UniProt functional annotation for O00499



	UniProt functional annotation for O00499

UniProt code: O00499.

Organism: Homo sapiens (Human).

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

Function: Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:24755653). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:27179792). In neuronal circuits, endocytosis regulation may influence the internalization of PHF-tau aggregates (By similarity). May be involved in the regulation of MYC activity and the control cell proliferation (PubMed:8782822). Has actin bundling activity and stabilizes actin filaments against depolymerization in vitro (PubMed:28893863). {ECO:0000250|UniProtKB:O08839, ECO:0000269|PubMed:24755653, ECO:0000269|PubMed:27179792, ECO:0000269|PubMed:28893863, ECO:0000269|PubMed:8782822}.

Subunit: Heterodimer with AMPH (By similarity). Binds SH3GLB1 (By similarity). Interacts (via SH3 domain) with DNM1. Interacts with SYNJ1 (By similarity). Interacts (via SH3 domain) with DNM2 (PubMed:17676042). Isoform IIA interacts with CLTC. Isoform IIB does not interact with CLTC. Isoform IIC1 does not interact with CLTC. Isoform IIC2 does not interact with CLTC (PubMed:9603201). Interacts with AP2A2. Interacts with AP2B1 (By similarity). Interacts with MYC (via N-terminal transactivation domain); the interaction requires the integrity of the conserved MYC box regions 1 and 2 (By similarity). Interacts with BIN2 (PubMed:10903846). Interacts with SNX4 (PubMed:12668730). Interacts (via BAR domain) with BACE1 (PubMed:27179792). Binds (via BAR domain) F-actin (PubMed:28893863). {ECO:0000250|UniProtKB:O08539, ECO:0000250|UniProtKB:O08839, ECO:0000269|PubMed:10903846, ECO:0000269|PubMed:12668730, ECO:0000269|PubMed:17676042, ECO:0000269|PubMed:27179792, ECO:0000269|PubMed:28893863, ECO:0000269|PubMed:9603201}.

Subunit: (Microbial infection) Interacts (SH3 domain) with HCV NS5A. {ECO:0000269|PubMed:16530520}.

Subcellular location: [Isoform BIN1]: Nucleus {ECO:0000269|PubMed:8782822}. Cytoplasm {ECO:0000269|PubMed:9182667}. Endosome {ECO:0000250|UniProtKB:O08539}. Cell membrane, sarcolemma, T- tubule {ECO:0000250|UniProtKB:O08839}.

Subcellular location: [Isoform IIA]: Cytoplasm {ECO:0000269|PubMed:9182667}.

Tissue specificity: Ubiquitous. Highest expression in the brain and muscle (PubMed:9182667). Expressed in oligodendrocytes (PubMed:27488240). Isoform IIA is expressed only in the brain, where it is detected in the gray matter, but not in the white matter (PubMed:27488240). Isoform BIN1 is widely expressed with highest expression in skeletal muscle. {ECO:0000269|PubMed:10903846, ECO:0000269|PubMed:27488240, ECO:0000269|PubMed:9182667}.

Ptm: Phosphorylated by protein kinase C. {ECO:0000250}.

Disease: Myopathy, centronuclear, 2 (CNM2) [MIM:255200]: 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:17676042, ECO:0000269|PubMed:20142620, ECO:0000269|PubMed:24755653, ECO:0000269|PubMed:29950440}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Note=BIN1 mutations have been found in families segregating autosomal dominant centronuclear myopathy. Patients show adult-onset, mildly progressive muscle weakness affecting selected proximal muscles and all distal muscles of the lower limbs. {ECO:0000269|PubMed:25260562}.

Sequence caution: Sequence=AAC23441.1; Type=Erroneous initiation; Note=Truncated 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:		Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:24755653). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:27179792). In neuronal circuits, endocytosis regulation may influence the internalization of PHF-tau aggregates (By similarity). May be involved in the regulation of MYC activity and the control cell proliferation (PubMed:8782822). Has actin bundling activity and stabilizes actin filaments against depolymerization in vitro (PubMed:28893863). {ECO:0000250\|UniProtKB:O08839, ECO:0000269\|PubMed:24755653, ECO:0000269\|PubMed:27179792, ECO:0000269\|PubMed:28893863, ECO:0000269\|PubMed:8782822}.


Subunit:		Heterodimer with AMPH (By similarity). Binds SH3GLB1 (By similarity). Interacts (via SH3 domain) with DNM1. Interacts with SYNJ1 (By similarity). Interacts (via SH3 domain) with DNM2 (PubMed:17676042). Isoform IIA interacts with CLTC. Isoform IIB does not interact with CLTC. Isoform IIC1 does not interact with CLTC. Isoform IIC2 does not interact with CLTC (PubMed:9603201). Interacts with AP2A2. Interacts with AP2B1 (By similarity). Interacts with MYC (via N-terminal transactivation domain); the interaction requires the integrity of the conserved MYC box regions 1 and 2 (By similarity). Interacts with BIN2 (PubMed:10903846). Interacts with SNX4 (PubMed:12668730). Interacts (via BAR domain) with BACE1 (PubMed:27179792). Binds (via BAR domain) F-actin (PubMed:28893863). {ECO:0000250\|UniProtKB:O08539, ECO:0000250\|UniProtKB:O08839, ECO:0000269\|PubMed:10903846, ECO:0000269\|PubMed:12668730, ECO:0000269\|PubMed:17676042, ECO:0000269\|PubMed:27179792, ECO:0000269\|PubMed:28893863, ECO:0000269\|PubMed:9603201}.
Subunit:		(Microbial infection) Interacts (SH3 domain) with HCV NS5A. {ECO:0000269\|PubMed:16530520}.
Subcellular location:		[Isoform BIN1]: Nucleus {ECO:0000269\|PubMed:8782822}. Cytoplasm {ECO:0000269\|PubMed:9182667}. Endosome {ECO:0000250\|UniProtKB:O08539}. Cell membrane, sarcolemma, T- tubule {ECO:0000250\|UniProtKB:O08839}.
Subcellular location:		[Isoform IIA]: Cytoplasm {ECO:0000269\|PubMed:9182667}.
Tissue specificity:		Ubiquitous. Highest expression in the brain and muscle (PubMed:9182667). Expressed in oligodendrocytes (PubMed:27488240). Isoform IIA is expressed only in the brain, where it is detected in the gray matter, but not in the white matter (PubMed:27488240). Isoform BIN1 is widely expressed with highest expression in skeletal muscle. {ECO:0000269\|PubMed:10903846, ECO:0000269\|PubMed:27488240, ECO:0000269\|PubMed:9182667}.
Ptm:		Phosphorylated by protein kinase C. {ECO:0000250}.
Disease:		Myopathy, centronuclear, 2 (CNM2) [MIM:255200]: 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:17676042, ECO:0000269\|PubMed:20142620, ECO:0000269\|PubMed:24755653, ECO:0000269\|PubMed:29950440}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Note=BIN1 mutations have been found in families segregating autosomal dominant centronuclear myopathy. Patients show adult-onset, mildly progressive muscle weakness affecting selected proximal muscles and all distal muscles of the lower limbs. {ECO:0000269\|PubMed:25260562}.
Sequence caution:		Sequence=AAC23441.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};