S35A1_HUMAN
ID S35A1_HUMAN Reviewed; 337 AA.
AC P78382; Q5W1L8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=CMP-sialic acid transporter;
DE Short=CMP-SA-Tr;
DE Short=CMP-Sia-Tr;
DE AltName: Full=Solute carrier family 35 member A1;
GN Name=SLC35A1;
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).
RC TISSUE=Liver;
RX PubMed=9010752; DOI=10.1093/oxfordjournals.jbchem.a021523;
RA Ishida N., Miura N., Yoshioka S., Kawakita M.;
RT "Molecular cloning and characterization of a novel isoform of the human
RT UDP-galactose transporter, and of related complementary DNAs belonging to
RT the nucleotide-sugar transporter gene family.";
RL J. Biochem. 120:1074-1078(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INVOLVEMENT IN CDG2F, AND
RP TRANSPORTER ACTIVITY.
RX PubMed=15576474; DOI=10.1182/blood-2004-09-3509;
RA Martinez-Duncker I., Dupre T., Piller V., Piller F., Candelier J.-J.,
RA Trichet C., Tchernia G., Oriol R., Mollicone R.;
RT "Genetic complementation reveals a novel human congenital disorder of
RT glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid
RT transporter.";
RL Blood 105:2671-2676(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP SUBUNIT.
RX PubMed=30985278; DOI=10.7554/elife.45221;
RA Ahuja S., Whorton M.R.;
RT "Structural basis for mammalian nucleotide sugar transport.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Transports CMP-sialic acid from the cytosol into Golgi
CC vesicles where glycosyltransferases function (PubMed:15576474).
CC Efficient CMP-sialic acid uptake depends on the presence of free CMP
CC inside the vesicles, suggesting the proteins functions as an
CC antiporter. Binds both CMP-sialic acid and free CMP, but has higher
CC affinity for free CMP (By similarity). Also mediates the transport of
CC CDP-ribitol (By similarity). {ECO:0000250|UniProtKB:Q61420,
CC ECO:0000269|PubMed:15576474}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP(out) + CMP-N-acetyl-beta-neuraminate(in) = CMP(in) + CMP-
CC N-acetyl-beta-neuraminate(out); Xref=Rhea:RHEA:67724,
CC ChEBI:CHEBI:57812, ChEBI:CHEBI:60377;
CC Evidence={ECO:0000269|PubMed:15576474};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CDP(out) + CDP-L-ribitol(in) = CDP(in) + CDP-L-ribitol(out);
CC Xref=Rhea:RHEA:71579, ChEBI:CHEBI:57608, ChEBI:CHEBI:58069;
CC Evidence={ECO:0000250|UniProtKB:Q61420};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:30985278}.
CC -!- INTERACTION:
CC P78382; Q13520: AQP6; NbExp=3; IntAct=EBI-12870360, EBI-13059134;
CC P78382; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-12870360, EBI-11343438;
CC P78382; P07307-3: ASGR2; NbExp=3; IntAct=EBI-12870360, EBI-12808270;
CC P78382; Q8WWH4: ASZ1; NbExp=3; IntAct=EBI-12870360, EBI-12239061;
CC P78382; Q9BXK5: BCL2L13; NbExp=3; IntAct=EBI-12870360, EBI-747430;
CC P78382; P19397: CD53; NbExp=3; IntAct=EBI-12870360, EBI-6657396;
CC P78382; Q9HA82: CERS4; NbExp=3; IntAct=EBI-12870360, EBI-2622997;
CC P78382; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-12870360, EBI-18013275;
CC P78382; O00559: EBAG9; NbExp=3; IntAct=EBI-12870360, EBI-8787095;
CC P78382; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-12870360, EBI-781551;
CC P78382; Q9Y624: F11R; NbExp=3; IntAct=EBI-12870360, EBI-742600;
CC P78382; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-12870360, EBI-18304435;
CC P78382; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-12870360, EBI-12142257;
CC P78382; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-12870360, EBI-12175685;
CC P78382; Q8TED1: GPX8; NbExp=3; IntAct=EBI-12870360, EBI-11721746;
CC P78382; Q8N743: KIR3DL3; NbExp=3; IntAct=EBI-12870360, EBI-17272405;
CC P78382; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12870360, EBI-2820517;
CC P78382; Q8NI22: MCFD2; NbExp=3; IntAct=EBI-12870360, EBI-2689785;
CC P78382; O14880: MGST3; NbExp=3; IntAct=EBI-12870360, EBI-724754;
CC P78382; Q9Y676: MRPS18B; NbExp=3; IntAct=EBI-12870360, EBI-750085;
CC P78382; Q96FE7: PIK3IP1; NbExp=3; IntAct=EBI-12870360, EBI-10285708;
CC P78382; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-12870360, EBI-10485931;
CC P78382; Q8NC24: RELL2; NbExp=3; IntAct=EBI-12870360, EBI-10269209;
CC P78382; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-12870360, EBI-3920694;
CC P78382; A0A0S2Z4U3: SDC3; NbExp=3; IntAct=EBI-12870360, EBI-10204280;
CC P78382; P43005: SLC1A1; NbExp=3; IntAct=EBI-12870360, EBI-745376;
CC P78382; O95436-2: SLC34A2; NbExp=3; IntAct=EBI-12870360, EBI-12811757;
CC P78382; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-12870360, EBI-17280858;
CC P78382; Q8N9I0: SYT2; NbExp=3; IntAct=EBI-12870360, EBI-8032987;
CC P78382; P57738: TCTA; NbExp=3; IntAct=EBI-12870360, EBI-6447595;
CC P78382; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-12870360, EBI-7238458;
CC P78382; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-12870360, EBI-12345267;
CC P78382; Q9Y320: TMX2; NbExp=3; IntAct=EBI-12870360, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q61420}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q61420}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78382-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78382-2; Sequence=VSP_042916;
CC -!- DISEASE: Congenital disorder of glycosylation 2F (CDG2F) [MIM:603585]:
CC CDGs are a family of severe inherited diseases caused by a defect in
CC protein N-glycosylation. They are characterized by under-glycosylated
CC serum proteins. These multisystem disorders present with a wide variety
CC of clinical features, such as disorders of the nervous system
CC development, psychomotor retardation, dysmorphic features, hypotonia,
CC coagulation disorders, and immunodeficiency. The broad spectrum of
CC features reflects the critical role of N-glycoproteins during embryonic
CC development, differentiation, and maintenance of cell functions.
CC {ECO:0000269|PubMed:15576474}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nucleotide-sugar transporter family. SLC35A
CC subfamily. {ECO:0000305}.
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DR EMBL; D87969; BAA13522.1; -; mRNA.
DR EMBL; AJ851888; CAH65468.1; -; mRNA.
DR EMBL; AL049697; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017807; AAH17807.1; -; mRNA.
DR CCDS; CCDS5010.1; -. [P78382-1]
DR CCDS; CCDS55043.1; -. [P78382-2]
DR PIR; JC5023; JC5023.
DR RefSeq; NP_001161870.1; NM_001168398.1. [P78382-2]
DR RefSeq; NP_006407.1; NM_006416.4. [P78382-1]
DR AlphaFoldDB; P78382; -.
DR SMR; P78382; -.
DR BioGRID; 115810; 61.
DR IntAct; P78382; 37.
DR MINT; P78382; -.
DR STRING; 9606.ENSP00000358565; -.
DR TCDB; 2.A.7.12.11; the drug/metabolite transporter (dmt) superfamily.
DR iPTMnet; P78382; -.
DR PhosphoSitePlus; P78382; -.
DR BioMuta; SLC35A1; -.
DR DMDM; 2499226; -.
DR EPD; P78382; -.
DR jPOST; P78382; -.
DR MassIVE; P78382; -.
DR MaxQB; P78382; -.
DR PaxDb; P78382; -.
DR PeptideAtlas; P78382; -.
DR PRIDE; P78382; -.
DR ProteomicsDB; 57606; -. [P78382-1]
DR ProteomicsDB; 57607; -. [P78382-2]
DR Antibodypedia; 46448; 25 antibodies from 12 providers.
DR DNASU; 10559; -.
DR Ensembl; ENST00000369552.9; ENSP00000358565.4; ENSG00000164414.19. [P78382-1]
DR Ensembl; ENST00000369556.7; ENSP00000358569.3; ENSG00000164414.19. [P78382-2]
DR GeneID; 10559; -.
DR KEGG; hsa:10559; -.
DR MANE-Select; ENST00000369552.9; ENSP00000358565.4; NM_006416.5; NP_006407.1.
DR UCSC; uc010kbx.4; human. [P78382-1]
DR CTD; 10559; -.
DR DisGeNET; 10559; -.
DR GeneCards; SLC35A1; -.
DR HGNC; HGNC:11021; SLC35A1.
DR HPA; ENSG00000164414; Low tissue specificity.
DR MalaCards; SLC35A1; -.
DR MIM; 603585; phenotype.
DR MIM; 605634; gene.
DR neXtProt; NX_P78382; -.
DR OpenTargets; ENSG00000164414; -.
DR Orphanet; 238459; SLC35A1-CDG.
DR PharmGKB; PA35889; -.
DR VEuPathDB; HostDB:ENSG00000164414; -.
DR eggNOG; KOG2234; Eukaryota.
DR GeneTree; ENSGT00950000182827; -.
DR HOGENOM; CLU_024645_1_0_1; -.
DR InParanoid; P78382; -.
DR OMA; WKLKSIV; -.
DR OrthoDB; 703674at2759; -.
DR PhylomeDB; P78382; -.
DR TreeFam; TF315345; -.
DR PathwayCommons; P78382; -.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR Reactome; R-HSA-5619037; Defective SLC35A1 causes congenital disorder of glycosylation 2F (CDG2F).
DR Reactome; R-HSA-5663020; Defective SLC35A1 causes congenital disorder of glycosylation 2F (CDG2F).
DR Reactome; R-HSA-727802; Transport of nucleotide sugars.
DR SignaLink; P78382; -.
DR SIGNOR; P78382; -.
DR BioGRID-ORCS; 10559; 79 hits in 1090 CRISPR screens.
DR ChiTaRS; SLC35A1; human.
DR GenomeRNAi; 10559; -.
DR Pharos; P78382; Tbio.
DR PRO; PR:P78382; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P78382; protein.
DR Bgee; ENSG00000164414; Expressed in monocyte and 98 other tissues.
DR ExpressionAtlas; P78382; baseline and differential.
DR Genevisible; P78382; 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:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0015297; F:antiporter activity; ISS:UniProtKB.
DR GO; GO:0005456; F:CMP-N-acetylneuraminate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005459; F:UDP-galactose transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0015782; P:CMP-N-acetylneuraminate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
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; Congenital disorder of glycosylation;
KW Golgi apparatus; Membrane; Reference proteome; Sugar transport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..337
FT /note="CMP-sialic acid transporter"
FT /id="PRO_0000213351"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 31..45
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 46..64
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 65..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 109..114
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 136..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 142..160
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 161..175
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 197..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 210..228
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 229..243
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 244..262
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 263..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 270..288
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 289..296
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 297..315
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT TOPO_DOM 316..337
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 316..337
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 55
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 101..102
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 117..124
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 188
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 210..214
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT BINDING 272
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000250|UniProtKB:Q61420"
FT VAR_SEQ 192..251
FT /note="GVYFEKVLKSSDTSLWVRNIQMYLSGIIVTLAGVYLSDGAEIKEKGFFYGYT
FT YYVWFVIF -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15576474"
FT /id="VSP_042916"
SQ SEQUENCE 337 AA; 36779 MW; 508DD77F5EEBB5A7 CRC64;
MAAPRDNVTL LFKLYCLAVM TLMAAVYTIA LRYTRTSDKE LYFSTTAVCI TEVIKLLLSV
GILAKETGSL GRFKASLREN VLGSPKELLK LSVPSLVYAV QNNMAFLALS NLDAAVYQVT
YQLKIPCTAL CTVLMLNRTL SKLQWVSVFM LCAGVTLVQW KPAQATKVVV EQNPLLGFGA
IAIAVLCSGF AGVYFEKVLK SSDTSLWVRN IQMYLSGIIV TLAGVYLSDG AEIKEKGFFY
GYTYYVWFVI FLASVGGLYT SVVVKYTDNI MKGFSAAAAI VLSTIASVML FGLQITLTFA
LGTLLVCVSI YLYGLPRQDT TSIQQGETAS KERVIGV
