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 27-MAR-2024, entry version 197. 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 -!- INTERACTION: CC P48200; Q9UKA1: FBXL5; NbExp=2; IntAct=EBI-2805796, EBI-2692340; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-21149; -. DR SMR; P48200; -. DR BioGRID; 109866; 69. DR IntAct; P48200; 14. 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; 9606-ENSP00000258886; -. DR PeptideAtlas; P48200; -. DR ProteomicsDB; 39753; -. DR ProteomicsDB; 55871; -. [P48200-1] DR Pumba; P48200; -. DR Antibodypedia; 27620; 365 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 AGR; HGNC:6115; -. 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; VYEPMFD; -. DR OrthoDB; 176941at2759; -. 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; 101 hits in 1173 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 193 other cell types or tissues. DR ExpressionAtlas; P48200; baseline and differential. 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: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:0006879; P:intracellular iron ion homeostasis; IMP:UniProtKB. DR GO; GO:0048255; P:mRNA stabilization; TAS:UniProtKB. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IEA:Ensembl. 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:0006417; P:regulation of translation; IEA:Ensembl. DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central. DR CDD; cd01586; AcnA_IRP; 1. DR CDD; cd01580; AcnA_IRP_Swivel; 1. DR Gene3D; 6.10.190.10; -; 1. DR Gene3D; 3.30.499.10; Aconitase, domain 3; 3. DR Gene3D; 3.20.19.10; Aconitase, domain 4; 1. 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 NCBIfam; TIGR01341; aconitase_1; 1. DR PANTHER; PTHR11670; ACONITASE/IRON-RESPONSIVE ELEMENT FAMILY MEMBER; 1. DR PANTHER; PTHR11670:SF31; IRON-RESPONSIVE ELEMENT-BINDING PROTEIN 2; 1. DR Pfam; PF00330; Aconitase; 2. DR Pfam; PF00694; Aconitase_C; 1. DR PRINTS; PR00415; ACONITASE. DR SUPFAM; SSF53732; Aconitase iron-sulfur domain; 1. DR SUPFAM; SSF52016; LeuD/IlvD-like; 1. DR PROSITE; PS00450; ACONITASE_1; 1. DR PROSITE; PS01244; ACONITASE_2; 1. DR Genevisible; P48200; HS. 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 //