Q0D2K0 (NIPA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Magnesium transporter NIPA4

Alternative name(s):
Ichthyin
NIPA-like protein 4
Non-imprinted in Prader-Willi/Angelman syndrome region protein 4

Gene names

Name:	NIPAL4
Synonyms:	ICHN, NIPA4

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	466 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 Ba2+, Mn2+, Sr2+ and Co2+ but to a much less extent than Mg2+ By similarity. May be a receptor for ligands (trioxilins A3 and B3) from the hepoxilin pathway. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Highly expressed in brain, lung, stomach, keratinocytes and leukocytes, and in all other tissues tested except liver, thyroid and fetal brain. Ref.1 Ref.5
Involvement in disease	Ichthyosis, congenital, autosomal recessive, ichthyin-related (ARCII) [MIM:612281]: A disorder of keratinization with abnormal differentiation and desquamation of the epidermis resulting in two major clinical entities. 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5
Sequence similarities	Belongs to the NIPA family.
Sequence caution	The sequence ABW69630.1 differs from that shown. Reason: Protein truncation is due to an exon 5 splice site mutation which is found in a ARCII patient.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Ichthyosis
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
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: Q0D2K0-1)

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: Q0D2K0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     156-174: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 466	466	Magnesium transporter NIPA4		PRO_0000284447
Regions
	Topological domain	1 – 117	117	Extracellular Potential
	Transmembrane	118 – 138	21	Helical; Potential
	Topological domain	139 – 164	26	Cytoplasmic Potential
	Transmembrane	165 – 185	21	Helical; Potential
	Topological domain	186	1	Extracellular Potential
	Transmembrane	187 – 207	21	Helical; Potential
	Topological domain	208 – 215	8	Cytoplasmic Potential
	Transmembrane	216 – 236	21	Helical; Potential
	Topological domain	237 – 257	21	Extracellular Potential
	Transmembrane	258 – 278	21	Helical; Potential
	Topological domain	279 – 285	7	Cytoplasmic Potential
	Transmembrane	286 – 306	21	Helical; Potential
	Topological domain	307 – 323	17	Extracellular Potential
	Transmembrane	324 – 344	21	Helical; Potential
	Topological domain	345 – 355	11	Cytoplasmic Potential
	Transmembrane	356 – 376	21	Helical; Potential
	Topological domain	377 – 386	10	Extracellular Potential
	Transmembrane	387 – 407	21	Helical; Potential
	Topological domain	408 – 466	59	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	69	1	N-linked (GlcNAc...) Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	102	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	156 – 174	19	Missing in isoform 2.		VSP_036122
	Natural variant	142	1	G → V in ARCII. Ref.5		VAR_031736
	Natural variant	176	1	A → D in ARCII; frequent mutation. Ref.1 Ref.5		VAR_031737
	Natural variant	208	1	S → F in ARCII. Ref.5		VAR_031738
	Natural variant	230	1	G → R in ARCII. Ref.1		VAR_054120
	Natural variant	237	1	H → N in ARCII. Ref.5		VAR_031739
	Natural variant	297	1	G → R in ARCII. Ref.5		VAR_031740
Experimental info
	Sequence conflict	213	1	R → G in BAG59515. Ref.2
	Sequence conflict	213	1	R → G in AAI05711. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 20, 2009. Version 3. Checksum: C84D024A68609C9E	FASTA	466	50,058
	10 20 30 40 50 60 MPGDSSPGTL PLWDASLSPP LGPDPGGFSR ASHAGDKSRP PAPELGSPGA VRPRVGSCAP 70 80 90 100 110 120 GPMELRVSNT SCENGSLLHL YCSSQEVLCQ IVNDLSPEVP SNATFHSWQE RIRQNYGFYI 130 140 150 160 170 180 GLGLAFLSSF LIGSSVILKK KGLLRLVATG ATRAVDGGFG YLKDAMWWAG FLTMAAGEVA 190 200 210 220 230 240 NFGAYAFAPA TVVTPLGALS VLISAILSSY FLRESLNLLG KLGCVICVAG STVMVIHAPE 250 260 270 280 290 300 EEKVTTIMEM ASKMKDTGFI VFAVLLLVSC LILIFVIAPR YGQRNILIYI IICSVIGAFS 310 320 330 340 350 360 VAAVKGLGIT IKNFFQGLPV VRHPLPYILS LILALSLSTQ VNFLNRALDI FNTSLVFPIY 370 380 390 400 410 420 YVFFTTVVVT SSIILFKEWY SMSAVDIAGT LSGFVTIILG VFMLHAFKDL DISCASLPHM 430 440 450 460 HKNPPPSPAP EPTVIRLEDK NVLVDNIELA STSSPEEKPK VFIIHS
	Isoform 2 [UniParc]. Checksum: EE032469DFA26FBD	FASTA	447	47,909
	10 20 30 40 50 60 MPGDSSPGTL PLWDASLSPP LGPDPGGFSR ASHAGDKSRP PAPELGSPGA VRPRVGSCAP 70 80 90 100 110 120 GPMELRVSNT SCENGSLLHL YCSSQEVLCQ IVNDLSPEVP SNATFHSWQE RIRQNYGFYI 130 140 150 160 170 180 GLGLAFLSSF LIGSSVILKK KGLLRLVATG ATRAVAAGEV ANFGAYAFAP ATVVTPLGAL 190 200 210 220 230 240 SVLISAILSS YFLRESLNLL GKLGCVICVA GSTVMVIHAP EEEKVTTIME MASKMKDTGF 250 260 270 280 290 300 IVFAVLLLVS CLILIFVIAP RYGQRNILIY IIICSVIGAF SVAAVKGLGI TIKNFFQGLP 310 320 330 340 350 360 VVRHPLPYIL SLILALSLST QVNFLNRALD IFNTSLVFPI YYVFFTTVVV TSSIILFKEW 370 380 390 400 410 420 YSMSAVDIAG TLSGFVTIIL GVFMLHAFKD LDISCASLPH MHKNPPPSPA PEPTVIRLED 430 440 KNVLVDNIEL ASTSSPEEKP KVFIIHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis." Dahlqvist J., Klar J., Hausser I., Anton-Lamprecht I., Pigg M.H., Gedde-Dahl T., Gaanemo A., Vahlquist A., Dahl N. J. Med. Genet. 44:615-620(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS ARCII ASP-176 AND ARG-230.
[2]	"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: Tongue.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." 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. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 117-466 (ISOFORM 1).
[5]	"Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis." Lefevre C., Bouadjar B., Karaduman A., Jobard F., Saker S., Ozguc M., Lathrop M., Prud'homme J.-F., Fischer J. Hum. Mol. Genet. 13:2473-2482(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARCII VAL-142; ASP-176; PHE-208; ASN-237 AND ARG-297, FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	EF599763 Genomic DNA. Translation: ABW69628.1. EF599764 Genomic DNA. Translation: ABW69629.1. EF599765 Genomic DNA. No translation available. EF599766 Genomic DNA. Translation: ABW69630.1. Sequence problems. AK296972 mRNA. Translation: BAG59515.1. AC008676 Genomic DNA. No translation available. BC105708 mRNA. Translation: AAI05709.1. BC105709 mRNA. Translation: AAI05710.1. BC105710 mRNA. Translation: AAI05711.1.
IPI	IPI00398054. IPI00917516.
RefSeq	NP_001092757.1. NM_001099287.1. NP_001165763.1. NM_001172292.1.
UniGene	Hs.4285.
3D structure databases
ProteinModelPortal	Q0D2K0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000311687.
Protein family/group databases
TCDB	2.A.7.25.4. drug/metabolite transporter (DMT) superfamily.
Polymorphism databases
DMDM	221222524.
Proteomic databases
PaxDb	Q0D2K0.
PRIDE	Q0D2K0.
Protocols and materials databases
DNASU	348938.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000311946; ENSP00000311687; ENSG00000172548. ENST00000435489; ENSP00000406456; ENSG00000172548.
GeneID	348938.
KEGG	hsa:348938.
UCSC	uc003lwx.4. human. uc011ddq.2. human.
Organism-specific databases
CTD	348938.
GeneCards	GC05P156887.
H-InvDB	HIX0005358.
HGNC	HGNC:28018. NIPAL4.
HPA	HPA038259.
MIM	609383. gene. 612281. phenotype.
neXtProt	NX_Q0D2K0.
Orphanet	79394. Congenital nonbullous ichthyosiform erythroderma. 313. Lamellar ichthyosis.
PharmGKB	PA164723956.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG298616.
InParanoid	Q0D2K0.
OMA	NFGAYAF.
Gene expression databases
ArrayExpress	Q0D2K0.
Bgee	Q0D2K0.
Genevestigator	Q0D2K0.
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	348938.
NextBio	99459.
SOURCE	Search...

Entry information

Entry name

NIPA4_HUMAN

Accession

Primary (citable) accession number: Q0D2K0
Secondary accession number(s): A8S6F1 , A8S6F5, A8S6F8, B4DLF3, Q0D2J8, Q0D2J9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 17, 2007
Last sequence update:	January 20, 2009
Last modified:	May 1, 2013
This is version 61 of the entry and version 3 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.