IREB2_MOUSE
ID IREB2_MOUSE Reviewed; 963 AA.
AC Q811J3; E9QPM2; O70235;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Iron-responsive element-binding protein 2;
DE Short=IRE-BP 2;
DE AltName: Full=Iron regulatory protein 2;
DE Short=IRP2;
GN Name=Ireb2; Synonyms=Irp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 140-214.
RX PubMed=9380695; DOI=10.1073/pnas.94.20.10681;
RA Schalinske K.L., Blemings K.P., Steffen D.W., Chen O.S., Eisenstein R.S.;
RT "Iron regulatory protein 1 is not required for the modulation of ferritin
RT and transferrin receptor expression by iron in a murine pro-B lymphocyte
RT cell line.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:10681-10686(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP INTERACTION WITH CIAO2A.
RX PubMed=23891004; DOI=10.1016/j.cmet.2013.06.015;
RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B.,
RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and
RT maturation of different subsets of cytosolic-nuclear iron-sulfur
RT proteins.";
RL Cell Metab. 18:187-198(2013).
CC -!- FUNCTION: RNA-binding protein that binds to iron-responsive elements
CC (IRES), which are stem-loop structures found in the 5'-UTR of ferritin,
CC and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of
CC transferrin receptor mRNA. Binding to the IRE element in ferritin
CC results in the repression of its mRNA translation. Binding of the
CC protein to the transferrin receptor mRNA inhibits the degradation of
CC this otherwise rapidly degraded mRNA. {ECO:0000250|UniProtKB:P48200}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. [4Fe-4S]-binding affects
CC RNA-binding activity, thereby inhibiting activity of the protein.
CC {ECO:0000250};
CC -!- SUBUNIT: Interacts with RBCK1 only in iron-rich conditions. Interacts
CC (when associated with the 4Fe-4S) with FBXL5 (By similarity). Interacts
CC with CIAO1 and CIAO2A (PubMed:23891004). {ECO:0000250|UniProtKB:P48200,
CC ECO:0000269|PubMed:23891004}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Ubiquitinated and degraded by the proteasome in presence of high
CC level of iron and oxygen. Ubiquitinated by a SCF complex containing
CC FBXL5. Upon iron and oxygen depletion FBXL5 is degraded, preventing
CC ubiquitination and allowing its RNA-binding activity (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; AC159892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC161264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044665; AAH44665.1; -; mRNA.
DR EMBL; AF016402; AAC05824.1; -; mRNA.
DR CCDS; CCDS23196.1; -.
DR RefSeq; NP_073146.2; NM_022655.3.
DR AlphaFoldDB; Q811J3; -.
DR SMR; Q811J3; -.
DR BioGRID; 211088; 5.
DR STRING; 10090.ENSMUSP00000034843; -.
DR iPTMnet; Q811J3; -.
DR PhosphoSitePlus; Q811J3; -.
DR EPD; Q811J3; -.
DR jPOST; Q811J3; -.
DR MaxQB; Q811J3; -.
DR PaxDb; Q811J3; -.
DR PeptideAtlas; Q811J3; -.
DR PRIDE; Q811J3; -.
DR ProteomicsDB; 267151; -.
DR Antibodypedia; 27620; 347 antibodies from 35 providers.
DR DNASU; 64602; -.
DR Ensembl; ENSMUST00000034843; ENSMUSP00000034843; ENSMUSG00000032293.
DR GeneID; 64602; -.
DR KEGG; mmu:64602; -.
DR UCSC; uc009prq.2; mouse.
DR CTD; 3658; -.
DR MGI; MGI:1928268; Ireb2.
DR VEuPathDB; HostDB:ENSMUSG00000032293; -.
DR eggNOG; KOG0452; Eukaryota.
DR GeneTree; ENSGT00940000157796; -.
DR HOGENOM; CLU_013476_2_1_1; -.
DR InParanoid; Q811J3; -.
DR OMA; ECPDSVV; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; Q811J3; -.
DR TreeFam; TF313476; -.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 64602; 11 hits in 74 CRISPR screens.
DR ChiTaRS; Ireb2; mouse.
DR PRO; PR:Q811J3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q811J3; protein.
DR Bgee; ENSMUSG00000032293; Expressed in animal zygote and 256 other tissues.
DR ExpressionAtlas; Q811J3; baseline and differential.
DR Genevisible; Q811J3; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISO:MGI.
DR GO; GO:0003994; F:aconitate hydratase activity; IBA:GO_Central.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001069; F:regulatory region RNA binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0030371; F:translation repressor activity; TAS:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IDA:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISO:MGI.
DR GO; GO:0071283; P:cellular response to iron(III) ion; ISO:MGI.
DR GO; GO:0071287; P:cellular response to manganese ion; ISO:MGI.
DR GO; GO:0072705; P:cellular response to mercaptoethanol; ISO:MGI.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; ISO:MGI.
DR GO; GO:0006101; P:citrate metabolic process; IBA:GO_Central.
DR GO; GO:0034101; P:erythrocyte homeostasis; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR GO; GO:0050892; P:intestinal absorption; IGI:MGI.
DR GO; GO:0055072; P:iron ion homeostasis; IGI:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IEP:DFLAT.
DR GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
DR GO; GO:0006417; P:regulation of translation; IMP:MGI.
DR GO; GO:0010041; P:response to iron(III) ion; ISO:MGI.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR CDD; cd01580; AcnA_IRP_Swivel; 1.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 3.
DR InterPro; IPR044137; AcnA_IRP_Swivel.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR006249; Aconitase/IRP2.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR InterPro; IPR029755; IRE-BP2.
DR PANTHER; PTHR11670; PTHR11670; 1.
DR PANTHER; PTHR11670:SF31; PTHR11670:SF31; 1.
DR Pfam; PF00330; Aconitase; 2.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR TIGRFAMs; TIGR01341; aconitase_1; 1.
DR PROSITE; PS00450; ACONITASE_1; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Cytoplasm; Iron; Iron-sulfur; Metal-binding; Reference proteome;
KW RNA-binding; Ubl conjugation.
FT CHAIN 1..963
FT /note="Iron-responsive element-binding protein 2"
FT /id="PRO_0000076685"
FT BINDING 512
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 578
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 581
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT CONFLICT 621
FT /note="V -> D (in Ref. 2; AAH44665)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 963 AA; 104920 MW; 809871B50DB04D67 CRC64;
MDSPSAGYTF EYLIETLNGN SQKKFFNVPK LGGTKYDILP YSIRVLLEAA VRNCDGFLMK
KEDVMNILDW KTKQSNVEVP FFPARVVLQD FTGIPAMVDF AAMREAVKTL GGDPKKVHPA
CPTDLTVDHS LQIDFSKCAI QNAPNPGGGD LQKAGKLSPL KVQSKKLPCR GQTTCRGSCD
SGELSRNSGT FSSQIENTPV LCPFHLQPVP EPETVLKNQE VEFGRNRERL QFFKWSSGAF
KNVAVIPPGT GMAHQVNLEY LSRVVFEETD LLFPDSVVGT DSHITMVNGL GILGWGVGGI
ETEAVMLGLP VTLTLPEVVG CELTGSSNAF VTSIDIVLGI TKHLRQVGVA GKFVEFFGSG
VSQLSIVDRT TIANMCPEYG AILSFFPVDN VTLRHLEHTG FDKTKLESME KYLKAVKLFR
NDENSSEPEY SQVIQINLNS IVASVSGPKR PQDRVAVTDM KSDFQACLNE KVGFKGFQVA
AEKQSDTVSV RYDGSEYKLS HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVEIGLRVKP
YIRTSLSPGS GMVTHYLSSS GVLPYLSKLG FDIVGYGCST CVGNTAPLSE AVLNAVKQGD
LVTCGVLSGN KHFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL GTDSTGKEIY
LHDIWPSREE VHQMEEEHVI LSMFKTLKEK VEMGNKRWNS LEAPDSVLFP WDVKSTYIRC
PSFFDKLTKE PAASQPIENA HVLLYLGDSV TTDHISPAGS IARSSAAAKY LTNRGLTPRE
FNSYGARRGN DAVMTRGTFA NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP
LIILAGKKYG SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LEFLPGENAD
SLGLSGREVF SLSFPEELFP GITLNIKTST GKEFSVIASF ANDVEITLYK HGGLLNFVAR
KFL
