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Protein

Equilibrative nucleoside transporter 4

Gene

SLC29A4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:16873718) 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.4 Publications

GO - Molecular functioni

Complete GO annotation...

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

Protein family/group databases

TCDBi2.A.57.1.5. the equilibrative nucleoside transporter (ent) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Equilibrative nucleoside transporter 4
Short name:
hENT4
Alternative name(s):
Plasma membrane monoamine transporter
Solute carrier family 29 member 4
Gene namesi
Name:SLC29A4
Synonyms:ENT4, PMAT
ORF Names:PSEC0113
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:23097. SLC29A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 68ExtracellularSequence analysisAdd BLAST68
Transmembranei69 – 89HelicalSequence analysisAdd BLAST21
Topological domaini90 – 101CytoplasmicSequence analysisAdd BLAST12
Transmembranei102 – 122HelicalSequence analysisAdd BLAST21
Topological domaini123 – 139ExtracellularSequence analysisAdd BLAST17
Transmembranei140 – 160HelicalSequence analysisAdd BLAST21
Topological domaini161 – 166CytoplasmicSequence analysis6
Transmembranei167 – 187HelicalSequence analysisAdd BLAST21
Topological domaini188 – 231ExtracellularSequence analysisAdd BLAST44
Transmembranei232 – 252HelicalSequence analysisAdd BLAST21
Topological domaini253 – 351CytoplasmicSequence analysisAdd BLAST99
Transmembranei352 – 372HelicalSequence analysisAdd BLAST21
Topological domaini373 – 381ExtracellularSequence analysis9
Transmembranei382 – 402HelicalSequence analysisAdd BLAST21
Topological domaini403 – 416CytoplasmicSequence analysisAdd BLAST14
Transmembranei417 – 437HelicalSequence analysisAdd BLAST21
Topological domaini438 – 450ExtracellularSequence analysisAdd BLAST13
Transmembranei451 – 471HelicalSequence analysisAdd BLAST21
Topological domaini472 – 486CytoplasmicSequence analysisAdd BLAST15
Transmembranei487 – 509HelicalSequence analysisAdd BLAST23
Topological domaini510 – 530ExtracellularSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91D → A: No significant change in cationic transport activity. 1 Publication1
Mutagenesisi107D → A: Loss of cationic transport activity. 1 Publication1
Mutagenesisi128E → A: No significant change in cationic transport activity. 1 Publication1
Mutagenesisi154D → A: Loss of cationic transport activity; increase in uridine uptake. 1 Publication1
Mutagenesisi163D → A: Loss of cationic transport activity. 1 Publication1
Mutagenesisi206E → A: Loss of cationic transport activity. 2 Publications1
Mutagenesisi206E → D: No loss of cationic transporter activity; no activity towards uridine. 2 Publications1
Mutagenesisi206E → Q: Loss of cationic transporter activity; increase in uridine uptake. 2 Publications1
Mutagenesisi206E → R: Loss of cationic transporter activity. 2 Publications1
Mutagenesisi220T → A: Reduced cationic transport activity. 1 Publication1
Mutagenesisi220T → I: Loss of cationic transporter activity. 1 Publication1
Mutagenesisi220T → S: Reduced cationic transport activity. 1 Publication1
Mutagenesisi227E → A: Functional with slight increased cationic transport activity. 1 Publication1
Mutagenesisi242E → A: Reduced cationic transport activity. 1 Publication1
Mutagenesisi336W → A: Loss of cationic transport activity. 1 Publication1
Mutagenesisi375E → A: Functional with slight increased cationic transport activity. 2 Publications1
Mutagenesisi375E → Q: No change in cationic activity and pH sensitivity. 2 Publications1

Organism-specific databases

DisGeNETi222962.
OpenTargetsiENSG00000164638.
PharmGKBiPA134976472.

Chemistry databases

ChEMBLiCHEMBL3509593.
DrugBankiDB00331. Metformin.
GuidetoPHARMACOLOGYi1120.

Polymorphism and mutation databases

BioMutaiSLC29A4.
DMDMi74713147.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003262511 – 530Equilibrative nucleoside transporter 4Add BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi523N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ7RTT9.
PeptideAtlasiQ7RTT9.
PRIDEiQ7RTT9.

PTM databases

iPTMnetiQ7RTT9.
PhosphoSitePlusiQ7RTT9.

Expressioni

Tissue specificityi

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.4 Publications

Gene expression databases

BgeeiENSG00000164638.
CleanExiHS_SLC29A4.
ExpressionAtlasiQ7RTT9. baseline and differential.
GenevisibleiQ7RTT9. HS.

Organism-specific databases

HPAiHPA052829.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000297195.

Structurei

3D structure databases

ProteinModelPortaliQ7RTT9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1479. Eukaryota.
ENOG410Y3MT. LUCA.
GeneTreeiENSGT00390000002232.
HOGENOMiHOG000048076.
HOVERGENiHBG095787.
InParanoidiQ7RTT9.
KOiK03323.
OMAiFYTTRPR.
OrthoDBiEOG091G0840.
PhylomeDBiQ7RTT9.
TreeFamiTF313950.

Family and domain databases

InterProiIPR030198. ENT4.
IPR002259. Eqnu_transpt.
IPR020846. MFS_dom.
[Graphical view]
PANTHERiPTHR10332. PTHR10332. 2 hits.
PTHR10332:SF4. PTHR10332:SF4. 2 hits.
PfamiPF01733. Nucleoside_tran. 1 hit.
[Graphical view]
PRINTSiPR01130. DERENTRNSPRT.
SUPFAMiSSF103473. SSF103473. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7RTT9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGSVGSQRLE EPSVAGTPDP GVVMSFTFDS HQLEEAAEAA QGQGLRARGV
60 70 80 90 100
PAFTDTTLDE PVPDDRYHAI YFAMLLAGVG FLLPYNSFIT DVDYLHHKYP
110 120 130 140 150
GTSIVFDMSL TYILVALAAV LLNNVLVERL TLHTRITAGY LLALGPLLFI
160 170 180 190 200
SICDVWLQLF SRDQAYAINL AAVGTVAFGC TVQQSSFYGY TGMLPKRYTQ
210 220 230 240 250
GVMTGESTAG VMISLSRILT KLLLPDERAS TLIFFLVSVA LELLCFLLHL
260 270 280 290 300
LVRRSRFVLF YTTRPRDSHR GRPGLGRGYG YRVHHDVVAG DVHFEHPAPA
310 320 330 340 350
LAPNESPKDS PAHEVTGSGG AYMRFDVPRP RVQRSWPTFR ALLLHRYVVA
360 370 380 390 400
RVIWADMLSI AVTYFITLCL FPGLESEIRH CILGEWLPIL IMAVFNLSDF
410 420 430 440 450
VGKILAALPV DWRGTHLLAC SCLRVVFIPL FILCVYPSGM PALRHPAWPC
460 470 480 490 500
IFSLLMGISN GYFGSVPMIL AAGKVSPKQR ELAGNTMTVS YMSGLTLGSA
510 520 530
VAYCTYSLTR DAHGSCLHAS TANGSILAGL
Length:530
Mass (Da):58,059
Last modified:December 15, 2003 - v1
Checksum:i3FE5D5ED1D248A13
GO
Isoform 2 (identifier: Q7RTT9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     139-182: GYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGCTV → ASATCGCSSSLGTRPTPSTWPLWAPWPSAA

Note: No experimental confirmation available.
Show »
Length:516
Mass (Da):56,401
Checksum:i601976FF77817BFD
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25S → C in BAC03836 (PubMed:14702039).Curated1
Sequence conflicti41Q → R in BAC03836 (PubMed:14702039).Curated1
Sequence conflicti196K → R in BAC03836 (PubMed:14702039).Curated1
Sequence conflicti261Y → H in BAC11612 (PubMed:14702039).Curated1
Sequence conflicti301L → P in BAC03836 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04004479V → E.1 PublicationCorresponds to variant rs17854505dbSNPEnsembl.1
Natural variantiVAR_040045124N → K.1 PublicationCorresponds to variant rs17855675dbSNPEnsembl.1
Natural variantiVAR_040046429P → T.1 PublicationCorresponds to variant rs17857336dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032647139 – 182GYLLA…FGCTV → ASATCGCSSSLGTRPTPSTW PLWAPWPSAA in isoform 2. 1 PublicationAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5340.1. [Q7RTT9-1]
CCDS75561.1. [Q7RTT9-2]
RefSeqiNP_001035751.1. NM_001040661.1. [Q7RTT9-1]
NP_001287776.1. NM_001300847.1. [Q7RTT9-2]
NP_694979.2. NM_153247.2. [Q7RTT9-1]
XP_005249715.1. XM_005249658.4. [Q7RTT9-2]
XP_006715730.1. XM_006715667.3. [Q7RTT9-1]
XP_011513502.1. XM_011515200.2. [Q7RTT9-1]
XP_011513503.1. XM_011515201.2. [Q7RTT9-1]
UniGeneiHs.4302.

Genome annotation databases

EnsembliENST00000297195; ENSP00000297195; ENSG00000164638. [Q7RTT9-1]
ENST00000396872; ENSP00000380081; ENSG00000164638. [Q7RTT9-1]
ENST00000406453; ENSP00000385845; ENSG00000164638. [Q7RTT9-2]
GeneIDi222962.
KEGGihsa:222962.
UCSCiuc003soc.4. human. [Q7RTT9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS5340.1. [Q7RTT9-1]
CCDS75561.1. [Q7RTT9-2]
RefSeqiNP_001035751.1. NM_001040661.1. [Q7RTT9-1]
NP_001287776.1. NM_001300847.1. [Q7RTT9-2]
NP_694979.2. NM_153247.2. [Q7RTT9-1]
XP_005249715.1. XM_005249658.4. [Q7RTT9-2]
XP_006715730.1. XM_006715667.3. [Q7RTT9-1]
XP_011513502.1. XM_011515200.2. [Q7RTT9-1]
XP_011513503.1. XM_011515201.2. [Q7RTT9-1]
UniGeneiHs.4302.

3D structure databases

ProteinModelPortaliQ7RTT9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000297195.

Chemistry databases

ChEMBLiCHEMBL3509593.
DrugBankiDB00331. Metformin.
GuidetoPHARMACOLOGYi1120.

Protein family/group databases

TCDBi2.A.57.1.5. the equilibrative nucleoside transporter (ent) family.

PTM databases

iPTMnetiQ7RTT9.
PhosphoSitePlusiQ7RTT9.

Polymorphism and mutation databases

BioMutaiSLC29A4.
DMDMi74713147.

Proteomic databases

PaxDbiQ7RTT9.
PeptideAtlasiQ7RTT9.
PRIDEiQ7RTT9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297195; ENSP00000297195; ENSG00000164638. [Q7RTT9-1]
ENST00000396872; ENSP00000380081; ENSG00000164638. [Q7RTT9-1]
ENST00000406453; ENSP00000385845; ENSG00000164638. [Q7RTT9-2]
GeneIDi222962.
KEGGihsa:222962.
UCSCiuc003soc.4. human. [Q7RTT9-1]

Organism-specific databases

CTDi222962.
DisGeNETi222962.
GeneCardsiSLC29A4.
HGNCiHGNC:23097. SLC29A4.
HPAiHPA052829.
MIMi609149. gene.
neXtProtiNX_Q7RTT9.
OpenTargetsiENSG00000164638.
PharmGKBiPA134976472.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1479. Eukaryota.
ENOG410Y3MT. LUCA.
GeneTreeiENSGT00390000002232.
HOGENOMiHOG000048076.
HOVERGENiHBG095787.
InParanoidiQ7RTT9.
KOiK03323.
OMAiFYTTRPR.
OrthoDBiEOG091G0840.
PhylomeDBiQ7RTT9.
TreeFamiTF313950.

Enzyme and pathway databases

ReactomeiR-HSA-83936. Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.

Miscellaneous databases

ChiTaRSiSLC29A4. human.
GeneWikiiSLC29A4.
GenomeRNAii222962.
PROiQ7RTT9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164638.
CleanExiHS_SLC29A4.
ExpressionAtlasiQ7RTT9. baseline and differential.
GenevisibleiQ7RTT9. HS.

Family and domain databases

InterProiIPR030198. ENT4.
IPR002259. Eqnu_transpt.
IPR020846. MFS_dom.
[Graphical view]
PANTHERiPTHR10332. PTHR10332. 2 hits.
PTHR10332:SF4. PTHR10332:SF4. 2 hits.
PfamiPF01733. Nucleoside_tran. 1 hit.
[Graphical view]
PRINTSiPR01130. DERENTRNSPRT.
SUPFAMiSSF103473. SSF103473. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiS29A4_HUMAN
AccessioniPrimary (citable) accession number: Q7RTT9
Secondary accession number(s): Q6PJ08
, Q86WY8, Q8NAR3, Q8NBM2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: December 15, 2003
Last modified: November 2, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.