UniProt functional annotation for Q29122



	UniProt functional annotation for Q29122

UniProt code: Q29122.

Organism: Sus scrofa (Pig).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.

Function: Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (By similarity). Has slow rate of actin-activated ADP release due to weak ATP binding (PubMed:15944696). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (PubMed:16917816). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (By similarity). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (By similarity). May act as a regulator of F-actin dynamics (PubMed:7929586). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (By similarity). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (By similarity). May play a role in the extension and network organization of neurites (By similarity). Required for structural integrity of inner ear hair cells (By similarity). Modulates RNA polymerase II-dependent transcription (By similarity). {ECO:0000250|UniProtKB:Q64331, ECO:0000250|UniProtKB:Q9UM54, ECO:0000269|PubMed:15944696, ECO:0000269|PubMed:16917816, ECO:0000269|PubMed:7929586}.

Subunit: Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (PubMed:25159143, PubMed:19664948). Component of the DISP/DOCK7-induced septin displacement complex, at least composed of DOCK7, LRCH3 and MYO6 (By similarity). Able to function as a monomer under specific conditions in vitro (By similarity). Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells (By similarity). Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal (PubMed:15037754). This interaction occurs only if the C- terminal lobe of calmodulin is occupied by calcium (PubMed:12682054, PubMed:15037754). Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (PubMed:7929586). Interacts with DAB2 (By similarity). In vitro, the C- terminal globular tail binds a C-terminal region of DAB2 (By similarity). Interacts with CFTR (By similarity). Interacts with OPTN (By similarity). Interacts with CABP5 (By similarity). {ECO:0000250|UniProtKB:E1BPK6, ECO:0000250|UniProtKB:Q64331, ECO:0000250|UniProtKB:Q9I8D1, ECO:0000250|UniProtKB:Q9UM54, ECO:0000269|PubMed:12682054, ECO:0000269|PubMed:15037754, ECO:0000269|PubMed:19664948, ECO:0000269|PubMed:25159143, ECO:0000269|PubMed:7929586}.

Subcellular location: Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q9UM54}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9UM54}. Golgi apparatus {ECO:0000250|UniProtKB:Q9UM54}. Nucleus {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q9UM54}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250|UniProtKB:Q9UM54}. Cell projection, filopodium {ECO:0000250|UniProtKB:Q9UM54}. Cell projection, ruffle membrane {ECO:0000269|PubMed:16917816}. Cell projection, microvillus {ECO:0000250|UniProtKB:Q9UM54}. Cytoplasm, cytosol {ECO:0000269|PubMed:7929586}. Note=Also present in endocytic vesicles (PubMed:16917816). Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage (By similarity). Recruited into membrane ruffles from cell surface by EGF- stimulation (By similarity). Colocalizes with DAB2 in clathrin-coated pits/vesicles (By similarity). Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q9I8D1, ECO:0000250|UniProtKB:Q9UM54, ECO:0000269|PubMed:16917816}.

Tissue specificity: Expressed in all tissues examined including kidney cortex, intestinal mucosa, liver, lung, heart, jowl muscle, brain cortex and medulla, and in the epithelial cell line, LLC-PK1 (at protein level) (PubMed:7929586). In the kidney, located to the brush border of adult kidney proximal tubule cells (PubMed:7929586). {ECO:0000269|PubMed:7929586}.

Developmental stage: Locates to the apical domain only during the final stages of kidney proximal tubule development.

Domain: Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding. {ECO:0000269|PubMed:19664948, ECO:0000269|PubMed:25159143}.

Domain: The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha- helical structure by ionic bonds. Its contribution to the mechanism confering the myosin movement on actin filaments is debated. {ECO:0000250|UniProtKB:Q9UM54}.

Ptm: Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK). {ECO:0000269|PubMed:12682054}.

Similarity: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Sus scrofa (Pig).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.



Function:		Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (By similarity). Has slow rate of actin-activated ADP release due to weak ATP binding (PubMed:15944696). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (PubMed:16917816). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (By similarity). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (By similarity). May act as a regulator of F-actin dynamics (PubMed:7929586). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (By similarity). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (By similarity). May play a role in the extension and network organization of neurites (By similarity). Required for structural integrity of inner ear hair cells (By similarity). Modulates RNA polymerase II-dependent transcription (By similarity). {ECO:0000250\|UniProtKB:Q64331, ECO:0000250\|UniProtKB:Q9UM54, ECO:0000269\|PubMed:15944696, ECO:0000269\|PubMed:16917816, ECO:0000269\|PubMed:7929586}.


Subunit:		Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (PubMed:25159143, PubMed:19664948). Component of the DISP/DOCK7-induced septin displacement complex, at least composed of DOCK7, LRCH3 and MYO6 (By similarity). Able to function as a monomer under specific conditions in vitro (By similarity). Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells (By similarity). Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal (PubMed:15037754). This interaction occurs only if the C- terminal lobe of calmodulin is occupied by calcium (PubMed:12682054, PubMed:15037754). Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (PubMed:7929586). Interacts with DAB2 (By similarity). In vitro, the C- terminal globular tail binds a C-terminal region of DAB2 (By similarity). Interacts with CFTR (By similarity). Interacts with OPTN (By similarity). Interacts with CABP5 (By similarity). {ECO:0000250\|UniProtKB:E1BPK6, ECO:0000250\|UniProtKB:Q64331, ECO:0000250\|UniProtKB:Q9I8D1, ECO:0000250\|UniProtKB:Q9UM54, ECO:0000269\|PubMed:12682054, ECO:0000269\|PubMed:15037754, ECO:0000269\|PubMed:19664948, ECO:0000269\|PubMed:25159143, ECO:0000269\|PubMed:7929586}.
Subcellular location:		Golgi apparatus, trans-Golgi network membrane {ECO:0000250\|UniProtKB:Q9UM54}; Peripheral membrane protein {ECO:0000250\|UniProtKB:Q9UM54}. Golgi apparatus {ECO:0000250\|UniProtKB:Q9UM54}. Nucleus {ECO:0000250\|UniProtKB:Q9UM54}. Cytoplasm, perinuclear region {ECO:0000250\|UniProtKB:Q9UM54}. Membrane, clathrin-coated pit {ECO:0000250\|UniProtKB:Q9UM54}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250\|UniProtKB:Q9UM54}. Cell projection, filopodium {ECO:0000250\|UniProtKB:Q9UM54}. Cell projection, ruffle membrane {ECO:0000269\|PubMed:16917816}. Cell projection, microvillus {ECO:0000250\|UniProtKB:Q9UM54}. Cytoplasm, cytosol {ECO:0000269\|PubMed:7929586}. Note=Also present in endocytic vesicles (PubMed:16917816). Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage (By similarity). Recruited into membrane ruffles from cell surface by EGF- stimulation (By similarity). Colocalizes with DAB2 in clathrin-coated pits/vesicles (By similarity). Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (By similarity). {ECO:0000250\|UniProtKB:Q9I8D1, ECO:0000250\|UniProtKB:Q9UM54, ECO:0000269\|PubMed:16917816}.
Tissue specificity:		Expressed in all tissues examined including kidney cortex, intestinal mucosa, liver, lung, heart, jowl muscle, brain cortex and medulla, and in the epithelial cell line, LLC-PK1 (at protein level) (PubMed:7929586). In the kidney, located to the brush border of adult kidney proximal tubule cells (PubMed:7929586). {ECO:0000269\|PubMed:7929586}.
Developmental stage:		Locates to the apical domain only during the final stages of kidney proximal tubule development.
Domain:		Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding. {ECO:0000269\|PubMed:19664948, ECO:0000269\|PubMed:25159143}.
Domain:		The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha- helical structure by ionic bonds. Its contribution to the mechanism confering the myosin movement on actin filaments is debated. {ECO:0000250\|UniProtKB:Q9UM54}.
Ptm:		Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK). {ECO:0000269\|PubMed:12682054}.
Similarity:		Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. {ECO:0000305}.