S35A3_HUMAN
ID S35A3_HUMAN Reviewed; 325 AA.
AC Q9Y2D2; A8K3F8; D3DT54; Q68CR2; Q9BSB7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=UDP-N-acetylglucosamine transporter;
DE AltName: Full=Golgi UDP-GlcNAc transporter;
DE AltName: Full=Solute carrier family 35 member A3;
GN Name=SLC35A3;
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 [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10393322; DOI=10.1093/oxfordjournals.jbchem.a022437;
RA Ishida N., Yoshioka S., Chiba Y., Takeuchi M., Kawakita M.;
RT "Molecular cloning and functional expression of the human Golgi UDP-N-
RT acetylglucosamine transporter.";
RL J. Biochem. 126:68-77(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
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 [7]
RP INTERACTION WITH SLC35A2.
RX PubMed=23089177; DOI=10.1016/j.febslet.2012.10.016;
RA Maszczak-Seneczko D., Sosicka P., Majkowski M., Olczak T., Olczak M.;
RT "UDP-N-acetylglucosamine transporter and UDP-galactose transporter form
RT heterologous complexes in the Golgi membrane.";
RL FEBS Lett. 586:4082-4087(2012).
RN [8]
RP INTERACTION WITH SLC35A2, IDENTIFICATION IN A COMPLEX WITH SLC35A2 AND
RP SLC35A4, AND SUBCELLULAR LOCATION.
RX PubMed=28167211; DOI=10.1016/j.bbamcr.2017.02.002;
RA Sosicka P., Maszczak-Seneczko D., Bazan B., Shauchuk Y., Kaczmarek B.,
RA Olczak M.;
RT "An insight into the orphan nucleotide sugar transporter SLC35A4.";
RL Biochim. Biophys. Acta 1864:825-838(2017).
RN [9]
RP INVOLVEMENT IN AMRS.
RX PubMed=24031089; DOI=10.1136/jmedgenet-2013-101753;
RA Edvardson S., Ashikov A., Jalas C., Sturiale L., Shaag A., Fedick A.,
RA Treff N.R., Garozzo D., Gerardy-Schahn R., Elpeleg O.;
RT "Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and
RT arthrogryposis.";
RL J. Med. Genet. 50:733-739(2013).
CC -!- FUNCTION: Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc)
CC transporter in the Golgi apparatus. May supply UDP-GlcNAc as substrate
CC for Golgi-resident glycosyltransferases that generate branching of
CC diantennary oligosaccharides. {ECO:0000269|PubMed:10393322}.
CC -!- SUBUNIT: Interacts with SLC35A2; the interaction is reduced in the
CC presence of SLC35A4 (PubMed:23089177, PubMed:28167211). Found in a
CC complex with SLC35A2 and SLC35A4 (PubMed:28167211).
CC {ECO:0000269|PubMed:23089177, ECO:0000269|PubMed:28167211}.
CC -!- INTERACTION:
CC Q9Y2D2; P78381-1: SLC35A2; NbExp=3; IntAct=EBI-3917581, EBI-8101118;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:10393322, ECO:0000269|PubMed:28167211}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y2D2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2D2-2; Sequence=VSP_012786;
CC Name=3;
CC IsoId=Q9Y2D2-3; Sequence=VSP_054232, VSP_054233;
CC -!- DISEASE: Arthrogryposis, intellectual disability, and seizures (AMRS)
CC [MIM:615553]: A disease characterized by arthrogryposis, intellectual
CC disability, autism spectrum disorder, and epilepsy. Additional features
CC include limb malformations, distal joint involvement, microcephaly,
CC retromicrognathia, and general muscle hypotonia.
CC {ECO:0000269|PubMed:24031089}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. In Golgi vesicles
CC isolated from patient fibroblasts the transport of the respective
CC nucleotide sugar is significantly reduced causing a massive decrease in
CC the content of cell surface expressed highly branched N-glycans and a
CC concomitant sharp increase of lower branched glycoforms.
CC -!- SIMILARITY: Belongs to the nucleotide-sugar transporter family. SLC35A
CC subfamily. {ECO:0000305}.
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DR EMBL; AB021981; BAA77841.1; -; mRNA.
DR EMBL; AK290573; BAF83262.1; -; mRNA.
DR EMBL; CR749816; CAH18676.1; -; mRNA.
DR EMBL; AC118553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW72977.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72978.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72979.1; -; Genomic_DNA.
DR EMBL; BC005136; AAH05136.1; -; mRNA.
DR CCDS; CCDS60204.1; -. [Q9Y2D2-2]
DR CCDS; CCDS60205.1; -. [Q9Y2D2-3]
DR CCDS; CCDS762.1; -. [Q9Y2D2-1]
DR RefSeq; NP_001258613.1; NM_001271684.1. [Q9Y2D2-3]
DR RefSeq; NP_001258614.1; NM_001271685.1. [Q9Y2D2-2]
DR RefSeq; NP_036375.1; NM_012243.2. [Q9Y2D2-1]
DR RefSeq; XP_005270748.1; XM_005270691.4. [Q9Y2D2-1]
DR RefSeq; XP_011539438.1; XM_011541136.2. [Q9Y2D2-1]
DR AlphaFoldDB; Q9Y2D2; -.
DR SMR; Q9Y2D2; -.
DR BioGRID; 117010; 11.
DR CORUM; Q9Y2D2; -.
DR IntAct; Q9Y2D2; 5.
DR MINT; Q9Y2D2; -.
DR STRING; 9606.ENSP00000359172; -.
DR TCDB; 2.A.7.12.7; the drug/metabolite transporter (dmt) superfamily.
DR iPTMnet; Q9Y2D2; -.
DR PhosphoSitePlus; Q9Y2D2; -.
DR BioMuta; SLC35A3; -.
DR DMDM; 9087207; -.
DR EPD; Q9Y2D2; -.
DR jPOST; Q9Y2D2; -.
DR MassIVE; Q9Y2D2; -.
DR MaxQB; Q9Y2D2; -.
DR PaxDb; Q9Y2D2; -.
DR PeptideAtlas; Q9Y2D2; -.
DR PRIDE; Q9Y2D2; -.
DR ProteomicsDB; 78874; -.
DR ProteomicsDB; 85734; -. [Q9Y2D2-1]
DR ProteomicsDB; 85735; -. [Q9Y2D2-2]
DR TopDownProteomics; Q9Y2D2-1; -. [Q9Y2D2-1]
DR Antibodypedia; 19975; 58 antibodies from 19 providers.
DR DNASU; 23443; -.
DR Ensembl; ENST00000370153.6; ENSP00000359172.1; ENSG00000117620.15. [Q9Y2D2-2]
DR Ensembl; ENST00000427993.7; ENSP00000414947.2; ENSG00000117620.15. [Q9Y2D2-1]
DR Ensembl; ENST00000465289.6; ENSP00000418527.2; ENSG00000117620.15. [Q9Y2D2-1]
DR Ensembl; ENST00000533028.8; ENSP00000433849.1; ENSG00000117620.15. [Q9Y2D2-1]
DR Ensembl; ENST00000638336.1; ENSP00000491145.1; ENSG00000117620.15. [Q9Y2D2-3]
DR GeneID; 23443; -.
DR KEGG; hsa:23443; -.
DR MANE-Select; ENST00000533028.8; ENSP00000433849.1; NM_012243.3; NP_036375.1.
DR UCSC; uc001dsp.3; human. [Q9Y2D2-1]
DR CTD; 23443; -.
DR DisGeNET; 23443; -.
DR GeneCards; SLC35A3; -.
DR HGNC; HGNC:11023; SLC35A3.
DR HPA; ENSG00000117620; Low tissue specificity.
DR MalaCards; SLC35A3; -.
DR MIM; 605632; gene.
DR MIM; 615553; phenotype.
DR neXtProt; NX_Q9Y2D2; -.
DR OpenTargets; ENSG00000117620; -.
DR Orphanet; 370943; Autism spectrum disorder-epilepsy-arthrogryposis syndrome.
DR PharmGKB; PA35891; -.
DR VEuPathDB; HostDB:ENSG00000117620; -.
DR eggNOG; KOG2234; Eukaryota.
DR GeneTree; ENSGT00950000182827; -.
DR HOGENOM; CLU_024645_1_0_1; -.
DR InParanoid; Q9Y2D2; -.
DR OMA; AFFSVTM; -.
DR OrthoDB; 703674at2759; -.
DR PhylomeDB; Q9Y2D2; -.
DR TreeFam; TF315345; -.
DR PathwayCommons; Q9Y2D2; -.
DR Reactome; R-HSA-5619083; Defective SLC35A3 causes arthrogryposis, mental retardation, and seizures (AMRS).
DR Reactome; R-HSA-727802; Transport of nucleotide sugars.
DR SignaLink; Q9Y2D2; -.
DR BioGRID-ORCS; 23443; 31 hits in 1069 CRISPR screens.
DR ChiTaRS; SLC35A3; human.
DR GenomeRNAi; 23443; -.
DR Pharos; Q9Y2D2; Tbio.
DR PRO; PR:Q9Y2D2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y2D2; protein.
DR Bgee; ENSG00000117620; Expressed in mucosa of sigmoid colon and 199 other tissues.
DR ExpressionAtlas; Q9Y2D2; baseline and differential.
DR Genevisible; Q9Y2D2; HS.
DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0005459; F:UDP-galactose transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005462; F:UDP-N-acetylglucosamine transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0006047; P:UDP-N-acetylglucosamine metabolic process; TAS:ProtInc.
DR GO; GO:1990569; P:UDP-N-acetylglucosamine transmembrane transport; IMP:UniProtKB.
DR InterPro; IPR007271; Nuc_sug_transpt.
DR PANTHER; PTHR10231; PTHR10231; 1.
DR Pfam; PF04142; Nuc_sug_transp; 1.
DR PIRSF; PIRSF005799; UDP-gal_transpt; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autism spectrum disorder; Epilepsy; Golgi apparatus;
KW Intellectual disability; Membrane; Reference proteome; Sugar transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..325
FT /note="UDP-N-acetylglucosamine transporter"
FT /id="PRO_0000213357"
FT TRANSMEM 8..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..311
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MSSRSVLSPVVGTDAPDQHLELKKPQELKEMERLPLANEDKTM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_012786"
FT VAR_SEQ 212..220
FT /note="GFFGSIFGL -> VSFSLEPSL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054232"
FT VAR_SEQ 221..325
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054233"
SQ SEQUENCE 325 AA; 35985 MW; 69DFD944E37206C8 CRC64;
MFANLKYVSL GILVFQTTSL VLTMRYSRTL KEEGPRYLSS TAVVVAELLK IMACILLVYK
DSKCSLRALN RVLHDEILNK PMETLKLAIP SGIYTLQNNL LYVALSNLDA ATYQVTYQLK
ILTTALFSVS MLSKKLGVYQ WLSLVILMTG VAFVQWPSDS QLDSKELSAG SQFVGLMAVL
TACFSSGFAG VYFEKILKET KQSVWIRNIQ LGFFGSIFGL MGVYIYDGEL VSKNGFFQGY
NRLTWIVVVL QALGGLVIAA VIKYADNILK GFATSLSIIL STLISYFWLQ DFVPTSVFFL
GAILVITATF LYGYDPKPAG NPTKA
