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UniProtKB - Q9C0K1 (S39A8_HUMAN)

Entry version 147 (02 Jun 2021)
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

    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:ENSG00000138821.12

    <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, 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, salivary gland)

    <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, 34 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

    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    		TAIVCEE

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

    This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><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

    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:rs1444255127Ensembl.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; ENSP00000349174; ENSG00000138821 [Q9C0K1-1]
    ENST00000394833; ENSP00000378310; ENSG00000138821 [Q9C0K1-1]
    ENST00000424970; ENSP00000394548; ENSG00000138821 [Q9C0K1-3]

    Database of genes from NCBI RefSeq genomes

    More...    GeneIDi    		64116

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		hsa:64116

    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

    SMRiQ9C0K1
    ModBaseiSearch...

    Protein-protein interaction databases

    BioGRIDi122072, 34 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, 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, 166 antibodies

    The DNASU plasmid repository

    More...    DNASUi    		64116

    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

    Comparative Toxicogenomics Database

    More...    CTDi    		64116
    DisGeNETi64116

    GeneCards: human genes, protein and diseases

    More...    GeneCardsi    		SLC39A8
    HGNCiHGNC:20862, SLC39A8
    HPAiENSG00000138821, Tissue enhanced (lung, salivary gland)
    MalaCardsiSLC39A8
    MIMi608732, gene
    616721, phenotype
    neXtProtiNX_Q9C0K1
    OpenTargetsiENSG00000138821
    Orphaneti468699, SLC39A8-CDG
    PharmGKBiPA134931507
    VEuPathDBiHostDB:ENSG00000138821.12

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiKOG2693, Eukaryota
    GeneTreeiENSGT00940000158926
    HOGENOMiCLU_015114_13_0_1
    InParanoidiQ9C0K1
    OMAiTAIVCEE
    OrthoDBi657777at2759
    PhylomeDBiQ9C0K1
    TreeFamiTF318470

    Enzyme and pathway databases

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

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...    BioGRID-ORCSi    		64116, 5 hits in 995 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: June 2, 2021
    This is version 147 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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