UniProt functional annotation for P63261



	UniProt functional annotation for P63261

UniProt code: P63261.

Organism: Homo sapiens (Human).

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

Function: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. {ECO:0000305|PubMed:29581253}.

Subunit: Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin (PubMed:28493397). {ECO:0000269|PubMed:28493397}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:28493397}.

Ptm: Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization. {ECO:0000250|UniProtKB:P63260}.

Ptm: Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. {ECO:0000269|PubMed:23673617}.

Ptm: [Actin, cytoplasmic 2, N-terminally processed]: N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins (PubMed:29581253). In contrast, filament nucleation by the Arp2/3 complex is not affected (PubMed:29581253). {ECO:0000269|PubMed:29581253}.

Ptm: Methylated at His-73 by SETD3. {ECO:0000269|PubMed:30626964}.

Ptm: (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin- dependent and independent manners (PubMed:26228148). {ECO:0000305|PubMed:19015515, ECO:0000305|PubMed:26228148}.

Disease: Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:13680526, ECO:0000269|PubMed:14684684, ECO:0000269|PubMed:16773128, ECO:0000269|PubMed:18804074, ECO:0000269|PubMed:19477959, ECO:0000269|PubMed:22938506, ECO:0000269|PubMed:25388789}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583]: A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss. {ECO:0000269|PubMed:22366783}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

Miscellaneous: In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

Similarity: Belongs to the actin family. {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:		Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. {ECO:0000305\|PubMed:29581253}.


Subunit:		Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin (PubMed:28493397). {ECO:0000269\|PubMed:28493397}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:28493397}.
Ptm:		Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization. {ECO:0000250\|UniProtKB:P63260}.
Ptm:		Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration. {ECO:0000269\|PubMed:23673617}.
Ptm:		[Actin, cytoplasmic 2, N-terminally processed]: N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins (PubMed:29581253). In contrast, filament nucleation by the Arp2/3 complex is not affected (PubMed:29581253). {ECO:0000269\|PubMed:29581253}.
Ptm:		Methylated at His-73 by SETD3. {ECO:0000269\|PubMed:30626964}.
Ptm:		(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin- dependent and independent manners (PubMed:26228148). {ECO:0000305\|PubMed:19015515, ECO:0000305\|PubMed:26228148}.
Disease:		Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269\|PubMed:13680526, ECO:0000269\|PubMed:14684684, ECO:0000269\|PubMed:16773128, ECO:0000269\|PubMed:18804074, ECO:0000269\|PubMed:19477959, ECO:0000269\|PubMed:22938506, ECO:0000269\|PubMed:25388789}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583]: A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss. {ECO:0000269\|PubMed:22366783}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269\|PubMed:28493397}.
Miscellaneous:		In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.
Similarity:		Belongs to the actin family. {ECO:0000305}.