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Q6P5W5 (S39A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc transporter ZIP4
Alternative name(s):
Solute carrier family 39 member 4
Zrt- and Irt-like protein 4
Short name=ZIP-4
Gene names
Name:SLC39A4
Synonyms:ZIP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 By similarity.

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.6

Tissue specificity

Highly expressed in kidney, small intestine, stomach, colon, jejunum and duodenum. Ref.1 Ref.5

Involvement in disease

Acrodermatitis enteropathica, zinc-deficiency type (AEZ) [MIM:201100]: A rare autosomal recessive disease caused by the inability to absorb sufficient zinc. The clinical features are growth retardation, immune-system dysfunction, alopecia, severe dermatitis, diarrhea and occasionally mental disorders.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.5 Ref.7

Sequence similarities

Belongs to the ZIP transporter (TC 2.A.5) family. [View classification]

Sequence caution

The sequence BAA91091.1 differs from that shown. Reason: Frameshift at positions 573, 598 and 618.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6P5W5-1)

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.
Isoform 2 (identifier: Q6P5W5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     26-64: AGLLSLLTSG...VHCANGPCGK → MVDVVGLERE...APLLTCLCPQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 647625Zinc transporter ZIP4
PRO_0000042620

Regions

Topological domain23 – 327305Extracellular Potential
Transmembrane328 – 34821Helical; Name=1; Potential
Topological domain349 – 35911Cytoplasmic Potential
Transmembrane360 – 38021Helical; Name=2; Potential
Topological domain381 – 40222Extracellular Potential
Transmembrane403 – 42321Helical; Name=3; Potential
Topological domain424 – 558135Cytoplasmic Potential
Transmembrane559 – 57921Helical; Name=4; Potential
Topological domain580 – 5867Extracellular Potential
Transmembrane587 – 60721Helical; Name=5; Potential
Topological domain608 – 61710Cytoplasmic Potential
Transmembrane618 – 63821Helical; Name=6; Potential
Topological domain639 – 6479Extracellular Potential

Amino acid modifications

Glycosylation2611N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2525Missing in isoform 2.
VSP_015911
Alternative sequence26 – 6439AGLLS…GPCGK → MVDVVGLERETGPRGSPWPG LPLPSLVGPAPLLTCLCPQ in isoform 2.
VSP_015912
Natural variant221A → E.
Corresponds to variant rs2280839 [ dbSNP | Ensembl ].
VAR_060487
Natural variant581A → T. Ref.2 Ref.4 Ref.5
Corresponds to variant rs2280838 [ dbSNP | Ensembl ].
VAR_023627
Natural variant841P → L in AEZ; unknown pathological significance. Ref.5
VAR_023628
Natural variant951R → C in AEZ. Ref.7
VAR_023629
Natural variant1061N → K in AEZ. Ref.5
VAR_023630
Natural variant1141A → T. Ref.2 Ref.4 Ref.5
Corresponds to variant rs17855765 [ dbSNP | Ensembl ].
VAR_023631
Natural variant1581T → M.
Corresponds to variant rs1871533 [ dbSNP | Ensembl ].
VAR_057481
Natural variant2001P → L in AEZ. Ref.1
VAR_023632
Natural variant2511R → W in AEZ; unknown pathological significance. Ref.3 Ref.5
Corresponds to variant rs2977838 [ dbSNP | Ensembl ].
VAR_023633
Natural variant2841E → K.
Corresponds to variant rs7823979 [ dbSNP | Ensembl ].
VAR_057482
Natural variant3031Q → H in AEZ. Ref.7
VAR_023634
Natural variant3091C → Y in AEZ; unknown pathological significance. Ref.2 Ref.5
VAR_023635
Natural variant3301G → D in AEZ. Ref.5
VAR_023636
Natural variant3571T → A. Ref.2 Ref.5
Corresponds to variant rs2272662 [ dbSNP | Ensembl ].
VAR_023637
Natural variant3721L → P in AEZ. Ref.5
VAR_023638
Natural variant3721L → V.
Corresponds to variant rs1871534 [ dbSNP | Ensembl ].
VAR_057483
Natural variant3741G → R in AEZ. Ref.1
VAR_023639
Natural variant3781L → V.
Corresponds to variant rs4483198 [ dbSNP | Ensembl ].
VAR_060488
Natural variant4101L → P in AEZ; unknown pathological significance. Ref.5
VAR_023640
Natural variant5261G → R in AEZ. Ref.1
VAR_023641
Natural variant6301G → R in AEZ. Ref.5
VAR_023642

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 1B482200EB78F881

FASTA64768,392
        10         20         30         40         50         60 
MASLVSLELG LLLAVLVVTA TASPPAGLLS LLTSGQGALD QEALGGLLNT LADRVHCANG 

        70         80         90        100        110        120 
PCGKCLSVED ALGLGEPEGS GLPPGPVLEA RYVARLSAAA VLYLSNPEGT CEDARAGLWA 

       130        140        150        160        170        180 
SHADHLLALL ESPKALTPGL SWLLQRMQAR AAGQTPKTAC VDIPQLLEEA VGAGAPGSAG 

       190        200        210        220        230        240 
GVLAALLDHV RSGSCFHALP SPQYFVDFVF QQHSSEVPMT LAELSALMQR LGVGREAHSD 

       250        260        270        280        290        300 
HSHRHRGASS RDPVPLISSS NSSSVWDTVC LSARDVMAAY GLSEQAGVTP EAWAQLSPAL 

       310        320        330        340        350        360 
LQQQLSGACT SQSRPPVQDQ LSQSERYLYG SLATLLICLC AVFGLLLLTC TGCRGVTHYI 

       370        380        390        400        410        420 
LQTFLSLAVG ALTGDAVLHL TPKVLGLHTH SEEGLSPQPT WRLLAMLAGL YAFFLFENLF 

       430        440        450        460        470        480 
NLLLPRDPED LEDGPCGHSS HSHGGHSHGV SLQLAPSELR QPKPPHEGSR ADLVAEESPE 

       490        500        510        520        530        540 
LLNPEPRRLS PELRLLPYMI TLGDAVHNFA DGLAVGAAFA SSWKTGLATS LAVFCHELPH 

       550        560        570        580        590        600 
ELGDFAALLH AGLSVRQALL LNLASALTAF AGLYVALAVG VSEESEAWIL AVATGLFLYV 

       610        620        630        640 
ALCDMLPAML KVRDPRPWLL FLLHNVGLLG GWTVLLLLSL YEDDITF 

« Hide

Isoform 2 [UniParc].

Checksum: AEC20AD677CB3D62
Show »

FASTA62266,162

References

« Hide 'large scale' references
[1]"Identification of SLC39A4, a gene involved in acrodermatitis enteropathica."
Kuery S., Dreno B., Bezieau S., Giraudet S., Kharfi M., Kamoun R., Moisan J.-P.
Nat. Genet. 31:239-240(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANTS AEZ LEU-200; ARG-374 AND ARG-526.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS THR-58; THR-114; AEZ TYR-309 AND ALA-357.
[3]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TRP-251.
[4]"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), VARIANTS THR-58 AND THR-114.
Tissue: Lung and Ovary.
[5]"A novel member of a zinc transporter family is defective in acrodermatitis enteropathica."
Wang K., Zhou B., Kuo Y.-M., Zemansky J., Gitschier J.
Am. J. Hum. Genet. 71:66-73(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANTS THR-58; THR-114 AND ALA-357, VARIANTS AEZ LEU-84; LYS-106; TRP-251; TYR-309; ASP-330; PRO-372; PRO-410 AND ARG-630.
[6]"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.
[7]"Novel SLC39A4 mutations in acrodermatitis enteropathica."
Nakano A., Nakano H., Nomura K., Toyomaki Y., Hanada K.
J. Invest. Dermatol. 120:963-966(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AEZ CYS-95 AND HIS-303.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK000334 mRNA. Translation: BAA91091.1. Frameshift.
AK025537 mRNA. Translation: BAB15164.1.
AF205589 Genomic DNA. No translation available.
BC001688 mRNA. Translation: AAH01688.2.
BC062625 mRNA. Translation: AAH62625.1.
RefSeqNP_060237.2. NM_017767.2.
NP_570901.2. NM_130849.3.
UniGeneHs.521934.

3D structure databases

ProteinModelPortalQ6P5W5.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120769. 1 interaction.
STRING9606.ENSP00000372700.

Protein family/group databases

TCDB2.A.5.4.1. the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.

PTM databases

PhosphoSiteQ6P5W5.

Polymorphism databases

DMDM296452970.

Proteomic databases

PaxDbQ6P5W5.
PRIDEQ6P5W5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301305; ENSP00000301305; ENSG00000147804.
GeneID55630.
KEGGhsa:55630.
UCSCuc003zco.3. human. [Q6P5W5-1]
uc003zcp.3. human. [Q6P5W5-2]

Organism-specific databases

CTD55630.
GeneCardsGC08M145637.
H-InvDBHIX0007856.
HGNCHGNC:17129. SLC39A4.
HPAHPA031507.
MIM201100. phenotype.
607059. gene.
neXtProtNX_Q6P5W5.
Orphanet37. Acrodermatitis enteropathica, zinc deficiency type.
PharmGKBPA38204.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0428.
HOGENOMHOG000293181.
HOVERGENHBG062532.
InParanoidQ6P5W5.
KOK14710.
PhylomeDBQ6P5W5.
TreeFamTF318470.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ6P5W5.
BgeeQ6P5W5.
CleanExHS_SLC39A4.
GenevestigatorQ6P5W5.

Family and domain databases

InterProIPR003689. ZIP.
[Graphical view]
PfamPF02535. Zip. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi55630.
NextBio60265.
PROQ6P5W5.
SOURCESearch...

Entry information

Entry nameS39A4_HUMAN
AccessionPrimary (citable) accession number: Q6P5W5
Secondary accession number(s): Q7L5S5, Q9H6T8, Q9NXC4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 90 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM