P48200 (IREB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	963 AA.
Sequence status	Complete.
Protein existence	Evidence 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 1 and isoform 2 only 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 component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	4Fe-4S Iron Iron-sulfur Metal-binding RNA-binding
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara cellular iron ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from electronic annotation. Source: Compara erythrocyte homeostasis Inferred from electronic annotation. Source: Compara intestinal absorption Inferred from electronic annotation. Source: Compara iron ion transport Traceable author statement PubMed 9924025. Source: UniProtKB osteoclast differentiation Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: Compara regulation of translation Inferred from electronic annotation. Source: Compara response to iron(II) ion Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Non-traceable author statement Ref.1. Source: UniProtKB cytosol Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 963	963	Iron-responsive element-binding protein 2		PRO_0000076684
Sites
	Metal binding	512	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	578	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	581	1	Iron-sulfur (4Fe-4S) By similarity
Natural variations
	Natural variant	159	1	V → 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 variant	580	1	I → 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 conflict	195	1	E → G in BAF85681. Ref.2
	Sequence conflict	239	1	F → L in AAA69901. Ref.1
	Sequence conflict	239	1	F → L in AAA79926. Ref.9
	Sequence conflict	452	1	Q → R in AAA79926. Ref.9
	Sequence conflict	458	1	T → P in BAF85681. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P48200 [UniParc]. Last modified October 5, 2010. Version 3. Checksum: F3585B6BEA8DC9CA	FASTA	963	105,045
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00008726.
PIR	B57238.
RefSeq	NP_004127.1. NM_004136.2.
UniGene	Hs.436031.
3D structure databases
ProteinModelPortal	P48200.
SMR	P48200. Positions 7-963.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48200. 2 interactions.
STRING	9606.ENSP00000258886.
PTM databases
PhosphoSite	P48200.
Polymorphism databases
DMDM	308153591.
Proteomic databases
PaxDb	P48200.
PRIDE	P48200.
Protocols and materials databases
DNASU	3658.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000258886; ENSP00000258886; ENSG00000136381.
GeneID	3658.
KEGG	hsa:3658.
UCSC	uc010unb.1. human.
Organism-specific databases
CTD	3658.
GeneCards	GC15P078730.
HGNC	HGNC:6115. IREB2.
HPA	CAB032885.
MIM	147582. gene.
neXtProt	NX_P48200.
PharmGKB	PA29914.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1048.
HOGENOM	HOG000025704.
HOVERGEN	HBG052147.
InParanoid	P48200.
OMA	PCRGQTT.
OrthoDB	EOG45HRWP.
PhylomeDB	P48200.
Gene expression databases
ArrayExpress	P48200.
Bgee	P48200.
CleanEx	HS_IREB2.
Genevestigator	P48200.
GermOnline	ENSG00000136381. Homo sapiens.
Family and domain databases
Gene3D	3.20.19.10. 1 hit. 3.30.499.10. 4 hits. 3.40.1060.10. 1 hit.
InterPro	IPR015931. 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]
PANTHER	PTHR11670. PTHR11670. 1 hit. PTHR11670:SF1. PTHR11670:SF1. 1 hit.
Pfam	PF00330. Aconitase. 2 hits. PF00694. Aconitase_C. 1 hit. [Graphical view]
PRINTS	PR00415. ACONITASE.
SUPFAM	SSF52016. Aconitase/3IPM_dehydase_swvl. 1 hit. SSF53732. Aconitase_N. 1 hit.
TIGRFAMs	TIGR01341. aconitase_1. 1 hit.
PROSITE	PS00450. ACONITASE_1. 1 hit. PS01244. ACONITASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IREB2. human.
GenomeRNAi	3658.
NextBio	14307.
SOURCE	Search...

Entry information

Entry name

IREB2_HUMAN

Accession

Primary (citable) accession number: P48200
Secondary accession number(s): A8KAC7 , Q13095, Q1HE21, Q59FQ7, Q9UF17

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 5, 2010
Last modified:	April 3, 2013
This is version 117 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.