Sodium-dependent noradrenaline transporter

Preferred order of sections

Names and origin

Protein names

Recommended name:
Sodium-dependent noradrenaline transporter

Alternative name(s):
Norepinephrine transporter
Short name=NET
Solute carrier family 6 member 2

Gene names

Name:	SLC6A2
Synonyms:	NAT1, NET1, SLC6A5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	617 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Subunit structure	Interacts with PRKCABP. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein.
Involvement in disease	Defects in SLC6A2 are a cause of orthostatic intolerance (OI) [MIM:604715]. OI is a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high. Ref.6
Miscellaneous	This protein is the target of psychomotor stimulants such as amphetamines or cocaine.
Sequence similarities	Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A2 subfamily. [View classification]

Ontologies

Keywords
Biological process	Neurotransmitter transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	norepinephrine:sodium symporter activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 617

617

Sodium-dependent noradrenaline transporter

PRO_0000214748

Regions

Topological domain

1 – 64

64

Cytoplasmic Potential

Transmembrane

65 – 85

21

Helical; Name=1; Potential

Transmembrane

93 – 112

20

Helical; Name=2; Potential

Transmembrane

136 – 156

21

Helical; Name=3; Potential

Topological domain

157 – 234

78

Extracellular Potential

Transmembrane

235 – 253

19

Helical; Name=4; Potential

Transmembrane

262 – 279

18

Helical; Name=5; Potential

Transmembrane

315 – 332

18

Helical; Name=6; Potential

Transmembrane

344 – 365

22

Helical; Name=7; Potential

Transmembrane

398 – 417

20

Helical; Name=8; Potential

Transmembrane

444 – 462

19

Helical; Name=9; Potential

Transmembrane

478 – 498

21

Helical; Name=10; Potential

Transmembrane

519 – 538

20

Helical; Name=11; Potential

Transmembrane

557 – 575

19

Helical; Name=12; Potential

Topological domain

576 – 617

42

Cytoplasmic Potential

Amino acid modifications

Glycosylation

184

1

N-linked (GlcNAc...) Potential

Glycosylation

192

1

N-linked (GlcNAc...) Potential

Glycosylation

198

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

7

1

N → K.
Corresponds to variant rs11568323 [ dbSNP | Ensembl ].

VAR_029157

Natural variant

69

1

V → I.
Corresponds to variant rs1805064 [ dbSNP | Ensembl ].

VAR_011756

Natural variant

99

1

T → I.
Corresponds to variant rs1805065 [ dbSNP | Ensembl ].

VAR_011757

Natural variant

245

1

V → I.
Corresponds to variant rs1805066 [ dbSNP | Ensembl ].

VAR_011758

Natural variant

283

1

T → R.
Corresponds to variant rs45564432 [ dbSNP | Ensembl ].

VAR_020048

Natural variant

292

1

N → T.
Corresponds to variant rs5563 [ dbSNP | Ensembl ].

VAR_011759

Natural variant

356

1

V → L.
Corresponds to variant rs5565 [ dbSNP | Ensembl ].

VAR_011760

Natural variant

369

1

A → P.
Corresponds to variant rs5566 [ dbSNP | Ensembl ].

VAR_011761

Natural variant

375

1

N → S.
Corresponds to variant rs5567 [ dbSNP | Ensembl ].

VAR_011762

Natural variant

449

1

V → I.
Corresponds to variant rs2234910 [ dbSNP | Ensembl ].

VAR_014800

Natural variant

457

1

A → P in OI; loss of function. Ref.6

VAR_010022

Natural variant

463

1

K → R.
Corresponds to variant rs5570 [ dbSNP | Ensembl ].

VAR_011763

Natural variant

478

1

G → S.
Corresponds to variant rs1805067 [ dbSNP | Ensembl ].

VAR_011764

Natural variant

528

1

F → C.
Corresponds to variant rs5558 [ dbSNP | Ensembl ].

VAR_011765

Natural variant

548

1

Y → H.
Corresponds to variant rs5559 [ dbSNP | Ensembl ].

VAR_011766

Natural variant

549

1

I → T.
Corresponds to variant rs3743788 [ dbSNP | Ensembl ].

VAR_021861

Sequences

Sequence

Length

Mass (Da)

Tools

P23975 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: BDC6DF31316907BB
Show »

FASTA

617

69,332

        10         20         30         40         50         60 
MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG 

        70         80         90        100        110        120 
KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL FLIIAGMPLF YMELALGQYN 

       130        140        150        160        170        180 
REGAATVWKI CPFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW 

       190        200        210        220        230        240 
NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC 

       250        260        270        280        290        300 
LMVVVIVLYF SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY 

       310        320        330        340        350        360 
RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSSIN CITSFVSGFA 

       370        380        390        400        410        420 
IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG STFWAVVFFV MLLALGLDSS 

       430        440        450        460        470        480 
MGGMEAVITG LADDFQVLKR HRKLFTFGVT FSTFLLALFC ITKGGIYVLT LLDTFAAGTS 

       490        500        510        520        530        540 
ILFAVLMEAI GVSWFYGVDR FSNDIQQMMG FRPGLYWRLC WKFVSPAFLL FVVVVSIINF 

       550        560        570        580        590        600 
KPLTYDDYIF PPWANWVGWG IALSSMVLVP IYVIYKFLST QGSLWERLAY GITPENEHHL 

       610 
VAQRDIRQFQ LQHWLAI

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter." Pacholczyk T., Blakely R.D., Amara S.G. Nature 350:350-354(1991) [PubMed: 2008212] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and organization of the coding region of the human norepinephrine transporter gene." Poerzgen P., Boenisch H., Bruss M. Biochem. Biophys. Res. Commun. 215:1145-1150(1995) [PubMed: 7488042] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lung.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1." Torres G.E., Yao W.-D., Mohn A.R., Quan H., Kim K.-M., Levey A.I., Staudinger J., Caron M.G. Neuron 30:121-134(2001) [PubMed: 11343649] [Abstract] Cited for: INTERACTION WITH PRKCABP.
[6]	"Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency." Shannon J.R., Flattem N.L., Jordan J., Jacob G., Black B.K., Biaggioni I., Blakely R.D., Robertson D. N. Engl. J. Med. 342:541-549(2000) [PubMed: 10684912] [Abstract] Cited for: VARIANT OI PRO-457.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M65105 mRNA. Translation: AAA59943.1. X91117 X91119 Genomic DNA. Translation: CAA62566.1. AK312793 mRNA. Translation: BAG35654.1. CH471092 Genomic DNA. Translation: EAW82831.1.
IPI	IPI00743489.
PIR	S14278.
RefSeq	NP_001034.1. NM_001043.3. NP_001165972.1. NM_001172501.1.
UniGene	Hs.78036.
3D structure databases
ProteinModelPortal	P23975.
SMR	P23975. Positions 55-570.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-197872.
STRING	P23975.
Protein family/group databases
TCDB	2.A.22.1.2. neurotransmitter:sodium symporter (NSS) family.
PTM databases
PhosphoSite	P23975.
Polymorphism databases
DMDM	128616.
Proteomic databases
PRIDE	P23975.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379906; ENSP00000369237; ENSG00000103546.
GeneID	6530.
KEGG	hsa:6530.
UCSC	uc002eif.1. human.
Organism-specific databases
CTD	6530.
GeneCards	GC16P055745.
H-InvDB	HIX0038519.
HGNC	HGNC:11048. SLC6A2.
HPA	HPA004057.
MIM	163970. gene. 604715. phenotype.
neXtProt	NX_P23975.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13649.
HOVERGEN	HBG071421.
OrthoDB	EOG46HG9B.
PhylomeDB	P23975.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_20679. Amine compound SLC transporters.
Gene expression databases
ArrayExpress	P23975.
Bgee	P23975.
CleanEx	HS_NAT1. HS_NET1. HS_SLC6A2. HS_SLC6A5.
Genevestigator	P23975.
GermOnline	ENSG00000103546. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR002435. Na/ntran_symport_noradrenaline. [Graphical view]
KO	K05035.
PANTHER	PTHR11616. Na/ntran_symport. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR00176. NANEUSMPORT. PR01201. NORTRANSPORT.
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB04836. Amineptine. DB00321. Amitriptyline. DB00543. Amoxapine. DB00289. Atomoxetine. DB00217. Bethanidine. DB01156. Bupropion. DB01242. Clomipramine. DB00907. Cocaine. DB04840. Debrisoquin. DB01151. Desipramine. DB00937. Diethylpropion. DB01142. Doxepin. DB00476. Duloxetine. DB00696. Ergotamine. DB00226. Guanadrel Sulfate. DB01170. Guanethidine. DB00458. Imipramine. DB00934. Maprotiline. DB00579. Mazindol. DB00422. Methylphenidate. DB04896. Milnacipran. DB01149. Nefazodone. DB00368. Norepinephrine. DB00540. Nortriptyline. DB00715. Paroxetine. DB00830. Phenmetrazine. DB00191. Phentermine. DB00344. Protriptyline. DB00234. Reboxetine. DB01105. Sibutramine. DB00193. Tramadol. DB00656. Trazodone. DB00726. Trimipramine. DB00285. Venlafaxine.
NextBio	25407.
SOURCE	Search...

Entry information

Entry name

SC6A2_HUMAN

Accession

Primary (citable) accession number: P23975
Secondary accession number(s): B2R707

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	March 1, 1992
Last modified:	January 25, 2012
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

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Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents