ID   NIPA1_HUMAN             Reviewed;         329 AA.
AC   Q7RTP0; B2RA76; Q5HYA9; Q7KZB0; Q86XW4;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   24-JAN-2024, entry version 153.
DE   RecName: Full=Magnesium transporter NIPA1;
DE   AltName: Full=Non-imprinted in Prader-Willi/Angelman syndrome region protein 1;
DE   AltName: Full=Spastic paraplegia 6 protein;
GN   Name=NIPA1; Synonyms=SPG6;
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).
RX   PubMed=14508708; DOI=10.1086/378816;
RA   Chai J.-H., Locke D.P., Greally J.M., Knoll J.H.M., Ohta T., Dunai J.,
RA   Yavor A., Eichler E.E., Nicholls R.D.;
RT   "Identification of four highly conserved genes between breakpoint hotspots
RT   BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that
RT   have undergone evolutionary transposition mediated by flanking duplicons.";
RL   Am. J. Hum. Genet. 73:898-925(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Amygdala, and Spinal cord;
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   [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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 163-329 (ISOFORMS 1/2).
RX   PubMed=12805275; DOI=10.1101/gr.709603;
RA   Toyoda N., Nagai S., Terashima Y., Motomura K., Haino M., Hashimoto S.,
RA   Takizawa H., Matsushima K.;
RT   "Analysis of mRNA with microsomal fractionation using a SAGE-based DNA
RT   microarray system facilitates identification of the genes encoding
RT   secretory proteins.";
RL   Genome Res. 13:1728-1736(2003).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [8]
RP   VARIANT SPG6 ARG-45, AND TISSUE SPECIFICITY.
RX   PubMed=14508710; DOI=10.1086/378817;
RA   Rainier S., Chai J.-H., Tokarz D., Nicholls R.D., Fink J.K.;
RT   "NIPA1 gene mutations cause autosomal dominant hereditary spastic
RT   paraplegia (SPG6).";
RL   Am. J. Hum. Genet. 73:967-971(2003).
RN   [9]
RP   VARIANT SPG6 ARG-106.
RX   PubMed=15643603; DOI=10.1002/humu.20126;
RA   Chen S., Song C., Guo H., Xu P., Huang W., Zhou Y., Sun J., Li C.X., Du Y.,
RA   Li X., Liu Z., Geng D., Maxwell P.H., Zhang C., Wang Y.;
RT   "Distinct novel mutations affecting the same base in the NIPA1 gene cause
RT   autosomal dominant hereditary spastic paraplegia in two Chinese families.";
RL   Hum. Mutat. 25:135-141(2005).
CC   -!- FUNCTION: Acts as a Mg(2+) transporter. Can also transport other
CC       divalent cations such as Fe(2+), Sr(2+), Ba(2+), Zn(2+) and Co(2+) but
CC       to a much less extent than Mg(2+) (By similarity).
CC       {ECO:0000250|UniProtKB:Q8BHK1}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Mg(2+)(in) = Mg(2+)(out); Xref=Rhea:RHEA:29827,
CC         ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q8BHK1};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8BHK1}.
CC   -!- INTERACTION:
CC       Q7RTP0; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-17702144, EBI-9083477;
CC       Q7RTP0; Q8WWX9: SELENOM; NbExp=3; IntAct=EBI-17702144, EBI-10277687;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8BHK1};
CC       Multi-pass membrane protein {ECO:0000255}. Early endosome
CC       {ECO:0000250|UniProtKB:Q8BHK1}. Note=Recruited to the cell membrane in
CC       response to low extracellular magnesium.
CC       {ECO:0000250|UniProtKB:Q8BHK1}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7RTP0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7RTP0-2; Sequence=VSP_017189;
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in neuronal
CC       tissues. {ECO:0000269|PubMed:14508710}.
CC   -!- DISEASE: Spastic paraplegia 6, autosomal dominant (SPG6) [MIM:600363]:
CC       A form of spastic paraplegia, a neurodegenerative disorder
CC       characterized by a slow, gradual, progressive weakness and spasticity
CC       of the lower limbs. Rate of progression and the severity of symptoms
CC       are quite variable. Initial symptoms may include difficulty with
CC       balance, weakness and stiffness in the legs, muscle spasms, and
CC       dragging the toes when walking. In some forms of the disorder, bladder
CC       symptoms (such as incontinence) may appear, or the weakness and
CC       stiffness may spread to other parts of the body.
CC       {ECO:0000269|PubMed:14508710, ECO:0000269|PubMed:15643603}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the NIPA family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC67707.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAC67707.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR   EMBL; BK001020; DAA01477.1; -; mRNA.
DR   EMBL; CR614719; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AK314073; BAG36773.1; -; mRNA.
DR   EMBL; BX537997; CAD97953.1; -; mRNA.
DR   EMBL; BX648722; CAI45979.2; -; mRNA.
DR   EMBL; CH471258; EAW65549.1; -; Genomic_DNA.
DR   EMBL; AB089319; BAC67707.1; ALT_INIT; mRNA.
DR   CCDS; CCDS73691.1; -. [Q7RTP0-1]
DR   CCDS; CCDS73692.1; -. [Q7RTP0-2]
DR   RefSeq; NP_001135747.1; NM_001142275.1. [Q7RTP0-2]
DR   RefSeq; NP_653200.2; NM_144599.4. [Q7RTP0-1]
DR   AlphaFoldDB; Q7RTP0; -.
DR   BioGRID; 125827; 13.
DR   IntAct; Q7RTP0; 6.
DR   MINT; Q7RTP0; -.
DR   STRING; 9606.ENSP00000337452; -.
DR   TCDB; 2.A.7.25.1; the drug/metabolite transporter (dmt) superfamily.
DR   iPTMnet; Q7RTP0; -.
DR   PhosphoSitePlus; Q7RTP0; -.
DR   BioMuta; NIPA1; -.
DR   DMDM; 73921215; -.
DR   EPD; Q7RTP0; -.
DR   jPOST; Q7RTP0; -.
DR   MassIVE; Q7RTP0; -.
DR   MaxQB; Q7RTP0; -.
DR   PaxDb; 9606-ENSP00000337452; -.
DR   PeptideAtlas; Q7RTP0; -.
DR   ProteomicsDB; 68877; -. [Q7RTP0-1]
DR   ProteomicsDB; 68878; -. [Q7RTP0-2]
DR   Pumba; Q7RTP0; -.
DR   Antibodypedia; 8965; 48 antibodies from 13 providers.
DR   DNASU; 123606; -.
DR   Ensembl; ENST00000337435.9; ENSP00000337452.4; ENSG00000170113.16. [Q7RTP0-1]
DR   Ensembl; ENST00000437912.6; ENSP00000393962.2; ENSG00000170113.16. [Q7RTP0-2]
DR   Ensembl; ENST00000561183.5; ENSP00000453722.1; ENSG00000170113.16. [Q7RTP0-2]
DR   Ensembl; ENST00000673033.1; ENSP00000500129.1; ENSG00000288478.1. [Q7RTP0-1]
DR   Ensembl; ENST00000673341.1; ENSP00000500344.1; ENSG00000288478.1. [Q7RTP0-1]
DR   GeneID; 123606; -.
DR   KEGG; hsa:123606; -.
DR   MANE-Select; ENST00000337435.9; ENSP00000337452.4; NM_144599.5; NP_653200.2.
DR   UCSC; uc001yvc.4; human. [Q7RTP0-1]
DR   AGR; HGNC:17043; -.
DR   CTD; 123606; -.
DR   DisGeNET; 123606; -.
DR   GeneCards; NIPA1; -.
DR   HGNC; HGNC:17043; NIPA1.
DR   HPA; ENSG00000170113; Tissue enriched (brain).
DR   MalaCards; NIPA1; -.
DR   MIM; 600363; phenotype.
DR   MIM; 608145; gene.
DR   neXtProt; NX_Q7RTP0; -.
DR   OpenTargets; ENSG00000170113; -.
DR   Orphanet; 261183; 15q11.2 microdeletion syndrome.
DR   Orphanet; 100988; Autosomal dominant spastic paraplegia type 6.
DR   PharmGKB; PA134967361; -.
DR   VEuPathDB; HostDB:ENSG00000170113; -.
DR   eggNOG; KOG2922; Eukaryota.
DR   GeneTree; ENSGT00940000159067; -.
DR   HOGENOM; CLU_012349_1_1_1; -.
DR   InParanoid; Q7RTP0; -.
DR   OMA; VPSCKGL; -.
DR   OrthoDB; 53219at2759; -.
DR   PhylomeDB; Q7RTP0; -.
DR   TreeFam; TF313214; -.
DR   PathwayCommons; Q7RTP0; -.
DR   Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR   SignaLink; Q7RTP0; -.
DR   BioGRID-ORCS; 123606; 10 hits in 1158 CRISPR screens.
DR   ChiTaRS; NIPA1; human.
DR   GeneWiki; NIPA1; -.
DR   GenomeRNAi; 123606; -.
DR   Pharos; Q7RTP0; Tbio.
DR   PRO; PR:Q7RTP0; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q7RTP0; Protein.
DR   Bgee; ENSG00000170113; Expressed in medial globus pallidus and 170 other cell types or tissues.
DR   ExpressionAtlas; Q7RTP0; baseline and differential.
DR   GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0015095; F:magnesium ion transmembrane transporter activity; TAS:Reactome.
DR   GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central.
DR   GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR   InterPro; IPR008521; Mg_trans_NIPA.
DR   PANTHER; PTHR12570:SF17; MAGNESIUM TRANSPORTER NIPA1; 1.
DR   PANTHER; PTHR12570; UNCHARACTERIZED; 1.
DR   Pfam; PF05653; Mg_trans_NIPA; 1.
DR   SUPFAM; SSF103481; Multidrug resistance efflux transporter EmrE; 1.
DR   Genevisible; Q7RTP0; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disease variant; Endosome;
KW   Hereditary spastic paraplegia; Ion transport; Magnesium; Membrane;
KW   Neurodegeneration; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..329
FT                   /note="Magnesium transporter NIPA1"
FT                   /id="PRO_0000191741"
FT   TOPO_DOM        1..27
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        28..48
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        49..66
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        67..87
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        88
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        89..109
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        110..117
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        139..159
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        160..180
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        181..183
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        184..204
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        205..224
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        246..259
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        260..280
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        281..290
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        291..311
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        312..329
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..75
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:17974005"
FT                   /id="VSP_017189"
FT   VARIANT         45
FT                   /note="T -> R (in SPG6; dbSNP:rs104894496)"
FT                   /evidence="ECO:0000269|PubMed:14508710"
FT                   /id="VAR_023440"
FT   VARIANT         106
FT                   /note="G -> R (in SPG6; dbSNP:rs104894490)"
FT                   /evidence="ECO:0000269|PubMed:15643603"
FT                   /id="VAR_023441"
SQ   SEQUENCE   329 AA;  34562 MW;  88B7506C93457A12 CRC64;
     MGTAAAAAAA AAAAAAGEGA RSPSPAAVSL GLGVAVVSSL VNGSTFVLQK KGIVRAKRRG
     TSYLTDIVWW AGTIAMAVGQ IGNFLAYTAV PTVLVTPLGA LGVPFGSILA SYLLKEKLNI
     LGKLGCLLSC AGSVVLIIHS PKSESVTTQA ELEEKLTNPV FVGYLCIVLL MLLLLIFWIA
     PAHGPTNIMV YISICSLLGS FTVPSTKGIG LAAQDILHNN PSSQRALCLC LVLLAVLGCS
     IIVQFRYINK ALECFDSSVF GAIYYVVFTT LVLLASAILF REWSNVGLVD FLGMACGFTT
     VSVGIVLIQV FKEFNFNLGE MNKSNMKTD
//