UniProt functional annotation for Q9HD67



	UniProt functional annotation for Q9HD67

UniProt code: Q9HD67.

Organism: Homo sapiens (Human).

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

Function: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as plus end-directed motor. The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. May play a role in neurite outgrowth and axon guidance. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts. {ECO:0000269|PubMed:16894163, ECO:0000269|PubMed:18570893}.

Function: [Isoform Headless]: Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity). {ECO:0000250}.

Subunit: Monomer, when in an inactive confomation in the cytosol. Homodimer in its active, membrane-bound conformation; antiparallel coiled coil-mediated dimer formation. Interacts strongly with CALM3 and weakly with CALM, the CALM3 interaction is essential for function in filopodial extension and motility. Interacts with ECPAS. Interacts with NEO1. Interacts with ITGB1 and ITGB3. Interacts with VASP (By similarity). Interacts with DCC and ITGB5; the presence of DCC inhibits ITGB5 binding. Interacts with tubulin; ITGB5 or DCC binding inhibits tubulin binding. {ECO:0000250, ECO:0000269|PubMed:11278607, ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:21321230, ECO:0000269|PubMed:21642953, ECO:0000269|PubMed:23012428}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:10984435}. Cell projection, lamellipodium {ECO:0000269|PubMed:10984435}. Cell projection, ruffle {ECO:0000269|PubMed:10984435}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10984435}. Cell projection, filopodium tip {ECO:0000269|PubMed:10984435}. Cytoplasm, cell cortex {ECO:0000269|PubMed:10984435}. Cell projection, filopodium membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=May be in an inactive, monomeric conformation in the cytosol. Detected in cytoplasmic punctae and in cell projections. Colocalizes with actin fibers. Undergoes forward and rearward movements within filopodia. Interacts with microtubules.

Tissue specificity: Ubiquitous. {ECO:0000269|PubMed:10984435}.

Domain: Interaction between the motor domain and the tail leads to an inactive, monomeric conformation. Phospholipid binding via the PH domains leads to the formation of the active, dimeric form of the protein and strongly increases actin-dependent ATPase activity and motor activity (By similarity). {ECO:0000250}.

Domain: Interacts with membranes containing phosphatidylinositol-3,4,5- trisphosphate via the PH domains. {ECO:0000250}.

Domain: IQ 3 domain mediates high-affinity calcium-dependent binding to CALM3/CLP.

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. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric; however, in its distal part seems to form a semirigid helical structure which overlaps with a region shown to mediate antiparallel coiled coil-mediated dimerization. {ECO:0000250|UniProtKB:F8VQB6, ECO:0000250|UniProtKB:P79114}.

Ptm: The initiator methionine for isoform Headless is removed. {ECO:0000250}.

Miscellaneous: [Isoform Headless]: Produced by alternative promoter usage. {ECO:0000305}.

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

Sequence caution: Sequence=BAA34519.2; Type=Erroneous initiation; Note=Extended N-terminus.; 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:		Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as plus end-directed motor. The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. May play a role in neurite outgrowth and axon guidance. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts. {ECO:0000269\|PubMed:16894163, ECO:0000269\|PubMed:18570893}.



Function:		[Isoform Headless]: Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity). {ECO:0000250}.


Subunit:		Monomer, when in an inactive confomation in the cytosol. Homodimer in its active, membrane-bound conformation; antiparallel coiled coil-mediated dimer formation. Interacts strongly with CALM3 and weakly with CALM, the CALM3 interaction is essential for function in filopodial extension and motility. Interacts with ECPAS. Interacts with NEO1. Interacts with ITGB1 and ITGB3. Interacts with VASP (By similarity). Interacts with DCC and ITGB5; the presence of DCC inhibits ITGB5 binding. Interacts with tubulin; ITGB5 or DCC binding inhibits tubulin binding. {ECO:0000250, ECO:0000269\|PubMed:11278607, ECO:0000269\|PubMed:20682791, ECO:0000269\|PubMed:21321230, ECO:0000269\|PubMed:21642953, ECO:0000269\|PubMed:23012428}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:10984435}. Cell projection, lamellipodium {ECO:0000269\|PubMed:10984435}. Cell projection, ruffle {ECO:0000269\|PubMed:10984435}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:10984435}. Cell projection, filopodium tip {ECO:0000269\|PubMed:10984435}. Cytoplasm, cell cortex {ECO:0000269\|PubMed:10984435}. Cell projection, filopodium membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=May be in an inactive, monomeric conformation in the cytosol. Detected in cytoplasmic punctae and in cell projections. Colocalizes with actin fibers. Undergoes forward and rearward movements within filopodia. Interacts with microtubules.
Tissue specificity:		Ubiquitous. {ECO:0000269\|PubMed:10984435}.
Domain:		Interaction between the motor domain and the tail leads to an inactive, monomeric conformation. Phospholipid binding via the PH domains leads to the formation of the active, dimeric form of the protein and strongly increases actin-dependent ATPase activity and motor activity (By similarity). {ECO:0000250}.
Domain:		Interacts with membranes containing phosphatidylinositol-3,4,5- trisphosphate via the PH domains. {ECO:0000250}.
Domain:		IQ 3 domain mediates high-affinity calcium-dependent binding to CALM3/CLP.
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. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric; however, in its distal part seems to form a semirigid helical structure which overlaps with a region shown to mediate antiparallel coiled coil-mediated dimerization. {ECO:0000250\|UniProtKB:F8VQB6, ECO:0000250\|UniProtKB:P79114}.
Ptm:		The initiator methionine for isoform Headless is removed. {ECO:0000250}.
Miscellaneous:		[Isoform Headless]: Produced by alternative promoter usage. {ECO:0000305}.
Similarity:		Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. {ECO:0000305}.
Sequence caution:		Sequence=BAA34519.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};