Amino acid transporter heavy chain SLC3A1

Details

Name

Amino acid transporter heavy chain SLC3A1

Kind

protein

Synonyms

• b(0,+)-type amino acid transporter-related heavy chain
• D2h
• NBAT
• Neutral and basic amino acid transport protein
• rBAT
• Solute carrier family 3 member 1

Gene Name

SLC3A1

UniProtKB Entry

Q07837Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0002248|Amino acid transporter heavy chain SLC3A1
MAEDKSKRDSIEMSMKGCQTNNGFVHNEDILEQTPDPGSSTDNLKHSTRGILGSQEPDFK
GVQPYAGMPKEVLFQFSGQARYRIPREILFWLTVASVLVLIAATIAIIALSPKCLDWWQE
GPMYQIYPRSFKDSNKDGNGDLKGIQDKLDYITALNIKTVWITSFYKSSLKDFRYGVEDF
REVDPIFGTMEDFENLVAAIHDKGLKLIIDFIPNHTSDKHIWFQLSRTRTGKYTDYYIWH
DCTHENGKTIPPNNWLSVYGNSSWHFDEVRNQCYFHQFMKEQPDLNFRNPDVQEEIKEIL
RFWLTKGVDGFSLDAVKFLLEAKHLRDEIQVNKTQIPDTVTQYSELYHDFTTTQVGMHDI
VRSFRQTMDQYSTEPGRYRFMGTEAYAESIDRTVMYYGLPFIQEADFPFNNYLSMLDTVS
GNSVYEVITSWMENMPEGKWPNWMIGGPDSSRLTSRLGNQYVNVMNMLLFTLPGTPITYY
GEEIGMGNIVAANLNESYDINTLRSKSPMQWDNSSNAGFSEASNTWLPTNSDYHTVNVDV
QKTQPRSALKLYQDLSLLHANELLLNRGWFCHLRNDSHYVVYTRELDGIDRIFIVVLNFG
ESTLLNLHNMISGLPAKMRIRLSTNSADKGSKVDTSGIFLDKGEGLIFEHNTKNLLHRQT
AFRDRCFVSNRACYSSVLNILYTSC

Number of residues

685

Molecular Weight

78851.4

Theoretical pI

5.81

GO Classification

Functions

amino acid transmembrane transporter activity / basic amino acid transmembrane transporter activity / L-cystine transmembrane transporter activity

Processes

amino acid transport / basic amino acid transport / carbohydrate metabolic process / L-cystine transport

Components

brush border membrane / extracellular exosome / membrane / plasma membrane / vacuolar membrane

General Function

Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heteromers to the plasma membrane (By similarity) (PubMed:10588648, PubMed:11318953, PubMed:16609684, PubMed:16825196, PubMed:32494597, PubMed:32817565, PubMed:7686906, PubMed:8486766, PubMed:8663184, PubMed:8663357). Associates with SLC7A9 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. SLC7A9-SLC3A1 transporter has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids. Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine. SLC7A9-SLC3A1 acts as a major transporter for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in early proximal tubules (PubMed:10588648, PubMed:11318953, PubMed:16609684, PubMed:16825196, PubMed:32494597, PubMed:32817565, PubMed:7686906, PubMed:8486766, PubMed:8663184, PubMed:8663357). Associates with SLC7A13 to form a functional complex that transports anionic and neutral amino acids via exchange or facilitated diffusion. SLC7A13-SLC3A1 may act as a major transporter for L-cystine in late proximal tubules, ensuring its reabsorption from the luminal fluid in exchange for cytosolic L-glutamate or L-aspartate (By similarity)

Specific Function

amino acid transmembrane transporter activity

Pfam Domain Function

• Alpha-amylase (PF00128)

Signal Regions

Not Available

Transmembrane Regions

88-108

Cellular Location

Cell membrane

Gene sequence

>lcl|BSEQ0020511|Neutral and basic amino acid transport protein rBAT (SLC3A1)
ATGGCTGAAGATAAAAGCAAGAGAGACTCCATCGAGATGAGTATGAAGGGATGCCAGACA
AACAACGGGTTTGTCCATAATGAAGACATTCTGGAGCAGACCCCGGATCCAGGAAGCTCA
ACAGACAACCTGAAGCACAGCACCAGGGGCATCCTTGGCTCCCAGGAGCCCGACTTCAAG
GGCGTCCAGCCCTATGCGGGGATGCCCAAGGAGGTGCTGTTCCAGTTCTCTGGCCAGGCC
CGCTACCGCATACCTCGGGAGATCCTCTTCTGGCTCACAGTGGCTTCTGTGCTGGTGCTC
ATCGCGGCCACCATAGCCATCATTGCCCTCTCTCCAAAGTGCCTAGACTGGTGGCAGGAG
GGGCCCATGTACCAGATCTACCCAAGGTCTTTCAAGGACAGTAACAAGGATGGGAACGGA
GATCTGAAAGGTATTCAAGATAAACTGGACTACATCACAGCTTTAAATATAAAAACTGTT
TGGATTACTTCATTTTATAAATCGTCCCTTAAAGATTTCAGATATGGTGTTGAAGATTTC
CGGGAAGTTGATCCCATTTTTGGAACGATGGAAGATTTTGAGAATCTGGTTGCAGCCATA
CATGATAAAGGTTTAAAATTAATCATCGATTTCATACCAAACCACACGAGTGATAAACAT
ATTTGGTTTCAATTGAGTCGGACACGGACAGGAAAATATACTGATTATTATATCTGGCAT
GACTGTACCCATGAAAATGGCAAAACCATTCCACCCAACAACTGGTTAAGTGTGTATGGA
AACTCCAGTTGGCACTTTGACGAAGTGCGAAACCAATGTTATTTTCATCAGTTTATGAAA
GAGCAACCTGATTTAAATTTCCGCAATCCTGATGTTCAAGAAGAAATAAAAGAAATTTTA
CGGTTCTGGCTCACAAAGGGTGTTGATGGTTTTAGTTTGGATGCTGTTAAATTCCTCCTA
GAAGCAAAGCACCTGAGAGATGAGATCCAAGTAAATAAGACCCAAATCCCGGACACGGTC
ACACAATACTCGGAGCTGTACCATGACTTCACCACCACGCAGGTGGGAATGCACGACATT
GTCCGCAGCTTCCGGCAGACCATGGACCAATACAGCACGGAGCCCGGCAGATACAGGTTC
ATGGGGACTGAAGCCTATGCAGAGAGTATTGACAGGACCGTGATGTACTATGGATTGCCA
TTTATCCAAGAAGCTGATTTTCCCTTCAACAATTACCTCAGCATGCTAGACACTGTTTCT
GGGAACAGCGTGTATGAGGTTATCACATCCTGGATGGAAAACATGCCAGAAGGAAAATGG
CCTAACTGGATGATTGGTGGACCAGACAGTTCACGGCTGACTTCGCGTTTGGGGAATCAG
TATGTCAACGTGATGAACATGCTTCTTTTCACACTCCCTGGAACTCCTATAACTTACTAT
GGAGAAGAAATTGGAATGGGAAATATTGTAGCCGCAAATCTCAATGAAAGCTATGATATT
AATACCCTTCGCTCAAAGTCACCAATGCAGTGGGACAATAGTTCAAATGCTGGTTTTTCT
GAAGCTAGTAACACCTGGTTACCTACCAATTCAGATTACCACACTGTGAATGTTGATGTC
CAAAAGACTCAGCCCAGATCGGCTTTGAAGTTATATCAAGATTTAAGTCTACTTCATGCC
AATGAGCTACTCCTCAACAGGGGCTGGTTTTGCCATTTGAGGAATGACAGCCACTATGTT
GTGTACACAAGAGAGCTGGATGGCATCGACAGAATCTTTATCGTGGTTCTGAATTTTGGA
GAATCAACACTGTTAAATCTACATAATATGATTTCGGGCCTTCCCGCTAAAATGAGAATA
AGGTTAAGTACCAATTCTGCCGACAAAGGCAGTAAAGTTGATACAAGTGGCATTTTTCTG
GACAAGGGAGAGGGACTCATCTTTGAACACAACACGAAGAATCTCCTTCATCGCCAAACA
GCTTTCAGAGATAGATGCTTTGTTTCCAATCGAGCATGCTATTCCAGTGTACTGAACATA
CTGTATACCTCGTGTTAG

Chromosome Location

2

Locus

2p21

External Identifiers

Resource	Link
UniProtKB ID	Q07837
UniProtKB Entry Name	SLC31_HUMAN
GenBank Protein ID	306442
GenBank Gene ID	M95548
GeneCard ID	SLC3A1
GenAtlas ID	SLC3A1
HGNC ID	HGNC:11025
PDB ID(s)	6LI9, 6LID, 6YUP, 6YUZ
KEGG ID	hsa:6519
NCBI Gene ID	6519

General References

1. Lee WS, Wells RG, Sabbag RV, Mohandas TK, Hediger MA: Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. J Clin Invest. 1993 May;91(5):1959-63. [Article]
2. Bertran J, Werner A, Chillaron J, Nunes V, Biber J, Testar X, Zorzano A, Estivill X, Murer H, Palacin M: Expression cloning of a human renal cDNA that induces high affinity transport of L-cystine shared with dibasic amino acids in Xenopus oocytes. J Biol Chem. 1993 Jul 15;268(20):14842-9. [Article]
3. Miyamoto K, Segawa H, Tatsumi S, Katai K, Yamamoto H, Taketani Y, Haga H, Morita K, Takeda E: Effects of truncation of the COOH-terminal region of a Na+-independent neutral and basic amino acid transporter on amino acid transport in Xenopus oocytes. J Biol Chem. 1996 Jul 12;271(28):16758-63. [Article]
4. Endsley JK, Phillips JA 3rd, Hruska KA, Denneberg T, Carlson J, George AL Jr: Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria. Kidney Int. 1997 Jun;51(6):1893-9. [Article]
5. Mizoguchi K, Cha SH, Chairoungdua A, Kim DK, Shigeta Y, Matsuo H, Fukushima J, Awa Y, Akakura K, Goya T, Ito H, Endou H, Kanai Y: Human cystinuria-related transporter: localization and functional characterization. Kidney Int. 2001 May;59(5):1821-33. [Article]
6. Parvari R, Gonen Y, Alshafee I, Buriakovsky S, Regev K, Hershkovitz E: The 2p21 deletion syndrome: characterization of the transcription content. Genomics. 2005 Aug;86(2):195-211. [Article]
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9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
10. Pfeiffer R, Loffing J, Rossier G, Bauch C, Meier C, Eggermann T, Loffing-Cueni D, Kuhn LC, Verrey F: Luminal heterodimeric amino acid transporter defective in cystinuria. Mol Biol Cell. 1999 Dec;10(12):4135-47. [Article]
11. Calonge MJ, Volpini V, Bisceglia L, Rousaud F, de Sanctis L, Beccia E, Zelante L, Testar X, Zorzano A, Estivill X, et al.: Genetic heterogeneity in cystinuria: the SLC3A1 gene is linked to type I but not to type III cystinuria. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9667-71. [Article]
12. Fernandez E, Carrascal M, Rousaud F, Abian J, Zorzano A, Palacin M, Chillaron J: rBAT-b(0,+)AT heterodimer is the main apical reabsorption system for cystine in the kidney. Am J Physiol Renal Physiol. 2002 Sep;283(3):F540-8. [Article]
13. Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G: Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. Epub 2005 Nov 23. [Article]
14. Calonge MJ, Gasparini P, Chillaron J, Chillon M, Gallucci M, Rousaud F, Zelante L, Testar X, Dallapiccola B, Di Silverio F, et al.: Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nat Genet. 1994 Apr;6(4):420-5. [Article]
15. Pras E, Raben N, Golomb E, Arber N, Aksentijevich I, Schapiro JM, Harel D, Katz G, Liberman U, Pras M, et al.: Mutations in the SLC3A1 transporter gene in cystinuria. Am J Hum Genet. 1995 Jun;56(6):1297-303. [Article]
16. Gasparini P, Calonge MJ, Bisceglia L, Purroy J, Dianzani I, Notarangelo A, Rousaud F, Gallucci M, Testar X, Ponzone A, et al.: Molecular genetics of cystinuria: identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. Am J Hum Genet. 1995 Oct;57(4):781-8. [Article]
17. Miyamoto K, Katai K, Tatsumi S, Sone K, Segawa H, Yamamoto H, Taketani Y, Takada K, Morita K, Kanayama H, et al.: Mutations of the basic amino acid transporter gene associated with cystinuria. Biochem J. 1995 Sep 15;310 ( Pt 3):951-5. [Article]
18. Gitomer WL, Reed BY, Pak CY: Identification of two novel mutations [P122S (364C>T) and 1601delAC] in the SLC3A1 gene in type I cystinurics. Hum Mutat. 2000 Apr;15(4):390. [Article]
19. Harnevik L, Fjellstedt E, Molbaek A, Tiselius HG, Denneberg T, Soderkvist P: Identification of 12 novel mutations in the SLC3A1 gene in Swedish cystinuria patients. Hum Mutat. 2001 Dec;18(6):516-25. [Article]
20. Botzenhart E, Vester U, Schmidt C, Hesse A, Halber M, Wagner C, Lang F, Hoyer P, Zerres K, Eggermann T: Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes. Kidney Int. 2002 Oct;62(4):1136-42. [Article]
21. Skopkova Z, Hrabincova E, Stastna S, Kozak L, Adam T: Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Czech and Slovak cystinuric patients. Ann Hum Genet. 2005 Sep;69(Pt 5):501-7. [Article]
22. Font-Llitjos M, Jimenez-Vidal M, Bisceglia L, Di Perna M, de Sanctis L, Rousaud F, Zelante L, Palacin M, Nunes V: New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype. J Med Genet. 2005 Jan;42(1):58-68. [Article]
23. Shigeta Y, Kanai Y, Chairoungdua A, Ahmed N, Sakamoto S, Matsuo H, Kim DK, Fujimura M, Anzai N, Mizoguchi K, Ueda T, Akakura K, Ichikawa T, Ito H, Endou H: A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter. Kidney Int. 2006 Apr;69(7):1198-206. [Article]
24. Bisceglia L, Fischetti L, Bonis PD, Palumbo O, Augello B, Stanziale P, Carella M, Zelante L: Large rearrangements detected by MLPA, point mutations, and survey of the frequency of mutations within the SLC3A1 and SLC7A9 genes in a cohort of 172 cystinuric Italian patients. Mol Genet Metab. 2010 Jan;99(1):42-52. doi: 10.1016/j.ymgme.2009.09.001. Epub . [Article]

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Cystine	approved, nutraceutical	unknown	transporter		Details