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Protein

Iron-responsive element-binding protein 2

Gene

Ireb2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster per subunit. [4Fe-4S]-binding affects RNA-binding activity, thereby inhibiting activity of the protein.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi512Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi578Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi581Iron-sulfur (4Fe-4S)By similarity1

GO - Molecular functioni

  • 4 iron, 4 sulfur cluster binding Source: UniProtKB
  • iron-responsive element binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • regulatory region RNA binding Source: RGD
  • RNA binding Source: RGD
  • translation repressor activity Source: InterPro

GO - Biological processi

  • aging Source: RGD
  • brain development Source: RGD
  • cellular iron ion homeostasis Source: InterPro
  • cellular response to epidermal growth factor stimulus Source: RGD
  • cellular response to hypoxia Source: RGD
  • cellular response to iron(III) ion Source: RGD
  • cellular response to manganese ion Source: RGD
  • cellular response to mercaptoethanol Source: RGD
  • cellular response to oxygen-glucose deprivation Source: RGD
  • cellular response to retinoic acid Source: RGD
  • iron ion homeostasis Source: UniProtKB
  • iron ion transport Source: InterPro
  • metabolic process Source: InterPro
  • negative regulation of translation Source: RGD
  • response to activity Source: RGD
  • response to copper ion Source: RGD
  • response to hypobaric hypoxia Source: RGD
  • response to iron(II) ion Source: RGD
  • response to iron(III) ion Source: RGD
  • response to kainic acid Source: RGD
  • response to retinoic acid Source: RGD
  • response to zinc ion Source: RGD
  • skeletal muscle atrophy Source: RGD

Keywordsi

Molecular functionRNA-binding
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Iron-responsive element-binding protein 2
Short name:
IRE-BP 2
Alternative name(s):
Iron regulatory protein 2
Short name:
IRP2
Gene namesi
Name:Ireb2
Synonyms:Irp2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi621539. Ireb2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766861 – 963Iron-responsive element-binding protein 2Add BLAST963

Post-translational modificationi

Ubiquitinated and degraded by the proteasome in presence of high level of iron and oxygen. Ubiquitinated by a SCF complex containing FBXL5. Upon iron and oxygen depletion FBXL5 is degraded, preventing ubiquitination and allowing its RNA-binding activity (By similarity).By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ62751.
PRIDEiQ62751.

PTM databases

iPTMnetiQ62751.
PhosphoSitePlusiQ62751.

Expressioni

Tissue specificityi

Ubiquitously expressed in rat tissues, the highest amounts present in skeletal muscle and heart.

Gene expression databases

BgeeiENSRNOG00000013271.
ExpressionAtlasiQ62751. baseline.

Interactioni

Subunit structurei

Interacts with RBCK1 only in iron-rich conditions. Interacts (when associated with the 4Fe-4S) with FBXL5 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017900.

Structurei

3D structure databases

ProteinModelPortaliQ62751.
SMRiQ62751.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the aconitase/IPM isomerase family.Curated

Phylogenomic databases

eggNOGiKOG0452. Eukaryota.
COG1048. LUCA.
GeneTreeiENSGT00890000139397.
HOGENOMiHOG000025704.
HOVERGENiHBG052147.
InParanoidiQ62751.
PhylomeDBiQ62751.
TreeFamiTF313476.

Family and domain databases

Gene3Di3.20.19.10. 1 hit.
3.30.499.10. 2 hits.
3.40.1060.10. 1 hit.
InterProiView protein in InterPro
IPR015931. Acnase/IPM_dHydase_lsu_aba_1/3.
IPR001030. Acoase/IPM_deHydtase_lsu_aba.
IPR015928. Aconitase/3IPM_dehydase_swvl.
IPR015932. Aconitase/IPMdHydase_lsu_aba_2.
IPR006249. Aconitase/IRP2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
IPR029755. IRE-BP2.
PANTHERiPTHR11670. PTHR11670. 1 hit.
PTHR11670:SF44. PTHR11670:SF44. 1 hit.
PfamiView protein in Pfam
PF00330. Aconitase. 2 hits.
PF00694. Aconitase_C. 1 hit.
PRINTSiPR00415. ACONITASE.
SUPFAMiSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 2 hits.
TIGRFAMsiTIGR01341. aconitase_1. 1 hit.
PROSITEiView protein in PROSITE
PS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q62751-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSPSAGYTF EYLIETLNGS SQKKFFNVPK LGGTKYDILP YSIRVLLEAA
60 70 80 90 100
VRNCDGFLMK KEDVINILDW KTKQSNVEVP FFPARVVLQD FTGIPAMVDF
110 120 130 140 150
AAMREAVKTL GGDPKKVHPA CPTDLTVDHS LQIDFSKCAI QNAPNPGGGD
160 170 180 190 200
LQKAGKLSPL KVQPKKLPCR GQTTCRGSCD SGELSRNSGT FSSQIENTPV
210 220 230 240 250
LCPFHLQPVP EPETVLKNQE VEFGRNRERL QFFKWSSGAF KNVAVIPPGT
260 270 280 290 300
GMAHQVNLEH LSRVVFEEAD LLFPDSVIGT DSHITMVNGL GILGWGVGGI
310 320 330 340 350
ETEAVMLGLP VTLTLPEVVG CELTGSSNAF VTSIDIVLGI TKHLRQVGVA
360 370 380 390 400
GKFVEFFGSG VSQLSIVDRT TIANMCPEYG AILSFFPVDN VTLRHLEHTG
410 420 430 440 450
FDKTKLESME EYLKAVKLFR NDENSSEPEY SQVIQINLNS IVASVSGPKR
460 470 480 490 500
PQDRVAVTDM KSDFQACLNE KVGFKGFQVA AEKQSDTVSV RYDGSEYKLS
510 520 530 540 550
HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVETGLRVKP YIRTSLSPGS
560 570 580 590 600
GMVTHYLSSS GVLPYLSKLG FEIVGYGCST CVGNTAPLSE AILNAVKQGD
610 620 630 640 650
LVTCGVLSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL
660 670 680 690 700
GTDSTGKNIY LHDIWPSREE VHQIEEEHVI LSMFKALKEK VEMGNKRWNS
710 720 730 740 750
LDAPDSVLFP WDVKSTYIRC PSFFDKLTKE PAASQPIENA HVLLYLGDSV
760 770 780 790 800
TTDHISPAGS IARSSAAAKY LTNRGLTPRE FNSYGARRGN DAVMTRGTFA
810 820 830 840 850
NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP LIILAGKKYG
860 870 880 890 900
SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LEFLPGENAD
910 920 930 940 950
SLGLSGREVF SLSFPEELFP GITLNIKTST GKEFSVIAAF ENDVEITLYK
960
HGGLLNFVAR KFL
Length:963
Mass (Da):104,802
Last modified:February 1, 2005 - v2
Checksum:i1C9DA13B7FAD314C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti107V → M in AAA79927 (PubMed:7622457).Curated1
Sequence conflicti602V → A in AAA79927 (PubMed:7622457).Curated1
Sequence conflicti765S → R in AAA79927 (PubMed:7622457).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20181 mRNA. Translation: AAA79927.1.
BC081798 mRNA. Translation: AAH81798.1.
PIRiA57238.
RefSeqiNP_074054.2. NM_022863.2.
UniGeneiRn.10132.

Genome annotation databases

EnsembliENSRNOT00000017900; ENSRNOP00000017900; ENSRNOG00000013271.
GeneIDi64831.
KEGGirno:64831.
UCSCiRGD:621539. rat.

Similar proteinsi

Entry informationi

Entry nameiIREB2_RAT
AccessioniPrimary (citable) accession number: Q62751
Secondary accession number(s): Q66HL4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 2005
Last modified: September 27, 2017
This is version 128 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families