ID   S35A1_MOUSE             Reviewed;         336 AA.
AC   Q61420; A2AT44;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   24-JAN-2024, entry version 154.
DE   RecName: Full=CMP-sialic acid transporter {ECO:0000303|PubMed:8755516};
DE            Short=CMP-SA-Tr {ECO:0000303|PubMed:8755516};
DE            Short=CMP-Sia-Tr;
DE            Short=CST {ECO:0000303|PubMed:30985278};
DE   AltName: Full=Solute carrier family 35 member A1;
GN   Name=Slc35a1 {ECO:0000312|MGI:MGI:1345622};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND TRANSPORTER ACTIVITY.
RX   PubMed=8755516; DOI=10.1073/pnas.93.15.7572;
RA   Eckhardt M., Muehlenhoff M., Bethe A., Gerardy-Schahn R.;
RT   "Expression cloning of the Golgi CMP-sialic acid transporter.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:7572-7576(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Salivary gland;
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   FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, AND TRANSPORTER
RP   ACTIVITY.
RX   PubMed=10085119; DOI=10.1074/jbc.274.13.8779;
RA   Eckhardt M., Gotza B., Gerardy-Schahn R.;
RT   "Membrane topology of the mammalian CMP-sialic acid transporter.";
RL   J. Biol. Chem. 274:8779-8787(1999).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney, and Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF MET-20; ALA-24; TYR-27;
RP   ALA-105; GLN-118; TYR-121; GLN-122; ALA-184; ALA-253; GLY-256 AND THR-260.
RX   PubMed=34015330; DOI=10.1016/j.jbc.2021.100789;
RA   Ury B., Potelle S., Caligiore F., Whorton M.R., Bommer G.T.;
RT   "The promiscuous binding pocket of SLC35A1 ensures redundant transport of
RT   CDP-ribitol to the Golgi.";
RL   J. Biol. Chem. 296:100789-100789(2021).
RN   [7]
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-336.
RX   PubMed=15932921; DOI=10.1093/glycob/cwi085;
RA   Kabuss R., Ashikov A., Oelmann S., Gerardy-Schahn R., Bakker H.;
RT   "Endoplasmic reticulum retention of the large splice variant of the UDP-
RT   galactose transporter is caused by a dilysine motif.";
RL   Glycobiology 15:905-911(2005).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 1-322 IN COMPLEX WITH CMP-SIALIC
RP   ACID, FUNCTION, TOPOLOGY, MUTAGENESIS OF 322-SER--VAL-336, TRANSPORTER
RP   ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 the Golgi
CC       apparatus, functioning as an antiporter that exchanges CMP-sialic acid
CC       for CMP (PubMed:8755516, PubMed:10085119, PubMed:30985278,
CC       PubMed:34015330). Binds both CMP-sialic acid and free CMP, but has
CC       higher affinity for free CMP (PubMed:30985278). Also able to exchange
CC       CMP-sialic acid for AMP and UMP (By similarity). Also mediates the
CC       transport of CDP-ribitol (PubMed:34015330) (By similarity).
CC       {ECO:0000250|UniProtKB:P78382, ECO:0000269|PubMed:10085119,
CC       ECO:0000269|PubMed:30985278, ECO:0000269|PubMed:34015330,
CC       ECO:0000269|PubMed:8755516}.
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:10085119, ECO:0000269|PubMed:30985278,
CC         ECO:0000269|PubMed:34015330, ECO:0000269|PubMed:8755516};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AMP(out) + CMP-N-acetyl-beta-neuraminate(in) = AMP(in) + CMP-
CC         N-acetyl-beta-neuraminate(out); Xref=Rhea:RHEA:74639,
CC         ChEBI:CHEBI:57812, ChEBI:CHEBI:456215;
CC         Evidence={ECO:0000250|UniProtKB:P78382};
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:0000269|PubMed:34015330};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=CMP-N-acetyl-beta-neuraminate(in) + UMP(out) = CMP-N-acetyl-
CC         beta-neuraminate(out) + UMP(in); Xref=Rhea:RHEA:74643,
CC         ChEBI:CHEBI:57812, ChEBI:CHEBI:57865;
CC         Evidence={ECO:0000250|UniProtKB:P78382};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=13.2 uM for CMP-N-acetyl-beta-neuraminate
CC         {ECO:0000269|PubMed:30985278};
CC         Vmax=6.5 nmol/min/mol enzyme for CMP-N-acetyl-beta-neuraminate
CC         {ECO:0000269|PubMed:30985278};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P78382}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC       {ECO:0000269|PubMed:10085119, ECO:0000269|PubMed:15932921,
CC       ECO:0000269|PubMed:8755516}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:10085119}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Found in all the tissues examined
CC       including skeletal muscle, brain, heart, liver, kidney and spleen.
CC       {ECO:0000269|PubMed:8755516}.
CC   -!- SIMILARITY: Belongs to the nucleotide-sugar transporter family. SLC35A
CC       subfamily. {ECO:0000305}.
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DR   EMBL; Z71268; CAA95855.1; -; mRNA.
DR   EMBL; AL928738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC012252; AAH12252.1; -; mRNA.
DR   CCDS; CCDS18030.1; -.
DR   RefSeq; NP_036025.2; NM_011895.3.
DR   PDB; 6OH2; X-ray; 2.58 A; A=1-322.
DR   PDB; 6OH3; X-ray; 2.75 A; A=1-322.
DR   PDB; 6OH4; X-ray; 3.38 A; A/B=1-336.
DR   PDB; 6XBO; X-ray; 1.80 A; A=1-322.
DR   PDBsum; 6OH2; -.
DR   PDBsum; 6OH3; -.
DR   PDBsum; 6OH4; -.
DR   PDBsum; 6XBO; -.
DR   AlphaFoldDB; Q61420; -.
DR   SMR; Q61420; -.
DR   STRING; 10090.ENSMUSP00000029970; -.
DR   TCDB; 2.A.7.12.1; the drug/metabolite transporter (dmt) superfamily.
DR   iPTMnet; Q61420; -.
DR   PhosphoSitePlus; Q61420; -.
DR   EPD; Q61420; -.
DR   MaxQB; Q61420; -.
DR   PaxDb; 10090-ENSMUSP00000029970; -.
DR   ProteomicsDB; 260771; -.
DR   Pumba; Q61420; -.
DR   Antibodypedia; 46448; 30 antibodies from 13 providers.
DR   DNASU; 24060; -.
DR   Ensembl; ENSMUST00000029970.14; ENSMUSP00000029970.8; ENSMUSG00000028293.15.
DR   GeneID; 24060; -.
DR   KEGG; mmu:24060; -.
DR   UCSC; uc012dbo.1; mouse.
DR   AGR; MGI:1345622; -.
DR   CTD; 10559; -.
DR   MGI; MGI:1345622; Slc35a1.
DR   VEuPathDB; HostDB:ENSMUSG00000028293; -.
DR   eggNOG; KOG2234; Eukaryota.
DR   GeneTree; ENSGT00950000182827; -.
DR   HOGENOM; CLU_024645_1_0_1; -.
DR   InParanoid; Q61420; -.
DR   OMA; QATKVQM; -.
DR   OrthoDB; 200085at2759; -.
DR   PhylomeDB; Q61420; -.
DR   TreeFam; TF315345; -.
DR   Reactome; R-MMU-4085001; Sialic acid metabolism.
DR   Reactome; R-MMU-727802; Transport of nucleotide sugars.
DR   BioGRID-ORCS; 24060; 27 hits in 83 CRISPR screens.
DR   ChiTaRS; Slc35a1; mouse.
DR   PRO; PR:Q61420; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; Q61420; Protein.
DR   Bgee; ENSMUSG00000028293; Expressed in conjunctival fornix and 255 other cell types or tissues.
DR   ExpressionAtlas; Q61420; baseline and differential.
DR   GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0015297; F:antiporter activity; IDA:UniProtKB.
DR   GO; GO:0005456; F:CMP-N-acetylneuraminate transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR   GO; GO:0015782; P:CMP-N-acetylneuraminate transmembrane transport; IDA:UniProtKB.
DR   InterPro; IPR007271; Nuc_sug_transpt.
DR   NCBIfam; TIGR00803; nst; 1.
DR   PANTHER; PTHR10231:SF66; CMP-SIALIC ACID TRANSPORTER; 1.
DR   PANTHER; PTHR10231; NUCLEOTIDE-SUGAR TRANSMEMBRANE TRANSPORTER; 1.
DR   Pfam; PF04142; Nuc_sug_transp; 1.
DR   PIRSF; PIRSF005799; UDP-gal_transpt; 1.
DR   SUPFAM; SSF103481; Multidrug resistance efflux transporter EmrE; 1.
DR   Genevisible; Q61420; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Antiport; Golgi apparatus; Membrane; Reference proteome;
KW   Sugar transport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..336
FT                   /note="CMP-sialic acid transporter"
FT                   /id="PRO_0000213352"
FT   TOPO_DOM        1..9
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:10085119,
FT                   ECO:0000269|PubMed:30985278"
FT   TRANSMEM        10..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        31..45
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        46..64
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        65..87
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        109..114
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        115..135
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        136..141
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        142..160
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        161..175
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        176..196
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        197..209
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        210..228
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        229..243
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        244..262
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        263..269
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        270..288
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        289..296
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TRANSMEM        297..315
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   TOPO_DOM        316..336
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:10085119,
FT                   ECO:0000269|PubMed:30985278"
FT   REGION          316..336
FT                   /note="Disordered"
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   BINDING         55
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   BINDING         101..102
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   BINDING         117..124
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   BINDING         188
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   BINDING         210..214
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   BINDING         272
FT                   /ligand="CMP-N-acetyl-beta-neuraminate"
FT                   /ligand_id="ChEBI:CHEBI:57812"
FT                   /evidence="ECO:0000269|PubMed:30985278,
FT                   ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT   MUTAGEN         20
FT                   /note="M->S: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         24
FT                   /note="A->Y: Loss of CMP-sialic acid transport activity but
FT                   no effect on CDP-ribitol transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         27
FT                   /note="Y->H: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         105
FT                   /note="A->V: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         118
FT                   /note="Q->A: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         121
FT                   /note="Y->S: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         122
FT                   /note="Q->A: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         184
FT                   /note="A->Y: Loss of CMP-sialic acid transport activity but
FT                   no effect on CDP-ribitol transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         253
FT                   /note="A->Q: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         256
FT                   /note="G->N: Loss of CMP-sialic acid transport activity but
FT                   no effect on CDP-ribitol transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         260
FT                   /note="T->M: No effect on CDP-ribitol and CMP-sialic acid
FT                   transport activity."
FT                   /evidence="ECO:0000269|PubMed:34015330"
FT   MUTAGEN         322..336
FT                   /note="Missing: No effect on CMP-sialic acid transport
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:30985278"
FT   MUTAGEN         336
FT                   /note="V->VGSKVKGS: Results in localization to the
FT                   endoplasmic reticulum."
FT                   /evidence="ECO:0000269|PubMed:15932921"
FT   CONFLICT        18
FT                   /note="T -> A (in Ref. 1; CAA95855 and 3; AAH12252)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        166
FT                   /note="T -> S (in Ref. 1; CAA95855 and 3; AAH12252)"
FT                   /evidence="ECO:0000305"
FT   HELIX           10..36
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           44..67
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           70..80
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   TURN            81..83
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           85..111
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           114..121
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           124..135
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           142..159
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           174..199
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           206..236
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   TURN            238..241
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           244..266
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           269..291
FT                   /evidence="ECO:0007829|PDB:6XBO"
FT   HELIX           297..313
FT                   /evidence="ECO:0007829|PDB:6XBO"
SQ   SEQUENCE   336 AA;  36453 MW;  A396528233904451 CRC64;
     MAPARENVSL FFKLYCLTVM TLVAAAYTVA LRYTRTTAEE LYFSTTAVCI TEVIKLLISV
     GLLAKETGSL GRFKASLSEN VLGSPKELAK LSVPSLVYAV QNNMAFLALS NLDAAVYQVT
     YQLKIPCTAL CTVLMLNRTL SKLQWISVFM LCGGVTLVQW KPAQATKVVV AQNPLLGFGA
     IAIAVLCSGF AGVYFEKVLK SSDTSLWVRN IQMYLSGIVV TLAGTYLSDG AEIQEKGFFY
     GYTYYVWFVI FLASVGGLYT SVVVKYTDNI MKGFSAAAAI VLSTIASVLL FGLQITLSFA
     LGALLVCVSI YLYGLPRQDT TSIQQEATSK ERIIGV
//