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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

Complete GO annotation...

Keywords - Biological processi

Ion transport, Transport, Zinc transport

Keywords - Ligandi

Zinc

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, membrane-bounded 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
Complete GO annotation...

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 Publication1
Natural variantiVAR_02362995R → C in AEZ. 1 Publication1
Natural variantiVAR_023630106N → K in AEZ. 1 Publication1
Natural variantiVAR_023632200P → L in AEZ. 1 Publication1
Natural variantiVAR_023633251R → W in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant rs2977838dbSNPEnsembl.1
Natural variantiVAR_023634303Q → H in AEZ. 1 Publication1
Natural variantiVAR_023635309C → Y in AEZ; unknown pathological significance. 2 Publications1
Natural variantiVAR_023636330G → D in AEZ. 1 Publication1
Natural variantiVAR_023638372L → P in AEZ. 1 Publication1
Natural variantiVAR_023639374G → R in AEZ. 1 Publication1
Natural variantiVAR_023640410L → P in AEZ; unknown pathological significance. 1 Publication1
Natural variantiVAR_023641526G → R in AEZ. 1 Publication1
Natural variantiVAR_023642630G → R in AEZ. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi55630.
MalaCardsiSLC39A4.
MIMi201100. phenotype.
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...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ6P5W5.
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. 101 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.
HOGENOMiHOG000293181.
HOVERGENiHBG062532.
InParanoidiQ6P5W5.
KOiK14710.
OrthoDBiEOG091G04FT.
PhylomeDBiQ6P5W5.
TreeFamiTF318470.

Family and domain databases

InterProiIPR003689. ZIP.
[Graphical view]
PfamiPF02535. Zip. 1 hit.
[Graphical view]

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
AAGQTPKTAC 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 ALTGDAVLHL 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):68,392
Last modified:May 18, 2010 - v3
Checksum:i1B482200EB78F881
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):66,162
Checksum:iAEC20AD677CB3D62
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 rs2280839dbSNPEnsembl.1
Natural variantiVAR_02362758A → T.3 PublicationsCorresponds to variant rs2280838dbSNPEnsembl.1
Natural variantiVAR_02362884P → L in AEZ; unknown pathological significance. 1 Publication1
Natural variantiVAR_02362995R → C in AEZ. 1 Publication1
Natural variantiVAR_023630106N → K in AEZ. 1 Publication1
Natural variantiVAR_023631114A → T.3 PublicationsCorresponds to variant rs17855765dbSNPEnsembl.1
Natural variantiVAR_057481158T → M.Corresponds to variant rs1871533dbSNPEnsembl.1
Natural variantiVAR_023632200P → L in AEZ. 1 Publication1
Natural variantiVAR_023633251R → W in AEZ; unknown pathological significance. 2 PublicationsCorresponds to variant rs2977838dbSNPEnsembl.1
Natural variantiVAR_057482284E → K.Corresponds to variant rs7823979dbSNPEnsembl.1
Natural variantiVAR_023634303Q → H in AEZ. 1 Publication1
Natural variantiVAR_023635309C → Y in AEZ; unknown pathological significance. 2 Publications1
Natural variantiVAR_023636330G → D in AEZ. 1 Publication1
Natural variantiVAR_023637357T → A.2 PublicationsCorresponds to variant rs2272662dbSNPEnsembl.1
Natural variantiVAR_023638372L → P in AEZ. 1 Publication1
Natural variantiVAR_057483372L → V.Corresponds to variant rs1871534dbSNPEnsembl.1
Natural variantiVAR_023639374G → R in AEZ. 1 Publication1
Natural variantiVAR_060488378L → V.Corresponds to variant rs4483198dbSNPEnsembl.1
Natural variantiVAR_023640410L → P in AEZ; unknown pathological significance. 1 Publication1
Natural variantiVAR_023641526G → R in AEZ. 1 Publication1
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. [Q6P5W5-2]
NP_570901.2. NM_130849.3. [Q6P5W5-1]
UniGeneiHs.521934.

Genome annotation databases

EnsembliENST00000301305; ENSP00000301305; ENSG00000147804.
GeneIDi55630.
KEGGihsa:55630.
UCSCiuc003zcq.4. human. [Q6P5W5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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. [Q6P5W5-2]
NP_570901.2. NM_130849.3. [Q6P5W5-1]
UniGeneiHs.521934.

3D structure databases

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

Protein-protein interaction databases

BioGridi120769. 101 interactors.
STRINGi9606.ENSP00000301305.

Protein family/group databases

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

PTM databases

iPTMnetiQ6P5W5.
PhosphoSitePlusiQ6P5W5.

Polymorphism and mutation databases

BioMutaiSLC39A4.
DMDMi296452970.

Proteomic databases

MaxQBiQ6P5W5.
PaxDbiQ6P5W5.
PeptideAtlasiQ6P5W5.
PRIDEiQ6P5W5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301305; ENSP00000301305; ENSG00000147804.
GeneIDi55630.
KEGGihsa:55630.
UCSCiuc003zcq.4. human. [Q6P5W5-1]

Organism-specific databases

CTDi55630.
DisGeNETi55630.
GeneCardsiSLC39A4.
H-InvDBHIX0007856.
HGNCiHGNC:17129. SLC39A4.
MalaCardsiSLC39A4.
MIMi201100. phenotype.
607059. gene.
neXtProtiNX_Q6P5W5.
Orphaneti37. Acrodermatitis enteropathica.
PharmGKBiPA38204.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii55630.
PROiQ6P5W5.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

InterProiIPR003689. ZIP.
[Graphical view]
PfamiPF02535. Zip. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS39A4_HUMAN
AccessioniPrimary (citable) accession number: Q6P5W5
Secondary accession number(s): Q7L5S5, Q9H6T8, Q9NXC4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 113 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.