ID S39AE_DANRE Reviewed; 494 AA. AC A0A0G2KQY6; DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2015, sequence version 1. DT 24-JAN-2024, entry version 45. DE RecName: Full=Metal cation symporter ZIP14 {ECO:0000250|UniProtKB:Q15043}; DE AltName: Full=Solute carrier family 39 member 14 {ECO:0000250|UniProtKB:Q15043}; DE AltName: Full=Zrt- and Irt-like protein 14 {ECO:0000303|PubMed:27231142}; DE Short=ZIP-14 {ECO:0000303|PubMed:27231142}; DE Flags: Precursor; GN Name=slc39a14 {ECO:0000303|PubMed:27231142}; GN Synonyms=zip14 {ECO:0000303|PubMed:27231142}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tuebingen; RX PubMed=23594743; DOI=10.1038/nature12111; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G., RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P., RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S., RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N., RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J., RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J., RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D., RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S., RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E., RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A., RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P., RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J., RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E., RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C., RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C., RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M., RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F., RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M., RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M., RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C., RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [2] RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL RP STAGE. RX PubMed=27231142; DOI=10.1038/ncomms11601; RA Tuschl K., Meyer E., Valdivia L.E., Zhao N., Dadswell C., Abdul-Sada A., RA Hung C.Y., Simpson M.A., Chong W.K., Jacques T.S., Woltjer R.L., Eaton S., RA Gregory A., Sanford L., Kara E., Houlden H., Cuno S.M., Prokisch H., RA Valletta L., Tiranti V., Younis R., Maher E.R., Spencer J., RA Straatman-Iwanowska A., Gissen P., Selim L.A., Pintos-Morell G., RA Coroleu-Lletget W., Mohammad S.S., Yoganathan S., Dale R.C., Thomas M., RA Rihel J., Bodamer O.A., Enns C.A., Hayflick S.J., Clayton P.T., Mills P.B., RA Kurian M.A., Wilson S.W.; RT "Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood- RT onset parkinsonism-dystonia."; RL Nat. Commun. 7:11601-11601(2016). CC -!- FUNCTION: Broad-scope metal ion transporter with a preference for zinc CC uptake. Also mediates cellular uptake of nontransferrin-bound iron. CC {ECO:0000269|PubMed:27231142}. CC -!- FUNCTION: Electroneutral transporter of the plasma membrane mediating CC the cellular uptake of the divalent metal cations zinc, manganese and CC iron that are important for tissue homeostasis, metabolism, development CC and immunity (PubMed:27231142). Functions as an energy-dependent CC symporter, transporting through the membranes an electroneutral complex CC composed of a divalent metal cation and two bicarbonate anions (By CC similarity). Beside these endogenous cellular substrates, can also CC import cadmium a non-essential metal which is cytotoxic and CC carcinogenic (By similarity). {ECO:0000250|UniProtKB:Q75N73, CC ECO:0000269|PubMed:27231142}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 hydrogencarbonate(out) + Zn(2+)(out) = 2 CC hydrogencarbonate(in) + Zn(2+)(in); Xref=Rhea:RHEA:62252, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62253; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 hydrogencarbonate(out) + Mn(2+)(out) = 2 CC hydrogencarbonate(in) + Mn(2+)(in); Xref=Rhea:RHEA:62260, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62261; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Fe(2+)(out) + 2 hydrogencarbonate(out) = Fe(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62368, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62369; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62256, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:48775; Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62257; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:Q15043}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27231142}; CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein CC {ECO:0000255}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q15043}; CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane CC {ECO:0000250|UniProtKB:Q15043}; Multi-pass membrane protein CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q15043}; Multi- CC pass membrane protein {ECO:0000255}. CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of embryonic and early CC larval development. {ECO:0000269|PubMed:27231142}. CC -!- DISRUPTION PHENOTYPE: Embryos with CRISPR-induced slc39a14 null CC mutations display altered manganese homeostasis. This is associated CC with manganese deposition in the brain and altered locomotor activity. CC Mutants survived into adulthood without any obvious morphological or CC developmental defects. {ECO:0000269|PubMed:27231142}. CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family. CC {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; CABZ01088693; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CABZ01088694; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CABZ01088695; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CABZ01088696; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CABZ01088697; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CABZ01088698; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; NP_001313628.1; NM_001326699.1. DR AlphaFoldDB; A0A0G2KQY6; -. DR SMR; A0A0G2KQY6; -. DR STRING; 7955.ENSDARP00000134809; -. DR GeneID; 799782; -. DR ZFIN; ZDB-GENE-060315-2; slc39a14. DR InParanoid; A0A0G2KQY6; -. DR OrthoDB; 5488029at2759; -. DR Reactome; R-DRE-442380; Zinc influx into cells by the SLC39 gene family. DR PRO; PR:A0A0G2KQY6; -. DR Proteomes; UP000000437; Chromosome 5. DR Bgee; ENSDARG00000102387; Expressed in proximal tubule and 32 other cell types or tissues. DR ExpressionAtlas; A0A0G2KQY6; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015296; F:monoatomic anion:monoatomic cation symporter activity; ISS:UniProtKB. DR GO; GO:0140410; F:monoatomic cation:bicarbonate symporter activity; IBA:GO_Central. DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB. DR GO; GO:0098739; P:import across plasma membrane; ISS:UniProtKB. DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:UniProtKB. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; ISS:UniProtKB. DR GO; GO:0033212; P:iron import into cell; ISS:UniProtKB. DR GO; GO:0034755; P:iron ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0055071; P:manganese ion homeostasis; IMP:ZFIN. DR GO; GO:0071421; P:manganese ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB. DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0071578; P:zinc ion import across plasma membrane; ISS:UniProtKB. DR GO; GO:0071577; P:zinc ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0006829; P:zinc ion transport; ISS:ZFIN. DR InterPro; IPR003689; ZIP. DR PANTHER; PTHR12191:SF5; METAL CATION SYMPORTER ZIP14; 1. DR PANTHER; PTHR12191; SOLUTE CARRIER FAMILY 39; 1. DR Pfam; PF02535; Zip; 1. PE 2: Evidence at transcript level; KW Cell membrane; Endosome; Ion transport; Lysosome; Membrane; KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport; KW Zinc; Zinc transport. FT SIGNAL 1..34 FT /evidence="ECO:0000255" FT CHAIN 35..494 FT /note="Metal cation symporter ZIP14" FT /evidence="ECO:0000255" FT /id="PRO_5002547407" FT TOPO_DOM 35..152 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 153..173 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 174..181 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 182..202 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 203..219 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 220..240 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 241..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 398..418 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 419..426 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 427..447 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 448..462 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 463..483 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 484..494 FT /note="Extracellular" FT /evidence="ECO:0000305" FT MOTIF 248..255 FT /note="HHHGHXHX-motif" FT /evidence="ECO:0000250|UniProtKB:Q15043" FT MOTIF 376..381 FT /note="XEXPHE-motif" FT /evidence="ECO:0000250|UniProtKB:Q15043" SQ SEQUENCE 494 AA; 53266 MW; 313E3DD0E8213C08 CRC64; MTLRRASGCR QLTLTIGLAL TLGLLQWPIG DVRGQDGASP AQVLQELLTR YGDNASISVP QLRSLLVRLN GGQSEDHDSK TQPTRTNASK CLAADTLAVY GMSEQSRIDE RGLQQICPTM IQQLDSQACK TQPNQESESS PRPTEAEVWG YGLLCVTVIS LCSLVGASVV PFMRKTFYKR LLLYFIALAI GTLYSNALFQ LIPEAFGFDP MEDYYVPKSA VVFGGFYLFF FTEKILKMIL KPKDTGGHGH GHSHFPAERY ANSNGDLEDG VMEKLQNGEA GGAALPRAEA DGRGVGEDDK MLSTGQTVQD TQSSGGGGTG GCYWLKGRAY SDIGTLAWMI TLSDGLHNFI DGLAIGASFT ASVFQGISTS VAILCEEFPH ELGDFVILLN AGMSIQQALF FNFLSACCCY LGMGFGILAG NNFSPNWIFA LAGGMFLYIA LADMFPEMNE VSREEEEAGG SGFLLTFALQ NAGLLTGFAI MLVLTIYSGQ IQLG //