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Q7RTT9 (S29A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. 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:
Equilibrative nucleoside transporter 4

Short name=hENT4
Alternative name(s):
Plasma membrane monoamine transporter
Solute carrier family 29 member 4
Gene names
Name:SLC29A4
Synonyms:ENT4, PMAT
ORF Names:PSEC0113
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length530 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine. In (Ref.6) adenosine is efficiently transported but in a fashion highly sensitive to extracellular pH, with maximal activity in the pH range 5.5 to 6.5. Glu-206 is essential for the cation selectivity and may function as the charge sensor for cationic substrates. Transport is chloride and sodium-independent but appears to be sensitive to changes in membrane potential. Weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. May play a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia. Ref.1 Ref.6 Ref.7 Ref.8

Subcellular location

Cell membrane; Multi-pass membrane protein Potential. Apical cell membrane; Multi-pass membrane protein Potential. Note: Located to the plasma membranes of ventricular myocytes and vascular endothelial cells. Targeted to the apical membranes of differentiated kidney epithelial cells. Ref.1 Ref.6

Tissue specificity

Expressed abundantly in the heart, in both cardiomyocytes and vascular endothelial cells (at protein level). Highly expressed in brain, kidney and skeletal muscle. In the brain expressed in cerebellum, cerebral cortex, medulla, occipital pole, frontal and temporal lobes putamen and in the spinal cord. Lower expression in liver, pancreas, and liver. Expressed in endometrial tissue, exclusively in the stroma. Expression is high in the proliferative phase, decreases during the secretory phase, and is no longer detectable in the menstrual phase. Ref.1 Ref.6 Ref.7 Ref.9

Post-translational modification

N-glycosylated. Ref.6

Sequence similarities

Belongs to the SLC29A/ENT transporter (TC 2.A.57) family. [View classification]

Sequence caution

The sequence BAC11612.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTransport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processtransmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionnucleoside transmembrane transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7RTT9-1)

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: Q7RTT9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     139-182: GYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGCTV → ASATCGCSSSLGTRPTPSTWPLWAPWPSAA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 530530Equilibrative nucleoside transporter 4
PRO_0000326251

Regions

Topological domain1 – 6868Extracellular Potential
Transmembrane69 – 8921Helical; Potential
Topological domain90 – 10112Cytoplasmic Potential
Transmembrane102 – 12221Helical; Potential
Topological domain123 – 13917Extracellular Potential
Transmembrane140 – 16021Helical; Potential
Topological domain161 – 1666Cytoplasmic Potential
Transmembrane167 – 18721Helical; Potential
Topological domain188 – 23144Extracellular Potential
Transmembrane232 – 25221Helical; Potential
Topological domain253 – 35199Cytoplasmic Potential
Transmembrane352 – 37221Helical; Potential
Topological domain373 – 3819Extracellular Potential
Transmembrane382 – 40221Helical; Potential
Topological domain403 – 41614Cytoplasmic Potential
Transmembrane417 – 43721Helical; Potential
Topological domain438 – 45013Extracellular Potential
Transmembrane451 – 47121Helical; Potential
Topological domain472 – 48615Cytoplasmic Potential
Transmembrane487 – 50923Helical; Potential
Topological domain510 – 53021Extracellular Potential

Amino acid modifications

Glycosylation5231N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence139 – 18244GYLLA…FGCTV → ASATCGCSSSLGTRPTPSTW PLWAPWPSAA in isoform 2.
VSP_032647
Natural variant791V → E. Ref.4
Corresponds to variant rs17854505 [ dbSNP | Ensembl ].
VAR_040044
Natural variant1241N → K. Ref.4
Corresponds to variant rs17855675 [ dbSNP | Ensembl ].
VAR_040045
Natural variant4291P → T. Ref.4
Corresponds to variant rs17857336 [ dbSNP | Ensembl ].
VAR_040046

Experimental info

Mutagenesis911D → A: No significant change in cationic transport activity. Ref.8
Mutagenesis1071D → A: Loss of cationic transport activity. Ref.8
Mutagenesis1281E → A: No significant change in cationic transport activity. Ref.8
Mutagenesis1541D → A: Loss of cationic transport activity; increase in uridine uptake. Ref.8
Mutagenesis1631D → A: Loss of cationic transport activity. Ref.8
Mutagenesis2061E → A: Loss of cationic transport activity. Ref.6 Ref.8
Mutagenesis2061E → D: No loss of cationic transporter activity; no activity towards uridine. Ref.6 Ref.8
Mutagenesis2061E → Q: Loss of cationic transporter activity; increase in uridine uptake. Ref.6 Ref.8
Mutagenesis2061E → R: Loss of cationic transporter activity. Ref.6 Ref.8
Mutagenesis2201T → A: Reduced cationic transport activity. Ref.8
Mutagenesis2201T → I: Loss of cationic transporter activity. Ref.8
Mutagenesis2201T → S: Reduced cationic transport activity. Ref.8
Mutagenesis2271E → A: Functional with slight increased cationic transport activity. Ref.8
Mutagenesis2421E → A: Reduced cationic transport activity. Ref.8
Mutagenesis3361W → A: Loss of cationic transport activity. Ref.8
Mutagenesis3751E → A: Functional with slight increased cationic transport activity. Ref.6 Ref.8
Mutagenesis3751E → Q: No change in cationic activity and pH sensitivity. Ref.6 Ref.8
Sequence conflict251S → C in BAC03836. Ref.2
Sequence conflict411Q → R in BAC03836. Ref.2
Sequence conflict1961K → R in BAC03836. Ref.2
Sequence conflict2611Y → H in BAC11612. Ref.2
Sequence conflict3011L → P in BAC03836. Ref.2

Sequences

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

Last modified December 15, 2003. Version 1.
Checksum: 3FE5D5ED1D248A13

FASTA53058,059
        10         20         30         40         50         60 
MGSVGSQRLE EPSVAGTPDP GVVMSFTFDS HQLEEAAEAA QGQGLRARGV PAFTDTTLDE 

        70         80         90        100        110        120 
PVPDDRYHAI YFAMLLAGVG FLLPYNSFIT DVDYLHHKYP GTSIVFDMSL TYILVALAAV 

       130        140        150        160        170        180 
LLNNVLVERL TLHTRITAGY LLALGPLLFI SICDVWLQLF SRDQAYAINL AAVGTVAFGC 

       190        200        210        220        230        240 
TVQQSSFYGY TGMLPKRYTQ GVMTGESTAG VMISLSRILT KLLLPDERAS TLIFFLVSVA 

       250        260        270        280        290        300 
LELLCFLLHL LVRRSRFVLF YTTRPRDSHR GRPGLGRGYG YRVHHDVVAG DVHFEHPAPA 

       310        320        330        340        350        360 
LAPNESPKDS PAHEVTGSGG AYMRFDVPRP RVQRSWPTFR ALLLHRYVVA RVIWADMLSI 

       370        380        390        400        410        420 
AVTYFITLCL FPGLESEIRH CILGEWLPIL IMAVFNLSDF VGKILAALPV DWRGTHLLAC 

       430        440        450        460        470        480 
SCLRVVFIPL FILCVYPSGM PALRHPAWPC IFSLLMGISN GYFGSVPMIL AAGKVSPKQR 

       490        500        510        520        530 
ELAGNTMTVS YMSGLTLGSA VAYCTYSLTR DAHGSCLHAS TANGSILAGL 

« Hide

Isoform 2 [UniParc].

Checksum: 601976FF77817BFD
Show »

FASTA51656,401

References

« Hide 'large scale' references
[1]"Identification and characterization of a novel monoamine transporter in the human brain."
Engel K., Zhou M., Wang J.
J. Biol. Chem. 279:50042-50049(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY.
Tissue: Kidney.
[2]"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] (ISOFORM 1).
Tissue: Teratocarcinoma.
[3]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].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS GLU-79; LYS-124 AND THR-429.
Tissue: Brain and Eye.
[5]"Molecular evolution of the equilibrative nucleoside transporter family: identification of novel family members in prokaryotes and eukaryotes."
Acimovic Y., Coe I.R.
Mol. Biol. Evol. 19:2199-2210(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[6]"Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH."
Barnes K., Dobrzynski H., Foppolo S., Beal P.R., Ismat F., Scullion E.R., Sun L., Tellez J., Ritzel M.W., Claycomb W.C., Cass C.E., Young J.D., Billeter-Clark R., Boyett M.R., Baldwin S.A.
Circ. Res. 99:510-519(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT ASN-523, MUTAGENESIS OF GLU-206 AND GLU-375.
[7]"Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells."
Xia L., Engel K., Zhou M., Wang J.
Am. J. Physiol. 292:F682-F690(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOPOLOGY, TISSUE SPECIFICITY.
[8]"Molecular determinants of substrate selectivity of a novel organic cation transporter (PMAT) in the SLC29 family."
Zhou M., Xia L., Engel K., Wang J.
J. Biol. Chem. 282:3188-3195(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-91; ASP-107; GLU-128; ASP-154; ASP-163; GLU-206; THR-220; GLU-227; GLU-242; TRP-336 AND GLU-375.
[9]"The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua."
Bottalico B., Noskova V., Pilka R., Larsson I., Domanski H., Casslen B., Hansson S.R.
Mol. Reprod. Dev. 74:1303-1311(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY485959 mRNA. Translation: AAS65965.1.
AK075422 mRNA. Translation: BAC11612.1. Different initiation.
AK092242 mRNA. Translation: BAC03836.1.
CH471144 Genomic DNA. Translation: EAW87329.1.
CH471144 Genomic DNA. Translation: EAW87330.1.
BC025325 mRNA. Translation: AAH25325.1.
BC047592 mRNA. Translation: AAH47592.1.
BK000627 Genomic DNA. Translation: DAA00308.1.
RefSeqNP_001035751.1. NM_001040661.1.
NP_694979.2. NM_153247.2.
XP_005249714.1. XM_005249657.1.
XP_005249715.1. XM_005249658.2.
UniGeneHs.4302.

3D structure databases

ProteinModelPortalQ7RTT9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000297195.

Chemistry

GuidetoPHARMACOLOGY1120.

Protein family/group databases

TCDB2.A.57.1.5. the equilibrative nucleoside transporter (ent) family.

PTM databases

PhosphoSiteQ7RTT9.

Polymorphism databases

DMDM74713147.

Proteomic databases

PaxDbQ7RTT9.
PRIDEQ7RTT9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297195; ENSP00000297195; ENSG00000164638. [Q7RTT9-1]
ENST00000396872; ENSP00000380081; ENSG00000164638. [Q7RTT9-1]
ENST00000406453; ENSP00000385845; ENSG00000164638. [Q7RTT9-2]
GeneID222962.
KEGGhsa:222962.
UCSCuc003soc.3. human. [Q7RTT9-1]
uc003soe.3. human. [Q7RTT9-2]

Organism-specific databases

CTD222962.
GeneCardsGC07P005289.
HGNCHGNC:23097. SLC29A4.
HPAHPA052829.
MIM609149. gene.
neXtProtNX_Q7RTT9.
PharmGKBPA134976472.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249415.
HOGENOMHOG000048076.
HOVERGENHBG095787.
InParanoidQ7RTT9.
KOK03323.
OMAFYTTRPR.
PhylomeDBQ7RTT9.
TreeFamTF313950.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ7RTT9.
BgeeQ7RTT9.
CleanExHS_SLC29A4.
GenevestigatorQ7RTT9.

Family and domain databases

InterProIPR002259. Eqnu_transpt.
IPR016196. MFS_dom_general_subst_transpt.
[Graphical view]
PANTHERPTHR10332. PTHR10332. 1 hit.
PfamPF01733. Nucleoside_tran. 1 hit.
[Graphical view]
PRINTSPR01130. DERENTRNSPRT.
SUPFAMSSF103473. SSF103473. 2 hits.
ProtoNetSearch...

Other

ChiTaRSSLC29A4. human.
GeneWikiSLC29A4.
GenomeRNAi222962.
NextBio91692.
PROQ7RTT9.
SOURCESearch...

Entry information

Entry nameS29A4_HUMAN
AccessionPrimary (citable) accession number: Q7RTT9
Secondary accession number(s): Q6PJ08 expand/collapse secondary AC list , Q86WY8, Q8NAR3, Q8NBM2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 15, 2003
Last modified: April 16, 2014
This is version 90 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 7

Human chromosome 7: entries, gene names and cross-references to MIM