Q9H161 (ALX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein aristaless-like 4

Gene names

Name:	ALX4
Synonyms:	KIAA1788

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	411 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor involved in skull and limb development. Plays an essential role in craniofacial development, skin and hair follicle development. Ref.5
Subunit structure	Binds DNA By similarity.
Subcellular location	Nucleus Ref.5.
Tissue specificity	Expression is likely to be restricted to bone. Found in parietal bone.
Involvement in disease	Parietal foramina 2 (PFM2) [MIM:609597]: Autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM2 is also a clinical feature of Potocki-Shaffer syndrome. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.3 Frontonasal dysplasia 2 (FND2) [MIM:613451]: The term frontonasal dysplasia describes an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism; broadening of the nasal root; median facial cleft affecting the nose and/or upper lip and palate; unilateral or bilateral clefting of the alae nasi; lack of formation of the nasal tip; anterior cranium bifidum occultum; a V-shaped or widow's peak frontal hairline. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Potocki-Shaffer syndrome (POSHS) [MIM:601224]: A syndrome characterized by foramina parietalia permagna, multiple exostoses, and craniofacial dysostosis and mental retardation in some cases. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the paired homeobox family. Contains 1 homeobox DNA-binding domain.
Sequence caution	The sequence AAG23961.1 differs from that shown. Reason: Frameshift at positions 314, 323 and 340. The sequence BAB47417.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara digestive tract development Inferred from electronic annotation. Source: Compara embryonic digit morphogenesis Inferred from electronic annotation. Source: Compara embryonic forelimb morphogenesis Inferred from electronic annotation. Source: Compara embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara embryonic skeletal system morphogenesis Inferred from electronic annotation. Source: Compara hair follicle development Inferred from mutant phenotype Ref.5. Source: UniProtKB muscle organ development Inferred from electronic annotation. Source: Compara palate development Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from electronic annotation. Source: Compara skeletal system development Non-traceable author statement Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.5. Source: UniProtKB transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Non-traceable author statement Ref.3. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 411

411

Homeobox protein aristaless-like 4

PRO_0000048814

Regions

DNA binding

214 – 273

60

Homeobox

Motif

391 – 404

14

OAR

Compositional bias

104 – 115

12

Poly-Gln

Natural variations

Natural variant

35

1

R → T. Ref.2 Ref.3

VAR_010783

Natural variant

102

1

P → S. Ref.3
Corresponds to variant rs12421995 [ dbSNP | Ensembl ].

VAR_010784

Natural variant

218

1

R → Q in PFM2. Ref.3

VAR_010785

Natural variant

257

1

R → T.
Corresponds to variant rs3824915 [ dbSNP | Ensembl ].

VAR_058413

Natural variant

272

1

R → P in PFM2. Ref.2

VAR_010897

Experimental info

Sequence conflict

134

1

D → N in AAG23961. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

411

Helix Strand Turn

Details...

Helix

223 – 235

13

Helix

241 – 251

11

Helix

255 – 269

15

Sequences

	Sequence		Length	Mass (Da)
	Q9H161 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: D41780B230C7E55C	FASTA	411	44,241
	10 20 30 40 50 60 MNAETCVSYC ESPAAAMDAY YSPVSQSREG SSPFRAFPGG DKFGTTFLSA AAKAQGFGDA 70 80 90 100 110 120 KSRARYGAGQ QDLATPLESG AGARGSFNKF QPQPSTPQPQ PPPQPQPQQQ QPQPQPPAQP 130 140 150 160 170 180 HLYLQRGACK TPPDGSLKLQ EGSSGHSAAL QVPCYAKESS LGEPELPPDS DTVGMDSSYL 190 200 210 220 230 240 SVKEAGVKGP QDRASSDLPS PLEKADSESN KGKKRRNRTT FTSYQLEELE KVFQKTHYPD 250 260 270 280 290 300 VYAREQLAMR TDLTEARVQV WFQNRRAKWR KRERFGQMQQ VRTHFSTAYE LPLLTRAENY 310 320 330 340 350 360 AQIQNPSWLG NNGAASPVPA CVVPCDPVPA CMSPHAHPPG SGASSVTDFL SVSGAGSHVG 370 380 390 400 410 QTHMGSLFGA ASLSPGLNGY ELNGEPDRKT SSIAALRMKA KEHSAAISWA T

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Haploinsufficiency of ALX4 as a potential cause of parietal foramina in the 11p11.2 contiguous gene-deletion syndrome." Wu Y.-Q., Badano J.L., McCaskill C., Vogel H., Potocki L., Shaffer L.G. Am. J. Hum. Genet. 67:1327-1332(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The ALX4 homeobox gene is mutated in patients with ossification defects of the skull (foramina parietalia permagna, OMIM 168500)." Wuyts W., Cleiren E., Homfray T., Rasore-Quartino A., Vanhoenacker F., Van Hul W. J. Med. Genet. 37:916-920(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-35, VARIANT PFM2 PRO-272.
[3]	"Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects." Mavrogiannis L.A., Antonopoulou I., Baxova A., Kutilek S., Kim C.A., Sugayama S.M., Salamanca A., Wall S.A., Morriss-Kay G.M., Wilkie A.O.M. Nat. Genet. 27:17-18(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS THR-35 AND SER-102, VARIANT PFM2 GLN-218.
[4]	"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O. DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"ALX4 dysfunction disrupts craniofacial and epidermal development." Kayserili H., Uz E., Niessen C., Vargel I., Alanay Y., Tuncbilek G., Yigit G., Uyguner O., Candan S., Okur H., Kaygin S., Balci S., Mavili E., Alikasifoglu M., Haase I., Wollnik B., Akarsu N.A. Hum. Mol. Genet. 18:4357-4366(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FND2, FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF294629 mRNA. Translation: AAG23961.1. Frameshift.
AF308822 , AF308823, AF308824, AF308825 Genomic DNA. Translation: AAK38835.1.
AJ404888 mRNA. Translation: CAC15060.1.
AJ279074 , AJ279075, AJ279076, AJ279077 Genomic DNA. Translation: CAC15120.1.
AB058691 mRNA. Translation: BAB47417.1. Different initiation.

IPI

IPI00334769.

RefSeq

NP_068745.2. NM_021926.3.

UniGene

Hs.436055.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M0C	NMR	-	A	209-280	[»]

ProteinModelPortal

Q9H161.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000332744.

PTM databases

PhosphoSite

Q9H161.

Polymorphism databases

DMDM

254763249.

Proteomic databases

PaxDb

Q9H161.

PRIDE

Q9H161.

Protocols and materials databases

DNASU

60529.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000329255; ENSP00000332744; ENSG00000052850.

GeneID

60529.

KEGG

hsa:60529.

UCSC

uc001myb.3. human.

Organism-specific databases

CTD

60529.

GeneCards

GC11M044238.

HGNC

HGNC:450. ALX4.

MIM

601224. phenotype.
605420. gene.
609597. phenotype.
613451. phenotype.

neXtProt

NX_Q9H161.

Orphanet

228390. Frontonasal dysplasia with alopecia and genital anomaly.
60015. Parietal foramina.
52022. Potocki-Shaffer syndrome.

PharmGKB

PA24755.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309608.

HOGENOM

HOG000231518.

HOVERGEN

HBG004214.

InParanoid

Q9H161.

KO

K09451.

OMA

KFQPQPS.

OrthoDB

EOG4ZGPCG.

PhylomeDB

Q9H161.

Gene expression databases

Bgee

Q9H161.

CleanEx

HS_ALX4.

Genevestigator

Q9H161.

GermOnline

ENSG00000052850. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR017970. Homeobox_CS.
IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
IPR003654. OAR_dom.
[Graphical view]

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

GenomeRNAi

60529.

NextBio

65433.

SOURCE

Search...

Entry information

Entry name

ALX4_HUMAN

Accession

Primary (citable) accession number: Q9H161
Secondary accession number(s): Q96JN7, Q9H198, Q9HAY9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	July 28, 2009
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 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.