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Protein

Iron-responsive element-binding protein 2

Gene

IREB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.1 Publication

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-KW
  • iron-responsive element binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA binding Source: UniProtKB
  • translation repressor activity Source: InterPro

GO - Biological processi

  • cellular iron ion homeostasis Source: Reactome
  • iron ion transport Source: UniProtKB
  • metabolic process Source: InterPro

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-917937 Iron uptake and transport
SIGNORiP48200

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000136381.12
HGNCiHGNC:6115 IREB2
MIMi147582 gene
neXtProtiNX_P48200

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi3658
PharmGKBiPA29914

Polymorphism and mutation databases

BioMutaiIREB2
DMDMi308153591

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766841 – 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.3 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiP48200
MaxQBiP48200
PaxDbiP48200
PeptideAtlasiP48200
PRIDEiP48200
ProteomicsDBi55871

PTM databases

iPTMnetiP48200
PhosphoSitePlusiP48200

Expressioni

Gene expression databases

BgeeiENSG00000136381
CleanExiHS_IREB2
ExpressionAtlasiP48200 baseline and differential
GenevisibleiP48200 HS

Organism-specific databases

HPAiCAB032885
HPA040371
HPA068982

Interactioni

Subunit structurei

Interacts with RBCK1 isoform 1 and isoform 2 only in iron-rich conditions. Interacts (when associated with the 4Fe-4S) with FBXL5.3 Publications

Protein-protein interaction databases

BioGridi109866, 27 interactors
IntActiP48200, 4 interactors
STRINGi9606.ENSP00000258886

Structurei

3D structure databases

ProteinModelPortaliP48200
SMRiP48200
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the aconitase/IPM isomerase family.Curated

Phylogenomic databases

eggNOGiKOG0452 Eukaryota
COG1048 LUCA
HOGENOMiHOG000025704
HOVERGENiHBG052147
InParanoidiP48200
KOiK22416
PhylomeDBiP48200
TreeFamiTF313476

Family and domain databases

Gene3Di3.20.19.10, 1 hit
3.30.499.10, 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
IPR006249 Aconitase/IRP2
IPR018136 Aconitase_4Fe-4S_BS
IPR036008 Aconitase_4Fe-4S_dom
IPR000573 AconitaseA/IPMdHydase_ssu_swvl
IPR029755 IRE-BP2
PANTHERiPTHR11670 PTHR11670, 1 hit
PTHR11670:SF31 PTHR11670:SF31, 1 hit
PfamiView protein in Pfam
PF00330 Aconitase, 2 hits
PF00694 Aconitase_C, 1 hit
PRINTSiPR00415 ACONITASE
SUPFAMiSSF53732 SSF53732, 2 hits
TIGRFAMsiTIGR01341 aconitase_1, 1 hit
PROSITEiView protein in PROSITE
PS00450 ACONITASE_1, 1 hit
PS01244 ACONITASE_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48200-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDAPKAGYAF EYLIETLNDS SHKKFFDVSK LGTKYDVLPY SIRVLLEAAV
60 70 80 90 100
RNCDGFLMKK EDVMNILDWK TKQSNVEVPF FPARVLLQDF TGIPAMVDFA
110 120 130 140 150
AMREAVKTLG GDPEKVHPAC PTDLTVDHSL QIDFSKCAIQ NAPNPGGGDL
160 170 180 190 200
QKAGKLSPVK VQPKKLPCRG QTTCRGSCDS GELGRNSGTF SSQIENTPIL
210 220 230 240 250
CPFHLQPVPE PETVLKNQEV EFGRNRERLQ FFKWSSRVFK NVAVIPPGTG
260 270 280 290 300
MAHQINLEYL SRVVFEEKDL LFPDSVVGTD SHITMVNGLG ILGWGVGGIE
310 320 330 340 350
TEAVMLGLPV SLTLPEVVGC ELTGSSNPFV TSIDVVLGIT KHLRQVGVAG
360 370 380 390 400
KFVEFFGSGV SQLSIVDRTT IANMCPEYGA ILSFFPVDNV TLKHLEHTGF
410 420 430 440 450
SKAKLESMET YLKAVKLFRN DQNSSGEPEY SQVIQINLNS IVPSVSGPKR
460 470 480 490 500
PQDRVAVTDM KSDFQACLNE KVGFKGFQIA AEKQKDIVSI HYEGSEYKLS
510 520 530 540 550
HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVEAGLRVKP YIRTSLSPGS
560 570 580 590 600
GMVTHYLSSS GVLPYLSKLG FEIVGYGCSI CVGNTAPLSD AVLNAVKQGD
610 620 630 640 650
LVTCGILSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL
660 670 680 690 700
GTDPTGKNIY LHDIWPSREE VHRVEEEHVI LSMFKALKDK IEMGNKRWNS
710 720 730 740 750
LEAPDSVLFP WDLKSTYIRC PSFFDKLTKE PIALQAIENA HVLLYLGDSV
760 770 780 790 800
TTDHISPAGS IARNSAAAKY LTNRGLTPRE FNSYGARRGN DAVMTRGTFA
810 820 830 840 850
NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP LIILAGKKYG
860 870 880 890 900
SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LQFLPGENAD
910 920 930 940 950
SLGLSGRETF SLTFPEELSP GITLNIQTST GKVFSVIASF EDDVEITLYK
960
HGGLLNFVAR KFS
Length:963
Mass (Da):105,045
Last modified:October 5, 2010 - v3
Checksum:iF3585B6BEA8DC9CA
GO
Isoform 2 (identifier: P48200-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     342-342: H → V
     343-962: Missing.

Show »
Length:343
Mass (Da):37,487
Checksum:i922D1072993318E5
GO

Sequence cautioni

The sequence AAA79926 differs from that shown. Reason: Frameshift at positions 605 and 611.Curated
The sequence BAD92640 differs from that shown. Reason: Frameshift at position 727.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195E → G in BAF85681 (PubMed:14702039).Curated1
Sequence conflicti239F → L in AAA69901 (PubMed:7983023).Curated1
Sequence conflicti239F → L in BAF85681 (PubMed:14702039).Curated1
Sequence conflicti239F → L in AAA79926 (PubMed:7622457).Curated1
Sequence conflicti452Q → R in AAA79926 (PubMed:7622457).Curated1
Sequence conflicti458T → P in BAF85681 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_058409159V → LCombined sources8 PublicationsCorresponds to variant dbSNP:rs2958720Ensembl.1
Natural variantiVAR_058410580I → T7 PublicationsCorresponds to variant dbSNP:rs2230940Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056823342H → V in isoform 2. 2 Publications1
Alternative sequenceiVSP_056824343 – 962Missing in isoform 2. 2 PublicationsAdd BLAST620

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58511 mRNA Translation: AAA69901.1
AB586699 mRNA Translation: BAJ19024.1
AK292992 mRNA Translation: BAF85681.1
AB209403 mRNA Translation: BAD92640.1 Frameshift.
DQ496102 Genomic DNA Translation: ABF47091.1
AC011270 Genomic DNA No translation available.
AC027228 Genomic DNA No translation available.
CH471136 Genomic DNA Translation: EAW99169.1
BC017880 mRNA Translation: AAH17880.1
BC117481 mRNA Translation: AAI17482.1
BC117483 mRNA Translation: AAI17484.1
U20180 mRNA Translation: AAA79926.1 Frameshift.
AL133439 mRNA Translation: CAB62825.1
CCDSiCCDS10302.1 [P48200-1]
CCDS81912.1 [P48200-2]
PIRiB57238
RefSeqiNP_001307870.1, NM_001320941.1
NP_001307872.1, NM_001320943.1
NP_004127.1, NM_004136.3
UniGeneiHs.436031

Genome annotation databases

EnsembliENST00000560440; ENSP00000452938; ENSG00000136381
GeneIDi3658
KEGGihsa:3658
UCSCiuc002bdq.4 human [P48200-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIREB2_HUMAN
AccessioniPrimary (citable) accession number: P48200
Secondary accession number(s): A8KAC7
, E1CJT9, H0YKU0, Q13095, Q1HE21, Q59FQ7, Q8WVK6, Q9UF17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 5, 2010
Last modified: June 20, 2018
This is version 162 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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