Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - Q15043 (S39AE_HUMAN)

Protein

Zinc transporter ZIP14

Gene

SLC39A14

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

Functioni

Broad-scope metal ion transporter with a preference for zinc uptake (PubMed:29621230). Also mediates cellular uptake of nontransferrin-bound iron.3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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.5.4.5 the zinc (zn(2+))-iron (fe(2+)) permease (zip) family

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc transporter ZIP14
Alternative name(s):
LIV-1 subfamily of ZIP zinc transporter 4
Short name:
LZT-Hs4
Solute carrier family 39 member 14
Zrt- and Irt-like protein 14
Short name:
ZIP-14
Gene namesi
Name:SLC39A14
Synonyms:KIAA0062, ZIP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104635.13
HGNCiHGNC:20858 SLC39A14
MIMi608736 gene
neXtProtiNX_Q15043

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 157ExtracellularSequence analysisAdd BLAST127
Transmembranei158 – 178HelicalSequence analysisAdd BLAST21
Topological domaini179 – 186CytoplasmicSequence analysis8
Transmembranei187 – 207HelicalSequence analysisAdd BLAST21
Topological domaini208 – 224ExtracellularSequence analysisAdd BLAST17
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 397CytoplasmicSequence analysisAdd BLAST152
Transmembranei398 – 418HelicalSequence analysisAdd BLAST21
Topological domaini419 – 424ExtracellularSequence analysis6
Transmembranei425 – 445HelicalSequence analysisAdd BLAST21
Topological domaini446 – 460CytoplasmicSequence analysisAdd BLAST15
Transmembranei461 – 481HelicalSequence analysisAdd BLAST21
Topological domaini482 – 492ExtracellularSequence analysisAdd BLAST11

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypermanganesemia with dystonia 2 (HMNDYT2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic autosomal recessive disorder characterized by increased blood manganese levels, neurodegeneration, and rapidly progressive parkinsonism and dystonia. Affected individuals present with loss of developmental milestones, progressive dystonia and bulbar dysfunction in infancy or early childhood. Towards the end of the first decade, they manifest severe generalized pharmacoresistant dystonia, spasticity, limb contractures and scoliosis, and loss of independent ambulation. Cognition may be impaired, but is better preserved than motor function.
See also OMIM:617013
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07700498F → V in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs879253763EnsemblClinVar.1
Natural variantiVAR_077005383G → R in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs879253766EnsemblClinVar.1
Natural variantiVAR_077006469N → K in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs750281602EnsemblClinVar.1
Hyperostosis cranialis interna (HCIN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. Conditional knockin mice overexpressing Arg-438 variant, which is the mouse equivalent of human variant Leu-441, in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients.1 Publication
Disease descriptionAn autosomal dominant bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII, its first symptoms often presenting during the second decade of life.
See also OMIM:144755
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080794441L → R in HCIN; loss of localization at the plasma membrane; loss of Zn uptake activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Dystonia, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi23516
MalaCardsiSLC39A14
MIMi144755 phenotype
617013 phenotype
OpenTargetsiENSG00000104635
PharmGKBiPA134863701

Polymorphism and mutation databases

BioMutaiSLC39A14
DMDMi313104191

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000031219431 – 492Zinc transporter ZIP14Add BLAST462

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi77N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi102N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ15043
MaxQBiQ15043
PaxDbiQ15043
PeptideAtlasiQ15043
PRIDEiQ15043
ProteomicsDBi60392
60393 [Q15043-2]
60394 [Q15043-3]

PTM databases

iPTMnetiQ15043
PhosphoSitePlusiQ15043

Expressioni

Tissue specificityi

Expressed in liver and in brain by large neurons in the globus pallidus, the insular cortex and the dentate nucleus and to a lower extent in the putamen and the caudate nucleus (at protein level) (PubMed:27231142). Isoform 1 is ubiquitously expressed, with increased expression in liver, pancreas, fetal liver, thyroid gland, left and right ventricle, right atrium and fetal heart. Weakly expressed in spleen, thymus, and peripheral blood leukocytes (PubMed:15642354, PubMed:7584044, PubMed:27231142). Isoform 3 is widely expressed but not detected in brain, heart, skeletal muscle and fetal skin (PubMed:27231142). Expressed in osteoblasts and giant osteoclast-like cells, but not in osteocytes found osteoblastoma and giant cell tumors (at protein level) (PubMed:29621230).4 Publications

Gene expression databases

BgeeiENSG00000104635 Expressed in 227 organ(s), highest expression level in right lobe of liver
CleanExiHS_SLC39A14
ExpressionAtlasiQ15043 baseline and differential
GenevisibleiQ15043 HS

Organism-specific databases

HPAiHPA016508

Interactioni

Subunit structurei

Homotrimer.1 Publication

Protein-protein interaction databases

BioGridi117063, 5 interactors
IntActiQ15043, 10 interactors
STRINGi9606.ENSP00000289952

Structurei

3D structure databases

ProteinModelPortaliQ15043
SMRiQ15043
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi251 – 258HHHGHXHX-motif8
Motifi376 – 381XEXPHE-motif6

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2693 Eukaryota
COG0428 LUCA
GeneTreeiENSGT00760000119115
HOGENOMiHOG000070225
HOVERGENiHBG108450
InParanoidiQ15043
KOiK14720
OMAiCCCYLGM
OrthoDBiEOG091G064Y
PhylomeDBiQ15043
TreeFamiTF318470

Family and domain databases

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

Sequences (3+)i

Sequence statusi: Complete.

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

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

This entry has 3 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q15043-1) [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
MKLLLLHPAF QSCLLLTLLG LWRTTPEAHA SSLGAPAISA ASFLQDLIHR 
        60         70         80         90        100
YGEGDSLTLQ QLKALLNHLD VGVGRGNVTQ HVQGHRNLST CFSSGDLFTA 
       110        120        130        140        150
HNFSEQSRIG SSELQEFCPT ILQQLDSRAC TSENQENEEN EQTEEGRPSA 
       160        170        180        190        200
VEVWGYGLLC VTVISLCSLL GASVVPFMKK TFYKRLLLYF IALAIGTLYS 
       210        220        230        240        250
NALFQLIPEA FGFNPLEDYY VSKSAVVFGG FYLFFFTEKI LKILLKQKNE 
       260        270        280        290        300
HHHGHSHYAS ESLPSKKDQE EGVMEKLQNG DLDHMIPQHC SSELDGKAPM 
       310        320        330        340        350
VDEKVIVGSL SVQDLQASQS ACYWLKGVRY SDIGTLAWMI TLSDGLHNFI 
       360        370        380        390        400
DGLAIGASFT VSVFQGISTS VAILCEEFPH ELGDFVILLN AGMSIQQALF 
       410        420        430        440        450
FNFLSACCCY LGLAFGILAG SHFSANWIFA LAGGMFLYIS LADMFPEMNE 
       460        470        480        490 
VCQEDERKGS ILIPFIIQNL GLLTGFTIMV VLTMYSGQIQ IG
Length:492
Mass (Da):54,212
Last modified:November 30, 2010 - v3
Checksum:iF2ACE1DA4656A5F0
GO
Isoform 2 (identifier: Q15043-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-492: FPEMNEVCQE...TMYSGQIQIG → MEFCSVAQAG...RLSCLSLPSN

Note: No experimental confirmation available.
Show »
Length:481
Mass (Da):52,839
Checksum:iDC2788F667F06D95
GO
Isoform 3 (identifier: Q15043-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     156-199: YGLLCVTVIS...FIALAIGTLY → FGFLSVSLIN...FIALSIGTLL

Show »
Length:492
Mass (Da):54,057
Checksum:i5D5503F24F952500
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RFT1E5RFT1_HUMAN
Zinc transporter ZIP14
SLC39A14
201Annotation score:
E5RFZ8E5RFZ8_HUMAN
Zinc transporter ZIP14
SLC39A14
89Annotation score:
E5RIP4E5RIP4_HUMAN
Zinc transporter ZIP14
SLC39A14
155Annotation score:
E5RJ40E5RJ40_HUMAN
Zinc transporter ZIP14
SLC39A14
122Annotation score:
E5RGA7E5RGA7_HUMAN
Zinc transporter ZIP14
SLC39A14
90Annotation score:
E5RJG5E5RJG5_HUMAN
Zinc transporter ZIP14
SLC39A14
127Annotation score:
E5RFF5E5RFF5_HUMAN
Zinc transporter ZIP14
SLC39A14
53Annotation score:

Sequence cautioni

The sequence BAA06685 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57L → P in BAD18780 (PubMed:14702039).Curated1
Sequence conflicti314D → G in BAG58625 (PubMed:14702039).Curated1
Sequence conflicti380H → R in BAD18780 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03745033L → P1 PublicationCorresponds to variant dbSNP:rs896378Ensembl.1
Natural variantiVAR_07700498F → V in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs879253763EnsemblClinVar.1
Natural variantiVAR_077005383G → R in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs879253766EnsemblClinVar.1
Natural variantiVAR_080794441L → R in HCIN; loss of localization at the plasma membrane; loss of Zn uptake activity. 1 Publication1
Natural variantiVAR_077006469N → K in HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity. 1 PublicationCorresponds to variant dbSNP:rs750281602EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040139156 – 199YGLLC…IGTLY → FGFLSVSLINLASLLGVLVL PCTEKAFFSRVLTYFIALSI GTLL in isoform 3. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_029728445 – 492FPEMN…QIQIG → MEFCSVAQAGVQWCHLSSLQ PLPLGLKRLSCLSLPSN in isoform 2. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31887 mRNA Translation: BAA06685.1 Different initiation.
AK172810 mRNA Translation: BAD18780.1
AK295807 mRNA Translation: BAG58625.1
AC087854 Genomic DNA No translation available.
AC105910 Genomic DNA No translation available.
CH471080 Genomic DNA Translation: EAW63681.1
CH471080 Genomic DNA Translation: EAW63682.1
CH471080 Genomic DNA Translation: EAW63683.1
BC015770 mRNA Translation: AAH15770.1
CCDSiCCDS47822.1 [Q15043-2]
CCDS47823.1 [Q15043-1]
CCDS6030.1 [Q15043-3]
RefSeqiNP_001121903.1, NM_001128431.2 [Q15043-1]
NP_001128625.1, NM_001135153.1 [Q15043-1]
NP_056174.2, NM_015359.4 [Q15043-3]
XP_005273522.1, XM_005273465.2
XP_005273523.1, XM_005273466.4 [Q15043-1]
XP_006716387.1, XM_006716324.2 [Q15043-1]
XP_011542780.1, XM_011544478.2 [Q15043-1]
XP_016868783.1, XM_017013294.1
XP_016868784.1, XM_017013295.1
UniGeneiHs.491232

Genome annotation databases

EnsembliENST00000240095; ENSP00000240095; ENSG00000104635 [Q15043-2]
ENST00000289952; ENSP00000289952; ENSG00000104635 [Q15043-1]
ENST00000359741; ENSP00000352779; ENSG00000104635 [Q15043-3]
ENST00000381237; ENSP00000370635; ENSG00000104635 [Q15043-1]
GeneIDi23516
KEGGihsa:23516
UCSCiuc003xbp.5 human [Q15043-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31887 mRNA Translation: BAA06685.1 Different initiation.
AK172810 mRNA Translation: BAD18780.1
AK295807 mRNA Translation: BAG58625.1
AC087854 Genomic DNA No translation available.
AC105910 Genomic DNA No translation available.
CH471080 Genomic DNA Translation: EAW63681.1
CH471080 Genomic DNA Translation: EAW63682.1
CH471080 Genomic DNA Translation: EAW63683.1
BC015770 mRNA Translation: AAH15770.1
CCDSiCCDS47822.1 [Q15043-2]
CCDS47823.1 [Q15043-1]
CCDS6030.1 [Q15043-3]
RefSeqiNP_001121903.1, NM_001128431.2 [Q15043-1]
NP_001128625.1, NM_001135153.1 [Q15043-1]
NP_056174.2, NM_015359.4 [Q15043-3]
XP_005273522.1, XM_005273465.2
XP_005273523.1, XM_005273466.4 [Q15043-1]
XP_006716387.1, XM_006716324.2 [Q15043-1]
XP_011542780.1, XM_011544478.2 [Q15043-1]
XP_016868783.1, XM_017013294.1
XP_016868784.1, XM_017013295.1
UniGeneiHs.491232

3D structure databases

ProteinModelPortaliQ15043
SMRiQ15043
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117063, 5 interactors
IntActiQ15043, 10 interactors
STRINGi9606.ENSP00000289952

Protein family/group databases

TCDBi2.A.5.4.5 the zinc (zn(2+))-iron (fe(2+)) permease (zip) family

PTM databases

iPTMnetiQ15043
PhosphoSitePlusiQ15043

Polymorphism and mutation databases

BioMutaiSLC39A14
DMDMi313104191

Proteomic databases

EPDiQ15043
MaxQBiQ15043
PaxDbiQ15043
PeptideAtlasiQ15043
PRIDEiQ15043
ProteomicsDBi60392
60393 [Q15043-2]
60394 [Q15043-3]

Protocols and materials databases

DNASUi23516
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000240095; ENSP00000240095; ENSG00000104635 [Q15043-2]
ENST00000289952; ENSP00000289952; ENSG00000104635 [Q15043-1]
ENST00000359741; ENSP00000352779; ENSG00000104635 [Q15043-3]
ENST00000381237; ENSP00000370635; ENSG00000104635 [Q15043-1]
GeneIDi23516
KEGGihsa:23516
UCSCiuc003xbp.5 human [Q15043-1]

Organism-specific databases

CTDi23516
DisGeNETi23516
EuPathDBiHostDB:ENSG00000104635.13
GeneCardsiSLC39A14
HGNCiHGNC:20858 SLC39A14
HPAiHPA016508
MalaCardsiSLC39A14
MIMi144755 phenotype
608736 gene
617013 phenotype
neXtProtiNX_Q15043
OpenTargetsiENSG00000104635
PharmGKBiPA134863701
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2693 Eukaryota
COG0428 LUCA
GeneTreeiENSGT00760000119115
HOGENOMiHOG000070225
HOVERGENiHBG108450
InParanoidiQ15043
KOiK14720
OMAiCCCYLGM
OrthoDBiEOG091G064Y
PhylomeDBiQ15043
TreeFamiTF318470

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiSLC39A14 human
GenomeRNAii23516
PROiPR:Q15043
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104635 Expressed in 227 organ(s), highest expression level in right lobe of liver
CleanExiHS_SLC39A14
ExpressionAtlasiQ15043 baseline and differential
GenevisibleiQ15043 HS

Family and domain databases

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

Entry informationi

Entry nameiS39AE_HUMAN
AccessioniPrimary (citable) accession number: Q15043
Secondary accession number(s): A6NH98
, B4DIW3, B6EU88, D3DSR4, Q6ZME8, Q96BB3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: November 30, 2010
Last modified: November 7, 2018
This is version 138 of the entry and version 3 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again