ID IRT1_ARATH Reviewed; 347 AA. AC Q38856; Q8LBP0; DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot. DT 31-MAY-2011, sequence version 2. DT 17-JUN-2020, entry version 153. DE RecName: Full=Fe(2+) transport protein 1; DE AltName: Full=Fe(II) transport protein 1; DE AltName: Full=Iron-regulated transporter 1; DE Flags: Precursor; GN Name=IRT1; OrderedLocusNames=At4g19690; ORFNames=T16H5.50; OS Arabidopsis thaliana (Mouse-ear cress). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis. OX NCBI_TaxID=3702; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Columbia; RX PubMed=10617198; DOI=10.1038/47134; RA Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T., RA Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B., RA Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M., RA de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M., RA Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D., RA Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J., RA Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B., RA Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J., RA Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R., RA Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M., RA Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P., RA Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S., RA Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C., RA Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J., RA Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S., RA Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A., RA Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M., RA Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M., RA Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D., RA Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E., RA Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S., RA Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R., RA Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M., RA Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E., RA Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P., RA Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K., RA Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K., RA de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K., RA Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M., RA Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G., RA Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K., RA Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K., RA Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W., RA Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H., RA Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B., RA Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J., RA Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K., RA O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N., RA Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A., RA Martienssen R., McCombie W.R.; RT "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana."; RL Nature 402:769-777(1999). RN [2] RP GENOME REANNOTATION. RC STRAIN=cv. Columbia; RX PubMed=27862469; DOI=10.1111/tpj.13415; RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S., RA Town C.D.; RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference RT genome."; RL Plant J. 89:789-804(2017). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B., RA Feldmann K.A.; RT "Full-length cDNA from Arabidopsis thaliana."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-347 (ISOFORM 1), AND CHARACTERIZATION. RC STRAIN=cv. Landsberg erecta; RX PubMed=8643627; DOI=10.1073/pnas.93.11.5624; RA Eide D., Broderius M., Fett J., Guerinot M.L.; RT "A novel iron-regulated metal transporter from plants identified by RT functional expression in yeast."; RL Proc. Natl. Acad. Sci. U.S.A. 93:5624-5628(1996). RN [5] RP CHARACTERIZATION, AND METAL-BINDING. RX PubMed=9784581; DOI=10.1007/s002329900442; RA Eng B.H., Guerinot M.L., Eide D., Saier M.H. Jr.; RT "Sequence analyses and phylogenetic characterization of the ZIP family of RT metal ion transport proteins."; RL J. Membr. Biol. 166:1-7(1998). RN [6] RP BROAD CATION RANGE. RX PubMed=10394943; DOI=10.1023/a:1026438615520; RA Korshunova Y.O., Eide D., Clark W.G., Guerinot M.L., Pakrasi H.B.; RT "The IRT1 protein from Arabidopsis thaliana is a metal transporter with a RT broad substrate range."; RL Plant Mol. Biol. 40:37-44(1999). RN [7] RP MUTAGENESIS OF HIS-104; ASP-108; GLU-111; ASP-144; HIS-205; SER-206; RP HIS-232 AND GLU-236. RX PubMed=11035780; DOI=10.1073/pnas.210214197; RA Rogers E.E., Eide D.J., Guerinot M.L.; RT "Altered selectivity in an Arabidopsis metal transporter."; RL Proc. Natl. Acad. Sci. U.S.A. 97:12356-12360(2000). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION RP PHENOTYPE. RX PubMed=12084823; DOI=10.1105/tpc.001388; RA Vert G., Grotz N., Dedaldechamp F., Gaymard F., Guerinot M.L., Briat J.-F., RA Curie C.; RT "IRT1, an Arabidopsis transporter essential for iron uptake from the soil RT and for plant growth."; RL Plant Cell 14:1223-1233(2002). RN [9] RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-154 AND LYS-179, UBIQUITINATION AT RP LYS-154 AND LYS-179, AND INDUCTION BY IRON STARVATION. RX PubMed=21628566; DOI=10.1073/pnas.1100659108; RA Barberon M., Zelazny E., Robert S., Conejero G., Curie C., Friml J., RA Vert G.; RT "Monoubiquitin-dependent endocytosis of the iron-regulated transporter 1 RT (IRT1) transporter controls iron uptake in plants."; RL Proc. Natl. Acad. Sci. U.S.A. 108:E450-458(2011). RN [10] RP INTERACTION WITH FREE1, AND SUBCELLULAR LOCATION. RX PubMed=24843126; DOI=10.1073/pnas.1402262111; RA Barberon M., Dubeaux G., Kolb C., Isono E., Zelazny E., Vert G.; RT "Polarization of IRON-REGULATED TRANSPORTER 1 (IRT1) to the plant-soil RT interface plays crucial role in metal homeostasis."; RL Proc. Natl. Acad. Sci. U.S.A. 111:8293-8298(2014). CC -!- FUNCTION: High-affinity iron transporter that plays a key role in the CC uptake of iron from the rhizosphere across the plasma membrane in the CC root epidermal layer. Acts as the principal regulator of iron CC homeostasis in planta. Also mediates the heavy metals uptake under CC iron-deficiency by its ability to transport cobalt, cadmium, manganese CC and/or zinc ions. {ECO:0000269|PubMed:12084823}. CC -!- SUBUNIT: Interacts with FREE1. {ECO:0000269|PubMed:24843126}. CC -!- INTERACTION: CC Q38856; P59263: UBQ16; NbExp=3; IntAct=EBI-15928951, EBI-1541543; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12084823, CC ECO:0000269|PubMed:21628566, ECO:0000269|PubMed:24843126}; Multi-pass CC membrane protein {ECO:0000269|PubMed:12084823}. Early endosome CC {ECO:0000269|PubMed:21628566, ECO:0000269|PubMed:24843126}. Golgi CC apparatus, trans-Golgi network {ECO:0000269|PubMed:21628566, CC ECO:0000269|PubMed:24843126}. Vacuole {ECO:0000269|PubMed:21628566}. CC Note=Cycles constitutively between early endosomes and the plasma CC membrane and is targeted to the vacuole for degradation. CC {ECO:0000269|PubMed:21628566}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q38856-1; Sequence=Displayed; CC Name=2; CC IsoId=Q38856-2; Sequence=VSP_008361, VSP_008362; CC -!- TISSUE SPECIFICITY: Expressed in the external cell layers of the root CC including the lateral branching zone. Also detected in flowers before CC pollination. {ECO:0000269|PubMed:12084823}. CC -!- INDUCTION: In roots by iron starvation. {ECO:0000269|PubMed:21628566}. CC -!- PTM: Monoubiquitinated on several Lys residues. Monoubiquitination CC controls trafficking from the plasma membrane and targeting to the CC vacuole. {ECO:0000269|PubMed:21628566}. CC -!- DISRUPTION PHENOTYPE: Plants exhibit a lethal chlorotic phenotype. CC {ECO:0000269|PubMed:12084823}. CC -!- MISCELLANEOUS: Inhibited by cadmium and Fe(2+) ions and at 100-fold CC excess inhibited by cobalt, manganese and zinc ions. CC -!- MISCELLANEOUS: The availability of secondary non-iron metal substrates CC (Zn, Mn, and Co) controls the localization of IRT1 between the outer CC polar domain of the plasma membrane and early endosome/trans-Golgi CC network in root epidermal cells. {ECO:0000269|PubMed:24843126}. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB01678.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA19686.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAB78971.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AL024486; CAA19686.1; ALT_INIT; Genomic_DNA. DR EMBL; AL161551; CAB78971.1; ALT_INIT; Genomic_DNA. DR EMBL; CP002687; AEE84216.1; -; Genomic_DNA. DR EMBL; CP002687; AEE84217.1; -; Genomic_DNA. DR EMBL; AY087095; AAM64655.1; -; mRNA. DR EMBL; U27590; AAB01678.1; ALT_INIT; mRNA. DR PIR; T04750; T04750. DR RefSeq; NP_567590.3; NM_118089.4. [Q38856-1] DR RefSeq; NP_849546.1; NM_179215.2. [Q38856-2] DR BioGRID; 13006; 3. DR DIP; DIP-60391N; -. DR IntAct; Q38856; 1. DR STRING; 3702.AT4G19690.2; -. DR TCDB; 2.A.5.1.2; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family. DR iPTMnet; Q38856; -. DR PaxDb; Q38856; -. DR ProteomicsDB; 247047; -. [Q38856-1] DR EnsemblPlants; AT4G19690.1; AT4G19690.1; AT4G19690. [Q38856-2] DR EnsemblPlants; AT4G19690.2; AT4G19690.2; AT4G19690. [Q38856-1] DR GeneID; 827713; -. DR Gramene; AT4G19690.1; AT4G19690.1; AT4G19690. [Q38856-2] DR Gramene; AT4G19690.2; AT4G19690.2; AT4G19690. [Q38856-1] DR KEGG; ath:AT4G19690; -. DR Araport; AT4G19690; -. DR TAIR; locus:2133965; AT4G19690. DR eggNOG; KOG1558; Eukaryota. DR eggNOG; ENOG4111GP2; LUCA. DR HOGENOM; CLU_027089_3_0_1; -. DR InParanoid; Q38856; -. DR KO; K14709; -. DR OMA; CASESAH; -. DR BioCyc; ARA:AT4G19690-MONOMER; -. DR BioCyc; MetaCyc:AT4G19690-MONOMER; -. DR PRO; PR:Q38856; -. DR Proteomes; UP000006548; Chromosome 4. DR ExpressionAtlas; Q38856; baseline and differential. DR Genevisible; Q38856; AT. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:TAIR. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:TAIR. DR GO; GO:0005802; C:trans-Golgi network; IDA:TAIR. DR GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell. DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IGI:TAIR. DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW. DR GO; GO:0030001; P:metal ion transport; IMP:TAIR. DR GO; GO:0015675; P:nickel cation transport; IMP:TAIR. DR GO; GO:0009617; P:response to bacterium; IEP:TAIR. DR GO; GO:0071577; P:zinc ion transmembrane transport; IBA:GO_Central. DR InterPro; IPR003689; ZIP. DR InterPro; IPR004698; Zn/Fe_permease_fun/pln. DR Pfam; PF02535; Zip; 1. DR TIGRFAMs; TIGR00820; zip; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Endosome; Golgi apparatus; KW Ion transport; Iron; Iron transport; Isopeptide bond; Membrane; KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation; Vacuole. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..347 FT /note="Fe(2+) transport protein 1" FT /id="PRO_0000041636" FT TOPO_DOM 23..52 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 53..73 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 74..84 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 85..105 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 106..125 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 126..146 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 147..192 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 193..213 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 214..224 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 225..245 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 246..254 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 255..275 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 276..286 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 287..307 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 308..326 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 327..347 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 205..206 FT /note="Heavy metals binding" FT CROSSLNK 154 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305|PubMed:21628566" FT CROSSLNK 179 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305|PubMed:21628566" FT VAR_SEQ 198..211 FT /note="LELGIIVHSVVIGL -> RTHIYTYRISLYFK (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_008361" FT VAR_SEQ 212..347 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_008362" FT MUTAGEN 104 FT /note="H->A: Suppresses transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 108 FT /note="D->A: Abolishes iron and manganese transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 111 FT /note="E->A: Abolishes zinc transport. Abolishes iron and FT manganese transport; when associated with A-108." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 144 FT /note="D->A: Abolishes iron and manganese transport. FT Reduces cadmium transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 154 FT /note="K->R: Suppresses ubiquitination and loss of FT activity; when associated with R-179." FT /evidence="ECO:0000269|PubMed:21628566" FT MUTAGEN 179 FT /note="K->R: Suppresses ubiquitination and loss of FT activity; when associated with R-154." FT /evidence="ECO:0000269|PubMed:21628566" FT MUTAGEN 205 FT /note="H->A,E: Suppresses transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 206 FT /note="S->A: Suppresses transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 232 FT /note="H->A: Suppresses transport." FT /evidence="ECO:0000269|PubMed:11035780" FT MUTAGEN 236 FT /note="E->A: Suppresses transport." FT /evidence="ECO:0000269|PubMed:11035780" SQ SEQUENCE 347 AA; 36727 MW; 1F94091668994EA4 CRC64; MASNSALLMK TIFLVLIFVS FAISPATSTA PEECGSESAN PCVNKAKALP LKVIAIFVIL IASMIGVGAP LFSRNVSFLQ PDGNIFTIIK CFASGIILGT GFMHVLPDSF EMLSSICLEE NPWHKFPFSG FLAMLSGLIT LAIDSMATSL YTSKNAVGIM PHGHGHGHGP ANDVTLPIKE DDSSNAQLLR YRVIAMVLEL GIIVHSVVIG LSLGATSDTC TIKGLIAALC FHQMFEGMGL GGCILQAEYT NMKKFVMAFF FAVTTPFGIA LGIALSTVYQ DNSPKALITV GLLNACSAGL LIYMALVDLL AAEFMGPKLQ GSIKMQFKCL IAALLGCGGM SIIAKWA //