IREB2_HUMAN
ID IREB2_HUMAN Reviewed; 963 AA.
AC P48200; A0A0A6YY96; A8KAC7; E1CJT9; H0YKU0; Q13095; Q1HE21; Q59FQ7; Q8WVK6;
AC Q9UF17;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 4.
DT 03-AUG-2022, entry version 188.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, RNA-BINDING, AND VARIANT
RP THR-580.
RX PubMed=7983023; DOI=10.1016/s0021-9258(18)47367-x;
RA Samaniego F., Chin J., Iwai K., Rouault T.A., Klausner R.D.;
RT "Molecular characterization of a second iron-responsive element binding
RT protein, iron regulatory protein 2. Structure, function, and post-
RT translational regulation.";
RL J. Biol. Chem. 269:30904-30910(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Ishiwata T., Sakurada M., Nishimura A., Nakagawa S., Nishi T., Kuga T.,
RA Sawada S., Takei M.;
RT "IgA nephropathy-related gene.";
RL Submitted (SEP-2010) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-580.
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-580.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-580.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-580.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP THR-580.
RC TISSUE=Brain;
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 [9]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-580.
RX PubMed=2172968; DOI=10.1073/pnas.87.20.7958;
RA Rouault T.A., Tang C.K., Kaptain S., Burgess W.H., Haile D.J.,
RA Samaniego F., McBride O.W., Harford J.B., Klausner R.D.;
RT "Cloning of the cDNA encoding an RNA regulatory protein -- the human iron-
RT responsive element-binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7958-7962(1990).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-963 (ISOFORM 1).
RC TISSUE=Brain;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 847-963 (ISOFORM 1).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP UBIQUITINATION, AND INTERACTION WITH RBCK1.
RX PubMed=12629548; DOI=10.1038/ncb952;
RA Yamanaka K., Ishikawa H., Megumi Y., Tokunaga F., Kanie M., Rouault T.A.,
RA Morishima I., Minato N., Ishimori K., Iwai K.;
RT "Identification of the ubiquitin-protein ligase that recognizes oxidized
RT IRP2.";
RL Nat. Cell Biol. 5:336-340(2003).
RN [13]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762596; DOI=10.1126/science.1176333;
RA Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A., Sun D.,
RA Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C., Leibold E.A.,
RA Wohlschlegel J.A.;
RT "Control of iron homeostasis by an iron-regulated ubiquitin ligase.";
RL Science 326:718-721(2009).
RN [14]
RP UBIQUITINATION, AND INTERACTION WITH FBXL5.
RX PubMed=19762597; DOI=10.1126/science.1176326;
RA Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N., Li Q.,
RA Grishin N.V., Bruick R.K.;
RT "An E3 ligase possessing an iron responsive hemerythrin domain is a
RT regulator of iron homeostasis.";
RL Science 326:722-726(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP INTERACTION WITH CIAO1 AND CIAO2A.
RX PubMed=23891004; DOI=10.1016/j.cmet.2013.06.015;
RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B.,
RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and
RT maturation of different subsets of cytosolic-nuclear iron-sulfur
RT proteins.";
RL Cell Metab. 18:187-198(2013).
RN [18]
RP INVOLVEMENT IN NDCAMA, VARIANTS NDCAMA 357-GLY--SER-963 DEL AND
RP 419-ARG--SER-963 DEL, AND CHARACTERIZATION OF VARIANTS NDCAMA
RP 357-GLY--SER-963 DEL AND 419-ARG--SER-963 DEL.
RX PubMed=30915432; DOI=10.1093/brain/awz072;
RA Costain G., Ghosh M.C., Maio N., Carnevale A., Si Y.C., Rouault T.A.,
RA Yoon G.;
RT "Absence of iron-responsive element-binding protein 2 causes a novel
RT neurodegenerative syndrome.";
RL Brain 142:1195-1202(2019).
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:0000269|PubMed:7983023}.
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 isoform 1 and isoform 2 only in iron-rich
CC conditions (PubMed:12629548). Interacts (when associated with the 4Fe-
CC 4S) with FBXL5 (PubMed:19762596, PubMed:19762597). Interacts with CIAO1
CC and CIAO2A (PubMed:23891004). {ECO:0000269|PubMed:12629548,
CC ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597,
CC ECO:0000269|PubMed:23891004}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48200-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48200-2; Sequence=VSP_056823, VSP_056824;
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.
CC {ECO:0000269|PubMed:12629548, ECO:0000269|PubMed:19762596,
CC ECO:0000269|PubMed:19762597}.
CC -!- DISEASE: Neurodegeneration, early-onset, with choreoathetoid movements
CC and microcytic anemia (NDCAMA) [MIM:618451]: An autosomal recessive
CC disorder characterized by severe neurological and extra-neurological
CC manifestations. Clinical features include early-onset global
CC developmental delay, absent speech, dystonia, spasticity,
CC choreoathetoid movement disorder, seizures, and microcytic hypochromic
CC anaemia unresponsive to iron supplementation.
CC {ECO:0000269|PubMed:30915432}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA79926.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD92640.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M58511; AAA69901.1; -; mRNA.
DR EMBL; AB586699; BAJ19024.1; -; mRNA.
DR EMBL; AK292992; BAF85681.1; -; mRNA.
DR EMBL; AB209403; BAD92640.1; ALT_FRAME; mRNA.
DR EMBL; DQ496102; ABF47091.1; -; Genomic_DNA.
DR EMBL; AC011270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF459563; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99169.1; -; Genomic_DNA.
DR EMBL; BC017880; AAH17880.1; -; mRNA.
DR EMBL; BC117481; AAI17482.1; -; mRNA.
DR EMBL; BC117483; AAI17484.1; -; mRNA.
DR EMBL; U20180; AAA79926.1; ALT_FRAME; mRNA.
DR EMBL; AL133439; CAB62825.1; -; mRNA.
DR CCDS; CCDS10302.1; -. [P48200-1]
DR CCDS; CCDS81912.1; -. [P48200-2]
DR PIR; B57238; B57238.
DR RefSeq; NP_001307870.1; NM_001320941.1.
DR RefSeq; NP_001307872.1; NM_001320943.1. [P48200-2]
DR RefSeq; NP_004127.1; NM_004136.3. [P48200-1]
DR PDB; 6VCD; EM; 3.00 A; A=1-963.
DR PDBsum; 6VCD; -.
DR AlphaFoldDB; P48200; -.
DR SMR; P48200; -.
DR BioGRID; 109866; 58.
DR IntAct; P48200; 13.
DR STRING; 9606.ENSP00000258886; -.
DR iPTMnet; P48200; -.
DR PhosphoSitePlus; P48200; -.
DR BioMuta; IREB2; -.
DR DMDM; 308153591; -.
DR EPD; P48200; -.
DR jPOST; P48200; -.
DR MassIVE; P48200; -.
DR PaxDb; P48200; -.
DR PeptideAtlas; P48200; -.
DR PRIDE; P48200; -.
DR ProteomicsDB; 39753; -.
DR ProteomicsDB; 55871; -. [P48200-1]
DR Antibodypedia; 27620; 347 antibodies from 35 providers.
DR DNASU; 3658; -.
DR Ensembl; ENST00000258886.13; ENSP00000258886.8; ENSG00000136381.13. [P48200-1]
DR Ensembl; ENST00000560440.5; ENSP00000452938.1; ENSG00000136381.13. [P48200-2]
DR GeneID; 3658; -.
DR KEGG; hsa:3658; -.
DR MANE-Select; ENST00000258886.13; ENSP00000258886.8; NM_004136.4; NP_004127.2.
DR UCSC; uc002bdq.4; human. [P48200-1]
DR CTD; 3658; -.
DR DisGeNET; 3658; -.
DR GeneCards; IREB2; -.
DR HGNC; HGNC:6115; IREB2.
DR HPA; ENSG00000136381; Low tissue specificity.
DR MalaCards; IREB2; -.
DR MIM; 147582; gene.
DR MIM; 618451; phenotype.
DR neXtProt; NX_P48200; -.
DR OpenTargets; ENSG00000136381; -.
DR PharmGKB; PA29914; -.
DR VEuPathDB; HostDB:ENSG00000136381; -.
DR eggNOG; KOG0452; Eukaryota.
DR GeneTree; ENSGT00940000157796; -.
DR HOGENOM; CLU_069045_0_0_1; -.
DR InParanoid; P48200; -.
DR OMA; ECPDSVV; -.
DR OrthoDB; 190960at2759; -.
DR PhylomeDB; P48200; -.
DR TreeFam; TF313476; -.
DR PathwayCommons; P48200; -.
DR Reactome; R-HSA-917937; Iron uptake and transport.
DR SignaLink; P48200; -.
DR SIGNOR; P48200; -.
DR BioGRID-ORCS; 3658; 97 hits in 1086 CRISPR screens.
DR ChiTaRS; IREB2; human.
DR GenomeRNAi; 3658; -.
DR Pharos; P48200; Tbio.
DR PRO; PR:P48200; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P48200; protein.
DR Bgee; ENSG00000136381; Expressed in tibia and 191 other tissues.
DR ExpressionAtlas; P48200; baseline and differential.
DR Genevisible; P48200; HS.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IBA:GO_Central.
DR GO; GO:0003994; F:aconitate hydratase activity; IBA:GO_Central.
DR GO; GO:0030350; F:iron-responsive element binding; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0030371; F:translation repressor activity; IEA:InterPro.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0006101; P:citrate metabolic process; IBA:GO_Central.
DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; TAS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:Ensembl.
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 3D-structure; 4Fe-4S; Alternative splicing; Cytoplasm; Disease variant;
KW Iron; Iron-sulfur; Metal-binding; Neurodegeneration; Reference proteome;
KW RNA-binding; Ubl conjugation.
FT CHAIN 1..963
FT /note="Iron-responsive element-binding protein 2"
FT /id="PRO_0000076684"
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 VAR_SEQ 342
FT /note="H -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_056823"
FT VAR_SEQ 343..962
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_056824"
FT VARIANT 357..963
FT /note="Missing (in NDCAMA; may drastically decrease protein
FT expression level)"
FT /evidence="ECO:0000269|PubMed:30915432"
FT /id="VAR_082271"
FT VARIANT 419..963
FT /note="Missing (in NDCAMA; may drastically decrease protein
FT expression level)"
FT /evidence="ECO:0000269|PubMed:30915432"
FT /id="VAR_082272"
FT VARIANT 580
FT /note="I -> T (in dbSNP:rs2230940)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2172968,
FT ECO:0000269|PubMed:7983023, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.5, ECO:0000269|Ref.7"
FT /id="VAR_058410"
FT CONFLICT 195
FT /note="E -> G (in Ref. 3; BAF85681)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="F -> L (in Ref. 1; AAA69901, 3; BAF85681 and 10;
FT AAA79926)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="Q -> R (in Ref. 10; AAA79926)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="T -> P (in Ref. 3; BAF85681)"
FT /evidence="ECO:0000305"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 19..22
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 33..37
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 93..107
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 216..224
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 255..259
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 283..289
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 298..304
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 332..346
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 355..359
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 365..372
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 373..379
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 389..398
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 402..414
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 434..437
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 438..440
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 669..672
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 674..677
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 679..688
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 706..708
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 722..724
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 739..745
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 752..755
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 766..773
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 778..780
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 783..785
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 791..795
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 807..809
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 814..817
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 819..821
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 824..826
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 827..836
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 841..844
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 847..849
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 851..853
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 860..865
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 869..873
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 877..884
FT /evidence="ECO:0007829|PDB:6VCD"
FT TURN 885..887
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 889..893
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 899..901
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 908..911
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 922..927
FT /evidence="ECO:0007829|PDB:6VCD"
FT STRAND 934..938
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 943..950
FT /evidence="ECO:0007829|PDB:6VCD"
FT HELIX 954..961
FT /evidence="ECO:0007829|PDB:6VCD"
SQ SEQUENCE 963 AA; 105059 MW; 051228C6CE5362FD CRC64;
MDAPKAGYAF EYLIETLNDS SHKKFFDVSK LGTKYDVLPY SIRVLLEAAV RNCDGFLMKK
EDVMNILDWK TKQSNVEVPF FPARVLLQDF TGIPAMVDFA AMREAVKTLG GDPEKVHPAC
PTDLTVDHSL QIDFSKCAIQ NAPNPGGGDL QKAGKLSPLK VQPKKLPCRG QTTCRGSCDS
GELGRNSGTF SSQIENTPIL CPFHLQPVPE PETVLKNQEV EFGRNRERLQ FFKWSSRVFK
NVAVIPPGTG MAHQINLEYL SRVVFEEKDL LFPDSVVGTD SHITMVNGLG ILGWGVGGIE
TEAVMLGLPV SLTLPEVVGC ELTGSSNPFV TSIDVVLGIT KHLRQVGVAG KFVEFFGSGV
SQLSIVDRTT IANMCPEYGA ILSFFPVDNV TLKHLEHTGF SKAKLESMET YLKAVKLFRN
DQNSSGEPEY SQVIQINLNS IVPSVSGPKR PQDRVAVTDM KSDFQACLNE KVGFKGFQIA
AEKQKDIVSI HYEGSEYKLS HGSVVIAAVI SCTNNCNPSV MLAAGLLAKK AVEAGLRVKP
YIRTSLSPGS GMVTHYLSSS GVLPYLSKLG FEIVGYGCSI CVGNTAPLSD AVLNAVKQGD
LVTCGILSGN KNFEGRLCDC VRANYLASPP LVVAYAIAGT VNIDFQTEPL GTDPTGKNIY
LHDIWPSREE VHRVEEEHVI LSMFKALKDK IEMGNKRWNS LEAPDSVLFP WDLKSTYIRC
PSFFDKLTKE PIALQAIENA HVLLYLGDSV TTDHISPAGS IARNSAAAKY LTNRGLTPRE
FNSYGARRGN DAVMTRGTFA NIKLFNKFIG KPAPKTIHFP SGQTLDVFEA AELYQKEGIP
LIILAGKKYG SGNSRDWAAK GPYLLGVKAV LAESYEKIHK DHLIGIGIAP LQFLPGENAD
SLGLSGRETF SLTFPEELSP GITLNIQTST GKVFSVIASF EDDVEITLYK HGGLLNFVAR
KFS
