S41A1_HUMAN
ID S41A1_HUMAN Reviewed; 513 AA.
AC Q8IVJ1; Q63HJ4; Q658Z5; Q659A4; Q6MZK2;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Solute carrier family 41 member 1;
GN Name=SLC41A1 {ECO:0000303|PubMed:22031603, ECO:0000312|HGNC:HGNC:19429};
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], AND TISSUE SPECIFICITY.
RX PubMed=12810078; DOI=10.1016/s0006-291x(03)01030-1;
RA Wabakken T., Rian E., Kveine M., Aasheim H.-C.;
RT "The human solute carrier SLC41A1 belongs to a novel eukaryotic subfamily
RT with homology to prokaryotic MgtE Mg2+ transporters.";
RL Biochem. Biophys. Res. Commun. 306:718-724(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrial tumor, Skeletal muscle, and Testis;
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 [3]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18367447; DOI=10.1074/jbc.m707276200;
RA Kolisek M., Launay P., Beck A., Sponder G., Serafini N., Brenkus M.,
RA Froschauer E.M., Martens H., Fleig A., Schweigel M.;
RT "SLC41A1 is a novel mammalian Mg2+ carrier.";
RL J. Biol. Chem. 283:16235-16247(2008).
RN [4]
RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION.
RX PubMed=22031603; DOI=10.1152/ajpcell.00289.2011;
RA Kolisek M., Nestler A., Vormann J., Schweigel-Roentgen M.;
RT "Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger.";
RL Am. J. Physiol. 302:C318-C326(2012).
RN [5]
RP FUNCTION.
RX PubMed=27074515; DOI=10.1038/nature17407;
RA Feeney K.A., Hansen L.L., Putker M., Olivares-Yanez C., Day J., Eades L.J.,
RA Larrondo L.F., Hoyle N.P., O'Neill J.S., van Ooijen G.;
RT "Daily magnesium fluxes regulate cellular timekeeping and energy balance.";
RL Nature 532:375-379(2016).
RN [6]
RP VARIANT NPHPL2 VAL-233, INVOLVEMENT IN NPHPL2, CHARACTERIZATION OF VARIANT
RP NPHPL2 VAL-233, SUBCELLULAR LOCATION, FUNCTION, TRANSPORTER ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=23661805; DOI=10.1681/asn.2012101034;
RA Hurd T.W., Otto E.A., Mishima E., Gee H.Y., Inoue H., Inazu M., Yamada H.,
RA Halbritter J., Seki G., Konishi M., Zhou W., Yamane T., Murakami S.,
RA Caridi G., Ghiggeri G., Abe T., Hildebrandt F.;
RT "Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-
RT like phenotype.";
RL J. Am. Soc. Nephrol. 24:967-977(2013).
RN [7]
RP VARIANT VAL-350, CHARACTERIZATION OF VARIANT VAL-350, FUNCTION, TRANSPORTER
RP ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=23976986; DOI=10.1371/journal.pone.0071096;
RA Kolisek M., Sponder G., Mastrototaro L., Smorodchenko A., Launay P.,
RA Vormann J., Schweigel-Roentgen M.;
RT "Substitution p.A350V in Na+/Mg2+ exchanger SLC41A1, potentially associated
RT with Parkinson's disease, is a gain-of-function mutation.";
RL PLoS ONE 8:e71096-e71096(2013).
CC -!- FUNCTION: Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+)
CC efflux system at the plasma membrane (PubMed:22031603, PubMed:23661805,
CC PubMed:18367447, PubMed:23976986). Transporter activity is driven by
CC the inwardly directed electrochemical gradient for Na(+) ions, thus
CC directly depends on the extracellular Na(+) ion concentration set by
CC Na(+)/K(+) pump (PubMed:22031603, PubMed:23661805). Generates circadian
CC cellular Mg(2+) fluxes that feed back to regulate clock-controlled gene
CC expression and metabolism and facilitate higher energetic demands
CC during the day (PubMed:27074515). Has a role in regulating the activity
CC of ATP-dependent enzymes, including those operating in Krebs cycle and
CC the electron transport chain (By similarity).
CC {ECO:0000250|UniProtKB:Q8BJA2, ECO:0000269|PubMed:18367447,
CC ECO:0000269|PubMed:22031603, ECO:0000269|PubMed:23661805,
CC ECO:0000269|PubMed:23976986, ECO:0000269|PubMed:27074515}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Mg(2+)(in) + 2 Na(+)(out) = Mg(2+)(out) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:66616, ChEBI:CHEBI:18420, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:18367447, ECO:0000269|PubMed:22031603,
CC ECO:0000269|PubMed:23661805, ECO:0000269|PubMed:23976986};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66617;
CC Evidence={ECO:0000305|PubMed:22031603};
CC -!- ACTIVITY REGULATION: The exchange activity is regulated by
CC phosphorylation in a cyclic AMP signaling-dependent way
CC (PubMed:22031603, PubMed:23661805). Temperature-sensitive, reduction or
CC elevation of the temperature significantly decreases or increases its
CC activity respectively (PubMed:18367447). {ECO:0000269|PubMed:18367447,
CC ECO:0000269|PubMed:22031603, ECO:0000269|PubMed:23976986}.
CC -!- INTERACTION:
CC Q8IVJ1; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-12266234, EBI-19125216;
CC Q8IVJ1; Q13520: AQP6; NbExp=3; IntAct=EBI-12266234, EBI-13059134;
CC Q8IVJ1; P30518: AVPR2; NbExp=3; IntAct=EBI-12266234, EBI-11675746;
CC Q8IVJ1; P11912: CD79A; NbExp=3; IntAct=EBI-12266234, EBI-7797864;
CC Q8IVJ1; A0A024R644: CLN5; NbExp=3; IntAct=EBI-12266234, EBI-12838990;
CC Q8IVJ1; A1L3X0: ELOVL7; NbExp=3; IntAct=EBI-12266234, EBI-10285373;
CC Q8IVJ1; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-12266234, EBI-781551;
CC Q8IVJ1; O15552: FFAR2; NbExp=3; IntAct=EBI-12266234, EBI-2833872;
CC Q8IVJ1; O14843: FFAR3; NbExp=3; IntAct=EBI-12266234, EBI-17762181;
CC Q8IVJ1; P36382: GJA5; NbExp=3; IntAct=EBI-12266234, EBI-750433;
CC Q8IVJ1; O95377: GJB5; NbExp=3; IntAct=EBI-12266234, EBI-3909454;
CC Q8IVJ1; Q96P66: GPR101; NbExp=3; IntAct=EBI-12266234, EBI-17935713;
CC Q8IVJ1; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12266234, EBI-13345167;
CC Q8IVJ1; O15529: GPR42; NbExp=3; IntAct=EBI-12266234, EBI-18076404;
CC Q8IVJ1; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-12266234, EBI-12808020;
CC Q8IVJ1; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-12266234, EBI-749265;
CC Q8IVJ1; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12266234, EBI-2820517;
CC Q8IVJ1; P35372-10: OPRM1; NbExp=3; IntAct=EBI-12266234, EBI-12807478;
CC Q8IVJ1; O15127: SCAMP2; NbExp=3; IntAct=EBI-12266234, EBI-712703;
CC Q8IVJ1; Q14973: SLC10A1; NbExp=3; IntAct=EBI-12266234, EBI-3923031;
CC Q8IVJ1; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-12266234, EBI-18159983;
CC Q8IVJ1; Q9UKG4: SLC13A4; NbExp=3; IntAct=EBI-12266234, EBI-12808018;
CC Q8IVJ1; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-12266234, EBI-17280858;
CC Q8IVJ1; Q9H7V2: SYNDIG1; NbExp=3; IntAct=EBI-12266234, EBI-726331;
CC Q8IVJ1; Q5VXT5-2: SYPL2; NbExp=3; IntAct=EBI-12266234, EBI-18196631;
CC Q8IVJ1; Q96RI9: TAAR9; NbExp=3; IntAct=EBI-12266234, EBI-12908048;
CC Q8IVJ1; Q0VAB0: TBXA2R; NbExp=3; IntAct=EBI-12266234, EBI-18271435;
CC Q8IVJ1; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-12266234, EBI-12947623;
CC Q8IVJ1; Q96Q45-2: TMEM237; NbExp=5; IntAct=EBI-12266234, EBI-10982110;
CC Q8IVJ1; Q9NWD8: TMEM248; NbExp=3; IntAct=EBI-12266234, EBI-10314986;
CC Q8IVJ1; P34981: TRHR; NbExp=3; IntAct=EBI-12266234, EBI-18055230;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18367447,
CC ECO:0000269|PubMed:23976986}; Multi-pass membrane protein
CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:23661805};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highest expression levels in heart and testis,
CC slightly less in skeletal muscles, prostate, adrenal gland and thyroid,
CC and weakest in the hematopoietic tissues bones marrow, lymph node,
CC thymus and spleen. In the kidney, it is expressed in the distal
CC convoluted tubules, macula densa, and thick ascending limb tubular
CC segments of the nephrons (PubMed:23661805).
CC {ECO:0000269|PubMed:12810078, ECO:0000269|PubMed:23661805}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:22031603}.
CC -!- DISEASE: Nephronophthisis-like nephropathy 2 (NPHPL2) [MIM:619468]: A
CC disorder with features of nephronophthisis, a cystic kidney disease
CC leading to end-stage renal failure. Nephronophthisis is histologically
CC characterized by modifications of the tubules with thickening of the
CC basement membrane, interstitial fibrosis and, in the advanced stages,
CC medullary cysts. Typical clinical manifestation are chronic renal
CC failure, anemia, polyuria, polydipsia, isosthenuria, and growth
CC retardation. Associations with extrarenal symptoms are frequent. NPHPL2
CC is an autosomal recessive form characterized by onset of progressive
CC renal insufficiency in the first decades of life.
CC {ECO:0000269|PubMed:23661805}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SLC41A transporter family. {ECO:0000305}.
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DR EMBL; AJ514402; CAD58404.1; -; mRNA.
DR EMBL; AL831974; CAH56217.1; -; mRNA.
DR EMBL; AL832001; CAH56211.1; -; mRNA.
DR EMBL; AL832362; CAH56213.1; -; mRNA.
DR EMBL; BX641054; CAE46028.1; -; mRNA.
DR EMBL; BX648979; CAH56135.1; -; mRNA.
DR CCDS; CCDS30988.1; -.
DR RefSeq; NP_776253.3; NM_173854.5.
DR RefSeq; XP_005245126.1; XM_005245069.2.
DR AlphaFoldDB; Q8IVJ1; -.
DR BioGRID; 129036; 37.
DR IntAct; Q8IVJ1; 32.
DR STRING; 9606.ENSP00000356105; -.
DR DrugBank; DB14513; Magnesium.
DR TCDB; 1.A.26.2.1; the mg(2+) transporter-e (mgte) family.
DR iPTMnet; Q8IVJ1; -.
DR PhosphoSitePlus; Q8IVJ1; -.
DR SwissPalm; Q8IVJ1; -.
DR BioMuta; SLC41A1; -.
DR DMDM; 152112285; -.
DR EPD; Q8IVJ1; -.
DR jPOST; Q8IVJ1; -.
DR MassIVE; Q8IVJ1; -.
DR MaxQB; Q8IVJ1; -.
DR PaxDb; Q8IVJ1; -.
DR PeptideAtlas; Q8IVJ1; -.
DR PRIDE; Q8IVJ1; -.
DR ProteomicsDB; 70715; -.
DR Antibodypedia; 2794; 43 antibodies from 15 providers.
DR DNASU; 254428; -.
DR Ensembl; ENST00000367137.4; ENSP00000356105.3; ENSG00000133065.11.
DR GeneID; 254428; -.
DR KEGG; hsa:254428; -.
DR MANE-Select; ENST00000367137.4; ENSP00000356105.3; NM_173854.6; NP_776253.3.
DR UCSC; uc001hdh.2; human.
DR CTD; 254428; -.
DR DisGeNET; 254428; -.
DR GeneCards; SLC41A1; -.
DR HGNC; HGNC:19429; SLC41A1.
DR HPA; ENSG00000133065; Tissue enhanced (heart muscle, pancreas, tongue).
DR MIM; 610801; gene.
DR MIM; 619468; phenotype.
DR neXtProt; NX_Q8IVJ1; -.
DR OpenTargets; ENSG00000133065; -.
DR PharmGKB; PA134889327; -.
DR VEuPathDB; HostDB:ENSG00000133065; -.
DR eggNOG; KOG3788; Eukaryota.
DR GeneTree; ENSGT00950000183042; -.
DR HOGENOM; CLU_018207_3_1_1; -.
DR InParanoid; Q8IVJ1; -.
DR OMA; YLERDDW; -.
DR OrthoDB; 1059294at2759; -.
DR PhylomeDB; Q8IVJ1; -.
DR TreeFam; TF313647; -.
DR PathwayCommons; Q8IVJ1; -.
DR Reactome; R-HSA-425410; Metal ion SLC transporters.
DR SignaLink; Q8IVJ1; -.
DR BioGRID-ORCS; 254428; 19 hits in 1081 CRISPR screens.
DR ChiTaRS; SLC41A1; human.
DR GenomeRNAi; 254428; -.
DR Pharos; Q8IVJ1; Tbio.
DR PRO; PR:Q8IVJ1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8IVJ1; protein.
DR Bgee; ENSG00000133065; Expressed in left ventricle myocardium and 168 other tissues.
DR ExpressionAtlas; Q8IVJ1; baseline and differential.
DR Genevisible; Q8IVJ1; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0022890; F:inorganic cation transmembrane transporter activity; ISS:ParkinsonsUK-UCL.
DR GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061768; F:magnesium:sodium antiporter activity; IMP:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010961; P:cellular magnesium ion homeostasis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071286; P:cellular response to magnesium ion; IGI:ParkinsonsUK-UCL.
DR GO; GO:1903830; P:magnesium ion transmembrane transport; IDA:ParkinsonsUK-UCL.
DR GO; GO:0015693; P:magnesium ion transport; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030001; P:metal ion transport; ISS:ParkinsonsUK-UCL.
DR Gene3D; 1.10.357.20; -; 2.
DR InterPro; IPR006667; SLC41_membr_dom.
DR InterPro; IPR036739; SLC41_membr_dom_sf.
DR InterPro; IPR045349; SLC41A1-3.
DR PANTHER; PTHR16228; PTHR16228; 1.
DR Pfam; PF01769; MgtE; 2.
DR SUPFAM; SSF161093; SSF161093; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Ion transport; Magnesium; Membrane;
KW Nephronophthisis; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..513
FT /note="Solute carrier family 41 member 1"
FT /id="PRO_0000295111"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 316..336
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 60..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 233
FT /note="G -> V (in NPHPL2; results in exon 6 skipping;
FT results in loss of magnesium ion transmembrane transporter
FT activity; does not affect localization to basolateral cell
FT membrane)"
FT /evidence="ECO:0000269|PubMed:23661805"
FT /id="VAR_086146"
FT VARIANT 350
FT /note="A -> V (increased magnesium ion transmembrane
FT transporter activity; no effect on plasma membrane
FT localization)"
FT /evidence="ECO:0000269|PubMed:23976986"
FT /id="VAR_086248"
FT CONFLICT 3
FT /note="S -> P (in Ref. 2; CAH56135)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="I -> T (in Ref. 2; CAH56213)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="I -> V (in Ref. 2; CAH56213)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="G -> D (in Ref. 2; CAH56135)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="L -> P (in Ref. 2; CAH56135)"
FT /evidence="ECO:0000305"
FT CONFLICT 272..275
FT /note="GISW -> ASAG (in Ref. 1; CAD58404)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="A -> T (in Ref. 2; CAE46028)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="V -> A (in Ref. 1; CAD58404)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="V -> A (in Ref. 2; CAH56135)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="V -> A (in Ref. 2; CAH56135)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 513 AA; 54901 MW; 2B6676F9C3AF6136 CRC64;
MSSKPEPKDV HQLNGTGPSA SPCSSDGPGR EPLAGTSEFL GPDGAGVEVV IESRANAKGV
REEDALLENG SQSNESDDVS TDRGPAPPSP LKETSFSIGL QVLFPFLLAG FGTVAAGMVL
DIVQHWEVFQ KVTEVFILVP ALLGLKGNLE MTLASRLSTA ANIGHMDTPK ELWRMITGNM
ALIQVQATVV GFLASIAAVV FGWIPDGHFS IPHAFLLCAS SVATAFIASL VLGMIMIGVI
IGSRKIGINP DNVATPIAAS LGDLITLALL SGISWGLYLE LNHWRYIYPL VCAFFVALLP
VWVVLARRSP ATREVLYSGW EPVIIAMAIS SVGGLILDKT VSDPNFAGMA VFTPVINGVG
GNLVAVQASR ISTFLHMNGM PGENSEQAPR RCPSPCTTFF SPDVNSRSAR VLFLLVVPGH
LVFLYTISCM QGGHTTLTLI FIIFYMTAAL LQVLILLYIA DWMVHWMWGR GLDPDNFSIP
YLTALGDLLG TGLLALSFHV LWLIGDRDTD VGD
