S39AE_DANRE
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 03-AUG-2022, entry version 37.
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}.
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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 Ensembl; ENSDART00000163942; ENSDARP00000134809; ENSDARG00000102387.
DR Ensembl; ENSDART00000185624; ENSDARP00000156772; ENSDARG00000102387.
DR GeneID; 799782; -.
DR KEGG; dre:799782; -.
DR CTD; 23516; -.
DR ZFIN; ZDB-GENE-060315-2; slc39a14.
DR GeneTree; ENSGT00940000157986; -.
DR OMA; GHSHYSA; -.
DR OrthoDB; 657777at2759; -.
DR Reactome; R-DRE-442380; Zinc influx into cells by the SLC39 gene family.
DR PRO; PR:A0A0G2KQY6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000102387; Expressed in proximal tubule and 32 other 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:0005887; C:integral component of plasma 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:0015296; F:anion:cation symporter activity; ISS: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: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:0006882; P:cellular zinc ion homeostasis; 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: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 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
