UniProt functional annotation for P50570



	UniProt functional annotation for P50570

UniProt code: P50570.

Organism: Homo sapiens (Human).

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

Function: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Plays an important role in vesicular trafficking processes, in particular endocytosis (PubMed:33713620). Involved in cytokinesis (PubMed:12498685). Regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). {ECO:0000250|UniProtKB:P39052, ECO:0000250|UniProtKB:P39054, ECO:0000269|PubMed:12498685, ECO:0000269|PubMed:33713620}.

Catalytic activity: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5;

Subunit: Interacts with MYOF (By similarity). Interacts with CTTN and ACTN1 (By similarity). Interacts with SHANK1, SHANK2, SH3BP4 and NOSTRIN. Interacts with SNX9. Interacts with SNX33 (via SH3 domain). Interacts with MYO1E (via SH3 domain). Interacts with PSTPIP1. Interacts with CTNND2 (PubMed:22022388). May interact with PIK3C3 (By similarity). May be a component of a complex composed of RAB5A (in GDP- bound form), DYN2 and PIK3C3 (By similarity). Interacts with BIN1 (PubMed:17676042). {ECO:0000250|UniProtKB:P39052, ECO:0000250|UniProtKB:P39054, ECO:0000269|PubMed:11583995, ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:16234328, ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:17676042, ECO:0000269|PubMed:18353773, ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:22022388}.

Subcellular location: Cytoplasm. Cytoplasm, cytoskeleton. Cell junction {ECO:0000250|UniProtKB:P39052}. Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:P39052}. Cell junction, synapse, postsynaptic density. Cell junction, synapse. Midbody. Cell projection, phagocytic cup {ECO:0000250|UniProtKB:P39054}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:P39054}; Peripheral membrane protein {ECO:0000250|UniProtKB:P39054}. Note=Colocalizes with CTTN at the basis of filopodia in hippocampus neuron growth zones (By similarity). Microtubule-associated. Also found in the postsynaptic density of neuronal cells. Co-localizes with PIK3C3 and RAB5A to the nascent phagosome (By similarity). {ECO:0000250|UniProtKB:P39052, ECO:0000250|UniProtKB:P39054}.

Tissue specificity: Ubiquitously expressed.

Ptm: Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry. It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis. Dephosphorylated by calcineurin/PP2 (By similarity). Phosphorylated on tyrosine residues after activation of SRC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P39052}.

Disease: Myopathy, centronuclear, 1 (CNM1) [MIM:160150]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269|PubMed:16227997, ECO:0000269|PubMed:17825552, ECO:0000269|PubMed:17932957, ECO:0000269|PubMed:19122038, ECO:0000269|PubMed:19623537, ECO:0000269|PubMed:19932619, ECO:0000269|PubMed:19932620, ECO:0000269|PubMed:20227276, ECO:0000269|PubMed:22396310}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Lethal congenital contracture syndrome 5 (LCCS5) [MIM:615368]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:23092955}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Charcot-Marie-Tooth disease, dominant, intermediate type, B (CMTDIB) [MIM:606482]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:15731758, ECO:0000269|PubMed:19623537}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Charcot-Marie-Tooth disease 2M (CMT2M) [MIM:606482]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:17636067, ECO:0000269|PubMed:18560793}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Overexpression of CNM- and CMT-related DNM2 mutants in COS7 cells, whatever the mutated domain, led to a reduction in clathrin-mediated receptor endocytosis associated with MAPK ERK-1 and ERK-2 impairment. The membrane trafficking impairment process may represent a common pathophysiological pathway in the autosomal forms of CNM DNM2-CMT neuropathy.

Similarity: Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE- ProRule:PRU01055}.

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:		Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Plays an important role in vesicular trafficking processes, in particular endocytosis (PubMed:33713620). Involved in cytokinesis (PubMed:12498685). Regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). {ECO:0000250\|UniProtKB:P39052, ECO:0000250\|UniProtKB:P39054, ECO:0000269\|PubMed:12498685, ECO:0000269\|PubMed:33713620}.


Catalytic activity:		Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5;
Subunit:		Interacts with MYOF (By similarity). Interacts with CTTN and ACTN1 (By similarity). Interacts with SHANK1, SHANK2, SH3BP4 and NOSTRIN. Interacts with SNX9. Interacts with SNX33 (via SH3 domain). Interacts with MYO1E (via SH3 domain). Interacts with PSTPIP1. Interacts with CTNND2 (PubMed:22022388). May interact with PIK3C3 (By similarity). May be a component of a complex composed of RAB5A (in GDP- bound form), DYN2 and PIK3C3 (By similarity). Interacts with BIN1 (PubMed:17676042). {ECO:0000250\|UniProtKB:P39052, ECO:0000250\|UniProtKB:P39054, ECO:0000269\|PubMed:11583995, ECO:0000269\|PubMed:15703209, ECO:0000269\|PubMed:16234328, ECO:0000269\|PubMed:16325581, ECO:0000269\|PubMed:17257598, ECO:0000269\|PubMed:17676042, ECO:0000269\|PubMed:18353773, ECO:0000269\|PubMed:18480402, ECO:0000269\|PubMed:22022388}.
Subcellular location:		Cytoplasm. Cytoplasm, cytoskeleton. Cell junction {ECO:0000250\|UniProtKB:P39052}. Membrane, clathrin-coated pit {ECO:0000250\|UniProtKB:P39052}. Cell junction, synapse, postsynaptic density. Cell junction, synapse. Midbody. Cell projection, phagocytic cup {ECO:0000250\|UniProtKB:P39054}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250\|UniProtKB:P39054}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P39054}. Note=Colocalizes with CTTN at the basis of filopodia in hippocampus neuron growth zones (By similarity). Microtubule-associated. Also found in the postsynaptic density of neuronal cells. Co-localizes with PIK3C3 and RAB5A to the nascent phagosome (By similarity). {ECO:0000250\|UniProtKB:P39052, ECO:0000250\|UniProtKB:P39054}.
Tissue specificity:		Ubiquitously expressed.
Ptm:		Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry. It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis. Dephosphorylated by calcineurin/PP2 (By similarity). Phosphorylated on tyrosine residues after activation of SRC (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:P39052}.
Disease:		Myopathy, centronuclear, 1 (CNM1) [MIM:160150]: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. {ECO:0000269\|PubMed:16227997, ECO:0000269\|PubMed:17825552, ECO:0000269\|PubMed:17932957, ECO:0000269\|PubMed:19122038, ECO:0000269\|PubMed:19623537, ECO:0000269\|PubMed:19932619, ECO:0000269\|PubMed:19932620, ECO:0000269\|PubMed:20227276, ECO:0000269\|PubMed:22396310}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Lethal congenital contracture syndrome 5 (LCCS5) [MIM:615368]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269\|PubMed:23092955}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Charcot-Marie-Tooth disease, dominant, intermediate type, B (CMTDIB) [MIM:606482]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269\|PubMed:15731758, ECO:0000269\|PubMed:19623537}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Charcot-Marie-Tooth disease 2M (CMT2M) [MIM:606482]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269\|PubMed:17636067, ECO:0000269\|PubMed:18560793}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Overexpression of CNM- and CMT-related DNM2 mutants in COS7 cells, whatever the mutated domain, led to a reduction in clathrin-mediated receptor endocytosis associated with MAPK ERK-1 and ERK-2 impairment. The membrane trafficking impairment process may represent a common pathophysiological pathway in the autosomal forms of CNM DNM2-CMT neuropathy.
Similarity:		Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255\|PROSITE- ProRule:PRU01055}.