Q9NP91 (S6A20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium- and chloride-dependent transporter XTRP3

Alternative name(s):
Sodium/imino-acid transporter 1
Solute carrier family 6 member 20
Transporter rB21A homolog

Gene names

Name:	SLC6A20
Synonyms:	SIT1, XT3, XTRP3

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	592 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the calcium-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N-methylated amino acids. Involved in the transport of glycine. Ref.7 Ref.8
Subcellular location	Apical cell membrane; Multi-pass membrane protein By similarity. Note: Located in the apical brush border membrane of kidney proximal tubule cells By similarity.
Tissue specificity	Kidney and small intestine. Expressed in the S3 segment of the proximal tubule. Ref.5 Ref.8
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.8 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 the gene represented in this entry. Haploinsufficiency of SLC6A20 combined with deficiency of the neutral amino acid transporter SLC6A19 or partially inactivating mutations in SLC36A2, is responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families. Ref.8
Sequence similarities	Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A20 subfamily. [View classification]
Sequence caution	The sequence AAL75944.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Amino-acid transport Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycine transport Inferred from mutant phenotype Ref.8. Source: UniProtKB proline transport Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	amino acid transmembrane transporter activity Inferred from direct assay Ref.7. Source: UniProtKB neurotransmitter:sodium symporter 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: Q9NP91-1)

Also known as: XT3;

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: Q9NP91-2)

Also known as: XT3a;

The sequence of this isoform differs from the canonical sequence as follows:
     195-231: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 592	592	Sodium- and chloride-dependent transporter XTRP3		PRO_0000214812
Regions
	Topological domain	1 – 5	5	Cytoplasmic Potential
	Transmembrane	6 – 26	21	Helical; Name=1; Potential
	Topological domain	27 – 42	16	Extracellular Potential
	Transmembrane	43 – 63	21	Helical; Name=2; Potential
	Topological domain	64 – 79	16	Cytoplasmic Potential
	Transmembrane	80 – 100	21	Helical; Name=3; Potential
	Topological domain	101 – 165	65	Extracellular Potential
	Transmembrane	166 – 186	21	Helical; Name=4; Potential
	Topological domain	187 – 194	8	Cytoplasmic Potential
	Transmembrane	195 – 215	21	Helical; Name=5; Potential
	Topological domain	216 – 241	26	Extracellular Potential
	Transmembrane	242 – 262	21	Helical; Name=6; Potential
	Topological domain	263 – 276	14	Cytoplasmic Potential
	Transmembrane	277 – 297	21	Helical; Name=7; Potential
	Topological domain	298 – 389	92	Extracellular Potential
	Transmembrane	390 – 410	21	Helical; Name=8; Potential
	Topological domain	411 – 431	21	Cytoplasmic Potential
	Transmembrane	432 – 452	21	Helical; Name=9; Potential
	Topological domain	453 – 465	13	Extracellular Potential
	Transmembrane	466 – 486	21	Helical; Name=10; Potential
	Topological domain	487 – 504	18	Cytoplasmic Potential
	Transmembrane	505 – 525	21	Helical; Name=11; Potential
	Topological domain	526 – 554	29	Extracellular Potential
	Transmembrane	555 – 575	21	Helical; Name=12; Potential
	Topological domain	576 – 592	17	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	131	1	N-linked (GlcNAc...) Potential
	Glycosylation	357	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	195 – 231	37	Missing in isoform 2.		VSP_050002
	Natural variant	9	1	A → G. Corresponds to variant rs2271615 [ dbSNP | Ensembl ].		VAR_021862
	Natural variant	199	1	T → M Common variant that contributes to hyperglycinuria and iminoglycinuria in patients carrying variants in SLC36A2, SLC6A19 or SLC6A18; results in SLC6A20 inactivation due to a 8-fold decrease of Vmax. Ref.8 Corresponds to variant rs17279437 [ dbSNP | Ensembl ].		VAR_052068
Experimental info
	Sequence conflict	31	1	F → N in AAC27755. Ref.2
	Sequence conflict	217	1	L → V in AAC27755. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (XT3) [UniParc]. Last modified October 1, 2000. Version 1. Checksum: AF6E94E19895377F	FASTA	592	65,914
	10 20 30 40 50 60 MEKARPLWAN SLQFVFACIS YAVGLGNVWR FPYLCQMYGG GSFLVPYIIM LIVEGMPLLY 70 80 90 100 110 120 LELAVGQRMR QGSIGAWRTI SPYLSGVGVA SVVVSFFLSM YYNVINAWAF WYLFHSFQDP 130 140 150 160 170 180 LPWSVCPLNG NHTGYDEECE KASSTQYFWY RKTLNISPSL QENGGVQWEP ALCLLLAWLV 190 200 210 220 230 240 VYLCILRGTE STGKVVYFTA SLPYCVLIIY LIRGLTLHGA TNGLMYMFTP KIEQLANPKA 250 260 270 280 290 300 WINAATQIFF SLGLGFGSLI AFASYNEPSN NCQKHAIIVS LINSFTSIFA SIVTFSIYGF 310 320 330 340 350 360 KATFNYENCL KKVSLLLTNT FDLEDGFLTA SNLEQVKGYL ASAYPSKYSE MFPQIKNCSL 370 380 390 400 410 420 ESELDTAVQG TGLAFIVYTE AIKNMEVSQL WSVLYFFMLL MLGIGSMLGN TAAILTPLTD 430 440 450 460 470 480 SKIISSHLPK EAISGLVCLV NCAIGMVFTM EAGNYWFDIF NDYAATLSLL LIVLVETIAV 490 500 510 520 530 540 CYVYGLRRFE SDLKAMTGRA VSWYWKVMWA GVSPLLIVSL FVFYLSDYIL TGTLKYQAWD 550 560 570 580 590 ASQGQLVTKD YPAYALAVIG LLVASSTMCI PLAALGTFVQ RRLKRGDADP VA
	Isoform 2 (XT3a) [UniParc]. Checksum: A7CE6C1CE318CF69	FASTA	555	61,751
	10 20 30 40 50 60 MEKARPLWAN SLQFVFACIS YAVGLGNVWR FPYLCQMYGG GSFLVPYIIM LIVEGMPLLY 70 80 90 100 110 120 LELAVGQRMR QGSIGAWRTI SPYLSGVGVA SVVVSFFLSM YYNVINAWAF WYLFHSFQDP 130 140 150 160 170 180 LPWSVCPLNG NHTGYDEECE KASSTQYFWY RKTLNISPSL QENGGVQWEP ALCLLLAWLV 190 200 210 220 230 240 VYLCILRGTE STGKIEQLAN PKAWINAATQ IFFSLGLGFG SLIAFASYNE PSNNCQKHAI 250 260 270 280 290 300 IVSLINSFTS IFASIVTFSI YGFKATFNYE NCLKKVSLLL TNTFDLEDGF LTASNLEQVK 310 320 330 340 350 360 GYLASAYPSK YSEMFPQIKN CSLESELDTA VQGTGLAFIV YTEAIKNMEV SQLWSVLYFF 370 380 390 400 410 420 MLLMLGIGSM LGNTAAILTP LTDSKIISSH LPKEAISGLV CLVNCAIGMV FTMEAGNYWF 430 440 450 460 470 480 DIFNDYAATL SLLLIVLVET IAVCYVYGLR RFESDLKAMT GRAVSWYWKV MWAGVSPLLI 490 500 510 520 530 540 VSLFVFYLSD YILTGTLKYQ AWDASQGQLV TKDYPAYALA VIGLLVASST MCIPLAALGT 550 FVQRRLKRGD ADPVA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The LZTFL1 gene is a part of a transcriptional map covering 250 kb within the common eliminated region 1 (C3CER1) in 3p21.3." Kiss H., Kedra D., Kiss C., Kost-Alimova M., Yang Y., Klein G., Imreh S., Dumanski J.P. Genomics 73:10-19(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
[2]	"Cloning of a new human cDNA similar to Rattus norvegicus neurotransmitter transporter rB21a." Zhou Y., Yu L., Zhao S.Y. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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. , 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).
[5]	"Cloning, gene structure, and genomic localization of an orphan transporter from mouse kidney with six alternatively-spliced isoforms." Nash S.R., Giros B., Kingsmore S.F., Kim K.M., El-Mestikawy S., Dong Q., Fumagalli F., Seldin M.F., Caron M.G. Recept. Channels 6:113-128(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-315 (ISOFORM 1), TISSUE SPECIFICITY.
[6]	The European IMAGE consortium Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 232-592.
[7]	"Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino." Takanaga H., Mackenzie B., Suzuki Y., Hediger M.A. J. Biol. Chem. 280:8974-8984(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"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 MET-199, CHARACTERIZATION OF VARIANT MET-199, INVOLVEMENT IN HG AND IG.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ276207 mRNA. Translation: CAB99310.1. AJ276208 mRNA. Translation: CAB99311.1. AJ289880 Genomic DNA. Translation: CAB96872.1. AF125107 mRNA. Translation: AAL75944.1. Different initiation. CH471055 Genomic DNA. Translation: EAW64748.1. BC126197 mRNA. Translation: AAI26198.1. BC136431 mRNA. Translation: AAI36432.1. AF075260 mRNA. Translation: AAC27755.1. AL389979 mRNA. Translation: CAB97535.1.
IPI	IPI00152803. IPI00216628.
RefSeq	NP_064593.1. NM_020208.3. NP_071800.1. NM_022405.3.
UniGene	Hs.413095.
3D structure databases
ProteinModelPortal	Q9NP91.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000346298.
Polymorphism databases
DMDM	46397768.
Proteomic databases
PaxDb	Q9NP91.
PRIDE	Q9NP91.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000353278; ENSP00000296133; ENSG00000163817. ENST00000358525; ENSP00000346298; ENSG00000163817.
GeneID	54716.
KEGG	hsa:54716.
UCSC	uc011bai.2. human. uc011baj.2. human.
Organism-specific databases
CTD	54716.
GeneCards	GC03M045796.
HGNC	HGNC:30927. SLC6A20.
HPA	HPA029873.
MIM	138500. phenotype. 242600. phenotype. 605616. gene.
neXtProt	NX_Q9NP91.
Orphanet	42062. Iminoglycinuria.
PharmGKB	PA134865308.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0733.
HOGENOM	HOG000116406.
HOVERGEN	HBG071421.
InParanoid	Q9NP91.
KO	K05048.
OMA	PNWYWKI.
OrthoDB	EOG483D47.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters. REACT_20679. Amine compound SLC transporters.
Gene expression databases
ArrayExpress	Q9NP91.
Bgee	Q9NP91.
CleanEx	HS_SIT1. HS_SLC6A20.
Genevestigator	Q9NP91.
GermOnline	ENSG00000163817. Homo sapiens.
Family and domain databases
InterPro	IPR000175. Na/ntran_symport. IPR002438. Na/ntran_symport_orphan. [Graphical view]
PANTHER	PTHR11616. PTHR11616. 1 hit.
Pfam	PF00209. SNF. 1 hit. [Graphical view]
PRINTS	PR00176. NANEUSMPORT. PR01206. ORPHTRNSPORT.
PROSITE	PS00610. NA_NEUROTRAN_SYMP_1. 1 hit. PS00754. NA_NEUROTRAN_SYMP_2. 1 hit. PS50267. NA_NEUROTRAN_SYMP_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	54716.
NextBio	57286.
SOURCE	Search...

Entry information

Entry name

S6A20_HUMAN

Accession

Primary (citable) accession number: Q9NP91
Secondary accession number(s): A1A4F2 , O75590, Q8TF10, Q9NPQ2, Q9NQ77

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 93 of the entry and version 1 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.