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Magnesium transporter NIPA4 (Ichthyin) (NIPA-like protein 4) (Non-imprinted in Prader-Willi/Angelman syndrome region protein 4)

 NIPA4_HUMAN             Reviewed;         466 AA.
Q0D2K0; A8S6F1; A8S6F5; A8S6F8; B4DLF3; Q0D2J8; Q0D2J9;
17-APR-2007, integrated into UniProtKB/Swiss-Prot.
20-JAN-2009, sequence version 3.
12-SEP-2018, entry version 102.
RecName: Full=Magnesium transporter NIPA4;
AltName: Full=Ichthyin;
AltName: Full=NIPA-like protein 4;
AltName: Full=Non-imprinted in Prader-Willi/Angelman syndrome region protein 4;
Name=NIPAL4; Synonyms=ICHN, NIPA4;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
VARIANTS ARCI6 ASP-176 AND ARG-230.
PubMed=17557927; DOI=10.1136/jmg.2007.050542;
Dahlqvist J., Klar J., Hausser I., Anton-Lamprecht I., Pigg M.H.,
Gedde-Dahl T., Gaanemo A., Vahlquist A., Dahl N.;
"Congenital ichthyosis: mutations in ichthyin are associated with
specific structural abnormalities in the granular layer of
epidermis.";
J. Med. Genet. 44:615-620(2007).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Tongue;
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).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15372022; DOI=10.1038/nature02919;
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
"The DNA sequence and comparative analysis of human chromosome 5.";
Nature 431:268-274(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 117-466 (ISOFORM 1).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
VARIANTS ARCI6 VAL-142; ASP-176; PHE-208; ASN-237 AND ARG-297,
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=15317751; DOI=10.1093/hmg/ddh263;
Lefevre C., Bouadjar B., Karaduman A., Jobard F., Saker S., Ozguc M.,
Lathrop M., Prud'homme J.-F., Fischer J.;
"Mutations in ichthyin a new gene on chromosome 5q33 in a new form of
autosomal recessive congenital ichthyosis.";
Hum. Mol. Genet. 13:2473-2482(2004).
[6]
VARIANT ARCI6 ARG-135.
PubMed=26456858; DOI=10.1111/ced.12740;
Maier D., Mazereeuw-Hautier J., Tilinca M., Cosgarea R., Jonca N.;
"Novel mutation in NIPAL4 in a Romanian family with autosomal
recessive congenital ichthyosis.";
Clin. Exp. Dermatol. 41:279-282(2016).
-!- FUNCTION: Acts as a Mg(2+) transporter. Can also transport other
divalent cations such as Ba(2+), Mn(2+), Sr(2+) and Co(2+) but to
a much less extent than Mg(2+) (By similarity). May be a receptor
for ligands (trioxilins A3 and B3) from the hepoxilin pathway.
{ECO:0000250, ECO:0000269|PubMed:15317751}.
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
protein {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q0D2K0-1; Sequence=Displayed;
Name=2;
IsoId=Q0D2K0-2; Sequence=VSP_036122;
-!- TISSUE SPECIFICITY: Highly expressed in brain, lung, stomach,
keratinocytes and leukocytes, and in all other tissues tested
except liver, thyroid and fetal brain.
{ECO:0000269|PubMed:15317751, ECO:0000269|PubMed:17557927}.
-!- DISEASE: Ichthyosis, congenital, autosomal recessive 6 (ARCI6)
[MIM:612281]: A form of autosomal recessive congenital ichthyosis,
a disorder of keratinization with abnormal differentiation and
desquamation of the epidermis, resulting in abnormal skin scaling
over the whole body. The main skin phenotypes are lamellar
ichthyosis (LI) and non-bullous congenital ichthyosiform
erythroderma (NCIE), although phenotypic overlap within the same
patient or among patients from the same family can occur. Lamellar
ichthyosis is a condition often associated with an embedment in a
collodion-like membrane at birth; skin scales later develop,
covering the entire body surface. Non-bullous congenital
ichthyosiform erythroderma characterized by fine whitish scaling
on an erythrodermal background; larger brownish scales are present
on the buttocks, neck and legs. {ECO:0000269|PubMed:15317751,
ECO:0000269|PubMed:17557927, ECO:0000269|PubMed:26456858}.
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=ABW69630.1; Type=Miscellaneous discrepancy; Note=Protein truncation is due to an exon 5 splice site mutation which is found in a ARCII patient.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; EF599763; ABW69628.1; -; Genomic_DNA.
EMBL; EF599764; ABW69629.1; -; Genomic_DNA.
EMBL; EF599765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; EF599766; ABW69630.1; ALT_SEQ; Genomic_DNA.
EMBL; AK296972; BAG59515.1; -; mRNA.
EMBL; AC008676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC105708; AAI05709.1; -; mRNA.
EMBL; BC105709; AAI05710.1; -; mRNA.
EMBL; BC105710; AAI05711.1; -; mRNA.
CCDS; CCDS47328.1; -. [Q0D2K0-1]
CCDS; CCDS54944.1; -. [Q0D2K0-2]
RefSeq; NP_001092757.1; NM_001099287.1. [Q0D2K0-1]
RefSeq; NP_001165763.1; NM_001172292.1. [Q0D2K0-2]
UniGene; Hs.4285; -.
ProteinModelPortal; Q0D2K0; -.
BioGrid; 131541; 1.
IntAct; Q0D2K0; 14.
STRING; 9606.ENSP00000311687; -.
TCDB; 2.A.7.25.4; the drug/metabolite transporter (dmt) superfamily.
iPTMnet; Q0D2K0; -.
PhosphoSitePlus; Q0D2K0; -.
BioMuta; NIPAL4; -.
DMDM; 221222524; -.
MaxQB; Q0D2K0; -.
PaxDb; Q0D2K0; -.
PeptideAtlas; Q0D2K0; -.
PRIDE; Q0D2K0; -.
ProteomicsDB; 58743; -.
ProteomicsDB; 58744; -. [Q0D2K0-2]
DNASU; 348938; -.
Ensembl; ENST00000311946; ENSP00000311687; ENSG00000172548. [Q0D2K0-1]
Ensembl; ENST00000435489; ENSP00000406456; ENSG00000172548. [Q0D2K0-2]
GeneID; 348938; -.
KEGG; hsa:348938; -.
UCSC; uc003lwx.5; human. [Q0D2K0-1]
CTD; 348938; -.
DisGeNET; 348938; -.
EuPathDB; HostDB:ENSG00000172548.14; -.
GeneCards; NIPAL4; -.
GeneReviews; NIPAL4; -.
H-InvDB; HIX0005358; -.
HGNC; HGNC:28018; NIPAL4.
HPA; HPA038259; -.
MalaCards; NIPAL4; -.
MIM; 609383; gene.
MIM; 612281; phenotype.
neXtProt; NX_Q0D2K0; -.
OpenTargets; ENSG00000172548; -.
Orphanet; 79394; Congenital non-bullous ichthyosiform erythroderma.
Orphanet; 313; Lamellar ichthyosis.
PharmGKB; PA164723956; -.
eggNOG; KOG2922; Eukaryota.
eggNOG; ENOG410XNR8; LUCA.
GeneTree; ENSGT00550000074395; -.
InParanoid; Q0D2K0; -.
KO; K22733; -.
OMA; QQVLCQI; -.
OrthoDB; EOG091G0M8A; -.
PhylomeDB; Q0D2K0; -.
TreeFam; TF313214; -.
Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
GenomeRNAi; 348938; -.
PRO; PR:Q0D2K0; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000172548; Expressed in 121 organ(s), highest expression level in skin of abdomen.
ExpressionAtlas; Q0D2K0; baseline and differential.
Genevisible; Q0D2K0; HS.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0016020; C:membrane; IBA:GO_Central.
GO; GO:0015095; F:magnesium ion transmembrane transporter activity; IEA:InterPro.
GO; GO:0015693; P:magnesium ion transport; IBA:GO_Central.
InterPro; IPR008521; Mg_trans_NIPA.
PANTHER; PTHR12570; PTHR12570; 1.
Pfam; PF05653; Mg_trans_NIPA; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Disease mutation;
Glycoprotein; Ichthyosis; Ion transport; Magnesium; Membrane;
Receptor; Reference proteome; Transmembrane; Transmembrane helix;
Transport.
CHAIN 1 466 Magnesium transporter NIPA4.
/FTId=PRO_0000284447.
TOPO_DOM 1 117 Extracellular. {ECO:0000255}.
TRANSMEM 118 138 Helical. {ECO:0000255}.
TOPO_DOM 139 164 Cytoplasmic. {ECO:0000255}.
TRANSMEM 165 185 Helical. {ECO:0000255}.
TOPO_DOM 186 186 Extracellular. {ECO:0000255}.
TRANSMEM 187 207 Helical. {ECO:0000255}.
TOPO_DOM 208 215 Cytoplasmic. {ECO:0000255}.
TRANSMEM 216 236 Helical. {ECO:0000255}.
TOPO_DOM 237 257 Extracellular. {ECO:0000255}.
TRANSMEM 258 278 Helical. {ECO:0000255}.
TOPO_DOM 279 285 Cytoplasmic. {ECO:0000255}.
TRANSMEM 286 306 Helical. {ECO:0000255}.
TOPO_DOM 307 323 Extracellular. {ECO:0000255}.
TRANSMEM 324 344 Helical. {ECO:0000255}.
TOPO_DOM 345 355 Cytoplasmic. {ECO:0000255}.
TRANSMEM 356 376 Helical. {ECO:0000255}.
TOPO_DOM 377 386 Extracellular. {ECO:0000255}.
TRANSMEM 387 407 Helical. {ECO:0000255}.
TOPO_DOM 408 466 Cytoplasmic. {ECO:0000255}.
CARBOHYD 69 69 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 74 74 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 102 102 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 156 174 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_036122.
VARIANT 135 135 S -> R (in ARCI6).
{ECO:0000269|PubMed:26456858}.
/FTId=VAR_075461.
VARIANT 142 142 G -> V (in ARCI6; dbSNP:rs775903553).
{ECO:0000269|PubMed:15317751}.
/FTId=VAR_031736.
VARIANT 176 176 A -> D (in ARCI6; frequent mutation;
dbSNP:rs199422217).
{ECO:0000269|PubMed:15317751,
ECO:0000269|PubMed:17557927}.
/FTId=VAR_031737.
VARIANT 208 208 S -> F (in ARCI6).
{ECO:0000269|PubMed:15317751}.
/FTId=VAR_031738.
VARIANT 230 230 G -> R (in ARCI6; dbSNP:rs370356566).
{ECO:0000269|PubMed:17557927}.
/FTId=VAR_054120.
VARIANT 237 237 H -> N (in ARCI6).
{ECO:0000269|PubMed:15317751}.
/FTId=VAR_031739.
VARIANT 297 297 G -> R (in ARCI6; dbSNP:rs375688767).
{ECO:0000269|PubMed:15317751}.
/FTId=VAR_031740.
CONFLICT 213 213 R -> G (in Ref. 2; BAG59515 and 4;
AAI05711). {ECO:0000305}.
SEQUENCE 466 AA; 50058 MW; C84D024A68609C9E CRC64;
MPGDSSPGTL PLWDASLSPP LGPDPGGFSR ASHAGDKSRP PAPELGSPGA VRPRVGSCAP
GPMELRVSNT SCENGSLLHL YCSSQEVLCQ IVNDLSPEVP SNATFHSWQE RIRQNYGFYI
GLGLAFLSSF LIGSSVILKK KGLLRLVATG ATRAVDGGFG YLKDAMWWAG FLTMAAGEVA
NFGAYAFAPA TVVTPLGALS VLISAILSSY FLRESLNLLG KLGCVICVAG STVMVIHAPE
EEKVTTIMEM ASKMKDTGFI VFAVLLLVSC LILIFVIAPR YGQRNILIYI IICSVIGAFS
VAAVKGLGIT IKNFFQGLPV VRHPLPYILS LILALSLSTQ VNFLNRALDI FNTSLVFPIY
YVFFTTVVVT SSIILFKEWY SMSAVDIAGT LSGFVTIILG VFMLHAFKDL DISCASLPHM
HKNPPPSPAP EPTVIRLEDK NVLVDNIELA STSSPEEKPK VFIIHS


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