S45A1_HUMAN
ID S45A1_HUMAN Reviewed; 782 AA.
AC Q9Y2W3; A0A0A0MT80; Q5VY46; Q5VY49;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 5.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Proton-associated sugar transporter A {ECO:0000305};
DE Short=PAST-A;
DE AltName: Full=Deleted in neuroblastoma 5 protein;
DE Short=DNb-5;
DE AltName: Full=Solute carrier family 45 member 1;
GN Name=SLC45A1 {ECO:0000312|HGNC:HGNC:17939}; Synonyms=DNB5;
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=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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 276-782, AND TISSUE SPECIFICITY.
RX PubMed=10729226; DOI=10.1006/geno.1999.6097;
RA Amler L.C., Bauer A., Corvi R., Dihlmann S., Praml C., Cavenee W.K.,
RA Schwab M., Hampton G.M.;
RT "Identification and characterization of novel genes located at the
RT t(1;15)(p36.2;q24) translocation breakpoint in the neuroblastoma cell line
RT NGP.";
RL Genomics 64:195-202(2000).
RN [4]
RP INVOLVEMENT IN IDDNPF, VARIANTS IDDNPF TRP-210 AND VAL-244,
RP CHARACTERIZATION OF VARIANTS IDDNPF THR-90; TRP-210 AND VAL-244, FUNCTION,
RP SUBCELLULAR LOCATION, AND TRANSPORTER ACTIVITY.
RX PubMed=28434495; DOI=10.1016/j.ajhg.2017.03.009;
RA Srour M., Shimokawa N., Hamdan F.F., Nassif C., Poulin C., Al Gazali L.,
RA Rosenfeld J.A., Koibuchi N., Rouleau G.A., Al Shamsi A., Michaud J.L.;
RT "Dysfunction of the cerebral glucose transporter SLC45A1 in individuals
RT with intellectual disability and epilepsy.";
RL Am. J. Hum. Genet. 100:824-830(2017).
RN [5]
RP VARIANT THR-90.
RX PubMed=27431290; DOI=10.1038/mp.2016.113;
RA Anazi S., Maddirevula S., Faqeih E., Alsedairy H., Alzahrani F.,
RA Shamseldin H.E., Patel N., Hashem M., Ibrahim N., Abdulwahab F., Ewida N.,
RA Alsaif H.S., Al Sharif H., Alamoudi W., Kentab A., Bashiri F.A.,
RA Alnaser M., AlWadei A.H., Alfadhel M., Eyaid W., Hashem A., Al Asmari A.,
RA Saleh M.M., AlSaman A., Alhasan K.A., Alsughayir M., Al Shammari M.,
RA Mahmoud A., Al-Hassnan Z.N., Al-Husain M., Osama Khalil R.,
RA Abd El Meguid N., Masri A., Ali R., Ben-Omran T., El Fishway P.,
RA Hashish A., Ercan Sencicek A., State M., Alazami A.M., Salih M.A.,
RA Altassan N., Arold S.T., Abouelhoda M., Wakil S.M., Monies D., Shaheen R.,
RA Alkuraya F.S.;
RT "Clinical genomics expands the morbid genome of intellectual disability and
RT offers a high diagnostic yield.";
RL Mol. Psychiatry 22:615-624(2017).
CC -!- FUNCTION: Proton-associated glucose transporter in the brain.
CC {ECO:0000269|PubMed:28434495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-galactose(in) + H(+)(in) = D-galactose(out) + H(+)(out);
CC Xref=Rhea:RHEA:29019, ChEBI:CHEBI:4139, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000250|UniProtKB:Q8K4S3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose(out) + H(+)(out) = D-glucose(in) + H(+)(in);
CC Xref=Rhea:RHEA:69556, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378;
CC Evidence={ECO:0000269|PubMed:28434495};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:28434495}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in adult heart, brain, muscle and kidney,
CC with very strong expression in brain. Also expressed in fetal brain,
CC kidney and lung. {ECO:0000269|PubMed:10729226}.
CC -!- DISEASE: Intellectual developmental disorder with neuropsychiatric
CC features (IDDNPF) [MIM:617532]: An autosomal recessive disorder
CC characterized by moderate to severe intellectual disability, epilepsy,
CC and variable neuropsychiatric features, such as anxiety, obsessive-
CC compulsive behavior, and autistic features. Mild facial dysmorphism may
CC also be present. {ECO:0000269|PubMed:28434495}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycoside-pentoside-hexuronide (GPH) cation
CC symporter transporter (TC 2.A.2) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD27583.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AL356072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71597.1; -; Genomic_DNA.
DR EMBL; AF118274; AAD27583.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001073866.2; NM_001080397.2.
DR AlphaFoldDB; Q9Y2W3; -.
DR IntAct; Q9Y2W3; 2.
DR STRING; 9606.ENSP00000289877; -.
DR TCDB; 2.A.2.4.10; the glycoside-pentoside-hexuronide (gph):cation symporter family.
DR iPTMnet; Q9Y2W3; -.
DR PhosphoSitePlus; Q9Y2W3; -.
DR BioMuta; SLC45A1; -.
DR DMDM; 311033543; -.
DR MassIVE; Q9Y2W3; -.
DR PaxDb; Q9Y2W3; -.
DR PeptideAtlas; Q9Y2W3; -.
DR PRIDE; Q9Y2W3; -.
DR ProteomicsDB; 85916; -.
DR Antibodypedia; 57179; 10 antibodies from 4 providers.
DR DNASU; 50651; -.
DR Ensembl; ENST00000471889.7; ENSP00000418096.3; ENSG00000162426.16.
DR GeneID; 50651; -.
DR KEGG; hsa:50651; -.
DR UCSC; uc001apb.3; human.
DR UCSC; uc057byt.1; human.
DR CTD; 50651; -.
DR DisGeNET; 50651; -.
DR GeneCards; SLC45A1; -.
DR HGNC; HGNC:17939; SLC45A1.
DR HPA; ENSG00000162426; Low tissue specificity.
DR MalaCards; SLC45A1; -.
DR MIM; 605763; gene.
DR MIM; 617532; phenotype.
DR neXtProt; NX_Q9Y2W3; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR VEuPathDB; HostDB:ENSG00000162426; -.
DR eggNOG; KOG0637; Eukaryota.
DR HOGENOM; CLU_015081_1_0_1; -.
DR InParanoid; Q9Y2W3; -.
DR OrthoDB; 1230185at2759; -.
DR PhylomeDB; Q9Y2W3; -.
DR TreeFam; TF325412; -.
DR PathwayCommons; Q9Y2W3; -.
DR SignaLink; Q9Y2W3; -.
DR BioGRID-ORCS; 50651; 13 hits in 1062 CRISPR screens.
DR ChiTaRS; SLC45A1; human.
DR GenomeRNAi; 50651; -.
DR Pharos; Q9Y2W3; Tdark.
DR PRO; PR:Q9Y2W3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y2W3; protein.
DR Bgee; ENSG00000162426; Expressed in prefrontal cortex and 104 other tissues.
DR ExpressionAtlas; Q9Y2W3; baseline and differential.
DR Genevisible; Q9Y2W3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0015517; F:galactose:proton symporter activity; ISS:UniProtKB.
DR GO; GO:0005356; F:glucose:proton symporter activity; IMP:UniProtKB.
DR GO; GO:0008506; F:sucrose:proton symporter activity; IBA:GO_Central.
DR GO; GO:0015757; P:galactose transmembrane transport; ISS:UniProtKB.
DR GO; GO:1904659; P:glucose transmembrane transport; IMP:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
PE 1: Evidence at protein level;
KW Disease variant; Epilepsy; Intellectual disability; Membrane;
KW Phosphoprotein; Reference proteome; Sugar transport; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..782
FT /note="Proton-associated sugar transporter A"
FT /id="PRO_0000122514"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 607..627
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 634..654
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 661..681
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 719..739
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 742..762
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..355
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 531
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8BIV7"
FT VARIANT 90
FT /note="I -> T (in IDDNPF; no effect on protein abundance;
FT no effect on glucose transport activity;
FT dbSNP:rs141816307)"
FT /evidence="ECO:0000269|PubMed:27431290,
FT ECO:0000269|PubMed:28434495"
FT /id="VAR_079344"
FT VARIANT 210
FT /note="R -> W (in IDDNPF; no effect on protein abundance;
FT decreased glucose transport activity; dbSNP:rs781036625)"
FT /evidence="ECO:0000269|PubMed:28434495"
FT /id="VAR_079345"
FT VARIANT 244
FT /note="A -> V (in IDDNPF; no effect on protein abundance;
FT decreased glucose transport activity; dbSNP:rs150539474)"
FT /evidence="ECO:0000269|PubMed:28434495"
FT /id="VAR_079346"
FT CONFLICT 282
FT /note="V -> L (in Ref. 3; AAD27583)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="L -> F (in Ref. 3; AAD27583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 782 AA; 84541 MW; CC841FDE4159A2DB CRC64;
MLQQPGPRPG RQQPSGDRDA CRLHPQGRPP ALPTMIPAAS STPPGDALFP SVAPQDFWRS
QVTGYSGSVT RHLSHRANNF KRHPKRRKCI RPSPPPPPNT PCPLELVDFG DLHPQRSFRE
LLFNGCILFG IEFSYAMETA YVTPVLLQMG LPDQLYSLVW FISPILGFLL QPLLGAWSDR
CTSRFGRRRP FILVLAIGAL LGLSLLLNGR DIGIALADVT GNHKWGLLLT VCGVVLMDFS
ADSADNPSHA YMMDVCSPAD QDRGLNIHAL LAGLGGGFGY VVGGIHWDKT GFGRALGGQL
RVIYLFTAVT LSVTTVLTLV SIPERPLRPP SEKRAAMKSP SLPLPPSPPV LPEEGPGDSL
PSHTATNFSS PISPPSPLTP KYGSFISRDS SLTGISEFAS SFGTANIDSV LIDCFTGGHD
SYLAIPGSVP RPPISVSFPR APDGFYRQDR GLLEGREGAL TSGCDGDILR VGSLDTSKPR
SSGILKRPQT LAIPDAAGGG GPETSRRRNV TFSQQVANIL LNGVKYESEL TGSSERAEQP
LSVGRLCSTI CNMPKALRTL CVNHFLGWLS FEGMLLFYTD FMGEVVFQGD PKAPHTSEAY
QKYNSGVTMG CWGMCIYAFS AAFYSAILEK LEEFLSVRTL YFIAYLAFGL GTGLATLSRN
LYVVLSLCIT YGILFSTLCT LPYSLLCDYY QSKKFAGSSA DGTRRGMGVD ISLLSCQYFL
AQILVSLVLG PLTSAVGSAN GVMYFSSLVS FLGCLYSSLF VIYEIPPSDA ADEEHRPLLL
NV
