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UniProtKB - P23975 (SC6A2_HUMAN)

Entry version 191 (11 Dec 2019)
Sequence version 1 (01 Mar 1992)
Previous versions | rss
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Protein

Sodium-dependent noradrenaline transporter

Gene

SLC6A2

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

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.1 Publication

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi71Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi73Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi74Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi78Sodium 2By similarity1
Metal bindingi318Sodium 2By similarity1
Metal bindingi350Sodium 2By similarity1
Metal bindingi415Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi418Sodium 1By similarity1
Metal bindingi419Sodium 1By similarity1

<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 processNeurotransmitter transport, Symport, Transport
LigandMetal-binding, Sodium

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-442660 Na+/Cl- dependent neurotransmitter transporters
R-HSA-5619109 Defective SLC6A2 causes orthostatic intolerance (OI)

SIGNOR Signaling Network Open Resource

More...SIGNORi		P23975

Protein family/group databases

Transport Classification Database

More...TCDBi		2.A.22.1.2 the neurotransmitter:sodium symporter (nss) 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_and_taxonomy_section">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:
Sodium-dependent noradrenaline transporter
Alternative name(s):
Norepinephrine transporter
Short name:
NET
Solute carrier family 6 member 2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:SLC6A2
Synonyms:NAT1, NET1, SLC6A5
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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 16

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000103546.18

Human Gene Nomenclature Database

More...HGNCi		HGNC:11048 SLC6A2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		163970 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P23975

<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

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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 domaini1 – 62CytoplasmicBy similarityAdd BLAST62
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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>Transmembranei63 – 88Helical; Name=1By similarityAdd BLAST26
Topological domaini89 – 92ExtracellularBy similarity4
Transmembranei93 – 116Helical; Name=2By similarityAdd BLAST24
Topological domaini117 – 135CytoplasmicBy similarityAdd BLAST19
Transmembranei136 – 166Helical; Name=3By similarityAdd BLAST31
Topological domaini167 – 233ExtracellularBy similarityAdd BLAST67
Transmembranei234 – 254Helical; Name=4By similarityAdd BLAST21
Topological domaini255 – 257CytoplasmicBy similarity3
Transmembranei258 – 282Helical; Name=5By similarityAdd BLAST25
Topological domaini283 – 306ExtracellularBy similarityAdd BLAST24
Transmembranei307 – 332Helical; Name=6By similarityAdd BLAST26
Topological domaini333 – 338CytoplasmicBy similarity6
Transmembranei339 – 362Helical; Name=7By similarityAdd BLAST24
Topological domaini363 – 402ExtracellularBy similarityAdd BLAST40
Transmembranei403 – 428Helical; Name=8By similarityAdd BLAST26
Topological domaini429 – 443CytoplasmicBy similarityAdd BLAST15
Transmembranei444 – 464Helical; Name=9By similarityAdd BLAST21
Topological domaini465ExtracellularBy similarity1
Transmembranei466 – 492Helical; Name=10By similarityAdd BLAST27
Topological domaini493 – 522CytoplasmicBy similarityAdd BLAST30
Transmembranei523 – 545Helical; Name=11By similarityAdd BLAST23
Topological domaini546 – 548ExtracellularBy similarity3
Transmembranei549 – 569Helical; Name=12By similarityAdd BLAST21
Topological domaini570 – 617CytoplasmicBy similarityAdd BLAST48

Keywords - Cellular componenti

Cell membrane, 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

Orthostatic intolerance (OI)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSyndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.
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_010022457A → P in OI; loss of function. 1 PublicationCorresponds to variant dbSNP:rs121918126EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		6530

MalaCards human disease database

More...MalaCardsi		SLC6A2
MIMi604715 phenotype

Open Targets

More...OpenTargetsi		ENSG00000103546

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

More...Orphaneti		443236 Postural orthostatic tachycardia syndrome due to NET deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA310

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P23975 Tclin

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL222

Drug and drug target database

More...DrugBanki		DB04836 Amineptine
DB05964 Amitifadine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB00289 Atomoxetine
DB00245 Benzatropine
DB04889 Bicifadine
DB01156 Bupropion
DB01114 Chlorphenamine
DB01242 Clomipramine
DB00907 Cocaine
DB05688 CRx-119
DB12305 Dasotraline
DB05642 DDP-225
DB04840 Debrisoquine
DB01151 Desipramine
DB06700 Desvenlafaxine
DB06701 Dexmethylphenidate
DB01576 Dextroamphetamine
DB00514 Dextromethorphan
DB00937 Diethylpropion
DB00988 Dopamine
DB09167 Dosulepin
DB01142 Doxepin
DB06262 Droxidopa
DB00476 Duloxetine
DB01363 Ephedra sinica root
DB01364 Ephedrine
DB00696 Ergotamine
DB01175 Escitalopram
DB09194 Etoperidone
DB01381 Ginkgo biloba
DB00226 Guanadrel
DB01170 Guanethidine
DB00458 Imipramine
DB06704 Iobenguane
DB09546 Iobenguane sulfate I-123
DB01221 Ketamine
DB08918 Levomilnacipran
DB00408 Loxapine
DB00934 Maprotiline
DB00579 Mazindol
DB00454 Meperidine
DB01577 Metamfetamine
DB00422 Methylphenidate
DB06148 Mianserin
DB01454 Midomafetamine
DB04896 Milnacipran
DB01442 MMDA
DB01149 Nefazodone
DB04821 Nomifensine
DB00368 Norepinephrine
DB00540 Nortriptyline
DB01173 Orphenadrine
DB00715 Paroxetine
DB01579 Phendimetrazine
DB00830 Phenmetrazine
DB00191 Phentermine
DB00344 Protriptyline
DB00852 Pseudoephedrine
DB09363 Rauwolfia serpentina root
DB00234 Reboxetine
DB01105 Sibutramine
DB14754 Solriamfetol
DB06204 Tapentadol
DB06156 Tesofensine
DB00193 Tramadol
DB00726 Trimipramine
DB06333 Trodusquemine
DB00285 Venlafaxine
DB09185 Viloxazine
DB05012 XEN2174
DB09225 Zotepine

DrugCentral

More...DrugCentrali		P23975

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		926

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SLC6A2

Domain mapping of disease mutations (DMDM)

More...DMDMi		128616

<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 describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002147481 – 617Sodium-dependent noradrenaline transporterAdd BLAST617

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi176 ↔ 185By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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>Glycosylationi184N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi192N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi198N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P23975

MaxQB - The MaxQuant DataBase

More...MaxQBi		P23975

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

More...PaxDbi		P23975

PeptideAtlas

More...PeptideAtlasi		P23975

PRoteomics IDEntifications database

More...PRIDEi		P23975

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		5409
54172 [P23975-1]
77077

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P23975

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

More...PhosphoSitePlusi		P23975

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000103546 Expressed in 94 organ(s), highest expression level in chorionic villus

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P23975 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P23975 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		CAB078195
HPA004057
HPA076311

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with PRKCABP.

1 Publication

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		112421, 3 interactors

Molecular INTeraction database

More...MINTi		P23975

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000219833

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P23975

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P23975 protein

<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

<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 sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A2 subfamily. [View classification]Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3659 Eukaryota
COG0733 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158960

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000116406

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P23975

KEGG Orthology (KO)

More...KOi		K05035

Identification of Orthologs from Complete Genome Data

More...OMAi		NEHQLVA

Database of Orthologous Groups

More...OrthoDBi		250396at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P23975

TreeFam database of animal gene trees

More...TreeFami		TF343812

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000175 Na/ntran_symport
IPR002435 Na/ntran_symport_noradrenaline
IPR037272 SNS_sf

The PANTHER Classification System

More...PANTHERi		PTHR11616 PTHR11616, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00209 SNF, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00176 NANEUSMPORT
PR01201 NORTRANSPORT

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF161070 SSF161070, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

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: P23975-1) [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
MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD 
        60         70         80         90        100
GDAQPRETWG KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL 
       110        120        130        140        150
FLIIAGMPLF YMELALGQYN REGAATVWKI CPFFKGVGYA VILIALYVGF 
       160        170        180        190        200
YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW NSPNCTDPKL LNGSVLGNHT 
       210        220        230        240        250
KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC LMVVVIVLYF 
       260        270        280        290        300
SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY 
       310        320        330        340        350
RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSSIN 
       360        370        380        390        400
CITSFVSGFA IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG 
       410        420        430        440        450
STFWAVVFFV MLLALGLDSS MGGMEAVITG LADDFQVLKR HRKLFTFGVT 
       460        470        480        490        500
FSTFLLALFC ITKGGIYVLT LLDTFAAGTS ILFAVLMEAI GVSWFYGVDR 
       510        520        530        540        550
FSNDIQQMMG FRPGLYWRLC WKFVSPAFLL FVVVVSIINF KPLTYDDYIF 
       560        570        580        590        600
PPWANWVGWG IALSSMVLVP IYVIYKFLST QGSLWERLAY GITPENEHHL 
       610 
VAQRDIRQFQ LQHWLAI
Length:617
Mass (Da):69,332
Last modified:March 1, 1992 - 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:iBDC6DF31316907BB
GO
Isoform 2 (identifier: P23975-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     611-617: LQHWLAI → MKTRQGRRRATNSCQISC

Show »
Length:628
Mass (Da):70,548
Checksum:i4CF79AD92F272587
GO
Isoform 3 (identifier: P23975-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: MLLARMNPQV...TVWKICPFFK → MGVQWWSHTQGEVAVGLGLGDSYLTPCPCP

Show »
Length:512
Mass (Da):57,370
Checksum:iB25C836CA8BA912F
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
H3BMY5H3BMY5_HUMAN
Transporter
SLC6A2
200Annotation score:

Annotation score:2 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>
H3BRE9H3BRE9_HUMAN
Transporter
SLC6A2 hCG_2025341
572Annotation score:

Annotation score:2 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>
H3BML6H3BML6_HUMAN
Transporter
SLC6A2
604Annotation score:

Annotation score:2 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>
H3BM11H3BM11_HUMAN
Transporter
SLC6A2
561Annotation score:

Annotation score:2 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>
H3BRS0H3BRS0_HUMAN
Transporter
SLC6A2
295Annotation score:

Annotation score:2 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>
I3L368I3L368_HUMAN
Sodium-dependent noradrenaline tran...
SLC6A2
58Annotation 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>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0291577N → K. Corresponds to variant dbSNP:rs11568323EnsemblClinVar.1
Natural variantiVAR_01175669V → I. Corresponds to variant dbSNP:rs1805064Ensembl.1
Natural variantiVAR_01175799T → I. Corresponds to variant dbSNP:rs1805065Ensembl.1
Natural variantiVAR_011758245V → I. Corresponds to variant dbSNP:rs1805066Ensembl.1
Natural variantiVAR_020048283T → R. Corresponds to variant dbSNP:rs45564432EnsemblClinVar.1
Natural variantiVAR_011759292N → T. Corresponds to variant dbSNP:rs5563Ensembl.1
Natural variantiVAR_011760356V → L. Corresponds to variant dbSNP:rs5565Ensembl.1
Natural variantiVAR_011761369A → P. Corresponds to variant dbSNP:rs5566Ensembl.1
Natural variantiVAR_011762375N → S. Corresponds to variant dbSNP:rs5567Ensembl.1
Natural variantiVAR_014800449V → I. Corresponds to variant dbSNP:rs2234910Ensembl.1
Natural variantiVAR_010022457A → P in OI; loss of function. 1 PublicationCorresponds to variant dbSNP:rs121918126EnsemblClinVar.1
Natural variantiVAR_011763463K → R. Corresponds to variant dbSNP:rs5570Ensembl.1
Natural variantiVAR_011764478G → S. Corresponds to variant dbSNP:rs1805067Ensembl.1
Natural variantiVAR_011765528F → C. Corresponds to variant dbSNP:rs5558Ensembl.1
Natural variantiVAR_011766548Y → H. Corresponds to variant dbSNP:rs5559Ensembl.1
Natural variantiVAR_021861549I → T. Corresponds to variant dbSNP:rs3743788EnsemblClinVar.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_0541191 – 135MLLAR…CPFFK → MGVQWWSHTQGEVAVGLGLG DSYLTPCPCP in isoform 3. 1 PublicationAdd BLAST135
Alternative sequenceiVSP_044479611 – 617LQHWLAI → MKTRQGRRRATNSCQISC in isoform 2. Curated7

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
M65105 mRNA Translation: AAA59943.1
X91117 X91119 Genomic DNA Translation: CAA62566.1
X91117 X91127 Genomic DNA Translation: CAC39181.1
AK301811 mRNA Translation: BAG63260.1
AK312793 mRNA Translation: BAG35654.1
AC136621 Genomic DNA No translation available.
CH471092 Genomic DNA Translation: EAW82831.1
CH471092 Genomic DNA Translation: EAW82833.1
CH471092 Genomic DNA Translation: EAW82835.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS10754.1 [P23975-1]
CCDS54011.1 [P23975-2]
CCDS58463.1 [P23975-3]

Protein sequence database of the Protein Information Resource

More...PIRi		S14278

NCBI Reference Sequences

More...RefSeqi		NP_001034.1, NM_001043.3 [P23975-1]
NP_001165972.1, NM_001172501.1 [P23975-1]
NP_001165973.1, NM_001172502.1 [P23975-3]
NP_001165975.1, NM_001172504.1 [P23975-2]
XP_006721326.1, XM_006721263.2 [P23975-2]
XP_011521597.1, XM_011523295.1 [P23975-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000219833; ENSP00000219833; ENSG00000103546 [P23975-2]
ENST00000379906; ENSP00000369237; ENSG00000103546 [P23975-1]
ENST00000567238; ENSP00000457375; ENSG00000103546 [P23975-3]
ENST00000568943; ENSP00000457473; ENSG00000103546 [P23975-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		6530

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:6530

UCSC genome browser

More...UCSCi		uc002eif.4 human [P23975-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<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
M65105 mRNA Translation: AAA59943.1
X91117 X91119 Genomic DNA Translation: CAA62566.1
X91117 X91127 Genomic DNA Translation: CAC39181.1
AK301811 mRNA Translation: BAG63260.1
AK312793 mRNA Translation: BAG35654.1
AC136621 Genomic DNA No translation available.
CH471092 Genomic DNA Translation: EAW82831.1
CH471092 Genomic DNA Translation: EAW82833.1
CH471092 Genomic DNA Translation: EAW82835.1
CCDSiCCDS10754.1 [P23975-1]
CCDS54011.1 [P23975-2]
CCDS58463.1 [P23975-3]
PIRiS14278
RefSeqiNP_001034.1, NM_001043.3 [P23975-1]
NP_001165972.1, NM_001172501.1 [P23975-1]
NP_001165973.1, NM_001172502.1 [P23975-3]
NP_001165975.1, NM_001172504.1 [P23975-2]
XP_006721326.1, XM_006721263.2 [P23975-2]
XP_011521597.1, XM_011523295.1 [P23975-2]

3D structure databases

Database of comparative protein structure models

More...ModBasei		Search...

SWISS-MODEL Interactive Workspace

More...SWISS-MODEL-Workspacei		Submit a new modelling project...

Protein-protein interaction databases

BioGridi112421, 3 interactors
MINTiP23975
STRINGi9606.ENSP00000219833

Chemistry databases

BindingDBiP23975
ChEMBLiCHEMBL222
DrugBankiDB04836 Amineptine
DB05964 Amitifadine
DB00321 Amitriptyline
DB00543 Amoxapine
DB00182 Amphetamine
DB00289 Atomoxetine
DB00245 Benzatropine
DB04889 Bicifadine
DB01156 Bupropion
DB01114 Chlorphenamine
DB01242 Clomipramine
DB00907 Cocaine
DB05688 CRx-119
DB12305 Dasotraline
DB05642 DDP-225
DB04840 Debrisoquine
DB01151 Desipramine
DB06700 Desvenlafaxine
DB06701 Dexmethylphenidate
DB01576 Dextroamphetamine
DB00514 Dextromethorphan
DB00937 Diethylpropion
DB00988 Dopamine
DB09167 Dosulepin
DB01142 Doxepin
DB06262 Droxidopa
DB00476 Duloxetine
DB01363 Ephedra sinica root
DB01364 Ephedrine
DB00696 Ergotamine
DB01175 Escitalopram
DB09194 Etoperidone
DB01381 Ginkgo biloba
DB00226 Guanadrel
DB01170 Guanethidine
DB00458 Imipramine
DB06704 Iobenguane
DB09546 Iobenguane sulfate I-123
DB01221 Ketamine
DB08918 Levomilnacipran
DB00408 Loxapine
DB00934 Maprotiline
DB00579 Mazindol
DB00454 Meperidine
DB01577 Metamfetamine
DB00422 Methylphenidate
DB06148 Mianserin
DB01454 Midomafetamine
DB04896 Milnacipran
DB01442 MMDA
DB01149 Nefazodone
DB04821 Nomifensine
DB00368 Norepinephrine
DB00540 Nortriptyline
DB01173 Orphenadrine
DB00715 Paroxetine
DB01579 Phendimetrazine
DB00830 Phenmetrazine
DB00191 Phentermine
DB00344 Protriptyline
DB00852 Pseudoephedrine
DB09363 Rauwolfia serpentina root
DB00234 Reboxetine
DB01105 Sibutramine
DB14754 Solriamfetol
DB06204 Tapentadol
DB06156 Tesofensine
DB00193 Tramadol
DB00726 Trimipramine
DB06333 Trodusquemine
DB00285 Venlafaxine
DB09185 Viloxazine
DB05012 XEN2174
DB09225 Zotepine
DrugCentraliP23975
GuidetoPHARMACOLOGYi926

Protein family/group databases

TCDBi2.A.22.1.2 the neurotransmitter:sodium symporter (nss) family

PTM databases

iPTMnetiP23975
PhosphoSitePlusiP23975

Polymorphism and mutation databases

BioMutaiSLC6A2
DMDMi128616

Proteomic databases

MassIVEiP23975
MaxQBiP23975
PaxDbiP23975
PeptideAtlasiP23975
PRIDEiP23975
ProteomicsDBi5409
54172 [P23975-1]
77077

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		6530

Genome annotation databases

EnsembliENST00000219833; ENSP00000219833; ENSG00000103546 [P23975-2]
ENST00000379906; ENSP00000369237; ENSG00000103546 [P23975-1]
ENST00000567238; ENSP00000457375; ENSG00000103546 [P23975-3]
ENST00000568943; ENSP00000457473; ENSG00000103546 [P23975-1]
GeneIDi6530
KEGGihsa:6530
UCSCiuc002eif.4 human [P23975-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		6530
DisGeNETi6530
EuPathDBiHostDB:ENSG00000103546.18

GeneCards: human genes, protein and diseases

More...GeneCardsi		SLC6A2
HGNCiHGNC:11048 SLC6A2
HPAiCAB078195
HPA004057
HPA076311
MalaCardsiSLC6A2
MIMi163970 gene
604715 phenotype
neXtProtiNX_P23975
OpenTargetsiENSG00000103546
Orphaneti443236 Postural orthostatic tachycardia syndrome due to NET deficiency
PharmGKBiPA310

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3659 Eukaryota
COG0733 LUCA
GeneTreeiENSGT00940000158960
HOGENOMiHOG000116406
InParanoidiP23975
KOiK05035
OMAiNEHQLVA
OrthoDBi250396at2759
PhylomeDBiP23975
TreeFamiTF343812

Enzyme and pathway databases

ReactomeiR-HSA-442660 Na+/Cl- dependent neurotransmitter transporters
R-HSA-5619109 Defective SLC6A2 causes orthostatic intolerance (OI)
SIGNORiP23975

Miscellaneous databases

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

More...ChiTaRSi		SLC6A2 human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Norepinephrine_transporter

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

More...GenomeRNAii		6530
PharosiP23975 Tclin

Protein Ontology

More...PROi		PR:P23975
RNActiP23975 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000103546 Expressed in 94 organ(s), highest expression level in chorionic villus
ExpressionAtlasiP23975 baseline and differential
GenevisibleiP23975 HS

Family and domain databases

InterProiView protein in InterPro
IPR000175 Na/ntran_symport
IPR002435 Na/ntran_symport_noradrenaline
IPR037272 SNS_sf
PANTHERiPTHR11616 PTHR11616, 1 hit
PfamiView protein in Pfam
PF00209 SNF, 1 hit
PRINTSiPR00176 NANEUSMPORT
PR01201 NORTRANSPORT
SUPFAMiSSF161070 SSF161070, 1 hit
PROSITEiView protein in PROSITE
PS00610 NA_NEUROTRAN_SYMP_1, 1 hit
PS00754 NA_NEUROTRAN_SYMP_2, 1 hit
PS50267 NA_NEUROTRAN_SYMP_3, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

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 nameiSC6A2_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: P23975
Secondary accession number(s): B2R707, B4DX48, Q96KH8
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: December 11, 2019
This is version 191 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
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