p63 Transcription Factor Activity Assay (TFAB00147)

Cofactor: Binds 1 zinc ion per subunit

By similarity.

Subunit structure: Binds DNA as a homotetramer. Isoform compositionof the tetramer may determine transactivation activity. Isoforms Alpha and Gamma interact with HIPK2. Interacts with SSRP1, leading to stimulate coactivator activity. Isoform 1 and isoform 2 interact with WWP1. Interacts with PDS5A. Isoform 5 (via activation domain) interacts with NOC2L. Ref.10 Ref.13 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23

Subcellular location: Nucleus Ref.17 Ref.23.

Tissue specificity: Widely expressed, notably in heart, kidney, placenta, prostate, skeletal muscle, testis and thymus, although the precise isoform variesaccording to tissue type. Progenitor cell layers of skin, breast, eye and prostate express high levels of DeltaN-type isoforms. Isoform 10 is predominantly expressed in skin squamous cell carcinomas, but not in normal skin tissues. Ref.3 Ref.8 Ref.14

Domain: The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms. Ref.17 Ref.18

Post-translational modification: May be sumoylated

By similarity.Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. Ref.21

Involvement in Disease: Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:103285]: A form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia and loss of permanent teeth. ADULT syndrome differs significantly from EEC3 syndrome by the absence of facial clefting.Note: The disease is caused by mutations affecting the gene represented in this entry.Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:106260]: An autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3) [MIM:604292]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Ref.27 Ref.30 Ref.32Split-hand/foot malformation 4 (SHFM4) [MIM:605289]: A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27 Ref.30Limb-mammary syndrome (LMS) [MIM:603543]: Characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers.Ectodermal dysplasia, Rapp-Hodgkin type (EDRH) [MIM:129400]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33 Ref.34 Ref.35 Ref.36Non-syndromic orofacial cleft 8 (OFC8) [MIM:129400]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities: Belongs to the p53 family.Contains 1 SAM (sterile alpha motif) domain.

Sequence caution: The sequence AAF43486.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF43487.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF43488.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF43489.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF61624.1 differs from that shown. Reason: Frameshift at position 26. The sequence BAA32592.1 differs from that shown. Reason: Frameshift at position 26. The sequence BAA32593.1 differs from that shown. Reason: Frameshift at position 26.