UniProtKB - Q495M3 (S36A2_HUMAN)
Protein
Proton-coupled amino acid transporter 2
Gene
SLC36A2
Organism
Homo sapiens (Human)
Status
Functioni
Involved in a pH-dependent electrogenic neuronal transport and sequestration of small amino acids. Transports glycine and proline. Inhibited by sarcosine (By similarity).By similarity1 Publication
GO - Molecular functioni
- amino acid:proton symporter activity Source: GO_Central
- amino acid transmembrane transporter activity Source: GO_Central
- glycine transmembrane transporter activity Source: UniProtKB
- L-alanine transmembrane transporter activity Source: GO_Central
- L-proline transmembrane transporter activity Source: GO_Central
GO - Biological processi
- amino acid transmembrane transport Source: GO_Central
- amino acid transport Source: Reactome
- glycine transport Source: GO_Central
- ion transport Source: Reactome
- L-alanine transport Source: GO_Central
- proline transmembrane transport Source: UniProtKB
- proline transport Source: Ensembl
- proton transmembrane transport Source: GO_Central
Keywordsi
Biological process | Amino-acid transport, Transport |
Enzyme and pathway databases
PathwayCommonsi | Q495M3 |
Reactomei | R-HSA-352230, Amino acid transport across the plasma membrane R-HSA-428559, Proton-coupled neutral amino acid transporters R-HSA-5619041, Defective SLC36A2 causes iminoglycinuria (IG) and hyperglycinuria (HG) |
Protein family/group databases
TCDBi | 2.A.18.8.6, the amino acid/auxin permease (aaap) family |
Names & Taxonomyi
Protein namesi | Recommended name: Proton-coupled amino acid transporter 2Short name: Proton/amino acid transporter 2 Alternative name(s): Solute carrier family 36 member 2 Tramdorin-1 |
Gene namesi | Name:SLC36A2 Synonyms:PAT2, TRAMD1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18762, SLC36A2 |
MIMi | 608331, gene |
neXtProti | NX_Q495M3 |
VEuPathDBi | HostDB:ENSG00000186335.8 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Plasma membrane
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- cytoplasm Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 58 | CytoplasmicSequence analysisAdd BLAST | 58 | |
Transmembranei | 59 – 79 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 80 – 81 | ExtracellularSequence analysis | 2 | |
Transmembranei | 82 – 102 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 103 – 148 | CytoplasmicSequence analysisAdd BLAST | 46 | |
Transmembranei | 149 – 169 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 170 – 197 | ExtracellularSequence analysisAdd BLAST | 28 | |
Transmembranei | 198 – 218 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 219 – 222 | CytoplasmicSequence analysis | 4 | |
Transmembranei | 223 – 243 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 244 – 264 | ExtracellularSequence analysisAdd BLAST | 21 | |
Transmembranei | 265 – 285 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 286 – 296 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 297 – 317 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 318 – 349 | ExtracellularSequence analysisAdd BLAST | 32 | |
Transmembranei | 350 – 370 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 371 – 379 | CytoplasmicSequence analysis | 9 | |
Transmembranei | 380 – 400 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 401 – 404 | ExtracellularSequence analysis | 4 | |
Transmembranei | 405 – 425 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 426 – 437 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 438 – 458 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 459 – 483 | ExtracellularSequence analysisAdd BLAST | 25 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Hyperglycinuria (HG)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA condition characterized by excess of glycine in the urine. In some cases it is associated with renal colic and renal oxalate stones.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064795 | 87 | G → 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. 1 PublicationCorresponds to variant dbSNP:rs77010315EnsemblClinVar. | 1 |
Iminoglycinuria (IG)1 Publication
The disease is caused by variants 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.
Disease descriptionA disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064795 | 87 | G → 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. 1 PublicationCorresponds to variant dbSNP:rs77010315EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 153201 |
MalaCardsi | SLC36A2 |
MIMi | 138500, phenotype 242600, phenotype |
OpenTargetsi | ENSG00000186335 |
Orphaneti | 42062, Iminoglycinuria |
PharmGKBi | PA134899820 |
Miscellaneous databases
Pharosi | Q495M3, Tchem |
Chemistry databases
DrugBanki | DB00260, Cycloserine |
GuidetoPHARMACOLOGYi | 1162 |
Genetic variation databases
BioMutai | SLC36A2 |
DMDMi | 121943282 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000324819 | 1 – 483 | Proton-coupled amino acid transporter 2Add BLAST | 483 |
Proteomic databases
jPOSTi | Q495M3 |
MassIVEi | Q495M3 |
PaxDbi | Q495M3 |
PeptideAtlasi | Q495M3 |
PRIDEi | Q495M3 |
ProteomicsDBi | 61963 [Q495M3-1] 61964 [Q495M3-2] 61965 [Q495M3-3] |
PTM databases
iPTMneti | Q495M3 |
PhosphoSitePlusi | Q495M3 |
Expressioni
Tissue specificityi
Abundantly expressed in kidney and muscle. Expressed in the S1 segment of the proximal tubule close to the glomerulus.2 Publications
Gene expression databases
Bgeei | ENSG00000186335, Expressed in muscle of leg and 52 other tissues |
ExpressionAtlasi | Q495M3, baseline and differential |
Organism-specific databases
HPAi | ENSG00000186335, Group enriched (kidney, skeletal muscle, tongue) |
Interactioni
Protein-protein interaction databases
IntActi | Q495M3, 2 interactors |
STRINGi | 9606.ENSP00000334223 |
Miscellaneous databases
RNActi | Q495M3, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the amino acid/polyamine transporter 2 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1304, Eukaryota |
GeneTreei | ENSGT00940000162044 |
InParanoidi | Q495M3 |
OMAi | VSKRWAL |
OrthoDBi | 464614at2759 |
PhylomeDBi | Q495M3 |
TreeFami | TF314873 |
Family and domain databases
InterProi | View protein in InterPro IPR013057, AA_transpt_TM |
Pfami | View protein in Pfam PF01490, Aa_trans, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q495M3-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSVTKSTEGP QGAVAIKLDL MSPPESAKKL ENKDSTFLDE SPSESAGLKK
60 70 80 90 100
TKGITVFQAL IHLVKGNMGT GILGLPLAVK NAGILMGPLS LLVMGFIACH
110 120 130 140 150
CMHILVKCAQ RFCKRLNKPF MDYGDTVMHG LEANPNAWLQ NHAHWGRHIV
160 170 180 190 200
SFFLIITQLG FCCVYIVFLA DNLKQVVEAV NSTTNNCYSN ETVILTPTMD
210 220 230 240 250
SRLYMLSFLP FLVLLVLIRN LRILTIFSML ANISMLVSLV IIIQYITQEI
260 270 280 290 300
PDPSRLPLVA SWKTYPLFFG TAIFSFESIG VVLPLENKMK NARHFPAILS
310 320 330 340 350
LGMSIVTSLY IGMAALGYLR FGDDIKASIS LNLPNCWLYQ SVKLLYIAGI
360 370 380 390 400
LCTYALQFYV PAEIIIPFAI SRVSTRWALP LDLSIRLVMV CLTCLLAILI
410 420 430 440 450
PRLDLVISLV GSVSGTALAL IIPPLLEVTT FYSEGMSPLT IFKDALISIL
460 470 480
GFVGFVVGTY QALDELLKSE DSHPFSNSTT FVR
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RJJ5 | E5RJJ5_HUMAN | Proton-coupled amino acid transport... | SLC36A2 | 395 | Annotation score: | ||
E5RGH8 | E5RGH8_HUMAN | Proton-coupled amino acid transport... | SLC36A2 | 147 | Annotation score: | ||
H0YB43 | H0YB43_HUMAN | Proton-coupled amino acid transport... | SLC36A2 | 107 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 156 | I → N in AAO11788 (PubMed:12809675).Curated | 1 | |
Sequence conflicti | 408 | S → P in AAO11788 (PubMed:12809675).Curated | 1 | |
Sequence conflicti | 410 | V → M in BAC85496 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 429 | T → P in BAC85496 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_064795 | 87 | G → 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. 1 PublicationCorresponds to variant dbSNP:rs77010315EnsemblClinVar. | 1 | |
Natural variantiVAR_039887 | 445 | A → V. Corresponds to variant dbSNP:rs10042608Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_032371 | 1 – 276 | Missing in isoform 3. 1 PublicationAdd BLAST | 276 | |
Alternative sequenceiVSP_032372 | 1 – 198 | Missing in isoform 2. 1 PublicationAdd BLAST | 198 | |
Alternative sequenceiVSP_032373 | 277 – 281 | ESIGV → MNDTA in isoform 3. 1 Publication | 5 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS4315.1 [Q495M3-1] |
RefSeqi | NP_861441.2, NM_181776.2 [Q495M3-1] XP_016864573.1, XM_017009084.1 [Q495M3-2] |
Genome annotation databases
Ensembli | ENST00000335244; ENSP00000334223; ENSG00000186335 [Q495M3-1] |
GeneIDi | 153201 |
KEGGi | hsa:153201 |
UCSCi | uc003lty.3, human [Q495M3-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS4315.1 [Q495M3-1] |
RefSeqi | NP_861441.2, NM_181776.2 [Q495M3-1] XP_016864573.1, XM_017009084.1 [Q495M3-2] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
IntActi | Q495M3, 2 interactors |
STRINGi | 9606.ENSP00000334223 |
Chemistry databases
DrugBanki | DB00260, Cycloserine |
GuidetoPHARMACOLOGYi | 1162 |
Protein family/group databases
TCDBi | 2.A.18.8.6, the amino acid/auxin permease (aaap) family |
PTM databases
iPTMneti | Q495M3 |
PhosphoSitePlusi | Q495M3 |
Genetic variation databases
BioMutai | SLC36A2 |
DMDMi | 121943282 |
Proteomic databases
jPOSTi | Q495M3 |
MassIVEi | Q495M3 |
PaxDbi | Q495M3 |
PeptideAtlasi | Q495M3 |
PRIDEi | Q495M3 |
ProteomicsDBi | 61963 [Q495M3-1] 61964 [Q495M3-2] 61965 [Q495M3-3] |
Protocols and materials databases
Antibodypediai | 28201, 120 antibodies |
Genome annotation databases
Ensembli | ENST00000335244; ENSP00000334223; ENSG00000186335 [Q495M3-1] |
GeneIDi | 153201 |
KEGGi | hsa:153201 |
UCSCi | uc003lty.3, human [Q495M3-1] |
Organism-specific databases
CTDi | 153201 |
DisGeNETi | 153201 |
GeneCardsi | SLC36A2 |
HGNCi | HGNC:18762, SLC36A2 |
HPAi | ENSG00000186335, Group enriched (kidney, skeletal muscle, tongue) |
MalaCardsi | SLC36A2 |
MIMi | 138500, phenotype 242600, phenotype 608331, gene |
neXtProti | NX_Q495M3 |
OpenTargetsi | ENSG00000186335 |
Orphaneti | 42062, Iminoglycinuria |
PharmGKBi | PA134899820 |
VEuPathDBi | HostDB:ENSG00000186335.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1304, Eukaryota |
GeneTreei | ENSGT00940000162044 |
InParanoidi | Q495M3 |
OMAi | VSKRWAL |
OrthoDBi | 464614at2759 |
PhylomeDBi | Q495M3 |
TreeFami | TF314873 |
Enzyme and pathway databases
PathwayCommonsi | Q495M3 |
Reactomei | R-HSA-352230, Amino acid transport across the plasma membrane R-HSA-428559, Proton-coupled neutral amino acid transporters R-HSA-5619041, Defective SLC36A2 causes iminoglycinuria (IG) and hyperglycinuria (HG) |
Miscellaneous databases
BioGRID-ORCSi | 153201, 2 hits in 978 CRISPR screens |
ChiTaRSi | SLC36A2, human |
GeneWikii | SLC36A2 |
GenomeRNAii | 153201 |
Pharosi | Q495M3, Tchem |
PROi | PR:Q495M3 |
RNActi | Q495M3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000186335, Expressed in muscle of leg and 52 other tissues |
ExpressionAtlasi | Q495M3, baseline and differential |
Family and domain databases
InterProi | View protein in InterPro IPR013057, AA_transpt_TM |
Pfami | View protein in Pfam PF01490, Aa_trans, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | S36A2_HUMAN | |
Accessioni | Q495M3Primary (citable) accession number: Q495M3 Secondary accession number(s): Q495M4 Q7Z6B5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | September 13, 2005 | |
Last modified: | April 7, 2021 | |
This is version 127 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families