Q78IQ7 (S39A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc transporter ZIP4

Alternative name(s):
Activated in W/Wv mouse stomach 2
Short name=mAWMS2
Solute carrier family 39 member 4
Zrt- and Irt-like protein 4
Short name=ZIP-4

Gene names

Name:	Slc39a4
Synonyms:	Zip4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	660 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an important role in cellular zinc homeostasis as a zinc transporter. Regulated in response to zinc availability. Ref.1
Subcellular location	Cell membrane; Multi-pass membrane protein. Recycling endosome membrane; Multi-pass membrane protein. Note: Colocalized with TFRC in the recycling endosomes. Cycles between endosomal compartments and the plasma membrane in response to zinc availability. Ref.5
Tissue specificity	Highly expressed in the small intestine and embryonic visceral yolk sac. Weakly expressed in the stomach and liver. Found to the apical surface of enterocytes and visceral endoderm cells during zinc deficiency. Ref.1
Induction	Up-regulated under conditions of dietary zinc deficiency. Down-regulated under conditions of dietary zinc excess. Ref.1
Sequence similarities	Belongs to the ZIP transporter (TC 2.A.5) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport Zinc transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix
Ligand	Zinc
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to zinc ion starvation Inferred from direct assay PubMed 15358787. Source: MGI cellular zinc ion homeostasis Inferred from direct assay Ref.5. Source: MGI zinc ion transport Inferred from direct assay Ref.1Ref.5. Source: MGI
Cellular_component	apical plasma membrane Inferred from direct assay Ref.1PubMed 15358787. Source: MGI cytoplasmic membrane-bounded vesicle Inferred from direct assay Ref.5. Source: MGI endosome Inferred from direct assay Ref.5. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell recycling endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	zinc ion transmembrane transporter activity Inferred from direct assay Ref.1Ref.5. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q78IQ7-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: More abundant.

Isoform 2 (identifier: Q78IQ7-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: Missing.
     48-63: NTLVARVHCTDGPCEK → MPGRLSLAQILSVCPQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 660	638	Zinc transporter ZIP4		PRO_0000042621
Regions
	Topological domain	23 – 337	315	Extracellular Potential
	Transmembrane	338 – 358	21	Helical; Name=1; Potential
	Topological domain	359 – 376	18	Cytoplasmic Potential
	Transmembrane	377 – 397	21	Helical; Name=2; Potential
	Topological domain	398 – 420	23	Extracellular Potential
	Transmembrane	421 – 441	21	Helical; Name=3; Potential
	Topological domain	442 – 571	130	Cytoplasmic Potential
	Transmembrane	572 – 592	21	Helical; Name=4; Potential
	Topological domain	593 – 599	7	Extracellular Potential
	Transmembrane	600 – 620	21	Helical; Name=5; Potential
	Topological domain	621 – 630	10	Cytoplasmic Potential
	Transmembrane	631 – 651	21	Helical; Name=6; Potential
	Topological domain	652 – 660	9	Extracellular Potential
	Compositional bias	223 – 269	47	His-rich
Amino acid modifications
	Modified residue	481	1	Phosphoserine Ref.6
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	219	1	N-linked (GlcNAc...) Potential
	Glycosylation	272	1	N-linked (GlcNAc...) Potential
	Glycosylation	657	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 47	47	Missing in isoform 2.		VSP_015913
	Alternative sequence	48 – 63	16	NTLVA…GPCEK → MPGRLSLAQILSVCPQ in isoform 2.		VSP_015914
Experimental info
	Sequence conflict	431 – 435	5	FFLFE → RPRVR Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: CA7236080C81B7BE	FASTA	660	71,063
	10 20 30 40 50 60 MLPKSVTQGL VLALLVGTVA VARPRNLLSL LALGQGALDR LELDGLLNTL VARVHCTDGP 70 80 90 100 110 120 CEKCLSVENV LALGKPDKPQ PAPESVLESR HIIYLSAAAA LYLNNPEKTC KDIQAGLLAS 130 140 150 160 170 180 HVDDYLATLE SPEAMTLGLS QLLQKIEAHA ASQPTGEKTC VDLPQLLEEA EAAGVSKSAG 190 200 210 220 230 240 LVLTALLDHV INGSCFQGLP SPQYFVDFVF RLHSSDPPNI TLHELENLMH HLGVGGEDHS 250 260 270 280 290 300 DHDDHGDHAD HSHPDRKASH QDSELHTPHN SNSSVWDTLC LSAKDIMAVY GLSEEAGVSP 310 320 330 340 350 360 QAWAQLTPAL VQQQLSGACS PYPTIRIQDQ LSQTERYLYG SLATLLICLC AVFGLLLLTC 370 380 390 400 410 420 AKCSTATHYI MQTFLSLAVG ALTGDALLHL IPKVLGLHTH GGEGHTHEEE VGVGGQATWR 430 440 450 460 470 480 LLAVLGGFYI FFLFESFFNL LLPRDQDSEK DGPCSHGGHS HGISLQLAPS NLRQSKQTHE 490 500 510 520 530 540 SSRSDLVAEE TPELLNPETR RLRAELRLLP YLITLGDAVH NFADGLAVGA AFSSSWKTGL 550 560 570 580 590 600 ATSLAVFCHE LPHELGDFAA LLHAGLSVKR ALLLNLASAL TAFAGLYVAL AVGVGEEGEA 610 620 630 640 650 660 WILAVATGLF LYVALCDMLP AMMNVRDQRP WLLFLLHNVG LLGGWTVLLL LSLYEDNITF
	Isoform 2 (Short) [UniParc]. Checksum: 87505A21C489E2A0	FASTA	613	66,171
	10 20 30 40 50 60 MPGRLSLAQI LSVCPQCLSV ENVLALGKPD KPQPAPESVL ESRHIIYLSA AAALYLNNPE 70 80 90 100 110 120 KTCKDIQAGL LASHVDDYLA TLESPEAMTL GLSQLLQKIE AHAASQPTGE KTCVDLPQLL 130 140 150 160 170 180 EEAEAAGVSK SAGLVLTALL DHVINGSCFQ GLPSPQYFVD FVFRLHSSDP PNITLHELEN 190 200 210 220 230 240 LMHHLGVGGE DHSDHDDHGD HADHSHPDRK ASHQDSELHT PHNSNSSVWD TLCLSAKDIM 250 260 270 280 290 300 AVYGLSEEAG VSPQAWAQLT PALVQQQLSG ACSPYPTIRI QDQLSQTERY LYGSLATLLI 310 320 330 340 350 360 CLCAVFGLLL LTCAKCSTAT HYIMQTFLSL AVGALTGDAL LHLIPKVLGL HTHGGEGHTH 370 380 390 400 410 420 EEEVGVGGQA TWRLLAVLGG FYIFFLFESF FNLLLPRDQD SEKDGPCSHG GHSHGISLQL 430 440 450 460 470 480 APSNLRQSKQ THESSRSDLV AEETPELLNP ETRRLRAELR LLPYLITLGD AVHNFADGLA 490 500 510 520 530 540 VGAAFSSSWK TGLATSLAVF CHELPHELGD FAALLHAGLS VKRALLLNLA SALTAFAGLY 550 560 570 580 590 600 VALAVGVGEE GEAWILAVAT GLFLYVALCD MLPAMMNVRD QRPWLLFLLH NVGLLGGWTV 610 LLLLSLYEDN ITF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice." Dufner-Beattie J., Wang F., Kuo Y.-M., Gitschier J., Eide D., Andrews G.K. J. Biol. Chem. 278:33474-33481(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Stomach.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"Isolation and characterization of novel human and mouse genes, which are expressed in the digestive tract." Daigo Y., Takayama I., Fujino M.A. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 431-660.
[5]	"Zn2+-stimulated endocytosis of the mZIP4 zinc transporter regulates its location at the plasma membrane." Kim B.-E., Wang F., Dufner-Beattie J., Andrews G.K., Eide D.J., Petris M.J. J. Biol. Chem. 279:4523-4530(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK146977 mRNA. Translation: BAE27581.1. AK147107 mRNA. Translation: BAE27679.1. BC023498 mRNA. Translation: AAH23498.1. AB052762 mRNA. Translation: BAC53795.1.
IPI	IPI00119029. IPI00623873.
RefSeq	NP_082340.1. NM_028064.2.
UniGene	Mm.276829.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000073134.
PTM databases
PhosphoSite	Q78IQ7.
Proteomic databases
PaxDb	Q78IQ7.
PRIDE	Q78IQ7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000073428; ENSMUSP00000073134; ENSMUSG00000063354.
GeneID	72027.
KEGG	mmu:72027.
UCSC	uc007wlb.1. mouse.
Organism-specific databases
CTD	55630.
MGI	MGI:1919277. Slc39a4.
Phylogenomic databases
eggNOG	COG0428.
GeneTree	ENSGT00700000104299.
HOVERGEN	HBG062532.
InParanoid	Q78IQ7.
KO	K14710.
OMA	LYEDNIT.
OrthoDB	EOG40S0FM.
Gene expression databases
ArrayExpress	Q78IQ7.
Bgee	Q78IQ7.
Genevestigator	Q78IQ7.
GermOnline	ENSMUSG00000063354. Mus musculus.
Family and domain databases
InterPro	IPR003689. ZIP. [Graphical view]
Pfam	PF02535. Zip. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	335258.
SOURCE	Search...

Entry information

Entry name

S39A4_MOUSE

Accession

Primary (citable) accession number: Q78IQ7
Secondary accession number(s): Q8CHL4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program