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UniProtKB - Q9C0K1 (S39A8_HUMAN)

Entry version 150 (25 May 2022)
Sequence version 1 (01 Jun 2001)
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Protein

Metal cation symporter ZIP8

Gene

SLC39A8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Electroneutral transporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis or immunity (PubMed:12504855, PubMed:22898811, PubMed:23403290, PubMed:29337306, PubMed:26637978, PubMed:29453449).

Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation, a bicarbonate and a selenite anion or yet a metal cation and two bicarbonate anions (PubMed:27166256, PubMed:31699897).

May also transport iron, mercury and cobalt through membranes (PubMed:22898811).

Beside these endogenous cellular substrates, also imports cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:27466201).

Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:29337306).

Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450).

Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290, PubMed:28056086).

Protects, for instance, cells from injury and death at the onset of inflammation (PubMed:18390834).

By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (By similarity).

At the apical membrane of hepatocytes, reclaims manganese from the bile and regulates, through the systemic levels of the nutrient, the activity of manganese-dependent enzymes (PubMed:28481222).

Also participates in manganese reabsorption in the proximal tubule of the kidney (PubMed:26637978).

By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain (PubMed:26637978, PubMed:31699897).

Through manganese cellular uptake also participates in mitochondrial proper function (PubMed:29453449).

Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR-mediated T cell activation (PubMed:19401385).

By similarity14 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=1.44 µM for Mn2+1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processIon transport, Transport, Zinc transport
LigandZinc

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q9C0K1

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-442380, Zinc influx into cells by the SLC39 gene family

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q9C0K1

Protein family/group databases

Transport Classification Database

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

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Metal cation symporter ZIP81 Publication
Alternative name(s):
BCG-induced integral membrane protein in monocyte clone 103 protein1 Publication
LIV-1 subfamily of ZIP zinc transporter 6
Short name:
LZT-Hs6
Solute carrier family 39 member 8Imported
Zrt- and Irt-like protein 8By similarity
Short name:
ZIP-8By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SLC39A8Imported
Synonyms:BIGM1031 Publication, ZIP81 Publication
ORF Names:PP3105
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:20862, SLC39A8

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		608732, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9C0K1

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000138821

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini23 – 132ExtracellularBy similarityAdd BLAST110
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
Topological domaini154 – 160CytoplasmicBy similarity7
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Topological domaini182 – 191ExtracellularBy similarity10
Transmembranei192 – 212HelicalSequence analysisAdd BLAST21
Topological domaini213 – 365CytoplasmicBy similarityAdd BLAST153
Transmembranei366 – 386HelicalSequence analysisAdd BLAST21
Topological domaini387 – 388ExtracellularBy similarity2
Transmembranei389 – 409HelicalSequence analysisAdd BLAST21
Topological domaini410 – 429CytoplasmicBy similarityAdd BLAST20
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 460ExtracellularBy similarity10

Keywords - Cellular componenti

Cell membrane, Lysosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Congenital disorder of glycosylation 2N (CDG2N)3 Publications
The disease is caused by variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07624133V → M in CDG2N. 1 PublicationCorresponds to variant dbSNP:rs373562040EnsemblClinVar.1
Natural variantiVAR_07624238G → R in CDG2N; loss of manganese ion transmembrane transport; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; no effect on protein abundance. 3 PublicationsCorresponds to variant dbSNP:rs778210210EnsemblClinVar.1
Natural variantiVAR_076243204G → C in CDG2N. 1 PublicationCorresponds to variant dbSNP:rs779241085EnsemblClinVar.1
Natural variantiVAR_076244335S → T in CDG2N. 1 PublicationCorresponds to variant dbSNP:rs864309660EnsemblClinVar.1
Natural variantiVAR_076245340I → N in CDG2N; no detectable serum or urinary manganese levels in an affected individual who also carries R-38 mutation. 1 PublicationCorresponds to variant dbSNP:rs864309659EnsemblClinVar.1
Rare variants in SLC39A8 may be a cause of Leigh-like mitochondrial syndrome characterized by profound developmental delay, dystonia, seizures and failure to thrive.1 Publication

Keywords - Diseasei

Congenital disorder of glycosylation

Organism-specific databases

DisGeNET

More...DisGeNETi		64116

MalaCards human disease database

More...MalaCardsi		SLC39A8
MIMi616721, phenotype

Open Targets

More...OpenTargetsi		ENSG00000138821

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		468699, SLC39A8-CDG

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA134931507

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9C0K1, Tbio

Chemistry databases

Drug and drug target database

More...DrugBanki		DB14533, Zinc chloride
DB14548, Zinc sulfate, unspecified form

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SLC39A8

Domain mapping of disease mutations (DMDM)

More...DMDMi		74733496

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 22Sequence analysisAdd BLAST22
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000031270723 – 460Metal cation symporter ZIP8Sequence analysisAdd BLAST438

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi40N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi88N-linked (GlcNAc...) asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylated (PubMed:18390834). N-glycosylation is not required for proper iron and zinc transport (By similarity).By similarity1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q9C0K1

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9C0K1

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9C0K1

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9C0K1

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9C0K1

PeptideAtlas

More...PeptideAtlasi		Q9C0K1

PRoteomics IDEntifications database

More...PRIDEi		Q9C0K1

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		80068 [Q9C0K1-1]
80069 [Q9C0K1-2]
80070 [Q9C0K1-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q9C0K1, 3 sites, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9C0K1

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9C0K1

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitously expressed (PubMed:12504855, PubMed:22898811, PubMed:28056086, PubMed:31699897). Expressed in thymus, placenta, lung, liver, pancreas, salivary gland and, to a lower extent, in spleen, testis, ovary, small intestine, colon, leukocyte, heart. Highest expression is observed in pancreas (PubMed:12504855). Expressed by macrophages (at protein level) (PubMed:28056086). Expressed by microvascular capillary endothelial cells that constitute the blood-brain barrier (at protein level) (PubMed:31699897).4 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Up-regulated by manganese (PubMed:29453449). Up-regulated by lipopolysaccharides (at protein level) (PubMed:23403290, PubMed:28056086). Up-regulated by inflammatory cytokines like TNF (PubMed:12504855, PubMed:18390834). Down-regulated following phorbol ester treatment (PubMed:12504855). Up-regulated by zinc and T-cell activation (PubMed:19401385).6 Publications
(Microbial infection) Up-regulated by live and heat-killed Mycobacterium bovis bacterial cell wall.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000138821, Expressed in upper lobe of lung and 223 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9C0K1, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9C0K1, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000138821, Tissue enhanced (lung)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

By similarity

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		122072, 35 interactors

Protein interaction database and analysis system

More...IntActi		Q9C0K1, 27 interactors

Molecular INTeraction database

More...MINTi		Q9C0K1

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000378310

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9C0K1, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		Q9C0K1

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9C0K1

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi343 – 348XEXPHE-motif1 Publication6

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2693, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158926

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_015114_13_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9C0K1

Identification of Orthologs from Complete Genome Data

More...OMAi		WLRGQRI

Database of Orthologous Groups

More...OrthoDBi		657777at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9C0K1

TreeFam database of animal gene trees

More...TreeFami		TF318470

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR003689, ZIP

Pfam protein domain database

More...Pfami		View protein in Pfam
PF02535, Zip, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9C0K1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

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

Show »
Length:444
Mass (Da):48,089
Checksum:i5EDFCF566871711A
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A804HJR0A0A804HJR0_HUMAN
Metal cation symporter ZIP8
SLC39A8
290Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A804HKW0A0A804HKW0_HUMAN
Metal cation symporter ZIP8
SLC39A8
450Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A804HKX2A0A804HKX2_HUMAN
Metal cation symporter ZIP8
SLC39A8
350Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A804HHS9A0A804HHS9_HUMAN
Metal cation symporter ZIP8
SLC39A8
143Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A804HHT0A0A804HHT0_HUMAN
Metal cation symporter ZIP8
SLC39A8
78Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A804HKQ9A0A804HKQ9_HUMAN
Metal cation symporter ZIP8
SLC39A8
87Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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 dbSNP:rs373562040EnsemblClinVar.1
Natural variantiVAR_07624238G → R in CDG2N; loss of manganese ion transmembrane transport; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; no effect on protein abundance. 3 PublicationsCorresponds to variant dbSNP:rs778210210EnsemblClinVar.1
Natural variantiVAR_083148113C → S Probable disease-associated variant found in patients with Leigh-like syndrome; no effect on protein abundance; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; loss of manganese ion transmembrane transport. 1 PublicationCorresponds to variant dbSNP:rs1444255127EnsemblClinVar.1
Natural variantiVAR_076243204G → C in CDG2N. 1 PublicationCorresponds to variant dbSNP:rs779241085EnsemblClinVar.1
Natural variantiVAR_076244335S → T in CDG2N. 1 PublicationCorresponds to variant dbSNP:rs864309660EnsemblClinVar.1
Natural variantiVAR_076245340I → N in CDG2N; no detectable serum or urinary manganese levels in an affected individual who also carries R-38 mutation. 1 PublicationCorresponds to variant dbSNP:rs864309659EnsemblClinVar.1
Natural variantiVAR_037551391A → T No effect on protein abundance; decreased cadmium ion transmembrane transport; increased resistance to cadmium cytotoxicity; associated with decreased activity of manganese-dependent enzymes. 2 PublicationsCorresponds to variant dbSNP:rs13107325Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>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:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS3656.1 [Q9C0K1-1]
CCDS47117.1 [Q9C0K1-3]

NCBI Reference Sequences

More...RefSeqi		NP_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
XP_016864030.1, XM_017008541.1 [Q9C0K1-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000356736.5; ENSP00000349174.4; ENSG00000138821.14
ENST00000394833.6; ENSP00000378310.2; ENSG00000138821.14
ENST00000682227.1; ENSP00000508363.1; ENSG00000138821.14
ENST00000682932.1; ENSP00000507414.1; ENSG00000138821.14
ENST00000683412.1; ENSP00000507538.1; ENSG00000138821.14

Database of genes from NCBI RefSeq genomes

More...GeneIDi		64116

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:64116

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000356736.5; ENSP00000349174.4; NM_001135146.2; NP_001128618.1

UCSC genome browser

More...UCSCi		uc003hwb.2, human [Q9C0K1-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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
XP_016864030.1, XM_017008541.1 [Q9C0K1-2]

3D structure databases

AlphaFoldDBiQ9C0K1
SMRiQ9C0K1
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi122072, 35 interactors
IntActiQ9C0K1, 27 interactors
MINTiQ9C0K1
STRINGi9606.ENSP00000378310

Chemistry databases

DrugBankiDB14533, Zinc chloride
DB14548, Zinc sulfate, unspecified form

Protein family/group databases

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

PTM databases

GlyGeniQ9C0K1, 3 sites, 1 O-linked glycan (1 site)
iPTMnetiQ9C0K1
PhosphoSitePlusiQ9C0K1

Genetic variation databases

BioMutaiSLC39A8
DMDMi74733496

Proteomic databases

EPDiQ9C0K1
jPOSTiQ9C0K1
MassIVEiQ9C0K1
MaxQBiQ9C0K1
PaxDbiQ9C0K1
PeptideAtlasiQ9C0K1
PRIDEiQ9C0K1
ProteomicsDBi80068 [Q9C0K1-1]
80069 [Q9C0K1-2]
80070 [Q9C0K1-3]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		45037, 176 antibodies from 29 providers

The DNASU plasmid repository

More...DNASUi		64116

Genome annotation databases

EnsembliENST00000356736.5; ENSP00000349174.4; ENSG00000138821.14
ENST00000394833.6; ENSP00000378310.2; ENSG00000138821.14
ENST00000682227.1; ENSP00000508363.1; ENSG00000138821.14
ENST00000682932.1; ENSP00000507414.1; ENSG00000138821.14
ENST00000683412.1; ENSP00000507538.1; ENSG00000138821.14
GeneIDi64116
KEGGihsa:64116
MANE-SelectiENST00000356736.5; ENSP00000349174.4; NM_001135146.2; NP_001128618.1
UCSCiuc003hwb.2, human [Q9C0K1-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		64116
DisGeNETi64116

GeneCards: human genes, protein and diseases

More...GeneCardsi		SLC39A8
HGNCiHGNC:20862, SLC39A8
HPAiENSG00000138821, Tissue enhanced (lung)
MalaCardsiSLC39A8
MIMi608732, gene
616721, phenotype
neXtProtiNX_Q9C0K1
OpenTargetsiENSG00000138821
Orphaneti468699, SLC39A8-CDG
PharmGKBiPA134931507
VEuPathDBiHostDB:ENSG00000138821

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2693, Eukaryota
GeneTreeiENSGT00940000158926
HOGENOMiCLU_015114_13_0_1
InParanoidiQ9C0K1
OMAiWLRGQRI
OrthoDBi657777at2759
PhylomeDBiQ9C0K1
TreeFamiTF318470

Enzyme and pathway databases

PathwayCommonsiQ9C0K1
ReactomeiR-HSA-442380, Zinc influx into cells by the SLC39 gene family
SignaLinkiQ9C0K1

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		64116, 13 hits in 1079 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		SLC39A8, human

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		64116
PharosiQ9C0K1, Tbio

Protein Ontology

More...PROi		PR:Q9C0K1
RNActiQ9C0K1, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000138821, Expressed in upper lobe of lung and 223 other tissues
ExpressionAtlasiQ9C0K1, baseline and differential
GenevisibleiQ9C0K1, HS

Family and domain databases

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

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiS39A8_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9C0K1
Secondary accession number(s): B4E2H3
, Q96SM9, Q9BVC0, Q9NSA4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2001
Last modified: May 25, 2022
This is version 150 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  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
UniProt is an ELIXIR core data resource
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