NIPA1_HUMAN
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 03-AUG-2022, entry version 145.
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+), Mn(2+) and Co(2+) but
CC to a much less extent than Mg(2+) (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
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:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Early endosome {ECO:0000250}. Note=Recruited to
CC the cell membrane in response to low extracellular magnesium.
CC {ECO:0000250}.
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; 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; 12.
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; Q7RTP0; -.
DR PeptideAtlas; Q7RTP0; -.
DR PRIDE; Q7RTP0; -.
DR ProteomicsDB; 68877; -. [Q7RTP0-1]
DR ProteomicsDB; 68878; -. [Q7RTP0-2]
DR Antibodypedia; 8965; 30 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 CTD; 123606; -.
DR DisGeNET; 123606; -.
DR GeneCards; NIPA1; -.
DR HGNC; HGNC:17043; NIPA1.
DR HPA; ENSG00000170113; Tissue enhanced (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; YLTDVVW; -.
DR OrthoDB; 754939at2759; -.
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 1078 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 168 other tissues.
DR ExpressionAtlas; Q7RTP0; baseline and differential.
DR Genevisible; Q7RTP0; HS.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; PTHR12570; 1.
DR Pfam; PF05653; Mg_trans_NIPA; 1.
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
