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Q96QS3 (ARX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 120. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein ARX
Alternative name(s):
Aristaless-related homeobox
Gene names
Name:ARX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length562 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor required for normal brain development. May be important for maintenance of specific neuronal subtypes in the cerebral cortex and axonal guidance in the floor plate.

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed predominantly in fetal and adult brain and skeletal muscle. Expression is specific to the telencephalon and ventral thalamus. There is an absence of expression in the cerebellum throughout development and also in adult. Ref.1 Ref.3 Ref.4

Involvement in disease

Lissencephaly, X-linked 2 (LISX2) [MIM:300215]: A classic type lissencephaly associated with abnormal genitalia. Patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6

Epileptic encephalopathy, early infantile, 1 (EIEE1) [MIM:308350]: A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.4

Partington syndrome (PRTS) [MIM:309510]: Characterized by mental retardation, episodic dystonic hand movements, and dysarthria.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4

Mental retardation, X-linked, ARX-related (MRXARX) [MIM:300419]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Agenesis of the corpus callosum, with abnormal genitalia (ACCAG) [MIM:300004]: A X-linked syndrome with variable expression in females. It is characterized by agenesis of corpus callosum, mental retardation and seizures. Manifestations in surviving males include severe acquired micrencephaly, mental retardation, limb contractures, scoliosis, tapered fingers with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityTriplet repeat expansion
   DiseaseDisease mutation
Epilepsy
Lissencephaly
Mental retardation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Inferred from electronic annotation. Source: Ensembl

cell proliferation in forebrain

Inferred from electronic annotation. Source: Ensembl

cerebral cortex GABAergic interneuron migration

Inferred from electronic annotation. Source: Ensembl

cerebral cortex tangential migration

Inferred from electronic annotation. Source: Ensembl

embryonic olfactory bulb interneuron precursor migration

Inferred from electronic annotation. Source: Ensembl

epithelial cell fate commitment

Inferred from electronic annotation. Source: Ensembl

globus pallidus development

Inferred from electronic annotation. Source: Ensembl

lipid digestion

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of organ growth

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 562562Homeobox protein ARX
PRO_0000048819

Regions

DNA binding328 – 38760Homeobox
Motif530 – 54314OAR
Compositional bias100 – 15556Ala-rich
Compositional bias224 – 25330Glu-rich
Compositional bias395 – 45965Pro-rich
Compositional bias425 – 544120Ala-rich

Natural variations

Natural variant331L → P in MRXARX. Ref.3
Corresponds to variant rs28936077 [ dbSNP | Ensembl ].
VAR_015669
Natural variant1151A → AAAAAAAA in EIEE1.
VAR_015177
Natural variant1551A → AAAAAAAAA in EIEE1 and PRTS; also found in non-specific mental retardation families; frequent mutation. Ref.2 Ref.4
VAR_015670
Natural variant2861G → S in MRXARX. Ref.3
Corresponds to variant rs28935479 [ dbSNP | Ensembl ].
VAR_015671
Natural variant3321R → H in LISX2. Ref.5 Ref.6
Corresponds to variant rs28936075 [ dbSNP | Ensembl ].
VAR_015178
Natural variant3321R → P in LISX2. Ref.6
VAR_033260
Natural variant3331T → N in ACCAG. Ref.6
Corresponds to variant rs28936078 [ dbSNP | Ensembl ].
VAR_033261
Natural variant3431L → Q in LISX2. Ref.5 Ref.6
Corresponds to variant rs28936076 [ dbSNP | Ensembl ].
VAR_015179
Natural variant3531P → L in EIEE1. Ref.4
Corresponds to variant rs28936074 [ dbSNP | Ensembl ].
VAR_015180
Natural variant3531P → R in LISX2. Ref.6
VAR_033262
Natural variant5211A → T in LISX2; severe phenotype. Ref.6
VAR_033263

Sequences

Sequence LengthMass (Da)Tools
Q96QS3 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: FBDF41E387C65532

FASTA56258,160
        10         20         30         40         50         60 
MSNQYQEEGC SERPECKSKS PTLLSSYCID SILGRRSPCK MRLLGAAQSL PAPLTSRADP 

        70         80         90        100        110        120 
EKAVQGSPKS SSAPFEAELH LPPKLRRLYG PGGGRLLQGA AAAAAAAAAA AAAAATATAG 

       130        140        150        160        170        180 
PRGEAPPPPP PTARPGERPD GAGAAAAAAA AAAAAWDTLK ISQAPQVSIS RSKSYRENGA 

       190        200        210        220        230        240 
PFVPPPPALD ELGGPGGVTH PEERLGVAGG PGSAPAAGGG TGTEDDEEEL LEDEEDEDEE 

       250        260        270        280        290        300 
EELLEDDEEE LLEDDARALL KEPRRCPVAA TGAVAAAAAA AVATEGGELS PKEELLLHPE 

       310        320        330        340        350        360 
DAEGKDGEDS VCLSAGSDSE EGLLKRKQRR YRTTFTSYQL EELERAFQKT HYPDVFTREE 

       370        380        390        400        410        420 
LAMRLDLTEA RVQVWFQNRR AKWRKREKAG AQTHPPGLPF PGPLSATHPL SPYLDASPFP 

       430        440        450        460        470        480 
PHHPALDSAW TAAAAAAAAA FPSLPPPPGS ASLPPSGAPL GLSTFLGAAV FRHPAFISPA 

       490        500        510        520        530        540 
FGRLFSTMAP LTSASTAAAL LRQPTPAVEG AVASGALADP ATAAADRRAS SIAALRLKAK 

       550        560 
EHAAQLTQLN ILPGTSTGKE VC 

« Hide

References

[1]"Human ARX gene: genomic characterization and expression."
Ohira R.H., Zhang Y.H., Guo W., Dipple K., Shih S., Doerr J., Huang B.-L., Fu L., Abu-Khalil A., Geschwind D., McCabe E.
Mol. Genet. Metab. 77:179-188(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation."
Turner G., Partington M., Kerr B., Mangelsdorf M., Gecz J.
Am. J. Med. Genet. 112:405-411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EIEE1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS.
[3]"ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation."
Bienvenu T., Poirier K., Friocourt G., Bahi N., Beaumont D., Fauchereau F., Ben-Jeema L., Zemni R., Vinet M.-C., Francis F., Couvert P., Gomot M., Moraine C., van Bokhoven H., Kalscheuer V., Frints S., Gecz J., Ohzaki K. expand/collapse author list , Chaabouni H., Fryns J.-P., Desportes V., Beldjord C., Chelly J.
Hum. Mol. Genet. 11:981-991(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MRXARX PRO-33 AND SER-286, TISSUE SPECIFICITY.
[4]"Mutations in the human ortholog of aristaless cause X-linked mental retardation and epilepsy."
Stroemme P., Mangelsdorf M.E., Shaw M.A., Lower K.M., Lewis S.M.E., Bruyere H., Luetcherath V., Gedeon A.K., Wallace R.H., Scheffer I.E., Turner G., Partington M., Frints S.G.M., Fryns J.-P., Sutherland G.R., Mulley J.C., Gecz J.
Nat. Genet. 30:441-445(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EIEE1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-115 INS; ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS AND LEU-353, VARIANT PRTS ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS, TISSUE SPECIFICITY.
[5]"Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans."
Kitamura K., Yanazawa M., Sugiyama N., Miura H., Iizuka-Kogo A., Kusaka M., Omichi K., Suzuki R., Kato-Fukui Y., Kamiirisa K., Matsuo M., Kamijo S., Kasahara M., Yoshioka H., Ogata T., Fukuda T., Kondo I., Kato M. expand/collapse author list , Dobyns W.B., Yokoyama M., Morohashi K.
Nat. Genet. 32:359-369(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LISX2 HIS-332 AND GLN-343.
[6]"Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation."
Kato M., Das S., Petras K., Kitamura K., Morohashi K., Abuelo D.N., Barr M., Bonneau D., Brady A.F., Carpenter N.J., Cipero K.L., Frisone F., Fukuda T., Guerrini R., Iida E., Itoh M., Lewanda A.F., Nanba Y. expand/collapse author list , Oka A., Proud V.K., Saugier-Veber P., Schelley S.L., Selicorni A., Shaner R., Silengo M., Stewart F., Sugiyama N., Toyama J., Toutain A., Vargas A.L., Yanazawa M., Zackai E.H., Dobyns W.B.
Hum. Mutat. 23:147-159(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LISX2 PRO-332; HIS-332; GLN-343; ARG-353 AND THR-521, VARIANT ACCAG ASN-333.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY038071 mRNA. Translation: AAK93901.1.
RefSeqNP_620689.1. NM_139058.2.
UniGeneHs.300304.

3D structure databases

ProteinModelPortalQ96QS3.
SMRQ96QS3. Positions 329-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000368332.

PTM databases

PhosphoSiteQ96QS3.

Polymorphism databases

DMDM27923733.

Proteomic databases

PaxDbQ96QS3.
PRIDEQ96QS3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379044; ENSP00000368332; ENSG00000004848.
GeneID170302.
KEGGhsa:170302.
UCSCuc004dbp.4. human.

Organism-specific databases

CTD170302.
GeneCardsGC0XM025021.
HGNCHGNC:18060. ARX.
MIM300004. phenotype.
300215. phenotype.
300382. gene.
300419. phenotype.
308350. phenotype.
309510. phenotype.
neXtProtNX_Q96QS3.
Orphanet1934. Early infantile epileptic encephalopathy.
364063. Infantile epileptic-dyskinetic encephalopathy.
2508. Micrencephaly - corpus callosum agenesis - abnormal genitalia.
94083. Partington syndrome.
3175. Spasticity - intellectual deficit - X-linked epilepsy.
3451. West syndrome.
452. X-linked lissencephaly with abnormal genitalia.
777. X-linked non-syndromic intellectual deficit.
PharmGKBPA25024.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG313402.
HOGENOMHOG000012381.
HOVERGENHBG004285.
InParanoidQ96QS3.
KOK09452.
OMACKVRLIG.
OrthoDBEOG7XPZ60.
PhylomeDBQ96QS3.
TreeFamTF350743.

Gene expression databases

BgeeQ96QS3.
CleanExHS_ARX.
GenevestigatorQ96QS3.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR003654. OAR_dom.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAristaless_related_homeobox.
GenomeRNAi170302.
NextBio88881.
PROQ96QS3.
SOURCESearch...

Entry information

Entry nameARX_HUMAN
AccessionPrimary (citable) accession number: Q96QS3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: December 1, 2001
Last modified: March 19, 2014
This is version 120 of the entry and version 1 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 X

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