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Protein

Zinc transporter 10

Gene

SLC30A10

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

Functioni

Plays a pivotal role in manganese transport. Manganese is an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. However, elevated levels of manganese are cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Acts as manganese efflux transporter and confers protection against manganese-induced cell death (PubMed:22341972, PubMed:22341971, PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc transporter involved in zinc homeostasis. Seems to mediate zinc transport into early endosomes and recycling endosomes to prevent zinc toxicity; the function may be regulated by heterodimerization with other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10 heterodimer is involved in zinc transport-dependent regulation of the EGFR/ERK transduction pathway in endosomes. May be involved in regulation of zinc-dependent senescence of vascular smooth muscle cells (PubMed:22706290, PubMed:22427991, PubMed:26728129).1 Publication5 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular response to angiotensin Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • manganese ion transmembrane transport Source: UniProtKB
  • manganese ion transport Source: UniProtKB
  • negative regulation of cellular senescence Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of reactive oxygen species biosynthetic process Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of cellular response to manganese ion Source: UniProtKB
  • regulation of sequestering of zinc ion Source: GO_Central
  • regulation of zinc ion transport Source: UniProtKB
  • response to zinc ion Source: GO_Central

Keywordsi

Biological processIon transport, Transport, Zinc transport
LigandManganese, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-425410. Metal ion SLC transporters.

Protein family/group databases

TCDBi2.A.4.2.5. the cation diffusion facilitator (cdf) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc transporter 10
Short name:
ZnT-10
Alternative name(s):
Manganese transporter SLC30A10
Solute carrier family 30 member 10
Gene namesi
Name:SLC30A10
Synonyms:ZNT10, ZNT8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000196660.10.
HGNCiHGNC:25355. SLC30A10.

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 domaini1 – 10CytoplasmicSequence analysis10
Transmembranei11 – 31HelicalSequence analysisAdd BLAST21
Topological domaini32 – 40ExtracellularSequence analysis9
Transmembranei41 – 61HelicalSequence analysisAdd BLAST21
Topological domaini62 – 81CytoplasmicSequence analysisAdd BLAST20
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Topological domaini103 – 113ExtracellularSequence analysisAdd BLAST11
Transmembranei114 – 134HelicalSequence analysisAdd BLAST21
Topological domaini135 – 244CytoplasmicSequence analysisAdd BLAST110
Transmembranei245 – 265HelicalSequence analysisAdd BLAST21
Topological domaini266 – 278ExtracellularSequence analysisAdd BLAST13
Transmembranei279 – 299HelicalSequence analysisAdd BLAST21
Topological domaini300 – 485CytoplasmicSequence analysisAdd BLAST186

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypermanganesemia with dystonia 1 (HMNDYT1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis.
See also OMIM:613280
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07257389L → P in HMNDYT1; abolishes cell surface localization. 2 PublicationsCorresponds to variant dbSNP:rs281860284Ensembl.1
Natural variantiVAR_072574105 – 107Missing in HMNDYT1; abolishes cell surface localization; decreases manganese efflux; decreases protection against manganese-induced neurotoxity. 2 Publications3
Natural variantiVAR_072576256Missing in HMNDYT1. 1 Publication1
Natural variantiVAR_072577349L → P in HMNDYT1. 1 PublicationCorresponds to variant dbSNP:rs281860291Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4Y → F: Decreases interaction with SLC30A3; no effect on self-association; decreases zinc transport; decreases EGF-induced ERK1/2 phosphorylation. 1 Publication1
Mutagenesisi25E → A: Abolishes manganese efflux activity. 1 Publication1
Mutagenesisi40D → A: Abolishes manganese efflux activity. 1 Publication1
Mutagenesisi127N → A: Abolishes manganese efflux activity; when associated with A-244. 1 Publication1
Mutagenesisi196T → P: Abolishes cell surface localization. 1 Publication1
Mutagenesisi244H → A: Abolishes manganese efflux activity; when associated with A-127. 1 Publication1
Mutagenesisi248D → A: Abolishes manganese efflux activity. 1 Publication1
Mutagenesisi333H → A: Decreases manganese efflux activity. 1 Publication1
Mutagenesisi350H → A: Decreases manganese efflux activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Dystonia, Neurodegeneration, Parkinsonism

Organism-specific databases

DisGeNETi55532.
GeneReviewsiSLC30A10.
MalaCardsiSLC30A10.
MIMi613280. phenotype.
OpenTargetsiENSG00000196660.
Orphaneti309854. Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome.
PharmGKBiPA142670903.

Polymorphism and mutation databases

BioMutaiSLC30A10.
DMDMi311033506.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003125801 – 485Zinc transporter 10Add BLAST485

Proteomic databases

PaxDbiQ6XR72.
PeptideAtlasiQ6XR72.
PRIDEiQ6XR72.

PTM databases

iPTMnetiQ6XR72.
PhosphoSitePlusiQ6XR72.

Expressioni

Tissue specificityi

Specifically expressed in fetal liver and fetal brain (PubMed:15154973). Expressed in adult tissues with relative levels small intestine > liver > testes > brain > ovary > colon > cervix > prostate > placenta (PubMed:22706290).2 Publications

Inductioni

Down-regulated by ZNF658 in response to zinc. Down-regulated by angiotensin-2.3 Publications

Gene expression databases

BgeeiENSG00000196660.
CleanExiHS_SLC30A10.
GenevisibleiQ6XR72. HS.

Organism-specific databases

HPAiHPA017989.

Interactioni

Subunit structurei

Forms homodimers. Forms heterodimers and high-molecular weight oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is mediated by covalent-bound tyrosine residues and occurs probably in a tissue-specific manner.2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

IntActiQ6XR72. 4 interactors.
STRINGi9606.ENSP00000355893.

Structurei

3D structure databases

ProteinModelPortaliQ6XR72.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni308 – 485Required for plasma membrane localization1 PublicationAdd BLAST178

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi253 – 256Poly-Val4
Compositional biasi396 – 399Poly-Leu4

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1483. Eukaryota.
COG1230. LUCA.
GeneTreeiENSGT00550000074381.
HOGENOMiHOG000166089.
HOVERGENiHBG000588.
InParanoidiQ6XR72.
KOiK14697.
OMAiIFQDCAA.
OrthoDBiEOG091G04DT.
PhylomeDBiQ6XR72.
TreeFamiTF313924.

Family and domain databases

Gene3Di3.30.70.1350. 1 hit.
InterProiView protein in InterPro
IPR002524. Cation_efflux.
IPR027470. Cation_efflux_CTD.
PfamiView protein in Pfam
PF01545. Cation_efflux. 1 hit.
TIGRFAMsiTIGR01297. CDF. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6XR72-4) [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
MGRYSGKTCR LLFMLVLTVA FFVAELVSGY LGNSIALLSD SFNMLSDLIS
60 70 80 90 100
LCVGLSAGYI ARRPTRGFSA TYGYARAEVV GALSNAVFLT ALCFTIFVEA
110 120 130 140 150
VLRLARPERI DDPELVLIVG VLGLLVNVVG LLIFQDCAAW FACCLRGRSR
160 170 180 190 200
RLQQRQQLAE GCVPGAFGGP QGAEDPRRAA DPTAPGSDSA VTLRGTSVER
210 220 230 240 250
KREKGATVFA NVAGDSFNTQ NEPEDMMKKE KKSEALNIRG VLLHVMGDAL
260 270 280 290 300
GSVVVVITAI IFYVLPLKSE DPCNWQCYID PSLTVLMVII ILSSAFPLIK
310 320 330 340 350
ETAAILLQMV PKGVNMEELM SKLSAVPGIS SVHEVHIWEL VSGKIIATLH
360 370 380 390 400
IKYPKDRGYQ DASTKIREIF HHAGIHNVTI QFENVDLKEP LEQKDLLLLC
410 420 430 440 450
NSPCISKGCA KQLCCPPGAL PLAHVNGCAE HNGGPSLDTY GSDGLSRRDA
460 470 480
REVAIEVSLD SCLSDHGQSL NKTQEDQCYV NRTHF
Length:485
Mass (Da):52,684
Last modified:November 2, 2010 - v2
Checksum:i96A3495EF026DE94
GO
Isoform 2 (identifier: Q6XR72-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-245: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:240
Mass (Da):26,289
Checksum:i8D3C17D391E719E6
GO
Isoform 3 (identifier: Q6XR72-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-223: GDSFNTQNEP → ELIHNTRFLL
     224-485: Missing.

Note: No experimental confirmation available.
Show »
Length:223
Mass (Da):24,009
Checksum:i3A7FDB2E11FF9459
GO

Sequence cautioni

The sequence AAP44332 differs from that shown. Contaminating sequence. Sequence of unknown origin in position 427.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07257389L → P in HMNDYT1; abolishes cell surface localization. 2 PublicationsCorresponds to variant dbSNP:rs281860284Ensembl.1
Natural variantiVAR_072574105 – 107Missing in HMNDYT1; abolishes cell surface localization; decreases manganese efflux; decreases protection against manganese-induced neurotoxity. 2 Publications3
Natural variantiVAR_072575167F → S1 PublicationCorresponds to variant dbSNP:rs281860286Ensembl.1
Natural variantiVAR_072576256Missing in HMNDYT1. 1 Publication1
Natural variantiVAR_072577349L → P in HMNDYT1. 1 PublicationCorresponds to variant dbSNP:rs281860291Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0298631 – 245Missing in isoform 2. 1 PublicationAdd BLAST245
Alternative sequenceiVSP_029864214 – 223GDSFNTQNEP → ELIHNTRFLL in isoform 3. 1 Publication10
Alternative sequenceiVSP_029865224 – 485Missing in isoform 3. 1 PublicationAdd BLAST262

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY212919 mRNA. Translation: AAP44332.1. Sequence problems.
AL359609 mRNA. Translation: CAB94880.1.
AC093562 Genomic DNA. No translation available.
BC036078 mRNA. Translation: AAH36078.1.
CCDSiCCDS31026.1. [Q6XR72-4]
PIRiT50628.
RefSeqiNP_061183.2. NM_018713.2. [Q6XR72-4]
UniGeneiHs.284450.

Genome annotation databases

EnsembliENST00000356609; ENSP00000349018; ENSG00000196660. [Q6XR72-3]
ENST00000366926; ENSP00000355893; ENSG00000196660. [Q6XR72-4]
GeneIDi55532.
KEGGihsa:55532.
UCSCiuc001hlw.4. human. [Q6XR72-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiZNT10_HUMAN
AccessioniPrimary (citable) accession number: Q6XR72
Secondary accession number(s): Q49AL9, Q9NPW0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: November 2, 2010
Last modified: September 27, 2017
This is version 114 of the entry and version 2 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 1
    Human chromosome 1: 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