UniProt functional annotation for Q15149



	UniProt functional annotation for Q15149

UniProt code: Q15149.

Organism: Homo sapiens (Human).

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

Function: Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}.

Subunit: Homodimer or homotetramer. Interacts (via actin-binding domain) with SYNE3. Interacts (via calponin-homology (CH) 1 domain) with VIM (via rod region) (By similarity). Interacts (via N-terminus) with DST isoform 2 (via N-terminus) (PubMed:19932097). Interacts with FER. Interacts with TOR1A (PubMed:18827015). Interacts with ANK3 (PubMed:21223964). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (By similarity). Interacts with COL17A1 (PubMed:12482924). {ECO:0000250, ECO:0000250|UniProtKB:P30427, ECO:0000250|UniProtKB:Q9QXS1, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:19932097, ECO:0000269|PubMed:21223964}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12482924}. Cell junction, hemidesmosome {ECO:0000269|PubMed:12482924}.

Tissue specificity: Widely expressed with highest levels in muscle, heart, placenta and spinal cord.

Domain: The N-terminus interacts with actin, the C-terminus with vimentin, desmin, GFAP, cytokeratins, lamin B; whereas both the N- and the C-terminus can bind integrin beta-4.

Ptm: Phosphorylated by CDK1; regulates dissociation from intermediate filaments during mitosis. {ECO:0000250}.

Disease: Epidermolysis bullosa simplex with pyloric atresia (EBS-PA) [MIM:612138]: Autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. This disorder is allelic to MD-EBS. {ECO:0000269|PubMed:14675180, ECO:0000269|PubMed:20665883}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Epidermolysis bullosa simplex, with muscular dystrophy (MD- EBS) [MIM:226670]: A form of epidermolysis bullosa characterized by the association of blister formation at the level of the hemidesmosome with late-onset muscular dystrophy. {ECO:0000269|PubMed:11159198, ECO:0000269|PubMed:20665883, ECO:0000269|PubMed:21263134, ECO:0000269|PubMed:8894687}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Epidermolysis bullosa simplex, Ogna type (O-EBS) [MIM:131950]: A form of intraepidermal epidermolysis bullosa characterized by generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, it is differentiated from classical cases of K-EBS, WC-EBS and DM-EBS, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates. {ECO:0000269|PubMed:11851880}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Muscular dystrophy, limb-girdle, autosomal recessive 17 (LGMDR17) [MIM:613723]: A form of limb-girdle muscular dystrophy characterized by early childhood onset of proximal muscle weakness. Limb-girdle muscular dystrophies are characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. {ECO:0000269|PubMed:21109228, ECO:0000269|PubMed:25556389, ECO:0000269|PubMed:27234031}. Note=The disease is caused by variants affecting the gene represented in this entry. A 9 bp deletion containing the initiation codon in exon 1f of PLEC have been found in limb-girdle muscular dystrophy patients. The mutation results in deficient expression of isoform 9 and disorganization of the myofibers, without any effect on the skin.

Disease: Epidermolysis bullosa simplex with nail dystrophy (EBSND) [MIM:616487]: A form of epidermolysis bullosa, a dermatologic disorder characterized by skin blistering. EBSND patients also manifest nail dystrophy. {ECO:0000269|PubMed:25712130}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the plakin or cytolinker 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:		Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269\|PubMed:12482924, ECO:0000269\|PubMed:21109228}.


Subunit:		Homodimer or homotetramer. Interacts (via actin-binding domain) with SYNE3. Interacts (via calponin-homology (CH) 1 domain) with VIM (via rod region) (By similarity). Interacts (via N-terminus) with DST isoform 2 (via N-terminus) (PubMed:19932097). Interacts with FER. Interacts with TOR1A (PubMed:18827015). Interacts with ANK3 (PubMed:21223964). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (By similarity). Interacts with COL17A1 (PubMed:12482924). {ECO:0000250, ECO:0000250\|UniProtKB:P30427, ECO:0000250\|UniProtKB:Q9QXS1, ECO:0000269\|PubMed:12482924, ECO:0000269\|PubMed:18827015, ECO:0000269\|PubMed:19932097, ECO:0000269\|PubMed:21223964}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:12482924}. Cell junction, hemidesmosome {ECO:0000269\|PubMed:12482924}.
Tissue specificity:		Widely expressed with highest levels in muscle, heart, placenta and spinal cord.
Domain:		The N-terminus interacts with actin, the C-terminus with vimentin, desmin, GFAP, cytokeratins, lamin B; whereas both the N- and the C-terminus can bind integrin beta-4.
Ptm:		Phosphorylated by CDK1; regulates dissociation from intermediate filaments during mitosis. {ECO:0000250}.
Disease:		Epidermolysis bullosa simplex with pyloric atresia (EBS-PA) [MIM:612138]: Autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. This disorder is allelic to MD-EBS. {ECO:0000269\|PubMed:14675180, ECO:0000269\|PubMed:20665883}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Epidermolysis bullosa simplex, with muscular dystrophy (MD- EBS) [MIM:226670]: A form of epidermolysis bullosa characterized by the association of blister formation at the level of the hemidesmosome with late-onset muscular dystrophy. {ECO:0000269\|PubMed:11159198, ECO:0000269\|PubMed:20665883, ECO:0000269\|PubMed:21263134, ECO:0000269\|PubMed:8894687}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Epidermolysis bullosa simplex, Ogna type (O-EBS) [MIM:131950]: A form of intraepidermal epidermolysis bullosa characterized by generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, it is differentiated from classical cases of K-EBS, WC-EBS and DM-EBS, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates. {ECO:0000269\|PubMed:11851880}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Muscular dystrophy, limb-girdle, autosomal recessive 17 (LGMDR17) [MIM:613723]: A form of limb-girdle muscular dystrophy characterized by early childhood onset of proximal muscle weakness. Limb-girdle muscular dystrophies are characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. {ECO:0000269\|PubMed:21109228, ECO:0000269\|PubMed:25556389, ECO:0000269\|PubMed:27234031}. Note=The disease is caused by variants affecting the gene represented in this entry. A 9 bp deletion containing the initiation codon in exon 1f of PLEC have been found in limb-girdle muscular dystrophy patients. The mutation results in deficient expression of isoform 9 and disorganization of the myofibers, without any effect on the skin.
Disease:		Epidermolysis bullosa simplex with nail dystrophy (EBSND) [MIM:616487]: A form of epidermolysis bullosa, a dermatologic disorder characterized by skin blistering. EBSND patients also manifest nail dystrophy. {ECO:0000269\|PubMed:25712130}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the plakin or cytolinker family. {ECO:0000305}.