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Protein

Zinc transporter ZIP8

Gene

SLC39A8

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

Functioni

Acts as a manganese and zinc influx transporter (PubMed:12504855, PubMed:26637978). Plays a role in manganese reabsorption in the proximal tubule of the kidney and in manganese uptake into the brain (PubMed:26637978).1 Publication1 Publication

GO - Molecular functioni

GO - Biological processi

  • cadmium ion transmembrane transport Source: Ensembl
  • cellular zinc ion homeostasis Source: GO_Central
  • zinc II ion transmembrane import Source: GO_Central
  • zinc II ion transport Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ion transport, Transport, Zinc transport

Keywords - Ligandi

Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138821-MONOMER.
ReactomeiR-HSA-442380. Zinc influx into cells by the SLC39 gene family.

Protein family/group databases

TCDBi2.A.5.4.15. the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc transporter ZIP8
Alternative name(s):
BCG-induced integral membrane protein in monocyte clone 103 protein
LIV-1 subfamily of ZIP zinc transporter 6
Short name:
LZT-Hs6
Solute carrier family 39 member 8
Zrt- and Irt-like protein 8
Short name:
ZIP-8
Gene namesi
Name:SLC39A8
Synonyms:BIGM103, ZIP8
ORF Names:PP3105
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:20862. SLC39A8.

Subcellular locationi

  • Membrane Curated; Multi-pass membrane protein Curated

  • Note: Associated with the lysosomal/endosomal compartment following transfection.1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8ExtracellularSequence analysis8
Transmembranei9 – 29HelicalSequence analysisAdd BLAST21
Topological domaini30 – 132CytoplasmicSequence analysisAdd BLAST103
Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
Topological domaini154 – 160ExtracellularSequence analysis7
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Topological domaini182 – 191CytoplasmicSequence analysis10
Transmembranei192 – 212HelicalSequence analysisAdd BLAST21
Topological domaini213 – 302ExtracellularSequence analysisAdd BLAST90
Transmembranei303 – 323HelicalSequence analysisAdd BLAST21
Topological domaini324 – 365CytoplasmicSequence analysisAdd BLAST42
Transmembranei366 – 386HelicalSequence analysisAdd BLAST21
Topological domaini387 – 388ExtracellularSequence analysis2
Transmembranei389 – 409HelicalSequence analysisAdd BLAST21
Topological domaini410 – 429CytoplasmicSequence analysisAdd BLAST20
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 460ExtracellularSequence analysis10

GO - Cellular componenti

  • integral component of plasma membrane Source: GO_Central
  • organelle membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital disorder of glycosylation 2N (CDG2N)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
See also OMIM:616721
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07624133V → M in CDG2N. 1 PublicationCorresponds to variant rs373562040dbSNPEnsembl.1
Natural variantiVAR_07624238G → R in CDG2N; lowered Mn and Zn blood levels and increased Mn and Zn urine levels in affected individuals. 2 PublicationsCorresponds to variant rs778210210dbSNPEnsembl.1
Natural variantiVAR_076243204G → C in CDG2N. 1 PublicationCorresponds to variant rs779241085dbSNPEnsembl.1
Natural variantiVAR_076244335S → T in CDG2N. 1 Publication1
Natural variantiVAR_076245340I → N in CDG2N; no detectable serum or urinary manganese levels in an affected individual who also carries R-38 mutation. 1 Publication1

Keywords - Diseasei

Congenital disorder of glycosylation

Organism-specific databases

DisGeNETi64116.
MIMi616721. phenotype.
OpenTargetsiENSG00000138821.
PharmGKBiPA134931507.

Polymorphism and mutation databases

BioMutaiSLC39A8.
DMDMi74733496.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003127071 – 460Zinc transporter ZIP8Add BLAST460

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi273N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9C0K1.
MaxQBiQ9C0K1.
PaxDbiQ9C0K1.
PeptideAtlasiQ9C0K1.
PRIDEiQ9C0K1.

PTM databases

iPTMnetiQ9C0K1.
PhosphoSitePlusiQ9C0K1.

Expressioni

Tissue specificityi

Expressed in thymus, placenta, lung, liver, pancreas and, to a lower extent, in spleen, testis, ovary, small intestine, colon, leukocyte, heart. Highest expression is observed in pancreas.1 Publication

Inductioni

By live and heat-killed Mycobacterium bovis bacterial cell wall and inflammatory cytokines like TNF. Down-regulated following phorbol ester treatment.1 Publication

Gene expression databases

BgeeiENSG00000138821.
CleanExiHS_SLC39A8.
ExpressionAtlasiQ9C0K1. baseline and differential.
GenevisibleiQ9C0K1. HS.

Organism-specific databases

HPAiHPA038832.
HPA038833.

Interactioni

Protein-protein interaction databases

BioGridi122072. 26 interactors.
STRINGi9606.ENSP00000349174.

Structurei

3D structure databases

ProteinModelPortaliQ9C0K1.
SMRiQ9C0K1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi343 – 348XEXPHE-motif6

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2693. Eukaryota.
COG0428. LUCA.
GeneTreeiENSGT00760000119115.
HOGENOMiHOG000070225.
HOVERGENiHBG108450.
InParanoidiQ9C0K1.
KOiK14714.
OMAiFFVERVL.
OrthoDBiEOG091G064Y.
PhylomeDBiQ9C0K1.
TreeFamiTF318470.

Family and domain databases

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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9C0K1-1) [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
MAPGRAVAGL LLLAAAGLGG VAEGPGLAFS EDVLSVFGAN LSLSAAQLQH
60 70 80 90 100
LLEQMGAASR VGVPEPGQLH FNQCLTAEEI FSLHGFSNAT QITSSKFSVI
110 120 130 140 150
CPAVLQQLNF HPCEDRPKHK TRPSHSEVWG YGFLSVTIIN LASLLGLILT
160 170 180 190 200
PLIKKSYFPK ILTFFVGLAI GTLFSNAIFQ LIPEAFGFDP KVDSYVEKAV
210 220 230 240 250
AVFGGFYLLF FFERMLKMLL KTYGQNGHTH FGNDNFGPQE KTHQPKALPA
260 270 280 290 300
INGVTCYANP AVTEANGHIH FDNVSVVSLQ DGKKEPSSCT CLKGPKLSEI
310 320 330 340 350
GTIAWMITLC DALHNFIDGL AIGASCTLSL LQGLSTSIAI LCEEFPHELG
360 370 380 390 400
DFVILLNAGM STRQALLFNF LSACSCYVGL AFGILVGNNF APNIIFALAG
410 420 430 440 450
GMFLYISLAD MFPEMNDMLR EKVTGRKTDF TFFMIQNAGM LTGFTAILLI
460
TLYAGEIELE
Length:460
Mass (Da):49,631
Last modified:June 1, 2001 - v1
Checksum:iE5C03F4576E11E2F
GO
Isoform 2 (identifier: Q9C0K1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: Missing.
     68-72: QLHFN → MHQHA

Note: No experimental confirmation available.
Show »
Length:393
Mass (Da):43,131
Checksum:i9ECB2D6D1FE89035
GO
Isoform 3 (identifier: Q9C0K1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     423-460: VTGRKTDFTFFMIQNAGMLTGFTAILLITLYAGEIELE → IIKWATDDIKSQLHLLWIYTAR

Note: No experimental confirmation available.
Show »
Length:444
Mass (Da):48,089
Checksum:i5EDFCF566871711A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241K → E in BAB55268 (PubMed:15498874).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07624133V → M in CDG2N. 1 PublicationCorresponds to variant rs373562040dbSNPEnsembl.1
Natural variantiVAR_07624238G → R in CDG2N; lowered Mn and Zn blood levels and increased Mn and Zn urine levels in affected individuals. 2 PublicationsCorresponds to variant rs778210210dbSNPEnsembl.1
Natural variantiVAR_076243204G → C in CDG2N. 1 PublicationCorresponds to variant rs779241085dbSNPEnsembl.1
Natural variantiVAR_076244335S → T in CDG2N. 1 Publication1
Natural variantiVAR_076245340I → N in CDG2N; no detectable serum or urinary manganese levels in an affected individual who also carries R-38 mutation. 1 Publication1
Natural variantiVAR_037551391A → T.Corresponds to variant rs13107325dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0298841 – 67Missing in isoform 2. 1 PublicationAdd BLAST67
Alternative sequenceiVSP_02988568 – 72QLHFN → MHQHA in isoform 2. 1 Publication5
Alternative sequenceiVSP_043675423 – 460VTGRK…EIELE → IIKWATDDIKSQLHLLWIYT AR in isoform 3. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020970 mRNA. Translation: BAA96442.1.
AB040120 mRNA. Translation: BAB21559.1.
AK027652 mRNA. Translation: BAB55268.1.
AK304274 mRNA. Translation: BAG65135.1.
AF193052 mRNA. Translation: AAG22480.1.
AC098487 Genomic DNA. No translation available.
AP002023 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06130.1.
BC001320 mRNA. Translation: AAH01320.1.
BC012125 mRNA. Translation: AAH12125.1.
CCDSiCCDS3656.1. [Q9C0K1-1]
CCDS47117.1. [Q9C0K1-3]
RefSeqiNP_001128618.1. NM_001135146.1. [Q9C0K1-1]
NP_001128619.1. NM_001135147.1. [Q9C0K1-3]
NP_001128620.1. NM_001135148.1. [Q9C0K1-2]
NP_071437.3. NM_022154.5. [Q9C0K1-1]
XP_005263234.1. XM_005263177.1. [Q9C0K1-1]
XP_016864029.1. XM_017008540.1. [Q9C0K1-1]
XP_016864030.1. XM_017008541.1. [Q9C0K1-2]
UniGeneiHs.288034.

Genome annotation databases

EnsembliENST00000356736; ENSP00000349174; ENSG00000138821. [Q9C0K1-1]
ENST00000394833; ENSP00000378310; ENSG00000138821. [Q9C0K1-1]
ENST00000424970; ENSP00000394548; ENSG00000138821. [Q9C0K1-3]
GeneIDi64116.
KEGGihsa:64116.
UCSCiuc003hwb.2. human. [Q9C0K1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020970 mRNA. Translation: BAA96442.1.
AB040120 mRNA. Translation: BAB21559.1.
AK027652 mRNA. Translation: BAB55268.1.
AK304274 mRNA. Translation: BAG65135.1.
AF193052 mRNA. Translation: AAG22480.1.
AC098487 Genomic DNA. No translation available.
AP002023 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06130.1.
BC001320 mRNA. Translation: AAH01320.1.
BC012125 mRNA. Translation: AAH12125.1.
CCDSiCCDS3656.1. [Q9C0K1-1]
CCDS47117.1. [Q9C0K1-3]
RefSeqiNP_001128618.1. NM_001135146.1. [Q9C0K1-1]
NP_001128619.1. NM_001135147.1. [Q9C0K1-3]
NP_001128620.1. NM_001135148.1. [Q9C0K1-2]
NP_071437.3. NM_022154.5. [Q9C0K1-1]
XP_005263234.1. XM_005263177.1. [Q9C0K1-1]
XP_016864029.1. XM_017008540.1. [Q9C0K1-1]
XP_016864030.1. XM_017008541.1. [Q9C0K1-2]
UniGeneiHs.288034.

3D structure databases

ProteinModelPortaliQ9C0K1.
SMRiQ9C0K1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122072. 26 interactors.
STRINGi9606.ENSP00000349174.

Protein family/group databases

TCDBi2.A.5.4.15. the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.

PTM databases

iPTMnetiQ9C0K1.
PhosphoSitePlusiQ9C0K1.

Polymorphism and mutation databases

BioMutaiSLC39A8.
DMDMi74733496.

Proteomic databases

EPDiQ9C0K1.
MaxQBiQ9C0K1.
PaxDbiQ9C0K1.
PeptideAtlasiQ9C0K1.
PRIDEiQ9C0K1.

Protocols and materials databases

DNASUi64116.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356736; ENSP00000349174; ENSG00000138821. [Q9C0K1-1]
ENST00000394833; ENSP00000378310; ENSG00000138821. [Q9C0K1-1]
ENST00000424970; ENSP00000394548; ENSG00000138821. [Q9C0K1-3]
GeneIDi64116.
KEGGihsa:64116.
UCSCiuc003hwb.2. human. [Q9C0K1-1]

Organism-specific databases

CTDi64116.
DisGeNETi64116.
GeneCardsiSLC39A8.
HGNCiHGNC:20862. SLC39A8.
HPAiHPA038832.
HPA038833.
MIMi608732. gene.
616721. phenotype.
neXtProtiNX_Q9C0K1.
OpenTargetsiENSG00000138821.
PharmGKBiPA134931507.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2693. Eukaryota.
COG0428. LUCA.
GeneTreeiENSGT00760000119115.
HOGENOMiHOG000070225.
HOVERGENiHBG108450.
InParanoidiQ9C0K1.
KOiK14714.
OMAiFFVERVL.
OrthoDBiEOG091G064Y.
PhylomeDBiQ9C0K1.
TreeFamiTF318470.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138821-MONOMER.
ReactomeiR-HSA-442380. Zinc influx into cells by the SLC39 gene family.

Miscellaneous databases

ChiTaRSiSLC39A8. human.
GenomeRNAii64116.
PROiQ9C0K1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138821.
CleanExiHS_SLC39A8.
ExpressionAtlasiQ9C0K1. baseline and differential.
GenevisibleiQ9C0K1. HS.

Family and domain databases

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

Entry informationi

Entry nameiS39A8_HUMAN
AccessioniPrimary (citable) accession number: Q9C0K1
Secondary accession number(s): B4E2H3
, Q96SM9, Q9BVC0, Q9NSA4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 117 of the entry and version 1 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 4
    Human chromosome 4: 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.