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Q9H161 (ALX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein aristaless-like 4
Gene names
Name:ALX4
Synonyms:KIAA1788
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Craniosynostosis 5 (CRS5) [MIM:615529]: A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6

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. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseCraniosynostosis
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

digestive tract development

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic forelimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

hair follicle development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

muscle organ development

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Non-traceable author statement Ref.2. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay Ref.5. Source: UniProtKB

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Non-traceable author statement Ref.3. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Homeobox protein aristaless-like 4
PRO_0000048814

Regions

DNA binding214 – 27360Homeobox
Motif391 – 40414OAR
Compositional bias104 – 11512Poly-Gln

Natural variations

Natural variant71V → F in CRS5; low-penetrance mutation associated with disease susceptibility; results in gain-of-function. Ref.6
VAR_069279
Natural variant351R → T. Ref.2 Ref.3
Corresponds to variant rs3824915 [ dbSNP | Ensembl ].
VAR_010783
Natural variant1021P → S. Ref.3
Corresponds to variant rs12421995 [ dbSNP | Ensembl ].
VAR_010784
Natural variant2111K → E in CRS5; low-penetrance mutation associated with disease susceptibility; results in gain-of-function. Ref.6
VAR_069280
Natural variant2181R → Q in PFM2. Ref.3
VAR_010785
Natural variant2571R → T.
Corresponds to variant rs3824915 [ dbSNP | Ensembl ].
VAR_058413
Natural variant2721R → P in PFM2. Ref.2
VAR_010897
Natural variant3061P → L. Ref.6
VAR_069281

Experimental info

Sequence conflict1341D → N in AAG23961. Ref.1

Secondary structure

....... 411
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9H161 [UniParc].

Last modified July 28, 2009. Version 2.
Checksum: D41780B230C7E55C

FASTA41144,241
        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 

« Hide

References

« Hide '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.
[6]"ALX4 gain-of-function mutations in nonsyndromic craniosynostosis."
Yagnik G., Ghuman A., Kim S., Stevens C.G., Kimonis V., Stoler J., Sanchez-Lara P.A., Bernstein J.A., Naydenov C., Drissi H., Cunningham M.L., Kim J., Boyadjiev S.A.
Hum. Mutat. 33:1626-1629(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CRS5 PHE-7 AND GLU-211, VARIANT LEU-306, CHARACTERIZATION OF VARIANTS CRS5 PHE-7 AND GLU-211, CHARACTERIZATION OF VARIANT LEU-306.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF294629 mRNA. Translation: AAG23961.1. Frameshift.
AF308822 expand/collapse EMBL AC list , AF308823, AF308824, AF308825 Genomic DNA. Translation: AAK38835.1.
AJ404888 mRNA. Translation: CAC15060.1.
AJ279074 expand/collapse EMBL AC list , AJ279075, AJ279076, AJ279077 Genomic DNA. Translation: CAC15120.1.
AB058691 mRNA. Translation: BAB47417.1. Different initiation.
CCDSCCDS31468.1.
RefSeqNP_068745.2. NM_021926.3.
UniGeneHs.436055.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2M0CNMR-A209-280[»]
ProteinModelPortalQ9H161.
SMRQ9H161. Positions 209-280.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121938. 10 interactions.
STRING9606.ENSP00000332744.

PTM databases

PhosphoSiteQ9H161.

Polymorphism databases

DMDM254763249.

Proteomic databases

MaxQBQ9H161.
PaxDbQ9H161.
PRIDEQ9H161.

Protocols and materials databases

DNASU60529.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329255; ENSP00000332744; ENSG00000052850.
GeneID60529.
KEGGhsa:60529.
UCSCuc001myb.3. human.

Organism-specific databases

CTD60529.
GeneCardsGC11M044238.
GeneReviewsALX4.
HGNCHGNC:450. ALX4.
MIM601224. phenotype.
605420. gene.
609597. phenotype.
613451. phenotype.
615529. phenotype.
neXtProtNX_Q9H161.
Orphanet228390. Frontonasal dysplasia with alopecia and genital anomaly.
35093. Isolated scaphocephaly.
60015. Parietal foramina.
52022. Potocki-Shaffer syndrome.
PharmGKBPA24755.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG309608.
HOGENOMHOG000231518.
HOVERGENHBG004214.
InParanoidQ9H161.
KOK09451.
OMAVSGAGGH.
OrthoDBEOG7DRJ35.
PhylomeDBQ9H161.
TreeFamTF350743.

Gene expression databases

BgeeQ9H161.
CleanExHS_ALX4.
GenevestigatorQ9H161.

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

GeneWikiALX4.
GenomeRNAi60529.
NextBio65433.
PROQ9H161.
SOURCESearch...

Entry information

Entry nameALX4_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 133 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 11

Human chromosome 11: entries, gene names and cross-references to MIM