PRRX1
Function
Master transcription factor of stromal fibroblasts for myofibroblastic lineage progression. Orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-beta signaling by remodeling a super-enhancer landscape. Through this function, plays an essential role in wound healing process (PubMed:35589735). Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer (By similarity). May play a role in homeostasis and regeneration of bone, white adipose tissue and derm (By similarity).
Isoform 1
Transcriptional activator, when transfected in fibroblastic or myoblastic cell lines. This activity may be masked by the C-terminal OAR domain.
Isoform 2
Transcriptional repressor, when transfected in fibroblastic or myoblastic cell lines.
Involvement in disease
Agnathia-otocephaly complex
AGOTC
A rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal.
None
The disease is caused by variants affecting the gene represented in this entry.
Strongly expressed in cancer-associated fibroblasts (CAFs) in various cancer types. Its expression correlates with unfavorable clinical outcome. May be essential for the tumorigenicity and metastasis-inducing capacity of CAFs. Can reprogram tumor-suppressive normal fibroblasts into CAFs.
Sequence Similarities
Belongs to the paired homeobox family.
Tissue Specificity
Isoform 1
Widely expressed in embryonic and adult tissues, with highest levels in skeletal muscle. Isoform 1 is either expressed at similar or higher levels compared to isoform 2 in all embryonic tissues but skeletal muscle and heart. In adult tissues, expressed at lower levels compared to isoform 2.
Isoform 2
Widely expressed in embryonic and adult tissues, with highest levels in skeletal muscle. Isoform 2 is either expressed at similar or lower levels compared to isoform 1 in all embryonic tissues but skeletal muscle and heart, where it is expressed at higher levels. In adult tissues, expressed at higher levels compared to isoform 1.
Cellular localization
- Nucleus
Alternative names
PMX1, PRRX1, Paired mesoderm homeobox protein 1, Homeobox protein PHOX1, Paired-related homeobox protein 1, PRX-1