Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P48200 (IREB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Iron-responsive element-binding protein 2

Short name=IRE-BP 2
Alternative name(s):
Iron regulatory protein 2
Short name=IRP2
Gene names
Name:IREB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length963 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Cofactor

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

Subunit structure

Interacts with RBCK1 isoform 1and isoform 2only in iron-rich conditions. Interacts (when associated with the 4Fe-4S) with FBXL5. Ref.11 Ref.12 Ref.13

Subcellular location

Cytoplasm.

Post-translational modification

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. Ref.11 Ref.12 Ref.13

Sequence similarities

Belongs to the aconitase/IPM isomerase family.

Sequence caution

The sequence AAA79926.1 differs from that shown. Reason: Frameshift at positions 605 and 611.

The sequence BAD92640.1 differs from that shown. Reason: Frameshift at position 727.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   Ligand4Fe-4S
Iron
Iron-sulfur
Metal-binding
RNA-binding
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cellular iron ion homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

erythrocyte homeostasis

Inferred from electronic annotation. Source: Ensembl

intestinal absorption

Inferred from electronic annotation. Source: Ensembl

iron ion transport

Traceable author statement PubMed 9924025. Source: UniProtKB

osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

protoporphyrinogen IX biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of translation

Inferred from electronic annotation. Source: Ensembl

response to iron(II) ion

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Non-traceable author statement Ref.1. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_function4 iron, 4 sulfur cluster binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

iron-responsive element binding

Traceable author statement PubMed 9924025. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 963963Iron-responsive element-binding protein 2
PRO_0000076684

Sites

Metal binding5121Iron-sulfur (4Fe-4S) By similarity
Metal binding5781Iron-sulfur (4Fe-4S) By similarity
Metal binding5811Iron-sulfur (4Fe-4S) By similarity

Natural variations

Natural variant1591V → L. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.8 Ref.15
Corresponds to variant rs2958720 [ dbSNP | Ensembl ].
VAR_058409
Natural variant5801I → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.8
Corresponds to variant rs2230940 [ dbSNP | Ensembl ].
VAR_058410

Experimental info

Sequence conflict1951E → G in BAF85681. Ref.2
Sequence conflict2391F → L in AAA69901. Ref.1
Sequence conflict2391F → L in AAA79926. Ref.9
Sequence conflict4521Q → R in AAA79926. Ref.9
Sequence conflict4581T → P in BAF85681. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P48200 [UniParc].

Last modified October 5, 2010. Version 3.
Checksum: F3585B6BEA8DC9CA

FASTA963105,045
        10         20         30         40         50         60 
MDAPKAGYAF EYLIETLNDS SHKKFFDVSK LGTKYDVLPY SIRVLLEAAV RNCDGFLMKK 

        70         80         90        100        110        120 
EDVMNILDWK TKQSNVEVPF FPARVLLQDF TGIPAMVDFA AMREAVKTLG GDPEKVHPAC 

       130        140        150        160        170        180 
PTDLTVDHSL QIDFSKCAIQ NAPNPGGGDL QKAGKLSPVK VQPKKLPCRG QTTCRGSCDS 

       190        200        210        220        230        240 
GELGRNSGTF SSQIENTPIL CPFHLQPVPE PETVLKNQEV EFGRNRERLQ FFKWSSRVFK 

       250        260        270        280        290        300 
NVAVIPPGTG MAHQINLEYL SRVVFEEKDL LFPDSVVGTD SHITMVNGLG ILGWGVGGIE 

       310        320        330        340        350        360 
TEAVMLGLPV SLTLPEVVGC ELTGSSNPFV TSIDVVLGIT KHLRQVGVAG KFVEFFGSGV 

       370        380        390        400        410        420 
SQLSIVDRTT IANMCPEYGA ILSFFPVDNV TLKHLEHTGF SKAKLESMET YLKAVKLFRN 

       430        440        450        460        470        480 
DQNSSGEPEY SQVIQINLNS IVPSVSGPKR PQDRVAVTDM KSDFQACLNE KVGFKGFQIA 

       490        500        510        520        530        540 
AEKQKDIVSI HYEGSEYKLS HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVEAGLRVKP 

       550        560        570        580        590        600 
YIRTSLSPGS GMVTHYLSSS GVLPYLSKLG FEIVGYGCSI CVGNTAPLSD AVLNAVKQGD 

       610        620        630        640        650        660 
LVTCGILSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL GTDPTGKNIY 

       670        680        690        700        710        720 
LHDIWPSREE VHRVEEEHVI LSMFKALKDK IEMGNKRWNS LEAPDSVLFP WDLKSTYIRC 

       730        740        750        760        770        780 
PSFFDKLTKE PIALQAIENA HVLLYLGDSV TTDHISPAGS IARNSAAAKY LTNRGLTPRE 

       790        800        810        820        830        840 
FNSYGARRGN DAVMTRGTFA NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP 

       850        860        870        880        890        900 
LIILAGKKYG SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LQFLPGENAD 

       910        920        930        940        950        960 
SLGLSGRETF SLTFPEELSP GITLNIQTST GKVFSVIASF EDDVEITLYK HGGLLNFVAR 


KFS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation."
Samaniego F., Chin J., Iwai K., Rouault T.A., Klausner R.D.
J. Biol. Chem. 269:30904-30910(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, VARIANTS LEU-159 AND THR-580.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-159 AND THR-580.
Tissue: Trachea.
[3]"Homo sapiens protein coding cDNA."
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-159 AND THR-580.
Tissue: Brain.
[4]NIEHS SNPs program
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-159 AND THR-580.
[5]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LEU-159 AND THR-580.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-159 AND THR-580.
Tissue: Brain.
[8]"Cloning of the cDNA encoding an RNA regulatory protein -- the human iron-responsive element-binding protein."
Rouault T.A., Tang C.K., Kaptain S., Burgess W.H., Haile D.J., Samaniego F., McBride O.W., Harford J.B., Klausner R.D.
Proc. Natl. Acad. Sci. U.S.A. 87:7958-7962(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-159 AND THR-580.
[9]"Characterization and expression of iron regulatory protein 2 (IRP2). Presence of multiple IRP2 transcripts regulated by intracellular iron levels."
Guo B., Brown F.M., Phillips J.D., Yu Y., Leibold E.A.
J. Biol. Chem. 270:16529-16535(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-963.
Tissue: Brain.
[10]The European IMAGE consortium
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 847-963.
[11]"Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2."
Yamanaka K., Ishikawa H., Megumi Y., Tokunaga F., Kanie M., Rouault T.A., Morishima I., Minato N., Ishimori K., Iwai K.
Nat. Cell Biol. 5:336-340(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH RBCK1.
[12]"Control of iron homeostasis by an iron-regulated ubiquitin ligase."
Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A., Sun D., Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C., Leibold E.A., Wohlschlegel J.A.
Science 326:718-721(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXL5.
[13]"An E3 ligase possessing an iron responsive hemerythrin domain is a regulator of iron homeostasis."
Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N., Li Q., Grishin N.V., Bruick R.K.
Science 326:722-726(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH FBXL5.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-159, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M58511 mRNA. Translation: AAA69901.1.
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.
BC117481 mRNA. Translation: AAI17482.1.
BC117483 mRNA. Translation: AAI17484.1.
U20180 mRNA. Translation: AAA79926.1. Frameshift.
AL133439 mRNA. Translation: CAB62825.1.
PIRB57238.
RefSeqNP_004127.1. NM_004136.2.
UniGeneHs.436031.

3D structure databases

ProteinModelPortalP48200.
SMRP48200. Positions 7-963.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109866. 12 interactions.
IntActP48200. 2 interactions.
STRING9606.ENSP00000258886.

PTM databases

PhosphoSiteP48200.

Polymorphism databases

DMDM308153591.

Proteomic databases

PaxDbP48200.
PRIDEP48200.

Protocols and materials databases

DNASU3658.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258886; ENSP00000258886; ENSG00000136381.
GeneID3658.
KEGGhsa:3658.
UCSCuc010unb.1. human.

Organism-specific databases

CTD3658.
GeneCardsGC15P078730.
HGNCHGNC:6115. IREB2.
HPACAB032885.
MIM147582. gene.
neXtProtNX_P48200.
PharmGKBPA29914.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1048.
HOGENOMHOG000025704.
HOVERGENHBG052147.
InParanoidP48200.
OMAPCRGQTT.
OrthoDBEOG7CG6Z7.
PhylomeDBP48200.
TreeFamTF313476.

Gene expression databases

ArrayExpressP48200.
BgeeP48200.
CleanExHS_IREB2.
GenevestigatorP48200.

Family and domain databases

Gene3D3.20.19.10. 1 hit.
3.30.499.10. 4 hits.
3.40.1060.10. 1 hit.
InterProIPR015931. Acnase/IPM_dHydase_lsu_aba_1/3.
IPR015937. Acoase/IPM_deHydtase.
IPR001030. Acoase/IPM_deHydtase_lsu_aba.
IPR015928. Aconitase/3IPM_dehydase_swvl.
IPR006249. Aconitase/Fe_reg_prot_2.
IPR015934. Aconitase/Fe_reg_prot_2/AcnD.
IPR015932. Aconitase/IPMdHydase_lsu_aba_2.
IPR018136. Aconitase_4Fe-4S_BS.
IPR000573. AconitaseA/IPMdHydase_ssu_swvl.
[Graphical view]
PANTHERPTHR11670. PTHR11670. 1 hit.
PTHR11670:SF1. PTHR11670:SF1. 1 hit.
PfamPF00330. Aconitase. 2 hits.
PF00694. Aconitase_C. 1 hit.
[Graphical view]
PRINTSPR00415. ACONITASE.
SUPFAMSSF52016. SSF52016. 1 hit.
SSF53732. SSF53732. 2 hits.
TIGRFAMsTIGR01341. aconitase_1. 1 hit.
PROSITEPS00450. ACONITASE_1. 1 hit.
PS01244. ACONITASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIREB2. human.
GenomeRNAi3658.
NextBio14307.
PROP48200.
SOURCESearch...

Entry information

Entry nameIREB2_HUMAN
AccessionPrimary (citable) accession number: P48200
Secondary accession number(s): A8KAC7 expand/collapse secondary AC list , Q13095, Q1HE21, Q59FQ7, Q9UF17
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM