IREB2_RAT
ID IREB2_RAT Reviewed; 963 AA.
AC Q62751; Q66HL4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 153.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7622457; DOI=10.1074/jbc.270.28.16529;
RA Guo B., Brown F.M., Phillips J.D., Yu Y., Leibold E.A.;
RT "Characterization and expression of iron regulatory protein 2 (IRP2).
RT Presence of multiple IRP2 transcripts regulated by intracellular iron
RT levels.";
RL J. Biol. Chem. 270:16529-16535(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 COFACTOR, RNA-BINDING, AND UBIQUITINATION.
RX PubMed=7665579; DOI=10.1074/jbc.270.37.21645;
RA Guo B., Phillips J.D., Yu Y., Leibold E.A.;
RT "Iron regulates the intracellular degradation of iron regulatory protein 2
RT by the proteasome.";
RL J. Biol. Chem. 270:21645-21651(1995).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). {ECO:0000250|UniProtKB:P48200,
CC ECO:0000250|UniProtKB:Q811J3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in rat tissues, the highest
CC amounts present in skeletal muscle and heart.
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}.
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; U20181; AAA79927.1; -; mRNA.
DR EMBL; BC081798; AAH81798.1; -; mRNA.
DR PIR; A57238; A57238.
DR RefSeq; NP_074054.2; NM_022863.2.
DR AlphaFoldDB; Q62751; -.
DR SMR; Q62751; -.
DR STRING; 10116.ENSRNOP00000017900; -.
DR iPTMnet; Q62751; -.
DR PhosphoSitePlus; Q62751; -.
DR PaxDb; Q62751; -.
DR PRIDE; Q62751; -.
DR Ensembl; ENSRNOT00000017900; ENSRNOP00000017900; ENSRNOG00000013271.
DR GeneID; 64831; -.
DR KEGG; rno:64831; -.
DR UCSC; RGD:621539; rat.
DR CTD; 3658; -.
DR RGD; 621539; Ireb2.
DR eggNOG; KOG0452; Eukaryota.
DR GeneTree; ENSGT00940000157796; -.
DR HOGENOM; CLU_013476_2_1_1; -.
DR InParanoid; Q62751; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; Q62751; -.
DR TreeFam; TF313476; -.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR PRO; PR:Q62751; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000013271; Expressed in duodenum and 18 other tissues.
DR ExpressionAtlas; Q62751; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0003994; F:aconitate hydratase activity; IBA:GO_Central.
DR GO; GO:0030350; F:iron-responsive element binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001069; F:regulatory region RNA binding; IPI:RGD.
DR GO; GO:0003723; F:RNA binding; IDA:RGD.
DR GO; GO:0030371; F:translation repressor activity; IEA:InterPro.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071283; P:cellular response to iron(III) ion; IDA:RGD.
DR GO; GO:0071287; P:cellular response to manganese ion; IDA:RGD.
DR GO; GO:0072705; P:cellular response to mercaptoethanol; IDA:RGD.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IDA:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR GO; GO:0006101; P:citrate metabolic process; IBA:GO_Central.
DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:RGD.
DR GO; GO:0050892; P:intestinal absorption; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IDA:RGD.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006417; P:regulation of translation; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:1990910; P:response to hypobaric hypoxia; IEP:RGD.
DR GO; GO:0010040; P:response to iron(II) ion; IEP:RGD.
DR GO; GO:0010041; P:response to iron(III) ion; IDA:RGD.
DR GO; GO:1904373; P:response to kainic acid; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0014732; P:skeletal muscle atrophy; IEP:RGD.
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_0000076686"
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 107
FT /note="V -> M (in Ref. 1; AAA79927)"
FT /evidence="ECO:0000305"
FT CONFLICT 602
FT /note="V -> A (in Ref. 1; AAA79927)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="S -> R (in Ref. 1; AAA79927)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 963 AA; 104802 MW; 1C9DA13B7FAD314C CRC64;
MDSPSAGYTF EYLIETLNGS SQKKFFNVPK LGGTKYDILP YSIRVLLEAA VRNCDGFLMK
KEDVINILDW KTKQSNVEVP FFPARVVLQD FTGIPAMVDF AAMREAVKTL GGDPKKVHPA
CPTDLTVDHS LQIDFSKCAI QNAPNPGGGD LQKAGKLSPL KVQPKKLPCR GQTTCRGSCD
SGELSRNSGT FSSQIENTPV LCPFHLQPVP EPETVLKNQE VEFGRNRERL QFFKWSSGAF
KNVAVIPPGT GMAHQVNLEH LSRVVFEEAD LLFPDSVIGT DSHITMVNGL GILGWGVGGI
ETEAVMLGLP VTLTLPEVVG CELTGSSNAF VTSIDIVLGI TKHLRQVGVA GKFVEFFGSG
VSQLSIVDRT TIANMCPEYG AILSFFPVDN VTLRHLEHTG FDKTKLESME EYLKAVKLFR
NDENSSEPEY SQVIQINLNS IVASVSGPKR PQDRVAVTDM KSDFQACLNE KVGFKGFQVA
AEKQSDTVSV RYDGSEYKLS HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVETGLRVKP
YIRTSLSPGS GMVTHYLSSS GVLPYLSKLG FEIVGYGCST CVGNTAPLSE AILNAVKQGD
LVTCGVLSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL GTDSTGKNIY
LHDIWPSREE VHQIEEEHVI LSMFKALKEK VEMGNKRWNS LDAPDSVLFP WDVKSTYIRC
PSFFDKLTKE PAASQPIENA HVLLYLGDSV TTDHISPAGS IARSSAAAKY LTNRGLTPRE
FNSYGARRGN DAVMTRGTFA NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP
LIILAGKKYG SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LEFLPGENAD
SLGLSGREVF SLSFPEELFP GITLNIKTST GKEFSVIAAF ENDVEITLYK HGGLLNFVAR
KFL
