ZNT4_MOUSE
ID ZNT4_MOUSE Reviewed; 430 AA.
AC O35149; O35154; Q3UYZ9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Zinc transporter 4 {ECO:0000305|PubMed:9354792};
DE Short=ZnT-4;
DE AltName: Full=Lethal milk protein {ECO:0000303|PubMed:9354792};
DE AltName: Full=Solute carrier family 30 member 4 {ECO:0000312|MGI:MGI:1345282};
GN Name=Slc30a4 {ECO:0000312|MGI:MGI:1345282};
GN Synonyms=Lm, Znt4 {ECO:0000303|PubMed:9354792};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TRANSPORTER ACTIVITY,
RP DISEASE, AND TISSUE SPECIFICITY.
RC STRAIN=B6/CBAF1, and C57BL/6J; TISSUE=Brain;
RX PubMed=9354792; DOI=10.1038/ng1197-292;
RA Huang L., Gitschier J.;
RT "A novel gene involved in zinc transport is deficient in the lethal milk
RT mouse.";
RL Nat. Genet. 17:292-297(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Forelimb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Zinc ion transporter mediating zinc import from cytoplasm
CC potentially into the endocytic compartment (PubMed:9354792). Controls
CC zinc deposition in milk (PubMed:9354792). {ECO:0000269|PubMed:9354792}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351,
CC ChEBI:CHEBI:29105; Evidence={ECO:0000305|PubMed:9354792};
CC -!- SUBUNIT: Homodimerization could regulate efficiency for zinc transport.
CC {ECO:0000250|UniProtKB:O14863}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:O55174};
CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane
CC {ECO:0000250|UniProtKB:O14863}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:O14863}; Multi-
CC pass membrane protein {ECO:0000255}. Note=Enriched in vesicles within
CC the basal region of epithelial cells. {ECO:0000250|UniProtKB:O55174}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in the brain and
CC in mammary epithelial cell lines. {ECO:0000269|PubMed:9354792}.
CC -!- DISEASE: Note=Defect in Slc30a4 is the cause of the lethal milk (lm)
CC phenotype. Mice with lm are defective in zinc transport into breast
CC milk, due to a premature translation termination codon at position 297.
CC Only homozygous mutant adults develop dermatitis, skin lesions, and
CC hair loss due to a systemic zinc deficiency. Pups of any genotype
CC suckled on homozygous mutant female also develop symptoms
CC characteristic of nutritional zinc deficiency, including dermatitis,
CC alopecia and stunted growth. {ECO:0000269|PubMed:9354792}.
CC -!- SIMILARITY: Belongs to the cation diffusion facilitator (CDF)
CC transporter (TC 2.A.4) family. SLC30A subfamily. {ECO:0000305}.
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DR EMBL; AF004099; AAB82413.1; -; Genomic_DNA.
DR EMBL; AF003747; AAB82593.1; -; mRNA.
DR EMBL; AF004098; AAB82412.1; -; Genomic_DNA.
DR EMBL; AF004097; AAB82411.1; -; Genomic_DNA.
DR EMBL; AF004100; AAB82414.1; -; Genomic_DNA.
DR EMBL; AK134245; BAE22062.1; -; mRNA.
DR EMBL; AL772253; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16667.1; -.
DR RefSeq; NP_001277922.1; NM_001290993.1.
DR RefSeq; NP_035904.2; NM_011774.3.
DR AlphaFoldDB; O35149; -.
DR SMR; O35149; -.
DR BioGRID; 204706; 2.
DR IntAct; O35149; 2.
DR STRING; 10090.ENSMUSP00000005952; -.
DR TCDB; 2.A.4.3.3; the cation diffusion facilitator (cdf) family.
DR iPTMnet; O35149; -.
DR PhosphoSitePlus; O35149; -.
DR EPD; O35149; -.
DR MaxQB; O35149; -.
DR PaxDb; O35149; -.
DR PRIDE; O35149; -.
DR ProteomicsDB; 275045; -.
DR Antibodypedia; 11839; 71 antibodies from 21 providers.
DR DNASU; 22785; -.
DR Ensembl; ENSMUST00000005952; ENSMUSP00000005952; ENSMUSG00000005802.
DR GeneID; 22785; -.
DR KEGG; mmu:22785; -.
DR UCSC; uc008mba.2; mouse.
DR CTD; 7782; -.
DR MGI; MGI:1345282; Slc30a4.
DR VEuPathDB; HostDB:ENSMUSG00000005802; -.
DR eggNOG; KOG1482; Eukaryota.
DR GeneTree; ENSGT00940000157545; -.
DR HOGENOM; CLU_013430_0_1_1; -.
DR InParanoid; O35149; -.
DR OMA; HDLHIWE; -.
DR OrthoDB; 820567at2759; -.
DR PhylomeDB; O35149; -.
DR TreeFam; TF313382; -.
DR BioGRID-ORCS; 22785; 6 hits in 73 CRISPR screens.
DR PRO; PR:O35149; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O35149; protein.
DR Bgee; ENSMUSG00000005802; Expressed in jejunum and 63 other tissues.
DR ExpressionAtlas; O35149; baseline and differential.
DR Genevisible; O35149; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0061088; P:regulation of sequestering of zinc ion; ISO:MGI.
DR GO; GO:0009636; P:response to toxic substance; ISO:MGI.
DR GO; GO:0010043; P:response to zinc ion; IBA:GO_Central.
DR GO; GO:0055069; P:zinc ion homeostasis; IMP:MGI.
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 Endosome; Ion transport; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc;
KW Zinc transport.
FT CHAIN 1..430
FT /note="Zinc transporter 4"
FT /id="PRO_0000206100"
FT TOPO_DOM 1..113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..143
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..216
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..311
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 240..265
FT /note="Zinc binding"
FT /evidence="ECO:0000250|UniProtKB:O55174"
FT REGION 245..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..264
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 426
FT /note="H -> Q (in Ref. 1; AAB82593)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 47800 MW; E2311FA6316D15C6 CRC64;
MAGPGAWKRL KSLLRKDDTP LFLNDTSAFD FSDEVSDEGL SRFNKLRVVV ADDDSEAPER
PVNGAHPALQ ADDDSLLDQD LPLTNSQLSL KMDPCDNCSK RRELLKQRKV KTRLTIAAVL
YLLFMIGELV GGYMANSLAI MTDALHMLTD LSAIILTLLA LWLSSKSPTR RFTFGFHRLE
VLSAMISVML VYVLMGFLLY EAVQRTIHMN YEINGDVMLI TAAVGVAVNV IMGFLLNQSG
HHHSHAHSHS LPSNSPSMVS SGHNHGQDSL AVRAAFVHAL GDLVQSVGVL IAAYIIRFKP
EYKIADPICT YIFSLLVAFT TFRIIWDTVV IILEGVPSHL NVDYIKESLM KIEDVYSVED
LNIWSLTSGK STAIVHMQLI PGSSSKWEEV QSKAKHLLLN TFGMYKCTIQ LQSYRQEVIR
TCANCHSSST
