Q96QS3 (ARX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein ARX

Alternative name(s):
Aristaless-related homeobox

Gene names

Name:

ARX

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	562 AA.
Sequence status	Complete.
Protein existence	Evidence 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.2 Ref.4 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. Ref.3 Defects in ARX are the cause of 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. Ref.6
Sequence similarities	Belongs to the paired homeobox family. Bicoid subfamily. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Triplet repeat expansion
Disease	Disease mutation Epilepsy Lissencephaly Mental retardation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 562	562	Homeobox protein ARX		PRO_0000048819
Regions
	DNA binding	328 – 387	60	Homeobox
	Motif	530 – 543	14	OAR
	Compositional bias	100 – 155	56	Ala-rich
	Compositional bias	224 – 253	30	Glu-rich
	Compositional bias	395 – 459	65	Pro-rich
	Compositional bias	425 – 544	120	Ala-rich
Natural variations
	Natural variant	33	1	L → P in MRXARX. Ref.3 Corresponds to variant rs28936077 [ dbSNP | Ensembl ].		VAR_015669
	Natural variant	115	1	A → AAAAAAAA in EIEE1.		VAR_015177
	Natural variant	155	1	A → AAAAAAAAA in EIEE1 and PRTS; also found in non-specific mental retardation families; frequent mutation. Ref.2 Ref.4		VAR_015670
	Natural variant	286	1	G → S in MRXARX. Ref.3 Corresponds to variant rs28935479 [ dbSNP | Ensembl ].		VAR_015671
	Natural variant	332	1	R → H in LISX2. Ref.5 Ref.6 Corresponds to variant rs28936075 [ dbSNP | Ensembl ].		VAR_015178
	Natural variant	332	1	R → P in LISX2. Ref.6		VAR_033260
	Natural variant	333	1	T → N in ACCAG. Ref.6 Corresponds to variant rs28936078 [ dbSNP | Ensembl ].		VAR_033261
	Natural variant	343	1	L → Q in LISX2. Ref.5 Ref.6 Corresponds to variant rs28936076 [ dbSNP | Ensembl ].		VAR_015179
	Natural variant	353	1	P → L in EIEE1. Ref.4 Corresponds to variant rs28936074 [ dbSNP | Ensembl ].		VAR_015180
	Natural variant	353	1	P → R in LISX2. Ref.6		VAR_033262
	Natural variant	521	1	A → T in LISX2; severe phenotype. Ref.6		VAR_033263

Sequences

	Sequence		Length	Mass (Da)
	Q96QS3 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: FBDF41E387C65532	FASTA	562	58,160
	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

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. , Chaabouni H., Fryns J.-P., Desportes V., Beldjord C., Chelly J. Hum. Mol. Genet. 11:981-991(2002) [PubMed: 11971879] [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: 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. , 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. , 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 ACCAG ASN-333.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY038071 mRNA. Translation: AAK93901.1.
IPI	IPI00045066.
RefSeq	NP_620689.1. NM_139058.2.
UniGene	Hs.300304.
3D structure databases
ProteinModelPortal	Q96QS3.
SMR	Q96QS3. Positions 329-385.
ModBase	Search...
Protein-protein interaction databases
STRING	Q96QS3.
PTM databases
PhosphoSite	Q96QS3.
Polymorphism databases
DMDM	27923733.
Proteomic databases
PRIDE	Q96QS3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379044; ENSP00000368332; ENSG00000004848.
GeneID	170302.
KEGG	hsa:170302.
UCSC	uc004dbp.2. human.
Organism-specific databases
CTD	170302.
GeneCards	GC0XM024931.
H-InvDB	HIX0056192.
HGNC	HGNC:18060. ARX.
MIM	300004. phenotype. 300215. phenotype. 300382. gene. 300419. phenotype. 308350. phenotype. 309510. phenotype.
neXtProt	NX_Q96QS3.
Orphanet	1934. Early infantile epileptic 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 nonsyndromic intellectual deficit.
PharmGKB	PA25024.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07568.
GeneTree	ENSGT00600000084088.
HOGENOM	HBG715732.
HOVERGEN	HBG004285.
InParanoid	Q96QS3.
OMA	RRSPCKV.
PhylomeDB	Q96QS3.
Gene expression databases
ArrayExpress	Q96QS3.
Bgee	Q96QS3.
CleanEx	HS_ARX.
Genevestigator	Q96QS3.
GermOnline	ENSG00000004848. Homo sapiens.
Family and domain databases
InterPro	IPR003654. Homeo_OAR. IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KO	K09452.
Pfam	PF00046. Homeobox. 1 hit. PF03826. OAR. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. PS50803. OAR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	88881.
SOURCE	Search...

Entry information

Entry name

ARX_HUMAN

Accession

Primary (citable) accession number: Q96QS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 27, 2003
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 100 of the entry and version 1 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.