Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Alx4. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a paired-like homeodomain transcription factor expressed in the mesenchyme of developing bones, limbs, hair, teeth, and mammary tissue. Mutations in this gene cause parietal foramina 2 (PFM2); an autosomal dominant disease characterized by deficient ossification of the parietal bones. Mutations in this gene also cause a form of frontonasal dysplasia with alopecia and hypogonadism; suggesting a role for this gene in craniofacial development, mesenchymal-epithelial communication, and hair follicle development. Deletion of a segment of chromosome 11 containing this gene, del(11)(p11p12), causes Potocki-Shaffer syndrome (PSS); a syndrome characterized by craniofacial anomalies, mental retardation, multiple exostoses, and genital abnormalities in males. In mouse, this gene has been shown to use dual translation initiation sites located 16 codons apart. [provided by RefSeq, Oct 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Alx4
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter ^{[5, 8]}
    • regulation of transcription from RNA polymerase II promoter ^[2]
  • performs the following molecular functions:
    • sequence-specific DNA binding ^[5]
    • sequence-specific DNA binding transcription factor activity ^{[2, 5, 8]}
  • is located in the following cellular components:
    • nucleus ^{[5, 7]}
    • transcription factor complex ^[8]
• The gene product of Alx4 has been shown to bind to the gene products of Lef1. ^{[2, 5]} Researchers have inferred, based on physical interactions, that the gene product of Alx4
  • performs the following molecular functions:
    • HMG box domain binding ^[9]
    • protein heterodimerization activity ^[8]
  • is located in the following cellular components:
    • transcription factor complex ^[2]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Alx4
  • participates in the following biological processes:
    • anterior/posterior pattern specification ^{[7, 8]}
    • digestive tract development ^[3]
    • embryonic digit morphogenesis ^[3]
    • embryonic skeletal system morphogenesis ^[6]
    • limb morphogenesis ^{[7, 8]}
    • muscle organ development ^[7]
    • post-embryonic development ^[3]
    • skeletal system morphogenesis ^[7]
• Researchers have inferred, based on genetic interactions, that the gene product of Alx4
  • participates in the following biological processes:
    • anterior/posterior pattern specification based on interactions with Alx1 ^[8]
    • embryonic digit morphogenesis based on interactions with Bmp4 ^[4]
    • embryonic forelimb morphogenesis based on interactions with Alx3 ^[1]
    • embryonic hindlimb morphogenesis based on interactions with Alx3 ^[1]
    • embryonic skeletal system morphogenesis based on interactions with Alx1, Alx3 ^{[1, 6, 8]}
    • limb morphogenesis based on interactions with Alx1 ^[8]
    • palate development based on interactions with Alx1 ^[8]
    • pattern specification process based on interactions with Alx3 ^[1]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Alx1 ^[8]
    • regulation of apoptotic process based on interactions with Alx3 ^[1]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Alx4:
  • participates in the following biological processes:
    • hair follicle development
  • is located in the following cellular components:
    • nucleus

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Summary text based on GO annotations supported by structural data

• Alx4 encodes a protein or proteins that contain the following InterPro domains: Homeobox, conserved site, Homeodomain, Homeodomain-like, OAR domain, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent
  • performs the following molecular functions:
    • DNA binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Alx4 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • regulation of transcription, DNA-dependent
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • DNA binding

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References

1. Beverdam A et al. (2001) Severe nasal clefting and abnormal embryonic apoptosis in Alx3/Alx4 double mutant mice. Development, 128:3975-86. (PubMed:11641221)
2. Boras K et al. (2002) Alx4 binding to LEF-1 regulates N-CAM promoter activity. J Biol Chem, 277:1120-7. (PubMed:11696550)
3. Dunn NR et al. (1997) Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol, 188:235-47. (PubMed:9268572)
4. Dunwoodie SL et al. (1997) Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Development, 124:3065-76. (PubMed:9272948)
5. Hudson R et al. (1998) Alx-4, a transcriptional activator whose expression is restricted to sites of epithelial-mesenchymal interactions. Dev Dyn, 213:159-69. (PubMed:9786416)
6. Kuijper S et al. (2005) Genetics of shoulder girdle formation: roles of Tbx15 and aristaless-like genes. Development, 132:1601-10. (PubMed:15728667)
7. Qu S et al. (1997) Polydactyly and ectopic ZPA formation in Alx-4 mutant mice. Development, 124:3999-4008. (PubMed:9374397)
8. Qu S et al. (1999) Physical and genetic interactions between Alx4 and Cart1. Development, 126:359-69. (PubMed:9847249)
9. Wissmuller S et al. (2006) The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors. Nucleic Acids Res, 34:1735-44. (PubMed:16582099)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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