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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in ALX4 are the cause of parietal foramina 2 (PFM2) [MIM:609597]; also known as foramina parietalia permagna (FPP). PFM2 is an 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. Ref.2 Ref.3 Defects in ALX4 are the cause of frontonasal dysplasia type 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. Ref.5 Involved in Potocki-Shaffer syndrome (PSS) [MIM:601224]. PSS is a contiguous gene syndrome caused by deletion of the 11p11.2 region.
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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	hair follicle development Inferred from mutant phenotype Ref.5. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
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

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: 11017806] [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: 11106354] [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: 11137991] [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: 11347906] [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: 19692347] [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
ProteinModelPortal	Q9H161.
SMR	Q9H161. Positions 215-271.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H161.
Polymorphism databases
DMDM	254763249.
Proteomic databases
PRIDE	Q9H161.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000329255; ENSP00000332744; ENSG00000052850.
GeneID	60529.
KEGG	hsa:60529.
UCSC	uc001myb.1. human.
Organism-specific databases
CTD	60529.
GeneCards	GC11M044238.
H-InvDB	HIX0009574.
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	prNOG06842.
GeneTree	ENSGT00600000084045.
HOGENOM	HBG713571.
HOVERGEN	HBG004214.
InParanoid	Q9H161.
OMA	KFQPQPS.
OrthoDB	EOG4ZGPCG.
PhylomeDB	Q9H161.
Gene expression databases
ArrayExpress	Q9H161.
Bgee	Q9H161.
CleanEx	HS_ALX4.
Genevestigator	Q9H161.
GermOnline	ENSG00000052850. 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	K09451.
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	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:	January 25, 2012
This is version 108 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.