S39A4_MOUSE
ID S39A4_MOUSE Reviewed; 660 AA.
AC Q78IQ7; Q8CHL4;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Zinc transporter ZIP4;
DE AltName: Full=Activated in W/Wv mouse stomach 2;
DE Short=mAWMS2;
DE AltName: Full=Solute carrier family 39 member 4;
DE AltName: Full=Zrt- and Irt-like protein 4;
DE Short=ZIP-4;
DE Flags: Precursor;
GN Name=Slc39a4; Synonyms=Zip4;
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 [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=12801924; DOI=10.1074/jbc.m305000200;
RA Dufner-Beattie J., Wang F., Kuo Y.-M., Gitschier J., Eide D., Andrews G.K.;
RT "The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific,
RT zinc-regulated zinc transporter in mice.";
RL J. Biol. Chem. 278:33474-33481(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Stomach;
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 MRNA] (ISOFORM 1).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 431-660.
RA Daigo Y., Takayama I., Fujino M.A.;
RT "Isolation and characterization of novel human and mouse genes, which are
RT expressed in the digestive tract.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=14612438; DOI=10.1074/jbc.m310799200;
RA Kim B.-E., Wang F., Dufner-Beattie J., Andrews G.K., Eide D.J.,
RA Petris M.J.;
RT "Zn2+-stimulated endocytosis of the mZIP4 zinc transporter regulates its
RT location at the plasma membrane.";
RL J. Biol. Chem. 279:4523-4530(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
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: Plays an important role in cellular zinc homeostasis as a
CC zinc transporter. Regulated in response to zinc availability.
CC {ECO:0000269|PubMed:12801924}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14612438};
CC Multi-pass membrane protein {ECO:0000269|PubMed:14612438}. Recycling
CC endosome membrane {ECO:0000269|PubMed:14612438}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:14612438}. Note=Colocalized with TFRC in
CC the recycling endosomes. Cycles between endosomal compartments and the
CC plasma membrane in response to zinc availability.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q78IQ7-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q78IQ7-2; Sequence=VSP_015913, VSP_015914;
CC -!- TISSUE SPECIFICITY: Highly expressed in the small intestine and
CC embryonic visceral yolk sac. Weakly expressed in the stomach and liver.
CC Found to the apical surface of enterocytes and visceral endoderm cells
CC during zinc deficiency. {ECO:0000269|PubMed:12801924}.
CC -!- INDUCTION: Up-regulated under conditions of dietary zinc deficiency.
CC Down-regulated under conditions of dietary zinc excess.
CC {ECO:0000269|PubMed:12801924}.
CC -!- MISCELLANEOUS: [Isoform 1]: More abundant.
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; AK146977; BAE27581.1; -; mRNA.
DR EMBL; AK147107; BAE27679.1; -; mRNA.
DR EMBL; BC023498; AAH23498.1; -; mRNA.
DR EMBL; AB052762; BAC53795.1; -; mRNA.
DR CCDS; CCDS27578.1; -. [Q78IQ7-1]
DR RefSeq; NP_082340.1; NM_028064.2. [Q78IQ7-1]
DR AlphaFoldDB; Q78IQ7; -.
DR SMR; Q78IQ7; -.
DR STRING; 10090.ENSMUSP00000073134; -.
DR GlyGen; Q78IQ7; 4 sites.
DR iPTMnet; Q78IQ7; -.
DR PhosphoSitePlus; Q78IQ7; -.
DR SwissPalm; Q78IQ7; -.
DR jPOST; Q78IQ7; -.
DR MaxQB; Q78IQ7; -.
DR PaxDb; Q78IQ7; -.
DR PRIDE; Q78IQ7; -.
DR ProteomicsDB; 260784; -. [Q78IQ7-1]
DR ProteomicsDB; 260785; -. [Q78IQ7-2]
DR Antibodypedia; 28508; 228 antibodies from 32 providers.
DR DNASU; 72027; -.
DR Ensembl; ENSMUST00000230977; ENSMUSP00000155442; ENSMUSG00000063354. [Q78IQ7-1]
DR GeneID; 72027; -.
DR KEGG; mmu:72027; -.
DR UCSC; uc007wlb.1; mouse. [Q78IQ7-1]
DR CTD; 55630; -.
DR MGI; MGI:1919277; Slc39a4.
DR VEuPathDB; HostDB:ENSMUSG00000063354; -.
DR eggNOG; KOG2693; Eukaryota.
DR GeneTree; ENSGT00940000160042; -.
DR HOGENOM; CLU_015114_12_0_1; -.
DR InParanoid; Q78IQ7; -.
DR OMA; IFFLFES; -.
DR OrthoDB; 657777at2759; -.
DR PhylomeDB; Q78IQ7; -.
DR TreeFam; TF318470; -.
DR Reactome; R-MMU-442380; Zinc influx into cells by the SLC39 gene family.
DR BioGRID-ORCS; 72027; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q78IQ7; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q78IQ7; protein.
DR Bgee; ENSMUSG00000063354; Expressed in small intestine Peyer's patch and 92 other tissues.
DR ExpressionAtlas; Q78IQ7; baseline and differential.
DR Genevisible; Q78IQ7; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0034224; P:cellular response to zinc ion starvation; IDA:MGI.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IBA:GO_Central.
DR GO; GO:0071578; P:zinc ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR003689; ZIP.
DR InterPro; IPR041137; ZIP4_N.
DR Pfam; PF02535; Zip; 1.
DR Pfam; PF18292; ZIP4_domain; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Endosome; Glycoprotein; Ion transport;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Transport; Zinc; Zinc transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..660
FT /note="Zinc transporter ZIP4"
FT /id="PRO_0000042621"
FT TOPO_DOM 23..337
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..420
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 421..441
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..571
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 572..592
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 593..599
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 621..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 652..660
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 233..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 233..264
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12801924"
FT /id="VSP_015913"
FT VAR_SEQ 48..63
FT /note="NTLVARVHCTDGPCEK -> MPGRLSLAQILSVCPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12801924"
FT /id="VSP_015914"
FT CONFLICT 431..435
FT /note="FFLFE -> RPRVR (in Ref. 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 660 AA; 71063 MW; CA7236080C81B7BE CRC64;
MLPKSVTQGL VLALLVGTVA VARPRNLLSL LALGQGALDR LELDGLLNTL VARVHCTDGP
CEKCLSVENV LALGKPDKPQ PAPESVLESR HIIYLSAAAA LYLNNPEKTC KDIQAGLLAS
HVDDYLATLE SPEAMTLGLS QLLQKIEAHA ASQPTGEKTC VDLPQLLEEA EAAGVSKSAG
LVLTALLDHV INGSCFQGLP SPQYFVDFVF RLHSSDPPNI TLHELENLMH HLGVGGEDHS
DHDDHGDHAD HSHPDRKASH QDSELHTPHN SNSSVWDTLC LSAKDIMAVY GLSEEAGVSP
QAWAQLTPAL VQQQLSGACS PYPTIRIQDQ LSQTERYLYG SLATLLICLC AVFGLLLLTC
AKCSTATHYI MQTFLSLAVG ALTGDALLHL IPKVLGLHTH GGEGHTHEEE VGVGGQATWR
LLAVLGGFYI FFLFESFFNL LLPRDQDSEK DGPCSHGGHS HGISLQLAPS NLRQSKQTHE
SSRSDLVAEE TPELLNPETR RLRAELRLLP YLITLGDAVH NFADGLAVGA AFSSSWKTGL
ATSLAVFCHE LPHELGDFAA LLHAGLSVKR ALLLNLASAL TAFAGLYVAL AVGVGEEGEA
WILAVATGLF LYVALCDMLP AMMNVRDQRP WLLFLLHNVG LLGGWTVLLL LSLYEDNITF
