Q14542 (S29A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Equilibrative nucleoside transporter 2

Alternative name(s):
36 kDa nucleolar protein HNP36
Delayed-early response protein 12
Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter
Short name=Equilibrative NBMPR-insensitive nucleoside transporter
Hydrophobic nucleolar protein, 36 kDa
Nucleoside transporter, ei-type
Solute carrier family 29 member 2

Gene names

Name:	SLC29A2
Synonyms:	DER12, ENT2, HNP36

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	456 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, dilazep and draflazine. Ref.2
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein. Nucleus membrane; Multi-pass membrane protein. Note: Localized at the basolateral cell membrane in polarized MDCK cells. Ref.4
Tissue specificity	Expressed in skeletal muscle, liver, lung, placenta, brain, heart, kidney and ovarian tissues. Ref.2 Ref.4
Induction	By PDGF/platelet derived growth factor and fibroblast growth factor (FGF).
Sequence similarities	Belongs to the SLC29A/ENT transporter (TC 2.A.57) family. [View classification]
Biophysicochemical properties	Kinetic parameters: Vmax for adenosine uptake is about the same for SLC29A1 and SLC29A2. KM=0.2 mM for uridine Ref.2 Ref.4 KM=0.75 mM for adenosine
Sequence caution	The sequence CAA60380.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Traceable author statement Ref.1. Source: ProtInc nucleobase-containing compound metabolic process Traceable author statement Ref.2. Source: ProtInc nucleoside transport Inferred from direct assay Ref.4. Source: UniProtKB
Cellular_component	basolateral plasma membrane Inferred from direct assay Ref.4. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Traceable author statement Ref.1. Source: ProtInc
Molecular_function	nucleoside transmembrane transporter activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14542-1)

Also known as: Long;

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: Q14542-2)

Also known as: Short; HNP36;

The sequence of this isoform differs from the canonical sequence as follows:
     93-202: VPETVRILGS...LGYFITPCVG → AGQGGHEPRT...PEVCPLLPGQ
     203-456: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 3 (identifier: Q14542-3)

The sequence of this isoform differs from the canonical sequence as follows:
     290-301: IWLTALCLVLVF → SPCPSSPPSQPW
     302-456: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 456	456	Equilibrative nucleoside transporter 2		PRO_0000209340
Regions
	Transmembrane	13 – 33	21	Helical; Potential
	Transmembrane	70 – 90	21	Helical; Potential
	Transmembrane	99 – 119	21	Helical; Potential
	Transmembrane	124 – 144	21	Helical; Potential
	Transmembrane	162 – 182	21	Helical; Potential
	Transmembrane	193 – 213	21	Helical; Potential
	Transmembrane	291 – 311	21	Helical; Potential
	Transmembrane	324 – 344	21	Helical; Potential
	Transmembrane	360 – 380	21	Helical; Potential
	Transmembrane	386 – 406	21	Helical; Potential
	Transmembrane	432 – 452	21	Helical; Potential
Amino acid modifications
	Modified residue	252	1	Phosphoserine Ref.10 Ref.11
	Glycosylation	48	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	57	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	225	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	93 – 202	110	VPETV…TPCVG → AGQGGHEPRTLLLHHHGLRL LHQLLQCSPTGQPLRAAGHH ALHLQHPLPQRPGPGWDLCC PCHAPVHGQWRGRRDLCPGV LYHALCGHPHVHRVLPEPAS PEVCPLLPGQ in isoform 2.		VSP_040728
	Alternative sequence	203 – 456	254	Missing in isoform 2.		VSP_040729
	Alternative sequence	290 – 301	12	IWLTA…LVLVF → SPCPSSPPSQPW in isoform 3.		VSP_040730
	Alternative sequence	302 – 456	155	Missing in isoform 3.		VSP_040731
	Natural variant	5	1	D → Y. Ref.12 Corresponds to variant rs8187643 [ dbSNP | Ensembl ].		VAR_029289
	Natural variant	68	1	N → K. Ref.12 Corresponds to variant rs8187644 [ dbSNP | Ensembl ].		VAR_029290
	Natural variant	94	1	P → L. Ref.12 Corresponds to variant rs8187648 [ dbSNP | Ensembl ].		VAR_029291
	Natural variant	184 – 186	3	SGV → M.		VAR_036822
Experimental info
	Mutagenesis	455	1	L → R: Reduces drastically localization at the cell surface. No effect on uptake of adenosine and thymidine. Reduces drastically localization at the cell surface and induces an significant reduction of adenosine or thymidine uptake; when associated with R-456. Ref.4
	Mutagenesis	456	1	L → R: Reduces drastically localization at the cell surface and induces an significant reduction of adenosine or thymidine uptake; when associated with R-455. Ref.4
	Sequence conflict	200	1	C → Y in CAA60380. Ref.1
	Sequence conflict	200	1	C → Y in AAC39526. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified October 17, 2006. Version 3. Checksum: ABCBD244306708E1	FASTA	456	50,113
	10 20 30 40 50 60 MARGDAPRDS YHLVGISFFI LGLGTLLPWN FFITAIPYFQ ARLAGAGNST ARILSTNHTG 70 80 90 100 110 120 PEDAFNFNNW VTLLSQLPLL LFTLLNSFLY QCVPETVRIL GSLLAILLLF ALTAALVKVD 130 140 150 160 170 180 MSPGPFFSIT MASVCFINSF SAVLQGSLFG QLGTMPSTYS TLFLSGQGLA GIFAALAMLL 190 200 210 220 230 240 SMASGVDAET SALGYFITPC VGILMSIVCY LSLPHLKFAR YYLANKSSQA QAQELETKAE 250 260 270 280 290 300 LLQSDENGIP SSPQKVALTL DLDLEKEPES EPDEPQKPGK PSVFTVFQKI WLTALCLVLV 310 320 330 340 350 360 FTVTLSVFPA ITAMVTSSTS PGKWSQFFNP ICCFLLFNIM DWLGRSLTSY FLWPDEDSRL 370 380 390 400 410 420 LPLLVCLRFL FVPLFMLCHV PQRSRLPILF PQDAYFITFM LLFAVSNGYL VSLTMCLAPR 430 440 450 QVLPHEREVA GALMTFFLAL GLSCGASLSF LFKALL
	Isoform 2 (Short) (HNP36) [UniParc]. Checksum: E1E980B5CCC29586	FASTA	202	22,276
	10 20 30 40 50 60 MARGDAPRDS YHLVGISFFI LGLGTLLPWN FFITAIPYFQ ARLAGAGNST ARILSTNHTG 70 80 90 100 110 120 PEDAFNFNNW VTLLSQLPLL LFTLLNSFLY QCAGQGGHEP RTLLLHHHGL RLLHQLLQCS 130 140 150 160 170 180 PTGQPLRAAG HHALHLQHPL PQRPGPGWDL CCPCHAPVHG QWRGRRDLCP GVLYHALCGH 190 200 PHVHRVLPEP ASPEVCPLLP GQ
	Isoform 3 [UniParc]. Checksum: 5DFD77C4226D4F15	FASTA	301	32,507
	10 20 30 40 50 60 MARGDAPRDS YHLVGISFFI LGLGTLLPWN FFITAIPYFQ ARLAGAGNST ARILSTNHTG 70 80 90 100 110 120 PEDAFNFNNW VTLLSQLPLL LFTLLNSFLY QCVPETVRIL GSLLAILLLF ALTAALVKVD 130 140 150 160 170 180 MSPGPFFSIT MASVCFINSF SAVLQGSLFG QLGTMPSTYS TLFLSGQGLA GIFAALAMLL 190 200 210 220 230 240 SMASGVDAET SALGYFITPC VGILMSIVCY LSLPHLKFAR YYLANKSSQA QAQELETKAE 250 260 270 280 290 300 LLQSDENGIP SSPQKVALTL DLDLEKEPES EPDEPQKPGK PSVFTVFQKS PCPSSPPSQP W

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mammalian delayed-early response gene encodes HNP36, a novel, conserved nucleolar protein." Williams J.B., Lanahan A.A. Biochem. Biophys. Res. Commun. 213:325-333(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Heart.
[2]	"Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta." Griffiths M., Yao S.Y., Abidi F., Phillips S.E., Cass C.E., Young J.D., Baldwin S.A. Biochem. J. 328:739-743(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Placenta.
[3]	"Cloning of the human equilibrative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside transporter ei by functional expression in a transport-deficient cell line." Crawford C.R., Patel D.H., Naeve C., Belt J.A. J. Biol. Chem. 273:5288-5293(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), RESPONSE TO NBMPR.
[4]	"Localization of human equilibrative nucleoside transporters, hENT1 and hENT2, in renal epithelial cells." Mangravite L.M., Xiao G., Giacomini K.M. Am. J. Physiol. 284:F902-F910(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LEU-455 AND LEU-456.
[5]	"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. , 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).
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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. , 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].
[8]	"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]. Tissue: Liver.
[9]	"Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2." Ward J.L., Leung G.P., Toan S.V., Tse C.-M. Arch. Biochem. Biophys. 411:19-26(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-48 AND ASN-57.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, MASS SPECTROMETRY.
[12]	"Functional characterization and haplotype analysis of polymorphisms in the human equilibrative nucleoside transporter, ENT2." Owen R.P., Lagpacan L.L., Taylor T.R., De La Cruz M., Huang C.C., Kawamoto M., Johns S.J., Stryke D., Ferrin T.E., Giacomini K.M. Drug Metab. Dispos. 34:12-15(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TYR-5; LYS-68; LEU-94 AND 184-SER--VAL-186 DELINS MET.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X86681 mRNA. Translation: CAA60380.1. Sequence problems. AF029358 mRNA. Translation: AAC39526.1. AF034102 mRNA. Translation: AAB97834.1. AK057041 mRNA. Translation: BAG51849.1. AF401235 mRNA. Translation: AAK92533.1. AP001107 Genomic DNA. No translation available. CH471076 Genomic DNA. Translation: EAW74521.1. CH471076 Genomic DNA. Translation: EAW74519.1. BC093634 mRNA. Translation: AAH93634.1.
IPI	IPI00031456. IPI00220195. IPI00978970.
PIR	JC4196.
RefSeq	NP_001523.2. NM_001532.2.
UniGene	Hs.569017.
3D structure databases
ProteinModelPortal	Q14542.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000350024.
PTM databases
PhosphoSite	Q14542.
Polymorphism databases
DMDM	116242781.
Proteomic databases
PaxDb	Q14542.
PRIDE	Q14542.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357440; ENSP00000350024; ENSG00000174669. ENST00000540386; ENSP00000444870; ENSG00000174669. ENST00000541567; ENSP00000442116; ENSG00000174669. ENST00000544554; ENSP00000439456; ENSG00000174669. ENST00000546034; ENSP00000440329; ENSG00000174669.
GeneID	3177.
KEGG	hsa:3177.
UCSC	uc001oht.3. human.
Organism-specific databases
CTD	3177.
GeneCards	GC11M066129.
HGNC	HGNC:11004. SLC29A2.
HPA	HPA018168.
MIM	602110. gene.
neXtProt	NX_Q14542.
PharmGKB	PA191.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG249415.
HOGENOM	HOG000007684.
HOVERGEN	HBG074626.
InParanoid	Q14542.
KO	K15014.
OMA	FINSFCA.
OrthoDB	EOG4MCX0R.
PhylomeDB	Q14542.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q14542.
Bgee	Q14542.
CleanEx	HS_SLC29A2.
Genevestigator	Q14542.
GermOnline	ENSG00000174669. Homo sapiens.
Family and domain databases
InterPro	IPR002259. Eqnu_transpt. [Graphical view]
PANTHER	PTHR10332. PTHR10332. 1 hit.
Pfam	PF01733. Nucleoside_tran. 1 hit. [Graphical view]
PIRSF	PIRSF016379. ENT. 1 hit.
PRINTS	PR01130. DERENTRNSPRT.
TIGRFAMs	TIGR00939. 2a57. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	3177.
NextBio	12610.
SOURCE	Search...

Entry information

Entry name

S29A2_HUMAN

Accession

Primary (citable) accession number: Q14542
Secondary accession number(s): B3KPY7 , O43530, Q52M84, Q96R00, Q9UPE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	April 3, 2013
This is version 119 of the entry and version 3 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.