Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q0D2K0 (NIPA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length466 AA.
Sequence statusComplete.
Protein existenceEvidence 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 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.
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 processIon transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Ichthyosis
   DomainTransmembrane
Transmembrane helix
   LigandMagnesium
   Molecular functionReceptor
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionmagnesium 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 466466Magnesium transporter NIPA4
PRO_0000284447

Regions

Topological domain1 – 117117Extracellular Potential
Transmembrane118 – 13821Helical; Potential
Topological domain139 – 16426Cytoplasmic Potential
Transmembrane165 – 18521Helical; Potential
Topological domain1861Extracellular Potential
Transmembrane187 – 20721Helical; Potential
Topological domain208 – 2158Cytoplasmic Potential
Transmembrane216 – 23621Helical; Potential
Topological domain237 – 25721Extracellular Potential
Transmembrane258 – 27821Helical; Potential
Topological domain279 – 2857Cytoplasmic Potential
Transmembrane286 – 30621Helical; Potential
Topological domain307 – 32317Extracellular Potential
Transmembrane324 – 34421Helical; Potential
Topological domain345 – 35511Cytoplasmic Potential
Transmembrane356 – 37621Helical; Potential
Topological domain377 – 38610Extracellular Potential
Transmembrane387 – 40721Helical; Potential
Topological domain408 – 46659Cytoplasmic Potential

Amino acid modifications

Glycosylation691N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation1021N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence156 – 17419Missing in isoform 2.
VSP_036122
Natural variant1421G → V in ARCI6. Ref.5
VAR_031736
Natural variant1761A → D in ARCI6; frequent mutation. Ref.1 Ref.5
Corresponds to variant rs199422217 [ dbSNP | Ensembl ].
VAR_031737
Natural variant2081S → F in ARCI6. Ref.5
VAR_031738
Natural variant2301G → R in ARCI6. Ref.1
VAR_054120
Natural variant2371H → N in ARCI6. Ref.5
VAR_031739
Natural variant2971G → R in ARCI6. Ref.5
VAR_031740

Experimental info

Sequence conflict2131R → G in BAG59515. Ref.2
Sequence conflict2131R → G in AAI05711. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 20, 2009. Version 3.
Checksum: C84D024A68609C9E

FASTA46650,058
        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 

« Hide

Isoform 2 [UniParc].

Checksum: EE032469DFA26FBD
Show »

FASTA44747,909

References

« Hide '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 ARCI6 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. expand/collapse author list , 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. expand/collapse author list , 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 ARCI6 VAL-142; ASP-176; PHE-208; ASN-237 AND ARG-297, FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Web resources

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.
RefSeqNP_001092757.1. NM_001099287.1.
NP_001165763.1. NM_001172292.1.
UniGeneHs.4285.

3D structure databases

ProteinModelPortalQ0D2K0.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000311687.

Protein family/group databases

TCDB2.A.7.25.4. the drug/metabolite transporter (dmt) superfamily.

Polymorphism databases

DMDM221222524.

Proteomic databases

PaxDbQ0D2K0.
PRIDEQ0D2K0.

Protocols and materials databases

DNASU348938.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311946; ENSP00000311687; ENSG00000172548. [Q0D2K0-1]
ENST00000435489; ENSP00000406456; ENSG00000172548. [Q0D2K0-2]
GeneID348938.
KEGGhsa:348938.
UCSCuc003lwx.4. human. [Q0D2K0-1]
uc011ddq.2. human. [Q0D2K0-2]

Organism-specific databases

CTD348938.
GeneCardsGC05P156887.
H-InvDBHIX0005358.
HGNCHGNC:28018. NIPAL4.
HPAHPA038259.
MIM609383. gene.
612281. phenotype.
neXtProtNX_Q0D2K0.
Orphanet79394. Congenital non-bullous ichthyosiform erythroderma.
313. Lamellar ichthyosis.
PharmGKBPA164723956.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG298616.
InParanoidQ0D2K0.
OMAWYSMSAV.
OrthoDBEOG73BVD7.
PhylomeDBQ0D2K0.
TreeFamTF313214.

Gene expression databases

ArrayExpressQ0D2K0.
BgeeQ0D2K0.
GenevestigatorQ0D2K0.

Family and domain databases

InterProIPR008521. Mg_trans_NIPA.
[Graphical view]
PANTHERPTHR12570. PTHR12570. 1 hit.
PfamPF05653. Mg_trans_NIPA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi348938.
NextBio99459.
PROQ0D2K0.
SOURCESearch...

Entry information

Entry nameNIPA4_HUMAN
AccessionPrimary (citable) accession number: Q0D2K0
Secondary accession number(s): A8S6F1 expand/collapse secondary AC list , A8S6F5, A8S6F8, B4DLF3, Q0D2J8, Q0D2J9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: January 20, 2009
Last modified: April 16, 2014
This is version 71 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM