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Magnesium transporter NIPA1 (Non-imprinted in Prader-Willi/Angelman syndrome region protein 1) (Spastic paraplegia 6 protein)

 NIPA1_HUMAN             Reviewed;         329 AA.
Q7RTP0; B2RA76; Q5HYA9; Q7KZB0; Q86XW4;
30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
15-DEC-2003, sequence version 1.
05-DEC-2018, entry version 125.
RecName: Full=Magnesium transporter NIPA1;
AltName: Full=Non-imprinted in Prader-Willi/Angelman syndrome region protein 1;
AltName: Full=Spastic paraplegia 6 protein;
Name=NIPA1; Synonyms=SPG6;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=14508708; DOI=10.1086/378816;
Chai J.-H., Locke D.P., Greally J.M., Knoll J.H.M., Ohta T., Dunai J.,
Yavor A., Eichler E.E., Nicholls R.D.;
"Identification of four highly conserved genes between breakpoint
hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion
region that have undergone evolutionary transposition mediated by
flanking duplicons.";
Am. J. Hum. Genet. 73:898-925(2003).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Li W.B., Gruber C., Jessee J., Polayes D.;
"Full-length cDNA libraries and normalization.";
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Amygdala, and Spinal cord;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 163-329 (ISOFORMS 1/2).
PubMed=12805275; DOI=10.1101/gr.709603;
Toyoda N., Nagai S., Terashima Y., Motomura K., Haino M.,
Hashimoto S., Takizawa H., Matsushima K.;
"Analysis of mRNA with microsomal fractionation using a SAGE-based DNA
microarray system facilitates identification of the genes encoding
secretory proteins.";
Genome Res. 13:1728-1736(2003).
[7]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[8]
VARIANT SPG6 ARG-45, AND TISSUE SPECIFICITY.
PubMed=14508710; DOI=10.1086/378817;
Rainier S., Chai J.-H., Tokarz D., Nicholls R.D., Fink J.K.;
"NIPA1 gene mutations cause autosomal dominant hereditary spastic
paraplegia (SPG6).";
Am. J. Hum. Genet. 73:967-971(2003).
[9]
VARIANT SPG6 ARG-106.
PubMed=15643603; DOI=10.1002/humu.20126;
Chen S., Song C., Guo H., Xu P., Huang W., Zhou Y., Sun J., Li C.X.,
Du Y., Li X., Liu Z., Geng D., Maxwell P.H., Zhang C., Wang Y.;
"Distinct novel mutations affecting the same base in the NIPA1 gene
cause autosomal dominant hereditary spastic paraplegia in two Chinese
families.";
Hum. Mutat. 25:135-141(2005).
-!- FUNCTION: Acts as a Mg(2+) transporter. Can also transport other
divalent cations such as Fe(2+), Sr(2+), Ba(2+), Mn(2+) and Co(2+)
but to a much less extent than Mg(2+) (By similarity).
{ECO:0000250}.
-!- SUBUNIT: Homodimer. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass
membrane protein {ECO:0000305}. Early endosome {ECO:0000250}.
Note=Recruited to the cell membrane in response to low
extracellular magnesium. {ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q7RTP0-1; Sequence=Displayed;
Name=2;
IsoId=Q7RTP0-2; Sequence=VSP_017189;
-!- TISSUE SPECIFICITY: Widely expressed with highest levels in
neuronal tissues. {ECO:0000269|PubMed:14508710}.
-!- DISEASE: Spastic paraplegia 6, autosomal dominant (SPG6)
[MIM:600363]: A form of spastic paraplegia, a neurodegenerative
disorder characterized by a slow, gradual, progressive weakness
and spasticity of the lower limbs. Rate of progression and the
severity of symptoms are quite variable. Initial symptoms may
include difficulty with balance, weakness and stiffness in the
legs, muscle spasms, and dragging the toes when walking. In some
forms of the disorder, bladder symptoms (such as incontinence) may
appear, or the weakness and stiffness may spread to other parts of
the body. {ECO:0000269|PubMed:14508710,
ECO:0000269|PubMed:15643603}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the NIPA family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BAC67707.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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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EMBL; BK001020; DAA01477.1; -; mRNA.
EMBL; CR614719; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AK314073; BAG36773.1; -; mRNA.
EMBL; BX537997; CAD97953.1; -; mRNA.
EMBL; BX648722; CAI45979.2; -; mRNA.
EMBL; CH471258; EAW65549.1; -; Genomic_DNA.
EMBL; AB089319; BAC67707.1; ALT_INIT; mRNA.
CCDS; CCDS73691.1; -. [Q7RTP0-1]
CCDS; CCDS73692.1; -. [Q7RTP0-2]
RefSeq; NP_001135747.1; NM_001142275.1. [Q7RTP0-2]
RefSeq; NP_653200.2; NM_144599.4. [Q7RTP0-1]
UniGene; Hs.511797; -.
ProteinModelPortal; Q7RTP0; -.
IntAct; Q7RTP0; 2.
STRING; 9606.ENSP00000337452; -.
TCDB; 2.A.7.25.1; the drug/metabolite transporter (dmt) superfamily.
iPTMnet; Q7RTP0; -.
PhosphoSitePlus; Q7RTP0; -.
BioMuta; NIPA1; -.
DMDM; 73921215; -.
EPD; Q7RTP0; -.
MaxQB; Q7RTP0; -.
PaxDb; Q7RTP0; -.
PeptideAtlas; Q7RTP0; -.
PRIDE; Q7RTP0; -.
ProteomicsDB; 68877; -.
ProteomicsDB; 68878; -. [Q7RTP0-2]
DNASU; 123606; -.
Ensembl; ENST00000337435; ENSP00000337452; ENSG00000170113. [Q7RTP0-1]
Ensembl; ENST00000437912; ENSP00000393962; ENSG00000170113. [Q7RTP0-2]
Ensembl; ENST00000561183; ENSP00000453722; ENSG00000170113. [Q7RTP0-2]
GeneID; 123606; -.
KEGG; hsa:123606; -.
UCSC; uc001yvc.4; human. [Q7RTP0-1]
CTD; 123606; -.
DisGeNET; 123606; -.
EuPathDB; HostDB:ENSG00000170113.15; -.
GeneCards; NIPA1; -.
HGNC; HGNC:17043; NIPA1.
HPA; HPA023269; -.
MalaCards; NIPA1; -.
MIM; 600363; phenotype.
MIM; 608145; gene.
neXtProt; NX_Q7RTP0; -.
OpenTargets; ENSG00000170113; -.
Orphanet; 100988; Autosomal dominant spastic paraplegia type 6.
PharmGKB; PA134967361; -.
eggNOG; KOG2922; Eukaryota.
eggNOG; ENOG410XNR8; LUCA.
GeneTree; ENSGT00940000159067; -.
HOGENOM; HOG000203962; -.
HOVERGEN; HBG055032; -.
InParanoid; Q7RTP0; -.
KO; K19364; -.
OMA; AAQDIFH; -.
OrthoDB; EOG091G0M8A; -.
PhylomeDB; Q7RTP0; -.
TreeFam; TF313214; -.
Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
ChiTaRS; NIPA1; human.
GeneWiki; NIPA1; -.
GenomeRNAi; 123606; -.
PRO; PR:Q7RTP0; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000170113; Expressed in 194 organ(s), highest expression level in brain.
CleanEx; HS_NIPA1; -.
ExpressionAtlas; Q7RTP0; baseline and differential.
Genevisible; Q7RTP0; HS.
GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0015095; F:magnesium ion transmembrane transporter activity; TAS:Reactome.
GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central.
GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
InterPro; IPR008521; Mg_trans_NIPA.
PANTHER; PTHR12570; PTHR12570; 1.
Pfam; PF05653; Mg_trans_NIPA; 1.
1: Evidence at protein level;
Alternative splicing; Cell membrane; Complete proteome;
Disease mutation; Endosome; Hereditary spastic paraplegia;
Ion transport; Magnesium; Membrane; Neurodegeneration;
Reference proteome; Transmembrane; Transmembrane helix; Transport.
CHAIN 1 329 Magnesium transporter NIPA1.
/FTId=PRO_0000191741.
TOPO_DOM 1 27 Extracellular. {ECO:0000255}.
TRANSMEM 28 48 Helical. {ECO:0000255}.
TOPO_DOM 49 66 Cytoplasmic. {ECO:0000255}.
TRANSMEM 67 87 Helical. {ECO:0000255}.
TOPO_DOM 88 88 Extracellular. {ECO:0000255}.
TRANSMEM 89 109 Helical. {ECO:0000255}.
TOPO_DOM 110 117 Cytoplasmic. {ECO:0000255}.
TRANSMEM 118 138 Helical. {ECO:0000255}.
TOPO_DOM 139 159 Extracellular. {ECO:0000255}.
TRANSMEM 160 180 Helical. {ECO:0000255}.
TOPO_DOM 181 183 Cytoplasmic. {ECO:0000255}.
TRANSMEM 184 204 Helical. {ECO:0000255}.
TOPO_DOM 205 224 Extracellular. {ECO:0000255}.
TRANSMEM 225 245 Helical. {ECO:0000255}.
TOPO_DOM 246 259 Cytoplasmic. {ECO:0000255}.
TRANSMEM 260 280 Helical. {ECO:0000255}.
TOPO_DOM 281 290 Extracellular. {ECO:0000255}.
TRANSMEM 291 311 Helical. {ECO:0000255}.
TOPO_DOM 312 329 Cytoplasmic. {ECO:0000255}.
VAR_SEQ 1 75 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:17974005}.
/FTId=VSP_017189.
VARIANT 45 45 T -> R (in SPG6; dbSNP:rs104894496).
{ECO:0000269|PubMed:14508710}.
/FTId=VAR_023440.
VARIANT 106 106 G -> R (in SPG6; dbSNP:rs104894490).
{ECO:0000269|PubMed:15643603}.
/FTId=VAR_023441.
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


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