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Reviewed, UniProtKB/Swiss-Prot Q96QS3 (ARX_HUMAN)

Last modified June 16, 2009. Version 72. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

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

Protein attributes

Sequence length562 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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

Defects in ARX are the cause of lissencephaly X-linked type 2 (LISX2) [MIM:300215]; also known as lissencephaly X-linked with ambiguous genitalia (XLAG). LISX2 is a classic type lissencephaly associated with abnormal genitalia. LISX2 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. Ref.5 Ref.6

Defects in ARX are the cause of epileptic encephalopathy early infantile type 1 (EIEE1) [MIM:308350]; also known as myoclonic epilepsy X-linked with intellectual disability and spasticity, X-linked West syndrome or X-linked infantile spasm syndrome (ISSX). EIEE1 is 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. Ref.4 Ref.2

Defects in ARX are a cause of Partington syndrome (PRTS) [MIM:309510]; also known as X-linked syndromic mental retardation 1 (MRXS1). PRTS is characterized by mental retardation, episodic dystonic hand movements, and dysarthria. Ref.4

Defects in ARX are the cause of mental retardation X-linked ARX-related (MRXARX) [MIM:300419]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.

Defects in ARX are the cause of agenesis of corpus callosum with abnormal genitalia (ACC with abnormal genitalia) [MIM:300004]. ACC with abnormal genitalia consists of a brain and genital malformations syndrome.

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Contains 1 OAR 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
Gene Ontology (GO)
   Biological processregulation of transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functionsequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

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 MRX54. Ref.3
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.
VAR_015670
Natural variant2861G → S in MRX54. dbSNP rs28935479. Ref.3
VAR_015671
Natural variant3321R → H in LISX2. Ref.5 Ref.6
VAR_015178
Natural variant3321R → P in LISX2. Ref.5 Ref.6
VAR_033260
Natural variant3331T → N in ACC with abnormal genitalia.
VAR_033261
Natural variant3431L → Q in LISX2. Ref.5 Ref.6
VAR_015179
Natural variant3531P → L in EIEE1. Ref.4
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
Q96QS3-1 [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: 12359145] [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: 12376946] [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: 11971879] [Abstract]
Cited for: VARIANTS MRX54 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: 11889467] [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: 12379852] [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: 14722918] [Abstract]
Cited for: VARIANTS LISX2 PRO-332; HIS-332; GLN-343; ARG-353 AND THR-521, VARIANT ACC WITH ABNORMAL GENITALIA ASN-333.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

AY038071 mRNA. Translation: AAK93901.1.
IPIIPI00045066.
RefSeqNP_620689.1.
UniGeneHs.300304

3D structure databases

HSSPHSSP built from PDB template 1FJL based on UniProtKB P06601.
ModBaseSearch...

Proteomic databases

PRIDEQ96QS3.

Genome annotation databases

EnsemblENSG00000004848. Homo sapiens. [Contig view]
GeneID170302.
KEGGhsa:170302.

Organism-specific databases

GeneCardsGC0XM024931.
H-InvDBHIX0056192.
HGNCHGNC:18060. ARX.
MIM300004. phenotype.
300215. phenotype.
300382. gene.
300419. phenotype.
308350. phenotype.
309510. phenotype.
Orphanet777. Intellectual deficit, X-linked, nonspecific.
452. Lissencephaly, X-linked - agenesis of the corpus callosum - genital anomalies.
2508. Micrencephaly - corpus callosum agenesis - abnormal genitalia.
94083. Partington syndrome.
3175. Spasticity - intellectual deficit - epilepsy, X-linked.
3451. West syndrome.
PharmGKBPA25024.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ96QS3.
HOVERGENQ96QS3.
OMAQ96QS3. KEPRRCS.

Gene expression databases

ArrayExpressQ96QS3.
BgeeQ96QS3.
CleanExHS_ARX.
GermOnlineENSG00000004848. Homo sapiens.

Family and domain databases

InterProIPR003654. Homeo_OAR.
IPR001356. Homeobox.
IPR017970. Homeobox_CS.
IPR012287. Homeodomain-rel.
[Graphical view]
Gene3DG3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
ProDomPD000010. Homeobox. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio88881.
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: June 16, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome X

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents