UniProt functional annotation for P51142



	UniProt functional annotation for P51142

UniProt code: P51142.

Organism: Xenopus laevis (African clawed frog).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.

Function: Involved in at least 2 independent signaling cascades, controlling cell fate via canonical Wnt signaling and cell polarity via a planar cell polarity (PCP) cascade. Acts synergistically with dal/dapple-like to activate Wnt signaling, stabilizing ctnnb1/beta- catenin and leading to dorsal axis formation. Also prevents degradation of ctnnb1/beta-catenin by displacing gsk3 from a complex with ARP/Axin- related protein. Has an additional role in anterior-posterior (A/P) axis formation, specifying different neuroectodermal cell fates along the A/P axis in a dose-dependent manner by activating several early patterning genes. In the PCP pathway, required at the cell membrane for PCP-mediated neural and mesodermal convergent extension during gastrulation and subsequent neural tube closure, acting to activate jnk. Also involved in blastopore closure and archenteron elongation during early, but not late, gastrulation. Associates with ephrin receptors and ligands and acts as part of a downstream PCP pathway to mediate ephrin-mediated cell repulsion via activation of rhoa. Required for efnb1/ephrin-B1-driven movement of non-retinal progenitor cells into the retina during eye field formation. Patterns the hindbrain. Required for ciliogenesis. Controls the docking of basal bodies to the apical plasma membrane; mediates the activation, but not localization of rhoa at the apical surface of ciliated cells during basal body docking. Furthermore, required for the association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein exoc4/sec8, and this association is in turn required for basal body docking. Once basal bodies are docked, required for the planar polarization of basal bodies that underlies ciliary beating and the directional fluid flow across ciliated epithelia. {ECO:0000269|PubMed:10427095, ECO:0000269|PubMed:10688669, ECO:0000269|PubMed:10811222, ECO:0000269|PubMed:11493574, ECO:0000269|PubMed:11941372, ECO:0000269|PubMed:11970895, ECO:0000269|PubMed:12421719, ECO:0000269|PubMed:12574121, ECO:0000269|PubMed:15548584, ECO:0000269|PubMed:15677333, ECO:0000269|PubMed:15936275, ECO:0000269|PubMed:16026968, ECO:0000269|PubMed:16362052, ECO:0000269|PubMed:18552847, ECO:0000269|PubMed:7600981, ECO:0000269|PubMed:8939601, ECO:0000269|PubMed:9076682}.

Subunit: Can form homomultimers. Interacts with prickle1. Interacts (via PDZ domain) with ccdc88c/dal and dact1-B/dpr. Interacts (via DIX domain) with ARP/Axin-related protein and dact1-A/frodo. Interacts with sdc4, possibly via fz7. Interacts directly (via DEP domain) with efnb1/ephrin-B1 and indirectly with the phosphorylated ephrin receptors ephb1 and ephb2, via association with SH domain-containing adapters. May interact with lrrc6. Interacts with custos (via NLS1 and NLS2); the interaction is negatively regulated by Wnt stimulation (PubMed:25157132). {ECO:0000269|PubMed:10688669, ECO:0000269|PubMed:10698942, ECO:0000269|PubMed:11941372, ECO:0000269|PubMed:11970895, ECO:0000269|PubMed:12574121, ECO:0000269|PubMed:12699625, ECO:0000269|PubMed:16026968, ECO:0000269|PubMed:16362052, ECO:0000269|PubMed:16604063, ECO:0000269|PubMed:18539122, ECO:0000269|PubMed:25157132}.

Subcellular location: Cytoplasm. Cytoplasmic vesicle. Cell projection, cilium. Nucleus. Cell membrane; Peripheral membrane protein. Note=Phosphorylated and recruited from the cytoplasm to the cell membrane by frizzled proteins. Also relocated to the cell membrane by sdc4 and ephb1/ephrin-B1. Concentrated at cell membrane in both ciliated and non-ciliated cells. Enriched at the apical surface of ciliated cells. Localized to the cilium rootlet.

Tissue specificity: Expressed equally in both animal-vegetal and dorsal-ventral directions of the early blastula. Becomes enriched on the dorsal side of the embryo after cortical rotation. Expressed along the anterior margin of eye field of neurulae (stage 16 embryos) and in the anterolateral crescent that borders the eye field. Continues to be expressed in the optic cup at stage 26. Expressed in the central nervous system throughout the early tailbud stage including the entire hindbrain. {ECO:0000269|PubMed:10427095, ECO:0000269|PubMed:12574121, ECO:0000269|PubMed:16362052, ECO:0000269|PubMed:7600981}.

Developmental stage: Expressed maternally. Most abundant in eggs and expressed at a low level in blastulae, gastrulae, neurulae and tailbud embryonic stages. {ECO:0000269|PubMed:7600981}.

Domain: The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base. {ECO:0000269|PubMed:10688669, ECO:0000269|PubMed:10698942, ECO:0000269|PubMed:18552847}.

Ptm: Phosphorylated. Phosphorylation is controlled by frizzled proteins, correlates with the onset of embryo dorsalizing events and is higher in the dorsal half of early cleavage embryos. Phosphorylated on tyrosine residues in response to association with efnb1/ephrin-B1. {ECO:0000269|PubMed:10698942}.

Similarity: Belongs to the DSH family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Xenopus laevis (African clawed frog).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.



Function:		Involved in at least 2 independent signaling cascades, controlling cell fate via canonical Wnt signaling and cell polarity via a planar cell polarity (PCP) cascade. Acts synergistically with dal/dapple-like to activate Wnt signaling, stabilizing ctnnb1/beta- catenin and leading to dorsal axis formation. Also prevents degradation of ctnnb1/beta-catenin by displacing gsk3 from a complex with ARP/Axin- related protein. Has an additional role in anterior-posterior (A/P) axis formation, specifying different neuroectodermal cell fates along the A/P axis in a dose-dependent manner by activating several early patterning genes. In the PCP pathway, required at the cell membrane for PCP-mediated neural and mesodermal convergent extension during gastrulation and subsequent neural tube closure, acting to activate jnk. Also involved in blastopore closure and archenteron elongation during early, but not late, gastrulation. Associates with ephrin receptors and ligands and acts as part of a downstream PCP pathway to mediate ephrin-mediated cell repulsion via activation of rhoa. Required for efnb1/ephrin-B1-driven movement of non-retinal progenitor cells into the retina during eye field formation. Patterns the hindbrain. Required for ciliogenesis. Controls the docking of basal bodies to the apical plasma membrane; mediates the activation, but not localization of rhoa at the apical surface of ciliated cells during basal body docking. Furthermore, required for the association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein exoc4/sec8, and this association is in turn required for basal body docking. Once basal bodies are docked, required for the planar polarization of basal bodies that underlies ciliary beating and the directional fluid flow across ciliated epithelia. {ECO:0000269\|PubMed:10427095, ECO:0000269\|PubMed:10688669, ECO:0000269\|PubMed:10811222, ECO:0000269\|PubMed:11493574, ECO:0000269\|PubMed:11941372, ECO:0000269\|PubMed:11970895, ECO:0000269\|PubMed:12421719, ECO:0000269\|PubMed:12574121, ECO:0000269\|PubMed:15548584, ECO:0000269\|PubMed:15677333, ECO:0000269\|PubMed:15936275, ECO:0000269\|PubMed:16026968, ECO:0000269\|PubMed:16362052, ECO:0000269\|PubMed:18552847, ECO:0000269\|PubMed:7600981, ECO:0000269\|PubMed:8939601, ECO:0000269\|PubMed:9076682}.


Subunit:		Can form homomultimers. Interacts with prickle1. Interacts (via PDZ domain) with ccdc88c/dal and dact1-B/dpr. Interacts (via DIX domain) with ARP/Axin-related protein and dact1-A/frodo. Interacts with sdc4, possibly via fz7. Interacts directly (via DEP domain) with efnb1/ephrin-B1 and indirectly with the phosphorylated ephrin receptors ephb1 and ephb2, via association with SH domain-containing adapters. May interact with lrrc6. Interacts with custos (via NLS1 and NLS2); the interaction is negatively regulated by Wnt stimulation (PubMed:25157132). {ECO:0000269\|PubMed:10688669, ECO:0000269\|PubMed:10698942, ECO:0000269\|PubMed:11941372, ECO:0000269\|PubMed:11970895, ECO:0000269\|PubMed:12574121, ECO:0000269\|PubMed:12699625, ECO:0000269\|PubMed:16026968, ECO:0000269\|PubMed:16362052, ECO:0000269\|PubMed:16604063, ECO:0000269\|PubMed:18539122, ECO:0000269\|PubMed:25157132}.
Subcellular location:		Cytoplasm. Cytoplasmic vesicle. Cell projection, cilium. Nucleus. Cell membrane; Peripheral membrane protein. Note=Phosphorylated and recruited from the cytoplasm to the cell membrane by frizzled proteins. Also relocated to the cell membrane by sdc4 and ephb1/ephrin-B1. Concentrated at cell membrane in both ciliated and non-ciliated cells. Enriched at the apical surface of ciliated cells. Localized to the cilium rootlet.
Tissue specificity:		Expressed equally in both animal-vegetal and dorsal-ventral directions of the early blastula. Becomes enriched on the dorsal side of the embryo after cortical rotation. Expressed along the anterior margin of eye field of neurulae (stage 16 embryos) and in the anterolateral crescent that borders the eye field. Continues to be expressed in the optic cup at stage 26. Expressed in the central nervous system throughout the early tailbud stage including the entire hindbrain. {ECO:0000269\|PubMed:10427095, ECO:0000269\|PubMed:12574121, ECO:0000269\|PubMed:16362052, ECO:0000269\|PubMed:7600981}.
Developmental stage:		Expressed maternally. Most abundant in eggs and expressed at a low level in blastulae, gastrulae, neurulae and tailbud embryonic stages. {ECO:0000269\|PubMed:7600981}.
Domain:		The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base. {ECO:0000269\|PubMed:10688669, ECO:0000269\|PubMed:10698942, ECO:0000269\|PubMed:18552847}.
Ptm:		Phosphorylated. Phosphorylation is controlled by frizzled proteins, correlates with the onset of embryo dorsalizing events and is higher in the dorsal half of early cleavage embryos. Phosphorylated on tyrosine residues in response to association with efnb1/ephrin-B1. {ECO:0000269\|PubMed:10698942}.
Similarity:		Belongs to the DSH family. {ECO:0000305}.