Q7RTP0 (NIPA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Magnesium transporter NIPA1

Alternative name(s):
Non-imprinted in Prader-Willi/Angelman syndrome region protein 1
Spastic paraplegia 6 protein

Gene names

Name:	NIPA1
Synonyms:	SPG6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	329 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a Mg2+ transporter. Can also transport other divalent cations such as Fe2+, Sr2+, Ba2+, Mn2+ and Co2+ but to a much less extent than Mg2+ By similarity.
Subunit structure	Homodimer By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein Potential. Early endosome By similarity. Note: Recruited to the cell membrane in response to low extracellular magnesium By similarity.
Tissue specificity	Widely expressed with highest levels in neuronal tissues. Ref.8
Involvement in disease	Spastic paraplegia autosomal dominant 6 (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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9
Sequence similarities	Belongs to the NIPA family.
Sequence caution	The sequence BAC67707.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC67707.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hereditary spastic paraplegia Neurodegeneration
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	early endosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	magnesium ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7RTP0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q7RTP0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 329	329	Magnesium transporter NIPA1		PRO_0000191741
Regions
	Topological domain	1 – 27	27	Extracellular Potential
	Transmembrane	28 – 48	21	Helical; Potential
	Topological domain	49 – 66	18	Cytoplasmic Potential
	Transmembrane	67 – 87	21	Helical; Potential
	Topological domain	88	1	Extracellular Potential
	Transmembrane	89 – 109	21	Helical; Potential
	Topological domain	110 – 117	8	Cytoplasmic Potential
	Transmembrane	118 – 138	21	Helical; Potential
	Topological domain	139 – 159	21	Extracellular Potential
	Transmembrane	160 – 180	21	Helical; Potential
	Topological domain	181 – 183	3	Cytoplasmic Potential
	Transmembrane	184 – 204	21	Helical; Potential
	Topological domain	205 – 224	20	Extracellular Potential
	Transmembrane	225 – 245	21	Helical; Potential
	Topological domain	246 – 259	14	Cytoplasmic Potential
	Transmembrane	260 – 280	21	Helical; Potential
	Topological domain	281 – 290	10	Extracellular Potential
	Transmembrane	291 – 311	21	Helical; Potential
	Topological domain	312 – 329	18	Cytoplasmic Potential
Natural variations
	Alternative sequence	1 – 75	75	Missing in isoform 2.		VSP_017189
	Natural variant	45	1	T → R in SPG6. Ref.8		VAR_023440
	Natural variant	106	1	G → R in SPG6. Ref.9		VAR_023441

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 15, 2003. Version 1. Checksum: 88B7506C93457A12	FASTA	329	34,562
	10 20 30 40 50 60 MGTAAAAAAA AAAAAAGEGA RSPSPAAVSL GLGVAVVSSL VNGSTFVLQK KGIVRAKRRG 70 80 90 100 110 120 TSYLTDIVWW AGTIAMAVGQ IGNFLAYTAV PTVLVTPLGA LGVPFGSILA SYLLKEKLNI 130 140 150 160 170 180 LGKLGCLLSC AGSVVLIIHS PKSESVTTQA ELEEKLTNPV FVGYLCIVLL MLLLLIFWIA 190 200 210 220 230 240 PAHGPTNIMV YISICSLLGS FTVPSTKGIG LAAQDILHNN PSSQRALCLC LVLLAVLGCS 250 260 270 280 290 300 IIVQFRYINK ALECFDSSVF GAIYYVVFTT LVLLASAILF REWSNVGLVD FLGMACGFTT 310 320 VSVGIVLIQV FKEFNFNLGE MNKSNMKTD
	Isoform 2 [UniParc]. Checksum: FCDF5586AAADACFE	FASTA	254	27,310
	10 20 30 40 50 60 MAVGQIGNFL AYTAVPTVLV TPLGALGVPF GSILASYLLK EKLNILGKLG CLLSCAGSVV 70 80 90 100 110 120 LIIHSPKSES VTTQAELEEK LTNPVFVGYL CIVLLMLLLL IFWIAPAHGP TNIMVYISIC 130 140 150 160 170 180 SLLGSFTVPS TKGIGLAAQD ILHNNPSSQR ALCLCLVLLA VLGCSIIVQF RYINKALECF 190 200 210 220 230 240 DSSVFGAIYY VVFTTLVLLA SAILFREWSN VGLVDFLGMA CGFTTVSVGI VLIQVFKEFN 250 FNLGEMNKSN MKTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." 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. Am. J. Hum. Genet. 73:898-925(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." 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. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala and Spinal cord.
[5]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Analysis of mRNA with microsomal fractionation using a SAGE-based DNA microarray system facilitates identification of the genes encoding secretory proteins." Toyoda N., Nagai S., Terashima Y., Motomura K., Haino M., Hashimoto S., Takizawa H., Matsushima K. Genome Res. 13:1728-1736(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 163-329 (ISOFORMS 1/2).
[7]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-322, MASS SPECTROMETRY. Tissue: Plasma.
[8]	"NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)." Rainier S., Chai J.-H., Tokarz D., Nicholls R.D., Fink J.K. Am. J. Hum. Genet. 73:967-971(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPG6 ARG-45, TISSUE SPECIFICITY.
[9]	"Distinct novel mutations affecting the same base in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese families." 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. Hum. Mutat. 25:135-141(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPG6 ARG-106.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	BK001020 mRNA. Translation: DAA01477.1. CR614719 mRNA. No translation available. AK314073 mRNA. Translation: BAG36773.1. BX537997 mRNA. Translation: CAD97953.1. BX648722 mRNA. Translation: CAI45979.2. CH471258 Genomic DNA. Translation: EAW65549.1. AB089319 mRNA. Translation: BAC67707.1. Different initiation.
IPI	IPI00394901. IPI00477060.
RefSeq	NP_001135747.1. NM_001142275.1. NP_653200.2. NM_144599.4.
UniGene	Hs.511797.
3D structure databases
ProteinModelPortal	Q7RTP0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000337452.
Protein family/group databases
TCDB	2.A.7.25.1. drug/metabolite transporter (DMT) superfamily.
PTM databases
PhosphoSite	Q7RTP0.
Polymorphism databases
DMDM	73921215.
Proteomic databases
PaxDb	Q7RTP0.
PRIDE	Q7RTP0.
Protocols and materials databases
DNASU	123606.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000337435; ENSP00000337452; ENSG00000170113. ENST00000437912; ENSP00000393962; ENSG00000170113. ENST00000561183; ENSP00000453722; ENSG00000170113.
GeneID	123606.
KEGG	hsa:123606.
UCSC	uc001yvc.3. human.
Organism-specific databases
CTD	123606.
GeneCards	GC15M023043.
HGNC	HGNC:17043. NIPA1.
HPA	HPA023269.
MIM	600363. phenotype. 608145. gene.
neXtProt	NX_Q7RTP0.
Orphanet	100988. Autosomal dominant spastic paraplegia type 6.
PharmGKB	PA134967361.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG287598.
HOGENOM	HOG000203962.
HOVERGEN	HBG055032.
InParanoid	Q7RTP0.
OMA	NPVFVGY.
OrthoDB	EOG45DWQD.
PhylomeDB	Q7RTP0.
Gene expression databases
ArrayExpress	Q7RTP0.
Bgee	Q7RTP0.
CleanEx	HS_NIPA1.
Genevestigator	Q7RTP0.
GermOnline	ENSG00000170113. Homo sapiens.
Family and domain databases
InterPro	IPR008521. Mg_trans_NIPA. [Graphical view]
PANTHER	PTHR12570. PTHR12570. 1 hit.
Pfam	PF05653. Mg_trans_NIPA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	123606.
NextBio	81115.
SOURCE	Search...

Entry information

Entry name

NIPA1_HUMAN

Accession

Primary (citable) accession number: Q7RTP0
Secondary accession number(s): B2RA76 , Q5HYA9, Q7KZB0, Q86XW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	December 15, 2003
Last modified:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.