ZNT10_HUMAN
ID ZNT10_HUMAN Reviewed; 485 AA.
AC Q6XR72; Q49AL9; Q9NPW0;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Zinc transporter 10;
DE Short=ZnT-10;
DE AltName: Full=Manganese transporter SLC30A10;
DE AltName: Full=Solute carrier family 30 member 10;
GN Name=SLC30A10; Synonyms=ZNT10, ZNT8;
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).
RA Huang L., Zhou B., Gitschier J.;
RT "Characterization of a novel mammalian zinc transporter, ZNT8.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 90-485 (ISOFORM 3).
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=15154973; DOI=10.1186/1471-2164-5-32;
RA Seve M., Chimienti F., Devergnas S., Favier A.;
RT "In silico identification and expression of SLC30 family genes: an
RT expressed sequence tag data mining strategy for the characterization of
RT zinc transporters' tissue expression.";
RL BMC Genomics 5:32-32(2004).
RN [6]
RP FUNCTION, INVOLVEMENT IN HMNDYT1, AND VARIANTS HMNDYT1 PRO-89;
RP 105-ALA--PRO-107 DEL; VAL-256 DEL AND PRO-349.
RX PubMed=22341972; DOI=10.1016/j.ajhg.2012.01.018;
RA Tuschl K., Clayton P.T., Gospe S.M. Jr., Gulab S., Ibrahim S., Singhi P.,
RA Aulakh R., Ribeiro R.T., Barsottini O.G., Zaki M.S., Del Rosario M.L.,
RA Dyack S., Price V., Rideout A., Gordon K., Wevers R.A., Chong W.K.,
RA Mills P.B.;
RT "Syndrome of hepatic cirrhosis, dystonia, polycythemia, and
RT hypermanganesemia caused by mutations in SLC30A10, a manganese transporter
RT in man.";
RL Am. J. Hum. Genet. 90:457-466(2012).
RN [7]
RP FUNCTION, INVOLVEMENT IN HMNDYT1, AND VARIANT SER-167.
RX PubMed=22341971; DOI=10.1016/j.ajhg.2012.01.017;
RA Quadri M., Federico A., Zhao T., Breedveld G.J., Battisti C., Delnooz C.,
RA Severijnen L.A., Di Toro Mammarella L., Mignarri A., Monti L., Sanna A.,
RA Lu P., Punzo F., Cossu G., Willemsen R., Rasi F., Oostra B.A.,
RA van de Warrenburg B.P., Bonifati V.;
RT "Mutations in SLC30A10 cause parkinsonism and dystonia with
RT hypermanganesemia, polycythemia, and chronic liver disease.";
RL Am. J. Hum. Genet. 90:467-477(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=22706290; DOI=10.1039/c2mt20088k;
RA Bosomworth H.J., Thornton J.K., Coneyworth L.J., Ford D., Valentine R.A.;
RT "Efflux function, tissue-specific expression and intracellular trafficking
RT of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis.";
RL Metallomics 4:771-779(2012).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC30A3, AND INDUCTION.
RX PubMed=22427991; DOI=10.1371/journal.pone.0033211;
RA Patrushev N., Seidel-Rogol B., Salazar G.;
RT "Angiotensin II requires zinc and downregulation of the zinc transporters
RT ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells.";
RL PLoS ONE 7:E33211-E33211(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-196, AND
RP CHARACTERIZATION OF VARIANTS HMNDYT1 PRO-89 AND 105-ALA--PRO-107 DEL.
RX PubMed=25319704; DOI=10.1523/jneurosci.2329-14.2014;
RA Leyva-Illades D., Chen P., Zogzas C.E., Hutchens S., Mercado J.M.,
RA Swaim C.D., Morrisett R.A., Bowman A.B., Aschner M., Mukhopadhyay S.;
RT "SLC30A10 is a cell surface-localized manganese efflux transporter, and
RT parkinsonism-causing mutations block its intracellular trafficking and
RT efflux activity.";
RL J. Neurosci. 34:14079-14095(2014).
RN [11]
RP INDUCTION.
RX PubMed=25582195; DOI=10.1128/mcb.01298-14;
RA Ogo O.A., Tyson J., Cockell S.J., Howard A., Valentine R.A., Ford D.;
RT "The zinc finger protein ZNF658 regulates the transcription of genes
RT involved in zinc homeostasis and affects ribosome biogenesis through the
RT zinc transcriptional regulatory element.";
RL Mol. Cell. Biol. 35:977-987(2015).
RN [12]
RP FUNCTION.
RX PubMed=27226609; DOI=10.1074/jbc.m116.728014;
RA Nishito Y., Tsuji N., Fujishiro H., Takeda T.A., Yamazaki T., Teranishi F.,
RA Okazaki F., Matsunaga A., Tuschl K., Rao R., Kono S., Miyajima H.,
RA Narita H., Himeno S., Kambe T.;
RT "Direct comparison of manganese detoxification/efflux proteins and
RT molecular characterization of ZnT10 protein as a manganese transporter.";
RL J. Biol. Chem. 291:14773-14787(2016).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF GLU-25; ASP-40; ASN-127; HIS-244; ASP-248;
RP HIS-333 AND HIS-350.
RX PubMed=27307044; DOI=10.1074/jbc.m116.726935;
RA Zogzas C.E., Aschner M., Mukhopadhyay S.;
RT "Structural elements in the transmembrane and cytoplasmic domains of the
RT metal transporter SLC30A10 are required for its manganese efflux
RT activity.";
RL J. Biol. Chem. 291:15940-15957(2016).
RN [14]
RP SELF-ASSOCIATION, INTERACTION WITH SLC30A2; SLC30A3 AND SLC30A4,
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF TYR-4.
RX PubMed=26728129; DOI=10.1111/tra.12371;
RA Zhao Y., Feresin R.G., Falcon-Perez J.M., Salazar G.;
RT "Differential targeting of SLC30A10/ZnT10 heterodimers to endolysosomal
RT compartments modulates EGF-induced MEK/ERK1/2 activity.";
RL Traffic 17:267-288(2016).
CC -!- FUNCTION: Plays a pivotal role in manganese transport. Manganese is an
CC essential cation for the function of several enzymes, including some
CC crucially important for the metabolism of neurotransmitters and other
CC neuronal metabolic pathways. However, elevated levels of manganese are
CC cytotoxic and induce oxidative stress, mitochondrial dysfunction and
CC apoptosis. Acts as manganese efflux transporter and confers protection
CC against manganese-induced cell death (PubMed:22341972, PubMed:22341971,
CC PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc
CC transporter involved in zinc homeostasis. Seems to mediate zinc
CC transport into early endosomes and recycling endosomes to prevent zinc
CC toxicity; the function may be regulated by heterodimerization with
CC other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10
CC heterodimer is involved in zinc transport-dependent regulation of the
CC EGFR/ERK transduction pathway in endosomes. May be involved in
CC regulation of zinc-dependent senescence of vascular smooth muscle cells
CC (PubMed:22706290, PubMed:22427991, PubMed:26728129).
CC {ECO:0000269|PubMed:22341971, ECO:0000269|PubMed:22341972,
CC ECO:0000269|PubMed:22427991, ECO:0000269|PubMed:25319704,
CC ECO:0000269|PubMed:27226609, ECO:0000305|PubMed:22706290}.
CC -!- SUBUNIT: Forms homodimers. Forms heterodimers and high-molecular weight
CC oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is
CC mediated by covalent-bound tyrosine residues and occurs probably in a
CC tissue-specific manner. {ECO:0000269|PubMed:22427991,
CC ECO:0000269|PubMed:26728129}.
CC -!- INTERACTION:
CC Q6XR72; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-13917996, EBI-8644112;
CC Q6XR72; Q99726: SLC30A3; NbExp=3; IntAct=EBI-13917996, EBI-10294651;
CC Q6XR72; O14863: SLC30A4; NbExp=2; IntAct=EBI-13917996, EBI-13918058;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22706290,
CC ECO:0000269|PubMed:25319704, ECO:0000269|PubMed:26728129}; Multi-pass
CC membrane protein {ECO:0000305}. Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:22706290}. Recycling endosome
CC {ECO:0000269|PubMed:22427991, ECO:0000269|PubMed:26728129}. Early
CC endosome {ECO:0000269|PubMed:22427991}. Note=Relocalized from the
CC trans-Golgi network to the plasma membrane upon elevated extracellular
CC Zn concentrations (PubMed:22706290). {ECO:0000269|PubMed:22706290}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6XR72-4; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6XR72-2; Sequence=VSP_029863;
CC Name=3;
CC IsoId=Q6XR72-3; Sequence=VSP_029864, VSP_029865;
CC -!- TISSUE SPECIFICITY: Specifically expressed in fetal liver and fetal
CC brain (PubMed:15154973). Expressed in adult tissues with relative
CC levels small intestine > liver > testes > brain > ovary > colon >
CC cervix > prostate > placenta (PubMed:22706290).
CC {ECO:0000269|PubMed:15154973, ECO:0000269|PubMed:22706290}.
CC -!- INDUCTION: Down-regulated by ZNF658 in response to zinc. Down-regulated
CC by angiotensin-2. {ECO:0000269|PubMed:22427991,
CC ECO:0000269|PubMed:22706290, ECO:0000269|PubMed:25582195}.
CC -!- DISEASE: Hypermanganesemia with dystonia 1 (HMNDYT1) [MIM:613280]: A
CC metabolic autosomal recessive disorder characterized by dystonia,
CC parkinsonism, extrapyramidal signs, severe hypermanganesemia,
CC polycythemia, and chronic hepatic disease, including steatosis and
CC cirrhosis. {ECO:0000269|PubMed:22341971, ECO:0000269|PubMed:22341972,
CC ECO:0000269|PubMed:25319704}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cation diffusion facilitator (CDF)
CC transporter (TC 2.A.4) family. SLC30A subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP44332.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in position 427.; Evidence={ECO:0000305};
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DR EMBL; AY212919; AAP44332.1; ALT_SEQ; mRNA.
DR EMBL; AL359609; CAB94880.1; -; mRNA.
DR EMBL; AC093562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036078; AAH36078.1; -; mRNA.
DR CCDS; CCDS31026.1; -. [Q6XR72-4]
DR PIR; T50628; T50628.
DR RefSeq; NP_061183.2; NM_018713.2. [Q6XR72-4]
DR AlphaFoldDB; Q6XR72; -.
DR SMR; Q6XR72; -.
DR BioGRID; 120703; 6.
DR IntAct; Q6XR72; 4.
DR STRING; 9606.ENSP00000355893; -.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR TCDB; 2.A.4.2.5; the cation diffusion facilitator (cdf) family.
DR iPTMnet; Q6XR72; -.
DR PhosphoSitePlus; Q6XR72; -.
DR BioMuta; SLC30A10; -.
DR DMDM; 311033506; -.
DR jPOST; Q6XR72; -.
DR MassIVE; Q6XR72; -.
DR MaxQB; Q6XR72; -.
DR PaxDb; Q6XR72; -.
DR PeptideAtlas; Q6XR72; -.
DR PRIDE; Q6XR72; -.
DR ProteomicsDB; 67813; -. [Q6XR72-4]
DR ProteomicsDB; 67814; -. [Q6XR72-2]
DR ProteomicsDB; 67815; -. [Q6XR72-3]
DR Antibodypedia; 3072; 114 antibodies from 19 providers.
DR DNASU; 55532; -.
DR Ensembl; ENST00000356609.2; ENSP00000349018.2; ENSG00000196660.11. [Q6XR72-3]
DR Ensembl; ENST00000366926.4; ENSP00000355893.4; ENSG00000196660.11. [Q6XR72-4]
DR GeneID; 55532; -.
DR KEGG; hsa:55532; -.
DR MANE-Select; ENST00000366926.4; ENSP00000355893.4; NM_018713.3; NP_061183.2.
DR UCSC; uc001hlw.4; human. [Q6XR72-4]
DR CTD; 55532; -.
DR DisGeNET; 55532; -.
DR GeneCards; SLC30A10; -.
DR GeneReviews; SLC30A10; -.
DR HGNC; HGNC:25355; SLC30A10.
DR HPA; ENSG00000196660; Tissue enhanced (intestine, liver).
DR MalaCards; SLC30A10; -.
DR MIM; 611146; gene.
DR MIM; 613280; phenotype.
DR neXtProt; NX_Q6XR72; -.
DR OpenTargets; ENSG00000196660; -.
DR Orphanet; 309854; Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome.
DR PharmGKB; PA142670903; -.
DR VEuPathDB; HostDB:ENSG00000196660; -.
DR eggNOG; KOG1483; Eukaryota.
DR GeneTree; ENSGT00940000159967; -.
DR HOGENOM; CLU_1239780_0_0_1; -.
DR InParanoid; Q6XR72; -.
DR OMA; IFHHAGI; -.
DR PhylomeDB; Q6XR72; -.
DR TreeFam; TF313924; -.
DR PathwayCommons; Q6XR72; -.
DR Reactome; R-HSA-425410; Metal ion SLC transporters.
DR SignaLink; Q6XR72; -.
DR BioGRID-ORCS; 55532; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; SLC30A10; human.
DR GenomeRNAi; 55532; -.
DR Pharos; Q6XR72; Tbio.
DR PRO; PR:Q6XR72; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6XR72; protein.
DR Bgee; ENSG00000196660; Expressed in jejunal mucosa and 75 other tissues.
DR Genevisible; Q6XR72; HS.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:1904385; P:cellular response to angiotensin; IDA:UniProtKB.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IBA:GO_Central.
DR GO; GO:0010312; P:detoxification of zinc ion; IBA:GO_Central.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0071421; P:manganese ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006828; P:manganese ion transport; IMP:UniProtKB.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:1905802; P:regulation of cellular response to manganese ion; IDA:UniProtKB.
DR GO; GO:0071579; P:regulation of zinc ion transport; IDA:UniProtKB.
DR GO; GO:0071577; P:zinc ion transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1510.10; -; 1.
DR InterPro; IPR002524; Cation_efflux.
DR InterPro; IPR027469; Cation_efflux_TMD_sf.
DR Pfam; PF01545; Cation_efflux; 1.
DR SUPFAM; SSF161111; SSF161111; 1.
DR TIGRFAMs; TIGR01297; CDF; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Dystonia; Endosome;
KW Golgi apparatus; Ion transport; Manganese; Membrane; Neurodegeneration;
KW Parkinsonism; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport; Zinc; Zinc transport.
FT CHAIN 1..485
FT /note="Zinc transporter 10"
FT /id="PRO_0000312580"
FT TOPO_DOM 1..10
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 11..31
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 32..40
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..278
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 300..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 167..196
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 308..485
FT /note="Required for plasma membrane localization"
FT /evidence="ECO:0000269|PubMed:25319704"
FT VAR_SEQ 1..245
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_029863"
FT VAR_SEQ 214..223
FT /note="GDSFNTQNEP -> ELIHNTRFLL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029864"
FT VAR_SEQ 224..485
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029865"
FT VARIANT 89
FT /note="L -> P (in HMNDYT1; abolishes cell surface
FT localization; dbSNP:rs281860284)"
FT /evidence="ECO:0000269|PubMed:22341972,
FT ECO:0000269|PubMed:25319704"
FT /id="VAR_072573"
FT VARIANT 105..107
FT /note="Missing (in HMNDYT1; abolishes cell surface
FT localization; decreases manganese efflux; decreases
FT protection against manganese-induced neurotoxity)"
FT /evidence="ECO:0000269|PubMed:22341972,
FT ECO:0000269|PubMed:25319704"
FT /id="VAR_072574"
FT VARIANT 167
FT /note="F -> S (in dbSNP:rs281860286)"
FT /evidence="ECO:0000269|PubMed:22341971"
FT /id="VAR_072575"
FT VARIANT 256
FT /note="Missing (in HMNDYT1)"
FT /evidence="ECO:0000269|PubMed:22341972"
FT /id="VAR_072576"
FT VARIANT 349
FT /note="L -> P (in HMNDYT1; dbSNP:rs281860291)"
FT /evidence="ECO:0000269|PubMed:22341972"
FT /id="VAR_072577"
FT MUTAGEN 4
FT /note="Y->F: Decreases interaction with SLC30A3; no effect
FT on self-association; decreases zinc transport; decreases
FT EGF-induced ERK1/2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:26728129"
FT MUTAGEN 25
FT /note="E->A: Abolishes manganese efflux activity."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 40
FT /note="D->A: Abolishes manganese efflux activity."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 127
FT /note="N->A: Abolishes manganese efflux activity; when
FT associated with A-244."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 196
FT /note="T->P: Abolishes cell surface localization."
FT /evidence="ECO:0000269|PubMed:25319704"
FT MUTAGEN 244
FT /note="H->A: Abolishes manganese efflux activity; when
FT associated with A-127."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 248
FT /note="D->A: Abolishes manganese efflux activity."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 333
FT /note="H->A: Decreases manganese efflux activity."
FT /evidence="ECO:0000269|PubMed:27307044"
FT MUTAGEN 350
FT /note="H->A: Decreases manganese efflux activity."
FT /evidence="ECO:0000269|PubMed:27307044"
SQ SEQUENCE 485 AA; 52684 MW; 96A3495EF026DE94 CRC64;
MGRYSGKTCR LLFMLVLTVA FFVAELVSGY LGNSIALLSD SFNMLSDLIS LCVGLSAGYI
ARRPTRGFSA TYGYARAEVV GALSNAVFLT ALCFTIFVEA VLRLARPERI DDPELVLIVG
VLGLLVNVVG LLIFQDCAAW FACCLRGRSR RLQQRQQLAE GCVPGAFGGP QGAEDPRRAA
DPTAPGSDSA VTLRGTSVER KREKGATVFA NVAGDSFNTQ NEPEDMMKKE KKSEALNIRG
VLLHVMGDAL GSVVVVITAI IFYVLPLKSE DPCNWQCYID PSLTVLMVII ILSSAFPLIK
ETAAILLQMV PKGVNMEELM SKLSAVPGIS SVHEVHIWEL VSGKIIATLH IKYPKDRGYQ
DASTKIREIF HHAGIHNVTI QFENVDLKEP LEQKDLLLLC NSPCISKGCA KQLCCPPGAL
PLAHVNGCAE HNGGPSLDTY GSDGLSRRDA REVAIEVSLD SCLSDHGQSL NKTQEDQCYV
NRTHF
