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Protein

Zinc transporter ZIP4

Gene

SLC39A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in cellular zinc homeostasis as a zinc transporter. Regulated in response to zinc availability (By similarity).By similarity

GO - Molecular functioni

  • zinc ion transmembrane transporter activity Source: CACAO

GO - Biological processi

Keywordsi

Biological processIon transport, Transport, Zinc transport
LigandZinc

Enzyme and pathway databases

ReactomeiR-HSA-442380. Zinc influx into cells by the SLC39 gene family.

Protein family/group databases

TCDBi2.A.5.4.1. the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc transporter ZIP4
Alternative name(s):
Solute carrier family 39 member 4
Zrt- and Irt-like protein 4
Short name:
ZIP-4
Gene namesi
Name:SLC39A4
Synonyms:ZIP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:17129. SLC39A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 327ExtracellularSequence analysisAdd BLAST305
Transmembranei328 – 348Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini349 – 359CytoplasmicSequence analysisAdd BLAST11
Transmembranei360 – 380Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini381 – 402ExtracellularSequence analysisAdd BLAST22
Transmembranei403 – 423Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini424 – 558CytoplasmicSequence analysisAdd BLAST135
Transmembranei559 – 579Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini580 – 586ExtracellularSequence analysis7
Transmembranei587 – 607Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini608 – 617CytoplasmicSequence analysis10
Transmembranei618 – 638Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini639 – 647ExtracellularSequence analysis9

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • cytoplasmic vesicle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Acrodermatitis enteropathica, zinc-deficiency type (AEZ)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:201100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02362884P → L in AEZ; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs117535951Ensembl.1
Natural variantiVAR_02362995R → C in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434292Ensembl.1
Natural variantiVAR_023630106N → K in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434290Ensembl.1
Natural variantiVAR_023632200P → L in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434287Ensembl.1
Natural variantiVAR_023633251R → W in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs2977838Ensembl.1
Natural variantiVAR_023634303Q → H in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434293Ensembl.1
Natural variantiVAR_023635309C → Y in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs782110796Ensembl.1
Natural variantiVAR_023636330G → D in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434291Ensembl.1
Natural variantiVAR_023638372V → P in AEZ; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_023639374G → R in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434289Ensembl.1
Natural variantiVAR_023640410L → P in AEZ; unknown pathological significance. 1 Publication1
Natural variantiVAR_023641526G → R in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434288Ensembl.1
Natural variantiVAR_023642630G → R in AEZ. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi55630.
MalaCardsiSLC39A4.
MIMi201100. phenotype.
OpenTargetsiENSG00000147804.
Orphaneti37. Acrodermatitis enteropathica.
PharmGKBiPA38204.

Polymorphism and mutation databases

BioMutaiSLC39A4.
DMDMi296452970.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000004262023 – 647Zinc transporter ZIP4Add BLAST625

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi261N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ6P5W5.
PeptideAtlasiQ6P5W5.
PRIDEiQ6P5W5.

PTM databases

iPTMnetiQ6P5W5.
PhosphoSitePlusiQ6P5W5.

Expressioni

Tissue specificityi

Highly expressed in kidney, small intestine, stomach, colon, jejunum and duodenum.2 Publications

Gene expression databases

BgeeiENSG00000147804.
CleanExiHS_SLC39A4.
ExpressionAtlasiQ6P5W5. baseline and differential.
GenevisibleiQ6P5W5. HS.

Interactioni

Protein-protein interaction databases

BioGridi120769. 103 interactors.
STRINGi9606.ENSP00000301305.

Structurei

3D structure databases

ProteinModelPortaliQ6P5W5.
SMRiQ6P5W5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2693. Eukaryota.
COG0428. LUCA.
GeneTreeiENSGT00760000119115.
HOGENOMiHOG000293181.
HOVERGENiHBG062532.
InParanoidiQ6P5W5.
KOiK14710.
OrthoDBiEOG091G04FT.
PhylomeDBiQ6P5W5.
TreeFamiTF318470.

Family and domain databases

InterProiView protein in InterPro
IPR003689. ZIP.
PfamiView protein in Pfam
PF02535. Zip. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6P5W5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASLVSLELG LLLAVLVVTA TASPPAGLLS LLTSGQGALD QEALGGLLNT
60 70 80 90 100
LADRVHCANG PCGKCLSVED ALGLGEPEGS GLPPGPVLEA RYVARLSAAA
110 120 130 140 150
VLYLSNPEGT CEDARAGLWA SHADHLLALL ESPKALTPGL SWLLQRMQAR
160 170 180 190 200
AAGQTPKMAC VDIPQLLEEA VGAGAPGSAG GVLAALLDHV RSGSCFHALP
210 220 230 240 250
SPQYFVDFVF QQHSSEVPMT LAELSALMQR LGVGREAHSD HSHRHRGASS
260 270 280 290 300
RDPVPLISSS NSSSVWDTVC LSARDVMAAY GLSEQAGVTP EAWAQLSPAL
310 320 330 340 350
LQQQLSGACT SQSRPPVQDQ LSQSERYLYG SLATLLICLC AVFGLLLLTC
360 370 380 390 400
TGCRGVTHYI LQTFLSLAVG AVTGDAVLHL TPKVLGLHTH SEEGLSPQPT
410 420 430 440 450
WRLLAMLAGL YAFFLFENLF NLLLPRDPED LEDGPCGHSS HSHGGHSHGV
460 470 480 490 500
SLQLAPSELR QPKPPHEGSR ADLVAEESPE LLNPEPRRLS PELRLLPYMI
510 520 530 540 550
TLGDAVHNFA DGLAVGAAFA SSWKTGLATS LAVFCHELPH ELGDFAALLH
560 570 580 590 600
AGLSVRQALL LNLASALTAF AGLYVALAVG VSEESEAWIL AVATGLFLYV
610 620 630 640
ALCDMLPAML KVRDPRPWLL FLLHNVGLLG GWTVLLLLSL YEDDITF
Length:647
Mass (Da):68,408
Last modified:April 12, 2017 - v4
Checksum:iAB84735F4BEF434F
GO
Isoform 2 (identifier: Q6P5W5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:622
Mass (Da):66,178
Checksum:i1E0E5B89D75C86AC
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06048722A → E. Corresponds to variant dbSNP:rs2280839Ensembl.1
Natural variantiVAR_02362758A → T3 PublicationsCorresponds to variant dbSNP:rs2280838Ensembl.1
Natural variantiVAR_02362884P → L in AEZ; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs117535951Ensembl.1
Natural variantiVAR_02362995R → C in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434292Ensembl.1
Natural variantiVAR_023630106N → K in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434290Ensembl.1
Natural variantiVAR_023631114A → T3 PublicationsCorresponds to variant dbSNP:rs17855765Ensembl.1
Natural variantiVAR_057481158M → T. Corresponds to variant dbSNP:rs1871533Ensembl.1
Natural variantiVAR_023632200P → L in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434287Ensembl.1
Natural variantiVAR_023633251R → W in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs2977838Ensembl.1
Natural variantiVAR_057482284E → K. Corresponds to variant dbSNP:rs7823979Ensembl.1
Natural variantiVAR_023634303Q → H in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434293Ensembl.1
Natural variantiVAR_023635309C → Y in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs782110796Ensembl.1
Natural variantiVAR_023636330G → D in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434291Ensembl.1
Natural variantiVAR_023637357T → A2 PublicationsCorresponds to variant dbSNP:rs2272662Ensembl.1
Natural variantiVAR_057483372V → L. Corresponds to variant dbSNP:rs1871534Ensembl.1
Natural variantiVAR_023638372V → P in AEZ; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_023639374G → R in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434289Ensembl.1
Natural variantiVAR_023640410L → P in AEZ; unknown pathological significance. 1 Publication1
Natural variantiVAR_023641526G → R in AEZ. 1 PublicationCorresponds to variant dbSNP:rs121434288Ensembl.1
Natural variantiVAR_023642630G → R in AEZ. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0159111 – 25Missing in isoform 2. 2 PublicationsAdd BLAST25
Alternative sequenceiVSP_01591226 – 64AGLLS…GPCGK → MVDVVGLERETGPRGSPWPG LPLPSLVGPAPLLTCLCPQ in isoform 2. 2 PublicationsAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS43782.1. [Q6P5W5-2]
CCDS6424.1. [Q6P5W5-1]
RefSeqiNP_060237.2. NM_017767.2.
NP_570901.2. NM_130849.3.
UniGeneiHs.521934.

Genome annotation databases

EnsembliENST00000276833; ENSP00000276833; ENSG00000147804. [Q6P5W5-2]
ENST00000301305; ENSP00000301305; ENSG00000147804. [Q6P5W5-1]
GeneIDi55630.
KEGGihsa:55630.
UCSCiuc003zcq.4. human. [Q6P5W5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiS39A4_HUMAN
AccessioniPrimary (citable) accession number: Q6P5W5
Secondary accession number(s): Q7L5S5, Q9H6T8, Q9NXC4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: April 12, 2017
Last modified: August 30, 2017
This is version 121 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families