S38A8_HUMAN
ID S38A8_HUMAN Reviewed; 435 AA.
AC A6NNN8;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Putative sodium-coupled neutral amino acid transporter 8;
DE AltName: Full=Solute carrier family 38 member 8;
GN Name=SLC38A8;
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 GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP TISSUE SPECIFICITY, AND VARIANTS FVH2 ARG-34; LYS-233; ASP-236; ALA-282 DEL
RP AND ARG-412.
RX PubMed=24290379; DOI=10.1016/j.ajhg.2013.11.002;
RA Poulter J.A., Al-Araimi M., Conte I., van Genderen M.M., Sheridan E.,
RA Carr I.M., Parry D.A., Shires M., Carrella S., Bradbury J., Khan K.,
RA Lakeman P., Sergouniotis P.I., Webster A.R., Moore A.T., Pal B.,
RA Mohamed M.D., Venkataramana A., Ramprasad V., Shetty R., Saktivel M.,
RA Kumaramanickavel G., Tan A., Mackey D.A., Hewitt A.W., Banfi S., Ali M.,
RA Inglehearn C.F., Toomes C.;
RT "Recessive mutations in SLC38A8 cause foveal hypoplasia and optic nerve
RT misrouting without albinism.";
RL Am. J. Hum. Genet. 93:1143-1150(2013).
RN [3]
RP VARIANT FVH2 SER-32.
RX PubMed=24045842; DOI=10.1038/ejhg.2013.212;
RA Perez Y., Gradstein L., Flusser H., Markus B., Cohen I., Langer Y.,
RA Marcus M., Lifshitz T., Kadir R., Birk O.S.;
RT "Isolated foveal hypoplasia with secondary nystagmus and low vision is
RT associated with a homozygous SLC38A8 mutation.";
RL Eur. J. Hum. Genet. 22:703-706(2014).
CC -!- FUNCTION: Putative sodium-dependent amino acid/proton antiporter.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal and adult brain, and spinal
CC cord. In the brain, it is localized in the cell body and axon of the
CC majority of neuronal cells and in a subset of glial cells. Found
CC throughout the neuronal retina, with higher expression levels in the
CC inner and outer plexiform layers and the photoreceptor layer. Very weak
CC expression is also present in the kidneys, thymus, and testes.
CC {ECO:0000269|PubMed:24290379}.
CC -!- DISEASE: Foveal hypoplasia 2 (FVH2) [MIM:609218]: An isolated form of
CC foveal hypoplasia, a developmental defect of the eye defined as the
CC lack of foveal depression with continuity of all neurosensory retinal
CC layers in the presumed foveal area. Clinical features include absence
CC of foveal pit on optical coherence tomography, absence of foveal
CC hyperpigmentation, absence of foveal avascularity, absence of foveal
CC and macular reflexes, decreased visual acuity, and nystagmus. Optic
CC nerve misrouting and anterior segment dysgenesis are observed in some
CC FVH2 patients. {ECO:0000269|PubMed:24045842,
CC ECO:0000269|PubMed:24290379}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the amino acid/polyamine transporter 2 family.
CC {ECO:0000305}.
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DR EMBL; AC040169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32495.1; -.
DR RefSeq; NP_001073911.1; NM_001080442.2.
DR RefSeq; XP_016878435.1; XM_017022946.1.
DR AlphaFoldDB; A6NNN8; -.
DR SMR; A6NNN8; -.
DR STRING; 9606.ENSP00000299709; -.
DR TCDB; 2.A.18.6.12; the amino acid/auxin permease (aaap) family.
DR iPTMnet; A6NNN8; -.
DR PhosphoSitePlus; A6NNN8; -.
DR BioMuta; SLC38A8; -.
DR PaxDb; A6NNN8; -.
DR PRIDE; A6NNN8; -.
DR Antibodypedia; 67804; 70 antibodies from 14 providers.
DR DNASU; 146167; -.
DR Ensembl; ENST00000299709.8; ENSP00000299709.3; ENSG00000166558.11.
DR GeneID; 146167; -.
DR KEGG; hsa:146167; -.
DR MANE-Select; ENST00000299709.8; ENSP00000299709.3; NM_001080442.3; NP_001073911.1.
DR UCSC; uc002fhg.1; human.
DR CTD; 146167; -.
DR DisGeNET; 146167; -.
DR GeneCards; SLC38A8; -.
DR HGNC; HGNC:32434; SLC38A8.
DR HPA; ENSG00000166558; Tissue enriched (brain).
DR MalaCards; SLC38A8; -.
DR MIM; 609218; phenotype.
DR MIM; 615585; gene.
DR neXtProt; NX_A6NNN8; -.
DR OpenTargets; ENSG00000166558; -.
DR Orphanet; 397618; Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome.
DR PharmGKB; PA162403773; -.
DR VEuPathDB; HostDB:ENSG00000166558; -.
DR eggNOG; KOG1305; Eukaryota.
DR GeneTree; ENSGT00940000157764; -.
DR HOGENOM; CLU_038973_0_0_1; -.
DR InParanoid; A6NNN8; -.
DR OMA; LQCHEAC; -.
DR OrthoDB; 697331at2759; -.
DR PhylomeDB; A6NNN8; -.
DR TreeFam; TF328787; -.
DR PathwayCommons; A6NNN8; -.
DR SignaLink; A6NNN8; -.
DR BioGRID-ORCS; 146167; 12 hits in 1070 CRISPR screens.
DR GenomeRNAi; 146167; -.
DR Pharos; A6NNN8; Tbio.
DR PRO; PR:A6NNN8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; A6NNN8; protein.
DR Bgee; ENSG00000166558; Expressed in amygdala and 58 other tissues.
DR ExpressionAtlas; A6NNN8; baseline and differential.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR013057; AA_transpt_TM.
DR Pfam; PF01490; Aa_trans; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Disease variant; Ion transport; Membrane;
KW Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..435
FT /note="Putative sodium-coupled neutral amino acid
FT transporter 8"
FT /id="PRO_0000319593"
FT TRANSMEM 29..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 32
FT /note="I -> S (in FVH2; dbSNP:rs587777253)"
FT /evidence="ECO:0000269|PubMed:24045842"
FT /id="VAR_071252"
FT VARIANT 34
FT /note="M -> R (in FVH2)"
FT /evidence="ECO:0000269|PubMed:24290379"
FT /id="VAR_071253"
FT VARIANT 220
FT /note="S -> T (in dbSNP:rs11862366)"
FT /id="VAR_048125"
FT VARIANT 233
FT /note="E -> K (in FVH2; dbSNP:rs372929441)"
FT /evidence="ECO:0000269|PubMed:24290379"
FT /id="VAR_071254"
FT VARIANT 236
FT /note="V -> D (in FVH2; dbSNP:rs587777254)"
FT /evidence="ECO:0000269|PubMed:24290379"
FT /id="VAR_071255"
FT VARIANT 282
FT /note="Missing (in FVH2)"
FT /evidence="ECO:0000269|PubMed:24290379"
FT /id="VAR_071256"
FT VARIANT 412
FT /note="G -> R (in FVH2; dbSNP:rs587777256)"
FT /evidence="ECO:0000269|PubMed:24290379"
FT /id="VAR_071257"
SQ SEQUENCE 435 AA; 46731 MW; BFB558790F654F9F CRC64;
MEGQTPGSRG LPEKPHPATA AATLSSMGAV FILMKSALGA GLLNFPWAFS KAGGVVPAFL
VELVSLVFLI SGLVILGYAA AVSGQATYQG VVRGLCGPAI GKLCEACFLL NLLMISVAFL
RVIGDQLEKL CDSLLSGTPP APQPWYADQR FTLPLLSVLV ILPLSAPREI AFQKYTSILG
TLAACYLALV ITVQYYLWPQ GLVRESHPSL SPASWTSVFS VFPTICFGFQ CHEAAVSIYC
SMRKRSLSHW ALVSVLSLLA CCLIYSLTGV YGFLTFGTEV SADVLMSYPG NDMVIIVARV
LFAVSIVTVY PIVLFLGRSV MQDFWRRSCL GGWGPSALAD PSGLWVRMPL TILWVTVTLA
MALFMPDLSE IVSIIGGISS FFIFIFPGLC LICAMGVEPI GPRVKCCLEV WGVVSVLVGT
FIFGQSTAAA VWEMF
