S6A17_HUMAN
ID S6A17_HUMAN Reviewed; 727 AA.
AC Q9H1V8; A6NEA8; A8K1R7; B9EIR5; Q5T5Q9;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Sodium-dependent neutral amino acid transporter SLC6A17;
DE AltName: Full=Sodium-dependent neurotransmitter transporter NTT4;
DE AltName: Full=Solute carrier family 6 member 17;
GN Name=SLC6A17; Synonyms=NTT4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-57.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION.
RX PubMed=16125675; DOI=10.1016/j.bbrc.2005.08.048;
RA Hoglund P.J., Adzic D., Scicluna S.J., Lindblom J., Fredriksson R.;
RT "The repertoire of solute carriers of family 6: identification of new human
RT and rodent genes.";
RL Biochem. Biophys. Res. Commun. 336:175-189(2005).
RN [5]
RP INVOLVEMENT IN MRT48, AND VARIANTS MRT48 ARG-162 AND ARG-633.
RX PubMed=25704603; DOI=10.1016/j.ajhg.2015.01.010;
RA Iqbal Z., Willemsen M.H., Papon M.A., Musante L., Benevento M., Hu H.,
RA Venselaar H., Wissink-Lindhout W.M., Vulto-van Silfhout A.T., Vissers L.E.,
RA de Brouwer A.P., Marouillat S., Wienker T.F., Ropers H.H., Kahrizi K.,
RA Nadif Kasri N., Najmabadi H., Laumonnier F., Kleefstra T., van Bokhoven H.;
RT "Homozygous SLC6A17 mutations cause autosomal-recessive intellectual
RT disability with progressive tremor, speech impairment, and behavioral
RT problems.";
RL Am. J. Hum. Genet. 96:386-396(2015).
CC -!- FUNCTION: Functions as a sodium-dependent vesicular transporter
CC selective for proline, glycine, leucine and alanine. In contrast to
CC other members of this neurotransmitter transporter family, does not
CC appear to be chloride-dependent (By similarity).
CC {ECO:0000250|UniProtKB:P31662}.
CC -!- INTERACTION:
CC Q9H1V8; Q12983: BNIP3; NbExp=3; IntAct=EBI-18396863, EBI-749464;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:P31662}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P31662}. Postsynapse
CC {ECO:0000250|UniProtKB:Q8BJI1}. Presynapse
CC {ECO:0000250|UniProtKB:Q8BJI1}. Note=Localizes at synaptic junctions
CC - at both pre- and post-synaptic sites - particularly in excitatory
CC glutamatergic terminals. {ECO:0000250|UniProtKB:Q8BJI1}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 48
CC (MRT48) [MIM:616269]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT48
CC patients show moderate to severe intellectual disability and additional
CC features including progressive tremor, speech impairment, and sometimes
CC behavioral problems. {ECO:0000269|PubMed:25704603}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A17 subfamily. {ECO:0000305}.
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DR EMBL; AK289982; BAF82671.1; -; mRNA.
DR EMBL; AL355990; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC140908; AAI40909.1; -; mRNA.
DR CCDS; CCDS30799.1; -.
DR RefSeq; NP_001010898.1; NM_001010898.3.
DR RefSeq; XP_006710706.1; XM_006710643.2.
DR AlphaFoldDB; Q9H1V8; -.
DR SMR; Q9H1V8; -.
DR BioGRID; 132799; 1.
DR IntAct; Q9H1V8; 1.
DR STRING; 9606.ENSP00000330199; -.
DR TCDB; 2.A.22.6.6; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; Q9H1V8; 2 sites.
DR iPTMnet; Q9H1V8; -.
DR PhosphoSitePlus; Q9H1V8; -.
DR BioMuta; SLC6A17; -.
DR DMDM; 59800227; -.
DR jPOST; Q9H1V8; -.
DR MassIVE; Q9H1V8; -.
DR PaxDb; Q9H1V8; -.
DR PeptideAtlas; Q9H1V8; -.
DR PRIDE; Q9H1V8; -.
DR ProteomicsDB; 80449; -.
DR Antibodypedia; 1942; 86 antibodies from 19 providers.
DR DNASU; 388662; -.
DR Ensembl; ENST00000331565.5; ENSP00000330199.3; ENSG00000197106.7.
DR GeneID; 388662; -.
DR KEGG; hsa:388662; -.
DR MANE-Select; ENST00000331565.5; ENSP00000330199.3; NM_001010898.4; NP_001010898.1.
DR UCSC; uc009wfq.4; human.
DR CTD; 388662; -.
DR DisGeNET; 388662; -.
DR GeneCards; SLC6A17; -.
DR HGNC; HGNC:31399; SLC6A17.
DR HPA; ENSG00000197106; Group enriched (brain, pituitary gland).
DR MalaCards; SLC6A17; -.
DR MIM; 610299; gene.
DR MIM; 616269; phenotype.
DR neXtProt; NX_Q9H1V8; -.
DR OpenTargets; ENSG00000197106; -.
DR Orphanet; 457212; Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome.
DR PharmGKB; PA134941636; -.
DR VEuPathDB; HostDB:ENSG00000197106; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000156542; -.
DR HOGENOM; CLU_006855_7_1_1; -.
DR InParanoid; Q9H1V8; -.
DR OMA; WSECPIV; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; Q9H1V8; -.
DR TreeFam; TF352709; -.
DR PathwayCommons; Q9H1V8; -.
DR SignaLink; Q9H1V8; -.
DR BioGRID-ORCS; 388662; 16 hits in 1060 CRISPR screens.
DR GenomeRNAi; 388662; -.
DR Pharos; Q9H1V8; Tbio.
DR PRO; PR:Q9H1V8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H1V8; protein.
DR Bgee; ENSG00000197106; Expressed in right frontal lobe and 130 other tissues.
DR Genevisible; Q9H1V8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0031224; C:intrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0032328; P:alanine transport; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0015816; P:glycine transport; ISS:UniProtKB.
DR GO; GO:0015820; P:leucine transport; ISS:UniProtKB.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR GO; GO:0015804; P:neutral amino acid transport; ISS:UniProtKB.
DR GO; GO:0015824; P:proline transport; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002438; Neutral_aa_SLC6.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR00176; NANEUSMPORT.
DR PRINTS; PR01206; ORPHTRNSPORT.
DR SUPFAM; SSF161070; SSF161070; 1.
DR PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasmic vesicle; Disease variant; Glycoprotein;
KW Intellectual disability; Membrane; Neurotransmitter transport;
KW Phosphoprotein; Reference proteome; Symport; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..727
FT /note="Sodium-dependent neutral amino acid transporter
FT SLC6A17"
FT /id="PRO_0000214803"
FT TOPO_DOM 1..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..222
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 254..274
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..300
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322..334
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 335..355
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 356..460
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 482..490
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 491..511
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 512..527
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 528..548
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 549..573
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 574..594
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 595..617
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 618..638
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 639..727
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 680..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 693..712
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT MOD_RES 377
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BJI1"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31662"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 57
FT /note="A -> T (in dbSNP:rs12737742)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_061814"
FT VARIANT 162
FT /note="G -> R (in MRT48; dbSNP:rs775085213)"
FT /evidence="ECO:0000269|PubMed:25704603"
FT /id="VAR_073371"
FT VARIANT 633
FT /note="P -> R (in MRT48; dbSNP:rs375380880)"
FT /evidence="ECO:0000269|PubMed:25704603"
FT /id="VAR_073372"
SQ SEQUENCE 727 AA; 81001 MW; 454FAE5ACF53D9EB CRC64;
MPKNSKVTQR EHSSEHVTES VADLLALEEP VDYKQSVLNV AGEAGGKQKA VEEELDAEDR
PAWNSKLQYI LAQIGFSVGL GNIWRFPYLC QKNGGGAYLV PYLVLLIIIG IPLFFLELAV
GQRIRRGSIG VWHYICPRLG GIGFSSCIVC LFVGLYYNVI IGWSIFYFFK SFQYPLPWSE
CPVVRNGSVA VVEAECEKSS ATTYFWYREA LDISDSISES GGLNWKMTLC LLVAWSIVGM
AVVKGIQSSG KVMYFSSLFP YVVLACFLVR GLLLRGAVDG ILHMFTPKLD KMLDPQVWRE
AATQVFFALG LGFGGVIAFS SYNKQDNNCH FDAALVSFIN FFTSVLATLV VFAVLGFKAN
IMNEKCVVEN AEKILGYLNT NVLSRDLIPP HVNFSHLTTK DYMEMYNVIM TVKEDQFSAL
GLDPCLLEDE LDKSVQGTGL AFIAFTEAMT HFPASPFWSV MFFLMLINLG LGSMIGTMAG
ITTPIIDTFK VPKEMFTVGC CVFAFLVGLL FVQRSGNYFV TMFDDYSATL PLTLIVILEN
IAVAWIYGTK KFMQELTEML GFRPYRFYFY MWKFVSPLCM AVLTTASIIQ LGVTPPGYSA
WIKEEAAERY LYFPNWAMAL LITLIVVATL PIPVVFVLRH FHLLSDGSNT LSVSYKKGRM
MKDISNLEEN DETRFILSKV PSEAPSPMPT HRSYLGPGST SPLETSGNPN GRYGSGYLLA
STPESEL
