UniProt functional annotation for Q9UPN3



	UniProt functional annotation for Q9UPN3

UniProt code: Q9UPN3.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: [Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus- ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}.

Subunit: Isoform 2: Interacts with MAPRE1, CLASP1, CLASP2, AXIN1 and LRP6 (By similarity). Isoform 2: Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Isoform 2: Interacts with GOLGA4 (PubMed:15265687). Isoform 2: Interacts with CAMSAP3 (PubMed:27693509, PubMed:27802168). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:27693509, ECO:0000269|PubMed:27802168}.

Subcellular location: [Isoform 2]: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:27693509}. Cytoplasm {ECO:0000269|PubMed:15265687}. Golgi apparatus {ECO:0000269|PubMed:15265687}. Cell membrane {ECO:0000269|PubMed:20937854}. Cell projection, ruffle membrane {ECO:0000269|PubMed:20937854}. Note=The phosphorylated form is found in the cytoplasm while the non-phosphorylated form associates with the microtubules (By similarity). Localizes to the tips of microtubules (PubMed:27693509). Associated with the minus-end of microtubules via interaction with CAMSAP3 (PubMed:27693509). APC controls its localization to the cell membrane which is critical for its function in microtubule stabilization (PubMed:20937854). {ECO:0000250|UniProtKB:Q9QXZ0, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:27693509}.

Subcellular location: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:16076900}. Golgi apparatus {ECO:0000269|PubMed:16076900}. Note=Localizes to the tips of microtubules. {ECO:0000269|PubMed:16076900}.

Tissue specificity: Isoform 2: Ubiquitously expressed. Isoform 1: Expressed in cell lines NCI-H460, A-549 and HaCaT. Isoform 4: Expressed in heart, lung, pituitary and placenta, not found in brain, kidney, liver, pancreas or skeletal muscle. {ECO:0000269|PubMed:11845288, ECO:0000269|PubMed:16076900}.

Domain: The C-terminal tail is required for phosphorylation by GSK3B and for microtubule-binding. {ECO:0000250|UniProtKB:Q9QXZ0}.

Ptm: Phosphorylated on serine residues in the C-terminal tail by GSK3B. Phosphorylation inhibits microtubule-binding and this plays a critical role in bulge stem cell migration and skin wound repair. Wnt-signaling can repress phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q9QXZ0}.

Disease: Lissencephaly 9 with complex brainstem malformation (LIS9) [MIM:618325]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly. {ECO:0000269|PubMed:30471716}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the plakin or cytolinker family. {ECO:0000305}.

Sequence caution: Sequence=BAA83821.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		[Isoform 2]: F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus- ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity). {ECO:0000250\|UniProtKB:Q9QXZ0, ECO:0000269\|PubMed:15265687, ECO:0000269\|PubMed:20937854, ECO:0000269\|PubMed:27693509}.


Subunit:		Isoform 2: Interacts with MAPRE1, CLASP1, CLASP2, AXIN1 and LRP6 (By similarity). Isoform 2: Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Isoform 2: Interacts with GOLGA4 (PubMed:15265687). Isoform 2: Interacts with CAMSAP3 (PubMed:27693509, PubMed:27802168). {ECO:0000250\|UniProtKB:Q9QXZ0, ECO:0000269\|PubMed:15265687, ECO:0000269\|PubMed:27693509, ECO:0000269\|PubMed:27802168}.
Subcellular location:		[Isoform 2]: Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:15265687, ECO:0000269\|PubMed:27693509}. Cytoplasm {ECO:0000269\|PubMed:15265687}. Golgi apparatus {ECO:0000269\|PubMed:15265687}. Cell membrane {ECO:0000269\|PubMed:20937854}. Cell projection, ruffle membrane {ECO:0000269\|PubMed:20937854}. Note=The phosphorylated form is found in the cytoplasm while the non-phosphorylated form associates with the microtubules (By similarity). Localizes to the tips of microtubules (PubMed:27693509). Associated with the minus-end of microtubules via interaction with CAMSAP3 (PubMed:27693509). APC controls its localization to the cell membrane which is critical for its function in microtubule stabilization (PubMed:20937854). {ECO:0000250\|UniProtKB:Q9QXZ0, ECO:0000269\|PubMed:20937854, ECO:0000269\|PubMed:27693509}.
Subcellular location:		[Isoform 1]: Cytoplasm {ECO:0000269\|PubMed:16076900}. Golgi apparatus {ECO:0000269\|PubMed:16076900}. Note=Localizes to the tips of microtubules. {ECO:0000269\|PubMed:16076900}.
Tissue specificity:		Isoform 2: Ubiquitously expressed. Isoform 1: Expressed in cell lines NCI-H460, A-549 and HaCaT. Isoform 4: Expressed in heart, lung, pituitary and placenta, not found in brain, kidney, liver, pancreas or skeletal muscle. {ECO:0000269\|PubMed:11845288, ECO:0000269\|PubMed:16076900}.
Domain:		The C-terminal tail is required for phosphorylation by GSK3B and for microtubule-binding. {ECO:0000250\|UniProtKB:Q9QXZ0}.
Ptm:		Phosphorylated on serine residues in the C-terminal tail by GSK3B. Phosphorylation inhibits microtubule-binding and this plays a critical role in bulge stem cell migration and skin wound repair. Wnt-signaling can repress phosphorylation (By similarity). {ECO:0000250\|UniProtKB:Q9QXZ0}.
Disease:		Lissencephaly 9 with complex brainstem malformation (LIS9) [MIM:618325]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly. {ECO:0000269\|PubMed:30471716}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the plakin or cytolinker family. {ECO:0000305}.
Sequence caution:		Sequence=BAA83821.1; Type=Frameshift; Evidence={ECO:0000305};