKEYS HCAWTIVRVE ILRNFYFINR
LTGYLRN
//
MIM
147640
*RECORD*
*FIELD* NO
147640
*FIELD* TI
*147640 INTERFERON, BETA-1; IFNB1
;;INTERFERON, FIBROBLAST; IFF;;
IFN, FIBROBLAST;;
read moreBETA-INTERFERON; IFB; IFNB
*FIELD* TX
CLONING
From the nucleotide sequence of the gene for fibroblast interferon,
cloned by recombinant DNA technology, Derynck et al. (1980) deduced the
complete amino acid sequence of the protein, which contains 166 amino
acids.
Cavalieri et al. (1977) showed that leukocyte and fibroblast interferon
are encoded by different species of mRNA. That these arise from separate
genes was demonstrated by Taniguchi et al. (1980). Between leukocyte
interferon, or interferon-alpha (IFNA; 147660), and fibroblast
interferon, or interferon-beta, they also found 45% homology at the
nucleotide level and 29% at the amino acid level.
GENE FUNCTION
Diaz et al. (1988) demonstrated homozygous deletion of both the beta and
alpha interferon genes in neoplastic hematopoietic cells, some of which
had gross chromosomal deletions of chromosome 9p22-p21. The cell lines
also demonstrated deficiency of the enzyme 5-prime-methylthioadenosine
phosphorylase. The authors speculated that the homozygous deletions may
be associated with the loss of a tumor-suppressor gene involved in
neoplastic development; an alternative hypothesis was that the
interferon genes themselves act as tumor-suppressor genes, and their
deletion or inactivation may be associated with the development of
neoplastic growth.
Siegal et al. (1999) demonstrated that purified interferon-producing
cells were the CD4(+)CD11c(-) type-2 dendritic cell precursors, which
produce 200 to 1,000 times more interferon than other blood cells after
microbial challenge. Dendritic cell precursors are thus an effector cell
type of the immune system, critical for antiviral and antitumor immune
responses.
Takayanagi et al. (2002) demonstrated that RANKL (602642) induces the
IFN-beta gene in osteoclast precursor cells, and that IFN-beta inhibits
the differentiation of osteoclasts by interfering with the RANKL-induced
expression of c-Fos (164810), an essential transcription factor for the
formation of osteoclasts. This IFN-beta gene induction mechanism is
distinct from that induced by virus, and is dependent on c-Fos itself.
Thus an autoregulatory mechanism operates--the RANKL-induced c-Fos
induces its own inhibitor. The importance of this regulatory mechanism
for bone homeostasis is emphasized by the observation that mice
deficient in IFN-beta signaling exhibit severe osteopenia accompanied by
enhanced osteoclastogenesis.
Takaoka et al. (2003) demonstrated that transcription of the p53 gene
(191170) is induced by IFNA/IFNB, accompanied by an increase in p53
protein level. IFNA/B signaling itself does not activate p53, but
contributes to boosting p53 responses to stress signals. Takaoka et al.
(2003) showed examples in which p53 gene induction by IFNA/B indeed
contributed to tumor suppression. Furthermore, they showed that p53 is
activated in virally infected cells to evoke an apoptotic response and
that p53 is critical for antiviral defense of the host. Takaoka et al.
(2003) showed that the p53 gene is transcriptionally induced by IFNA/B
through ISGF3 (147574), demonstrating p53 gene induction by its
cytokine. Whereas IFNA/B induce p53 mRNA and increase its protein level,
p53-mediated responses such as cell cycle arrest or apoptosis were not
observed in cells treated with IFNA/B alone.
Because type I IFNs are critical for regulation of osteoclastogenesis in
mice, Coelho et al. (2005) compared the effects of IFNA2 (147562) and
IFNB on differentiation of human monocytes into osteoclasts. Although
primary monocytes undergoing osteoclastic differentiation were highly
and equally sensitive to both proteins, IFNB was 100-fold more potent
than IFNA2 at inhibiting osteoclastogenesis. Microarray and RT-PCR
analyses showed that CXCL11 (604852) was the only gene differentially
upregulated in this cellular system by IFNB compared with IFNA2.
Treatment of monocytes with CXCL11 inhibited osteoclastic
differentiation, and CXCL11 acted through a receptor distinct from CXCR3
(300574) and not through antagonism of CCR5 (601373). Coelho et al.
(2005) proposed that IFNB may have clinical relevance in preventing
osteolysis.
Using microarray, PCR, and complementarity analyses, Pedersen et al.
(2007) identified 8 miRNAs that were rapidly upregulated in
IFNB-stimulated mouse and human liver cell lines that showed sequence
complementarity to hepatitis C virus (HCV; see 609532), an RNA virus,
but not to hepatitis B virus (HBV; see 610424), a DNA virus. Of the 8
upregulated miRNAs, miR196 (MIRN196; 608632), miR296 (MIRN296; 610945),
miR351 (MIRN351), miR431 (MIRN431; 611708), and miR448 (MIRN448; 300686)
had anti-HCV activity, and miR196 and miR448 directly targeted HCV
genomic RNA. IFNB stimulation downregulated miR122 (MIRN122A; 609582), a
liver-specific miRNA essential for HCV replication. Pedersen et al.
(2007) concluded that IFNA and IFNB, a common treatment regimen for HCV
infection, use cellular miRNA, at least in part, to combat viral
infections.
Wilson et al. (2013) demonstrated in mice infected with lymphocytic
choriomeningitis virus (LCMV) that blockade of type I interferon (IFN-I)
signaling diminished chronic immune activation and immune suppression,
restored lymphoid tissue architecture, and increased immune parameters
associated with control of virus replication, ultimately facilitating
clearance of the persistent infection. The accelerated control of
persistent infection induced by blocking IFN-I signaling required CD4 T
cells and was associated with enhanced IFN-gamma (IFNG; 147570)
production. Wilson et al. (2013) concluded that interfering with chronic
IFN-I signaling during persistent infection redirects the immune
environment to enable control of infection. Wilson et al. (2013) noted
that human HIV and HCV infections are also associated with immune
activation driven by chronic IFN-I signaling and suggested that a
similar blockade of IFN-I may improve control of these infections.
Using RT-PCR and immunohistochemistry, Teles et al. (2013) demonstrated
increased expression of the type I interferon IFNB in lesions of
lepromatous leprosy (i.e., multibacillary, or L-lep) patients compared
with tuberculoid leprosy (i.e., paucibacillary, or T-lep) patients (see
609888). Expression of an IFNB receptor, IFNAR1 (107450), was also
increased in L-lep lesions. Increased expression of IFNB was associated
with increased expression of IL10 (124092), and IFNB alone induced IL10
expression in mononuclear cells in vitro. There was an inverse
correlation between IL10 expression and expression of the antimicrobial
peptides CAMP (600474) and DEFB4 (DEFB4A; 602215). Measurement of
uncultivable Mycobacterium leprae viability based on the ratio of M.
leprae 16S rRNA to M. leprae repetitive element DNA indicated that IFNG
induced antimicrobial activity against M. leprae in monocytes by about
35%, which was abrogated by the addition of either IFNB or IL10. Teles
et al. (2013) concluded that the type I interferon gene expression
program prominently expressed in L-lep lesions inhibits the IFNG-induced
antimicrobial response against M. leprae through an intermediary, IL10.
MAPPING
By study of human-mouse cell hybrids, Meager et al. (1979) concluded
that chromosome 5 is not involved in production of interferon. Instead
they found correlation between interferon production and chromosome 9,
and the interferon produced by the hybrids was predominantly of the
fibroblast type. Chany et al. (1980) likewise concluded that chromosome
9 carries a locus for an interferon, which they referred to as beta.
Chromosome 13 also appeared to be involved. Chany et al. (1980)
suggested that the locus on chromosome 13 might have something to do
with IFNA synthesis.
Tavernier et al. (1981) presented evidence for a single fibroblast
interferon gene. As in the case of IFN-alpha, no intervening sequences
were discovered. Houghton et al. (1981) independently arrived at the
same findings. Using radioactive probes from purified cDNA clones of
interferons, Owerbach et al. (1981) located at least 8 leukocyte
interferon genes and a fibroblast interferon gene on chromosome 9. Ohno
and Taniguchi (1981) also showed that the beta-interferon gene(s), like
the alpha-interferon genes, lacks intervening sequences. Comparison of
the cDNA sequence of alpha and beta interferons showed apparent homology
in amino acid sequence and in nucleotide sequence, indicating that they
were presumably derived from a common ancestor. The fact that they are
syntenic supports that conclusion.
By in situ hybridization, Trent et al. (1982) confirmed the location of
IFF and IFL on chromosome 9p and concluded that IFF is distal to IFL.
They mapped IFB to chromosome 9pter-p21. Studying 2 patients with
unbalanced rearrangements of 9p, Henry et al. (1984) used a genomic
clone for IFNB1 and concluded that the gene is located on chromosome
9p21.
Sagar et al. (1984) concluded that IFN-beta-related DNA is dispersed in
the human genome. The data from study of human-rodent somatic cell
hybrids induced with poly(I)poly(C) or with viral inducers were
consistent with assignment of IFB mRNA species of different lengths to
chromosomes 9, 5, and 2 (reviewed by Sagar et al., 1984). Another
IFN-beta had been assigned to chromosome 4 (Sehgal et al., 1983).
Ohlsson et al. (1985) identified 5 RFLPs associated with the alpha- and
beta-interferon gene cluster. Heterozygosities made them excellent
markers for the short arm of chromosome 9. In a study of 25 Caucasian
families, no recombination was found between the alpha and beta markers.
Furthermore, 12 of 32 possible haplotypes were found, indicating linkage
disequilibrium which was of similar magnitude between various alpha
markers as it was between alpha and beta markers. Thus, the alpha and
beta genes must be clustered within a few hundred kilobases. Duplication
of the beta gene, apparently of recent origin, was found in some persons
and segregated regularly.
By studying an acute monocytic leukemia (AMoL)-associated translocation
t(9;11)(p22;q23), Diaz et al. (1986) concluded that the IFNB1 gene is
located in chromosome 9p22, distal to alpha-interferon.
CYTOGENETICS
In 3 patients with AMoL and t(9;11)(p22;q23), Diaz et al. (1986) showed
that the breakpoint on 9p split the interferon genes and that IFNB1 gene
was translocated to chromosome 11. The ETS1 gene (164720) was
translocated from chromosome 11 to 9p adjacent to the interferon genes.
They suggested that juxtaposition of interferon and ETS1 genes may be
involved in the pathogenesis of AMoL.
*FIELD* SA
Erickson et al. (1984); Houghton et al. (1980); Knight (1980); May
et al. (1985); Meager et al. (1979); Pitha et al. (1982); Shepard
et al. (1981); Stewart (1979); Taniguchi et al. (1980); Taniguchi
et al. (1980); Tavernier et al. (1983); Weissenbach et al. (1980);
Zinn et al. (1983)
*FIELD* RF
1. Cavalieri, R. L.; Havell, E. A.; Vilcek, J.; Pestka, S.: Synthesis
of human interferon by Xenopus laevis oocytes: two structural genes
for interferons in human cells. Proc. Nat. Acad. Sci. 74: 3287-3291,
1977.
2. Chany, C.; Finaz, C.; Weil, D.; Vignal, M.; Van Cong, N.; de Grouchy,
J.: Investigations on the chromosomal localizations of the human
and chimpanzee interferon genes: possible role of chromosomes 9 and
13. Ann. Genet. 23: 201-207, 1980.
3. Coelho, L. F. L.; Magno de Freitas Almeida, G. M. F.; Mennechet,
F. J. D.; Blangy, A.; Uze, G.: Interferon-alpha and -beta differentially
regulate osteoclastogenesis: role of differential induction of chemokine
CXCL11 expression. Proc. Nat. Acad. Sci. 102: 11917-11922, 2005.
4. Derynck, R.; Content, J.; DeClercq, E.; Volckaert, G.; Tavernier,
J.; Devos, R.; Fiers, W.: Isolation and structure of a human fibroblast
interferon gene. Nature 285: 542-547, 1980.
5. Diaz, M. O.; Le Beau, M. M.; Pitha, P.; Rowley, J. D.: Interferon
and c-ets-1 genes in the translocation (9;11)(p22;q23) in human acute
monocytic leukemia. Science 231: 265-267, 1986.
6. Diaz, M. O.; Ziemin, S.; Le Beau, M. M.; Pitha, P.; Smith, S. D.;
Chilcote, R. R.; Rowley, J. D.: Homozygous deletion of the alpha-
and beta(1)-interferon genes in human leukemia and derived cell lines. Proc.
Nat. Acad. Sci. 85: 5259-5263, 1988.
7. Erickson, B. W.; May, L. T.; Sehgal, P. B.: Internal duplication
in human alpha-1 and beta-1 interferons. Proc. Nat. Acad. Sci. 81:
7171-7175, 1984.
8. Henry, L.; Sizun, J.; Turleau, C.; Boue, J.; Azoulay, M.; Junien,
C.: The gene for human fibroblast interferon (IFB) maps to 9p21. Hum.
Genet. 68: 67-69, 1984.
9. Houghton, M.; Eaton, M. A. W.; Stewart, A. G.; Smith, J. C.; Doel,
S. M.; Catlin, G. H.; Lewis, H. M.; Patel, T. P.; Emtage, J. S.; Carey,
N. H.; Porter, A. G.: The complete amino acid sequence of human fibroblast
interferon as deduced using synthetic oligodeoxyribonucleotide primers
of reverse transcriptase. Nucleic Acids Res. 8: 2885-2894, 1980.
10. Houghton, M.; Jackson, I. J.; Porter, A. G.; Doel, S. M.; Catlin,
G. H.; Barber, C.; Carey, N. H.: The absence of introns within a
human fibroblast interferon gene. Nucleic Acids Res. 9: 247-266,
1981.
11. Knight, E., Jr.: Human fibroblast interferon: amino acid analysis
and amino terminal amino acid sequence. Science 207: 525-527, 1980.
12. May, L. T.; Landsberger, F. R.; Inouye, M.; Sehgal, P. B.: Significance
of similarities in patterns: an application to beta interferon-related
DNA on human chromosome 2. Proc. Nat. Acad. Sci. 82: 4090-4094,
1985.
13. Meager, A.; Graves, H.; Burke, D. C.; Swallow, D. M.: Involvement
of a gene on chromosome 9 in human fibroblast interferon production. Nature 280:
493-495, 1979.
14. Meager, A.; Graves, H. E.; Walker, J. R.; Burke, D. C.; Swallow,
D. M.; Westerveld, A.: Tentative assignment of the gene for human
fibroblast interferon to chromosome 9. (Abstract) Cytogenet. Cell
Genet. 25: 183-184, 1979.
15. Ohlsson, M.; Feder, J.; Cavalli-Sforza, L. L.; von Gabain, A.
: Close linkage of alpha and beta interferons and infrequent duplication
of beta interferon in humans. Proc. Nat. Acad. Sci. 82: 4473-4476,
1985.
16. Ohno, S.; Taniguchi, T.: Structure of a chromosomal gene for
human interferon beta. Proc. Nat. Acad. Sci. 78: 5305-5309, 1981.
17. Owerbach, D.; Rutter, W. J.; Shows, T. B.; Gray, P.; Goeddel,
D. V.; Lawn, R. M.: Leukocyte and fibroblast interferon genes are
located on human chromosome 9. Proc. Nat. Acad. Sci. 78: 3123-3127,
1981.
18. Pedersen, I. M.; Cheng, G.; Wieland, S.; Volinia, S.; Croce, C.
M.; Chisari, F. V.; David, M.: Interferon modulation of cellular
microRNAs as an antiviral mechanism. Nature 449: 919-922, 2007.
19. Pitha, P. M.; Slate, D. L.; Raj, N. B. K.; Ruddle, F. H.: Human
beta interferon gene localization and expression in somatic cell hybrids. Molec.
Cell. Biol. 2: 564-570, 1982.
20. Sagar, A. D.; Sehgal, P. B.; May, L. T.; Inouye, M.; Slate, D.
L.; Shulman, L.; Ruddle, F. H.: Interferon-beta-related DNA is dispersed
in the human genome. Science 223: 1312-1315, 1984.
21. Sehgal, P. B.; May, L. T.; Sagar, A. D.; LaForge, K. S.; Inouye,
M.: Isolation of novel human genomic DNA clones related to human
interferon-beta(1) cDNA. Proc. Nat. Acad. Sci. 80: 3632-3636, 1983.
22. Shepard, H. M.; Leung, D.; Stebbing, N.; Goeddel, D. V.: A single
amino acid change in IFN-beta(1) abolishes its antiviral activity. Nature 294:
563-567, 1981.
23. Siegal, F. P.; Kadowaki, N.; Shodell, M.; Fitzgerald-Bocarsly,
P. A.; Shah, K.; Ho, S.; Antonenko, S.; Liu, Y.-J.: The nature of
the principal type 1 interferon-producing cells in human blood. Science 284:
1835-1837, 1999.
24. Stewart, W. E., II: The Interferon System. Berlin: Springer
(pub.) 1979.
25. Takaoka, A.; Hayakawa, S.; Yanai, H.; Stolber, D.; Negishi, H.;
Kikuchi, H.; Sasaki, S.; Imai, K.; Shibue, T.; Honda, K.; Taniguchi,
T.: Integration of interferon-alpha/beta signalling to p53 responses
in tumour suppression and antiviral defence. Nature 424: 516-523,
2003.
26. Takayanagi, H.; Kim, S.; Matsuo, K.; Suzuki, H.; Suzuki, T.; Sato,
K.; Yokochi, T.; Oda, H.; Nakamura, K.; Ida, N.; Wagner, E. F.; Taniguchi,
T.: RANKL maintains bone homeostasis through c-Fos-dependent induction
of interferon-B. Nature 416: 744-749, 2002.
27. Taniguchi, T.; Fujii-Kuriyama, Y.; Muramatsu, M.: Molecular cloning
of human interferon cDNA. Proc. Nat. Acad. Sci. 77: 4003-4006, 1980.
28. Taniguchi, T.; Mantei, N.; Schwarzstein, M.; Nagata, S.; Muramatsu,
M.; Weissmann, C.: Human leukocyte and fibroblast interferons are
structurally related. Nature 285: 547-549, 1980.
29. Taniguchi, T.; Ohno, S.; Fujii-Kuriyama, Y.; Muramatsu, M.: The
nucleotide sequence of human fibroblast interferon cDNA. Gene 10:
11-15, 1980.
30. Tavernier, J.; Derynck, R.; Fiers, W.: Evidence for a unique
human fibroblast interferon (IFN-beta1) chromosomal gene devoid of
intervening sequences. Nucleic Acids Res. 9: 461-471, 1981.
31. Tavernier, J.; Gheysen, D.; Duerinck, F.; Van der Heyden, J.;
Fiers, W.: Deletion mapping of the inducible promoter of human IFN-beta
gene. Nature 301: 634-636, 1983.
32. Teles, R. M. B.; Graeber, T. G.; Krutzik, S. R.; Montoya, D.;
Schenk, M.; Lee, D. J.; Komisopoulou, E.; Kelly-Scumpia, K.; Chun,
R.; Iyer, S. S.; Sarno, E. N.; Rea, T. H.; Hewison, M.; Adams, J.
S.; Popper, S. J.; Relman, D. A.; Stenger, S.; Bloom, B. R.; Cheng,
G.; Modlin, R. L.: Type I interferon suppresses type II interferon-triggered
human anti-mycobacterial responses. Science 339: 1448-1453, 2013.
33. Trent, J. M.; Olson, S.; Lawn, R.: Chromosomal localization of
human leukocyte, fibroblast, and immune interferon genes by means
of in situ hybridization. Proc. Nat. Acad. Sci. 79: 7809-7813, 1982.
34. Weissenbach, J.; Chernajovsky, Y.; Zeevi, M.; Shulman, L.; Soreq,
H.; Nir, U.; Wallach, D.; Perricaudet, M.; Tiollais, P.; Revel, M.
: Two interferon mRNAs in human fibroblasts: in vitro translation
and Escherichia coli cloning studies. Proc. Nat. Acad. Sci. 77:
7152-7156, 1980.
35. Wilson, E. B.; Yamada, D. H.; Elsaesser, H.; Herskovitz, J.; Deng,
J.; Cheng, G.; Aronow, B. J.; Karp, C. L.; Brooks, D. G.: Blockade
of chronic type I interferon signaling to control persistent LCMV
infection. Science 340: 202-207, 2013.
36. Zinn, K.; DiMaio, D.; Maniatis, T.: Identification of two distinct
regulatory regions adjacent to the human beta-interferon gene. Cell 34:
865-879, 1983.
*FIELD* CN
Paul J. Converse - updated: 05/24/2013
Ada Hamosh - updated: 5/6/2013
Paul J. Converse - updated: 12/20/2007
Paul J. Converse - updated: 11/3/2006
Ada Hamosh - updated: 7/24/2003
Ada Hamosh - updated: 4/30/2002
Ada Hamosh - updated: 6/11/1999
*FIELD* CD
Victor A. McKusick: 6/23/1986
*FIELD* ED
mgross: 05/24/2013
alopez: 5/6/2013
mgross: 9/4/2008
mgross: 1/2/2008
mgross: 12/20/2007
mgross: 11/3/2006
terry: 5/17/2005
alopez: 8/29/2003
carol: 7/25/2003
terry: 7/24/2003
alopez: 4/30/2002
terry: 4/30/2002
alopez: 6/11/1999
psherman: 1/13/1999
carol: 5/16/1994
carol: 4/1/1992
supermim: 3/16/1992
carol: 11/8/1991
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
147640
*FIELD* TI
*147640 INTERFERON, BETA-1; IFNB1
;;INTERFERON, FIBROBLAST; IFF;;
IFN, FIBROBLAST;;
read moreBETA-INTERFERON; IFB; IFNB
*FIELD* TX
CLONING
From the nucleotide sequence of the gene for fibroblast interferon,
cloned by recombinant DNA technology, Derynck et al. (1980) deduced the
complete amino acid sequence of the protein, which contains 166 amino
acids.
Cavalieri et al. (1977) showed that leukocyte and fibroblast interferon
are encoded by different species of mRNA. That these arise from separate
genes was demonstrated by Taniguchi et al. (1980). Between leukocyte
interferon, or interferon-alpha (IFNA; 147660), and fibroblast
interferon, or interferon-beta, they also found 45% homology at the
nucleotide level and 29% at the amino acid level.
GENE FUNCTION
Diaz et al. (1988) demonstrated homozygous deletion of both the beta and
alpha interferon genes in neoplastic hematopoietic cells, some of which
had gross chromosomal deletions of chromosome 9p22-p21. The cell lines
also demonstrated deficiency of the enzyme 5-prime-methylthioadenosine
phosphorylase. The authors speculated that the homozygous deletions may
be associated with the loss of a tumor-suppressor gene involved in
neoplastic development; an alternative hypothesis was that the
interferon genes themselves act as tumor-suppressor genes, and their
deletion or inactivation may be associated with the development of
neoplastic growth.
Siegal et al. (1999) demonstrated that purified interferon-producing
cells were the CD4(+)CD11c(-) type-2 dendritic cell precursors, which
produce 200 to 1,000 times more interferon than other blood cells after
microbial challenge. Dendritic cell precursors are thus an effector cell
type of the immune system, critical for antiviral and antitumor immune
responses.
Takayanagi et al. (2002) demonstrated that RANKL (602642) induces the
IFN-beta gene in osteoclast precursor cells, and that IFN-beta inhibits
the differentiation of osteoclasts by interfering with the RANKL-induced
expression of c-Fos (164810), an essential transcription factor for the
formation of osteoclasts. This IFN-beta gene induction mechanism is
distinct from that induced by virus, and is dependent on c-Fos itself.
Thus an autoregulatory mechanism operates--the RANKL-induced c-Fos
induces its own inhibitor. The importance of this regulatory mechanism
for bone homeostasis is emphasized by the observation that mice
deficient in IFN-beta signaling exhibit severe osteopenia accompanied by
enhanced osteoclastogenesis.
Takaoka et al. (2003) demonstrated that transcription of the p53 gene
(191170) is induced by IFNA/IFNB, accompanied by an increase in p53
protein level. IFNA/B signaling itself does not activate p53, but
contributes to boosting p53 responses to stress signals. Takaoka et al.
(2003) showed examples in which p53 gene induction by IFNA/B indeed
contributed to tumor suppression. Furthermore, they showed that p53 is
activated in virally infected cells to evoke an apoptotic response and
that p53 is critical for antiviral defense of the host. Takaoka et al.
(2003) showed that the p53 gene is transcriptionally induced by IFNA/B
through ISGF3 (147574), demonstrating p53 gene induction by its
cytokine. Whereas IFNA/B induce p53 mRNA and increase its protein level,
p53-mediated responses such as cell cycle arrest or apoptosis were not
observed in cells treated with IFNA/B alone.
Because type I IFNs are critical for regulation of osteoclastogenesis in
mice, Coelho et al. (2005) compared the effects of IFNA2 (147562) and
IFNB on differentiation of human monocytes into osteoclasts. Although
primary monocytes undergoing osteoclastic differentiation were highly
and equally sensitive to both proteins, IFNB was 100-fold more potent
than IFNA2 at inhibiting osteoclastogenesis. Microarray and RT-PCR
analyses showed that CXCL11 (604852) was the only gene differentially
upregulated in this cellular system by IFNB compared with IFNA2.
Treatment of monocytes with CXCL11 inhibited osteoclastic
differentiation, and CXCL11 acted through a receptor distinct from CXCR3
(300574) and not through antagonism of CCR5 (601373). Coelho et al.
(2005) proposed that IFNB may have clinical relevance in preventing
osteolysis.
Using microarray, PCR, and complementarity analyses, Pedersen et al.
(2007) identified 8 miRNAs that were rapidly upregulated in
IFNB-stimulated mouse and human liver cell lines that showed sequence
complementarity to hepatitis C virus (HCV; see 609532), an RNA virus,
but not to hepatitis B virus (HBV; see 610424), a DNA virus. Of the 8
upregulated miRNAs, miR196 (MIRN196; 608632), miR296 (MIRN296; 610945),
miR351 (MIRN351), miR431 (MIRN431; 611708), and miR448 (MIRN448; 300686)
had anti-HCV activity, and miR196 and miR448 directly targeted HCV
genomic RNA. IFNB stimulation downregulated miR122 (MIRN122A; 609582), a
liver-specific miRNA essential for HCV replication. Pedersen et al.
(2007) concluded that IFNA and IFNB, a common treatment regimen for HCV
infection, use cellular miRNA, at least in part, to combat viral
infections.
Wilson et al. (2013) demonstrated in mice infected with lymphocytic
choriomeningitis virus (LCMV) that blockade of type I interferon (IFN-I)
signaling diminished chronic immune activation and immune suppression,
restored lymphoid tissue architecture, and increased immune parameters
associated with control of virus replication, ultimately facilitating
clearance of the persistent infection. The accelerated control of
persistent infection induced by blocking IFN-I signaling required CD4 T
cells and was associated with enhanced IFN-gamma (IFNG; 147570)
production. Wilson et al. (2013) concluded that interfering with chronic
IFN-I signaling during persistent infection redirects the immune
environment to enable control of infection. Wilson et al. (2013) noted
that human HIV and HCV infections are also associated with immune
activation driven by chronic IFN-I signaling and suggested that a
similar blockade of IFN-I may improve control of these infections.
Using RT-PCR and immunohistochemistry, Teles et al. (2013) demonstrated
increased expression of the type I interferon IFNB in lesions of
lepromatous leprosy (i.e., multibacillary, or L-lep) patients compared
with tuberculoid leprosy (i.e., paucibacillary, or T-lep) patients (see
609888). Expression of an IFNB receptor, IFNAR1 (107450), was also
increased in L-lep lesions. Increased expression of IFNB was associated
with increased expression of IL10 (124092), and IFNB alone induced IL10
expression in mononuclear cells in vitro. There was an inverse
correlation between IL10 expression and expression of the antimicrobial
peptides CAMP (600474) and DEFB4 (DEFB4A; 602215). Measurement of
uncultivable Mycobacterium leprae viability based on the ratio of M.
leprae 16S rRNA to M. leprae repetitive element DNA indicated that IFNG
induced antimicrobial activity against M. leprae in monocytes by about
35%, which was abrogated by the addition of either IFNB or IL10. Teles
et al. (2013) concluded that the type I interferon gene expression
program prominently expressed in L-lep lesions inhibits the IFNG-induced
antimicrobial response against M. leprae through an intermediary, IL10.
MAPPING
By study of human-mouse cell hybrids, Meager et al. (1979) concluded
that chromosome 5 is not involved in production of interferon. Instead
they found correlation between interferon production and chromosome 9,
and the interferon produced by the hybrids was predominantly of the
fibroblast type. Chany et al. (1980) likewise concluded that chromosome
9 carries a locus for an interferon, which they referred to as beta.
Chromosome 13 also appeared to be involved. Chany et al. (1980)
suggested that the locus on chromosome 13 might have something to do
with IFNA synthesis.
Tavernier et al. (1981) presented evidence for a single fibroblast
interferon gene. As in the case of IFN-alpha, no intervening sequences
were discovered. Houghton et al. (1981) independently arrived at the
same findings. Using radioactive probes from purified cDNA clones of
interferons, Owerbach et al. (1981) located at least 8 leukocyte
interferon genes and a fibroblast interferon gene on chromosome 9. Ohno
and Taniguchi (1981) also showed that the beta-interferon gene(s), like
the alpha-interferon genes, lacks intervening sequences. Comparison of
the cDNA sequence of alpha and beta interferons showed apparent homology
in amino acid sequence and in nucleotide sequence, indicating that they
were presumably derived from a common ancestor. The fact that they are
syntenic supports that conclusion.
By in situ hybridization, Trent et al. (1982) confirmed the location of
IFF and IFL on chromosome 9p and concluded that IFF is distal to IFL.
They mapped IFB to chromosome 9pter-p21. Studying 2 patients with
unbalanced rearrangements of 9p, Henry et al. (1984) used a genomic
clone for IFNB1 and concluded that the gene is located on chromosome
9p21.
Sagar et al. (1984) concluded that IFN-beta-related DNA is dispersed in
the human genome. The data from study of human-rodent somatic cell
hybrids induced with poly(I)poly(C) or with viral inducers were
consistent with assignment of IFB mRNA species of different lengths to
chromosomes 9, 5, and 2 (reviewed by Sagar et al., 1984). Another
IFN-beta had been assigned to chromosome 4 (Sehgal et al., 1983).
Ohlsson et al. (1985) identified 5 RFLPs associated with the alpha- and
beta-interferon gene cluster. Heterozygosities made them excellent
markers for the short arm of chromosome 9. In a study of 25 Caucasian
families, no recombination was found between the alpha and beta markers.
Furthermore, 12 of 32 possible haplotypes were found, indicating linkage
disequilibrium which was of similar magnitude between various alpha
markers as it was between alpha and beta markers. Thus, the alpha and
beta genes must be clustered within a few hundred kilobases. Duplication
of the beta gene, apparently of recent origin, was found in some persons
and segregated regularly.
By studying an acute monocytic leukemia (AMoL)-associated translocation
t(9;11)(p22;q23), Diaz et al. (1986) concluded that the IFNB1 gene is
located in chromosome 9p22, distal to alpha-interferon.
CYTOGENETICS
In 3 patients with AMoL and t(9;11)(p22;q23), Diaz et al. (1986) showed
that the breakpoint on 9p split the interferon genes and that IFNB1 gene
was translocated to chromosome 11. The ETS1 gene (164720) was
translocated from chromosome 11 to 9p adjacent to the interferon genes.
They suggested that juxtaposition of interferon and ETS1 genes may be
involved in the pathogenesis of AMoL.
*FIELD* SA
Erickson et al. (1984); Houghton et al. (1980); Knight (1980); May
et al. (1985); Meager et al. (1979); Pitha et al. (1982); Shepard
et al. (1981); Stewart (1979); Taniguchi et al. (1980); Taniguchi
et al. (1980); Tavernier et al. (1983); Weissenbach et al. (1980);
Zinn et al. (1983)
*FIELD* RF
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*FIELD* CN
Paul J. Converse - updated: 05/24/2013
Ada Hamosh - updated: 5/6/2013
Paul J. Converse - updated: 12/20/2007
Paul J. Converse - updated: 11/3/2006
Ada Hamosh - updated: 7/24/2003
Ada Hamosh - updated: 4/30/2002
Ada Hamosh - updated: 6/11/1999
*FIELD* CD
Victor A. McKusick: 6/23/1986
*FIELD* ED
mgross: 05/24/2013
alopez: 5/6/2013
mgross: 9/4/2008
mgross: 1/2/2008
mgross: 12/20/2007
mgross: 11/3/2006
terry: 5/17/2005
alopez: 8/29/2003
carol: 7/25/2003
terry: 7/24/2003
alopez: 4/30/2002
terry: 4/30/2002
alopez: 6/11/1999
psherman: 1/13/1999
carol: 5/16/1994
carol: 4/1/1992
supermim: 3/16/1992
carol: 11/8/1991
supermim: 3/20/1990
ddp: 10/27/1989