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Q495M3 (S36A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 78. 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:
Proton-coupled amino acid transporter 2

Short name=Proton/amino acid transporter 2
Alternative name(s):
Solute carrier family 36 member 2
Tramdorin-1
Gene names
Name:SLC36A2
Synonyms:PAT2, TRAMD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length483 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in a pH-dependent electrogenic neuronal transport and sequestration of small amino acids. Transports glycine and proline. Inhibited by sarcosine By similarity. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein. Cytoplasm By similarity.

Tissue specificity

Abundantly expressed in kidney and muscle. Expressed in the S1 segment of the proximal tubule close to the glomerulus. Ref.5 Ref.6

Involvement in disease

Hyperglycinuria (HG) [MIM:138500]: A condition characterized by excess of glycine in the urine. In some cases it is associated with renal colic and renal oxalate stones.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Iminoglycinuria (IG) [MIM:242600]: A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine.
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Mutations in SLC36A2 that retain residual transport activity result in the IG phenotype only when combined with haploinsufficiency of the imino acid transporter SLC6A20 or deficiency of the neutral amino acid transporter SLC6A19. Additional polymorphisms and mutations in SLC6A18 can contribute to iminoglycinuria in some families. Ref.6

Sequence similarities

Belongs to the amino acid/polyamine transporter 2 family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q495M3-1)

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: Q495M3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-198: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q495M3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-276: Missing.
     277-281: ESIGV → MNDTA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 483483Proton-coupled amino acid transporter 2
PRO_0000324819

Regions

Topological domain1 – 5858Cytoplasmic Potential
Transmembrane59 – 7921Helical; Potential
Topological domain80 – 812Extracellular Potential
Transmembrane82 – 10221Helical; Potential
Topological domain103 – 14846Cytoplasmic Potential
Transmembrane149 – 16921Helical; Potential
Topological domain170 – 19728Extracellular Potential
Transmembrane198 – 21821Helical; Potential
Topological domain219 – 2224Cytoplasmic Potential
Transmembrane223 – 24321Helical; Potential
Topological domain244 – 26421Extracellular Potential
Transmembrane265 – 28521Helical; Potential
Topological domain286 – 29611Cytoplasmic Potential
Transmembrane297 – 31721Helical; Potential
Topological domain318 – 34932Extracellular Potential
Transmembrane350 – 37021Helical; Potential
Topological domain371 – 3799Cytoplasmic Potential
Transmembrane380 – 40021Helical; Potential
Topological domain401 – 4044Extracellular Potential
Transmembrane405 – 42521Helical; Potential
Topological domain426 – 43712Cytoplasmic Potential
Transmembrane438 – 45821Helical; Potential
Topological domain459 – 48325Extracellular Potential

Natural variations

Alternative sequence1 – 276276Missing in isoform 3.
VSP_032371
Alternative sequence1 – 198198Missing in isoform 2.
VSP_032372
Alternative sequence277 – 2815ESIGV → MNDTA in isoform 3.
VSP_032373
Natural variant871G → V in HG and IG; partially inactivating mutation; results in a 3-fold increase of Km value for proline and a 5-fold increase of Km for glycine. Ref.6
Corresponds to variant rs77010315 [ dbSNP | Ensembl ].
VAR_064795
Natural variant4451A → V.
Corresponds to variant rs10042608 [ dbSNP | Ensembl ].
VAR_039887

Experimental info

Sequence conflict1561I → N in AAO11788. Ref.1
Sequence conflict4081S → P in AAO11788. Ref.1
Sequence conflict4101V → M in BAC85496. Ref.2
Sequence conflict4291T → P in BAC85496. Ref.2

Sequences

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

Last modified September 13, 2005. Version 1.
Checksum: E283B8C6F0C63666

FASTA48353,216
        10         20         30         40         50         60 
MSVTKSTEGP QGAVAIKLDL MSPPESAKKL ENKDSTFLDE SPSESAGLKK TKGITVFQAL 

        70         80         90        100        110        120 
IHLVKGNMGT GILGLPLAVK NAGILMGPLS LLVMGFIACH CMHILVKCAQ RFCKRLNKPF 

       130        140        150        160        170        180 
MDYGDTVMHG LEANPNAWLQ NHAHWGRHIV SFFLIITQLG FCCVYIVFLA DNLKQVVEAV 

       190        200        210        220        230        240 
NSTTNNCYSN ETVILTPTMD SRLYMLSFLP FLVLLVLIRN LRILTIFSML ANISMLVSLV 

       250        260        270        280        290        300 
IIIQYITQEI PDPSRLPLVA SWKTYPLFFG TAIFSFESIG VVLPLENKMK NARHFPAILS 

       310        320        330        340        350        360 
LGMSIVTSLY IGMAALGYLR FGDDIKASIS LNLPNCWLYQ SVKLLYIAGI LCTYALQFYV 

       370        380        390        400        410        420 
PAEIIIPFAI SRVSTRWALP LDLSIRLVMV CLTCLLAILI PRLDLVISLV GSVSGTALAL 

       430        440        450        460        470        480 
IIPPLLEVTT FYSEGMSPLT IFKDALISIL GFVGFVVGTY QALDELLKSE DSHPFSNSTT 


FVR 

« Hide

Isoform 2 [UniParc].

Checksum: EA3F89C90602A4CE
Show »

FASTA28531,642
Isoform 3 [UniParc].

Checksum: 6320177505ED6D96
Show »

FASTA20722,680

References

« Hide 'large scale' references
[1]"A cluster of proton/amino acid transporter genes in the human and mouse genomes."
Boll M., Foltz M., Rubio-Aliaga I., Daniel H.
Genomics 82:47-56(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[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: Kidney.
[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 (SEP-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; 2 AND 3).
[5]"Organization and expression of the SLC36 cluster of amino acid transporter genes."
Bermingham J.R. Jr., Pennington J.
Mamm. Genome 15:114-125(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters."
Broer S., Bailey C.G., Kowalczuk S., Ng C., Vanslambrouck J.M., Rodgers H., Auray-Blais C., Cavanaugh J.A., Broer A., Rasko J.E.
J. Clin. Invest. 118:3881-3892(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, VARIANT IG VAL-87, VARIANT HG VAL-87, CHARACTERIZATION OF VARIANT HG VAL-87.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY162214 mRNA. Translation: AAO11788.1.
AK122630 mRNA. Translation: BAC85496.1.
CH471062 Genomic DNA. Translation: EAW61678.1.
BC101100 mRNA. Translation: AAI01101.1.
BC101101 mRNA. Translation: AAI01102.1.
BC101102 mRNA. Translation: AAI01103.1.
BC101103 mRNA. Translation: AAI01104.1.
RefSeqNP_861441.2. NM_181776.2.
UniGeneHs.483877.

3D structure databases

ProteinModelPortalQ495M3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ495M3. 1 interaction.
STRING9606.ENSP00000334223.

Chemistry

GuidetoPHARMACOLOGY1162.

Protein family/group databases

TCDB2.A.18.8.6. the amino acid/auxin permease (aaap) family.

PTM databases

PhosphoSiteQ495M3.

Polymorphism databases

DMDM121943282.

Proteomic databases

PaxDbQ495M3.
PRIDEQ495M3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335244; ENSP00000334223; ENSG00000186335. [Q495M3-1]
ENST00000450886; ENSP00000399479; ENSG00000186335. [Q495M3-3]
GeneID153201.
KEGGhsa:153201.
UCSCuc003lty.3. human. [Q495M3-1]

Organism-specific databases

CTD153201.
GeneCardsGC05M150674.
HGNCHGNC:18762. SLC36A2.
HPAHPA044002.
MIM138500. phenotype.
242600. phenotype.
608331. gene.
neXtProtNX_Q495M3.
Orphanet42062. Iminoglycinuria.
PharmGKBPA134899820.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0814.
HOGENOMHOG000006823.
HOVERGENHBG057183.
InParanoidQ495M3.
KOK14209.
OMAFYSEGMN.
OrthoDBEOG73V6KC.
PhylomeDBQ495M3.
TreeFamTF314873.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

BgeeQ495M3.
CleanExHS_SLC36A2.
GenevestigatorQ495M3.

Family and domain databases

InterProIPR013057. AA_transpt_TM.
[Graphical view]
PfamPF01490. Aa_trans. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC36A2. human.
GeneWikiSLC36A2.
GenomeRNAi153201.
NextBio87082.
PROQ495M3.
SOURCESearch...

Entry information

Entry nameS36A2_HUMAN
AccessionPrimary (citable) accession number: Q495M3
Secondary accession number(s): Q495M4 expand/collapse secondary AC list , Q495M6, Q6ZWK5, Q7Z6B5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: September 13, 2005
Last modified: April 16, 2014
This is version 78 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 5

Human chromosome 5: entries, gene names and cross-references to MIM