Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P23975 (SC6A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length617 AA.
Sequence statusComplete.
Protein existenceEvidence 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.7

Subcellular location

Membrane; Multi-pass membrane protein.

Involvement in disease

Orthostatic intolerance (OI) [MIM:604715]: Syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

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 processNeurotransmitter transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmonoamine transport

Inferred from direct assay PubMed 16024787. Source: MGI

norepinephrine transport

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

membrane

Traceable author statement Ref.1. Source: ProtInc

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionmonoamine transmembrane transporter activity

Inferred from direct assay PubMed 16024787. Source: MGI

norepinephrine:sodium symporter activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction Ref.7PubMed 17156375. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P23975-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P23975-2)

The sequence of this isoform differs from the canonical sequence as follows:
     611-617: LQHWLAI → MKTRQGRRRATNSCQISC
Isoform 3 (identifier: P23975-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 617617Sodium-dependent noradrenaline transporter
PRO_0000214748

Regions

Topological domain1 – 6464Cytoplasmic Potential
Transmembrane65 – 8521Helical; Name=1; Potential
Transmembrane93 – 11220Helical; Name=2; Potential
Transmembrane136 – 15621Helical; Name=3; Potential
Topological domain157 – 23478Extracellular Potential
Transmembrane235 – 25319Helical; Name=4; Potential
Transmembrane262 – 27918Helical; Name=5; Potential
Transmembrane315 – 33218Helical; Name=6; Potential
Transmembrane344 – 36522Helical; Name=7; Potential
Transmembrane398 – 41720Helical; Name=8; Potential
Transmembrane444 – 46219Helical; Name=9; Potential
Transmembrane478 – 49821Helical; Name=10; Potential
Transmembrane519 – 53820Helical; Name=11; Potential
Transmembrane557 – 57519Helical; Name=12; Potential
Topological domain576 – 61742Cytoplasmic Potential

Amino acid modifications

Glycosylation1841N-linked (GlcNAc...) Potential
Glycosylation1921N-linked (GlcNAc...) Potential
Glycosylation1981N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 135135MLLAR…CPFFK → MGVQWWSHTQGEVAVGLGLG DSYLTPCPCP in isoform 3.
VSP_054119
Alternative sequence611 – 6177LQHWLAI → MKTRQGRRRATNSCQISC in isoform 2.
VSP_044479
Natural variant71N → K.
Corresponds to variant rs11568323 [ dbSNP | Ensembl ].
VAR_029157
Natural variant691V → I.
Corresponds to variant rs1805064 [ dbSNP | Ensembl ].
VAR_011756
Natural variant991T → I.
Corresponds to variant rs1805065 [ dbSNP | Ensembl ].
VAR_011757
Natural variant2451V → I.
Corresponds to variant rs1805066 [ dbSNP | Ensembl ].
VAR_011758
Natural variant2831T → R.
Corresponds to variant rs45564432 [ dbSNP | Ensembl ].
VAR_020048
Natural variant2921N → T.
Corresponds to variant rs5563 [ dbSNP | Ensembl ].
VAR_011759
Natural variant3561V → L.
Corresponds to variant rs5565 [ dbSNP | Ensembl ].
VAR_011760
Natural variant3691A → P.
Corresponds to variant rs5566 [ dbSNP | Ensembl ].
VAR_011761
Natural variant3751N → S.
Corresponds to variant rs5567 [ dbSNP | Ensembl ].
VAR_011762
Natural variant4491V → I.
Corresponds to variant rs2234910 [ dbSNP | Ensembl ].
VAR_014800
Natural variant4571A → P in OI; loss of function. Ref.8
VAR_010022
Natural variant4631K → R.
Corresponds to variant rs5570 [ dbSNP | Ensembl ].
VAR_011763
Natural variant4781G → S.
Corresponds to variant rs1805067 [ dbSNP | Ensembl ].
VAR_011764
Natural variant5281F → C.
Corresponds to variant rs5558 [ dbSNP | Ensembl ].
VAR_011765
Natural variant5481Y → H.
Corresponds to variant rs5559 [ dbSNP | Ensembl ].
VAR_011766
Natural variant5491I → T.
Corresponds to variant rs3743788 [ dbSNP | Ensembl ].
VAR_021861

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

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

FASTA61769,332
        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

Isoform 2 [UniParc].

Checksum: 4CF79AD92F272587
Show »

FASTA62870,548
Isoform 3 [UniParc].

Checksum: B25C836CA8BA912F
Show »

FASTA51257,370

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lung.
[3]"The human noradrenaline transporter gene contains multiple polyadenylation sites and two alternatively spliced C-terminal exons."
Porzgen P., Bonisch H., Hammermann R., Bruss M.
Biochim. Biophys. Acta 1398:365-370(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), ALTERNATIVE SPLICING.
Tissue: Lung.
[4]"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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Testis.
[5]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[8]"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] [Europe PMC] [Abstract]
Cited for: VARIANT OI PRO-457.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M65105 mRNA. Translation: AAA59943.1.
X91117 expand/collapse EMBL AC list , X91120, X91121, X91122, X91123, X91124, X91125, X91126, X91127, X91118, X91119 Genomic DNA. Translation: CAA62566.1.
X91117 expand/collapse EMBL AC list , X91118, X91119, X91120, X91121, X91122, X91123, X91124, X91125, X91126, 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.
CCDSCCDS10754.1. [P23975-1]
CCDS54011.1. [P23975-2]
PIRS14278.
RefSeqNP_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_006721263.1. [P23975-2]
UniGeneHs.78036.

3D structure databases

ProteinModelPortalP23975.
SMRP23975. Positions 56-594.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112421. 3 interactions.
MINTMINT-197872.
STRING9606.ENSP00000369237.

Chemistry

BindingDBP23975.
ChEMBLCHEMBL2363064.
DrugBankDB04836. 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.
GuidetoPHARMACOLOGY926.

Protein family/group databases

TCDB2.A.22.1.2. the neurotransmitter:sodium symporter (nss) family.

PTM databases

PhosphoSiteP23975.

Polymorphism databases

DMDM128616.

Proteomic databases

PaxDbP23975.
PRIDEP23975.

Protocols and materials databases

DNASU6530.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219833; ENSP00000219833; ENSG00000103546. [P23975-2]
ENST00000379906; ENSP00000369237; ENSG00000103546. [P23975-1]
ENST00000567238; ENSP00000457375; ENSG00000103546.
ENST00000568943; ENSP00000457473; ENSG00000103546. [P23975-1]
GeneID6530.
KEGGhsa:6530.
UCSCuc002eif.3. human. [P23975-1]
uc021tio.1. human. [P23975-2]

Organism-specific databases

CTD6530.
GeneCardsGC16P055745.
HGNCHGNC:11048. SLC6A2.
HPAHPA004057.
MIM163970. gene.
604715. phenotype.
neXtProtNX_P23975.
PharmGKBPA310.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0733.
HOGENOMHOG000116406.
HOVERGENHBG071421.
KOK05035.
OMAAYCITPE.
OrthoDBEOG793B71.
PhylomeDBP23975.
TreeFamTF343812.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_20679. Amine compound SLC transporters.

Gene expression databases

ArrayExpressP23975.
BgeeP23975.
CleanExHS_NAT1.
HS_NET1.
HS_SLC6A2.
HS_SLC6A5.
GenevestigatorP23975.

Family and domain databases

InterProIPR000175. Na/ntran_symport.
IPR002435. Na/ntran_symport_noradrenaline.
[Graphical view]
PANTHERPTHR11616. PTHR11616. 1 hit.
PfamPF00209. SNF. 1 hit.
[Graphical view]
PRINTSPR00176. NANEUSMPORT.
PR01201. NORTRANSPORT.
PROSITEPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNorepinephrine_transporter.
GenomeRNAi6530.
NextBio25407.
PROP23975.
SOURCESearch...

Entry information

Entry nameSC6A2_HUMAN
AccessionPrimary (citable) accession number: P23975
Secondary accession number(s): B2R707, B4DX48, Q96KH8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: July 9, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

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