UniProt functional annotation for Q14315



	UniProt functional annotation for Q14315

UniProt code: Q14315.

Organism: Homo sapiens (Human).

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

Function: Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.

Subunit: Homodimer; the filamin repeat 24 and the second hinge domain are important for dimer formation. Interacts with FLNB, INPPL1, ITGB1A, KCND2, MYOT, MYOZ1 and MYOZ3. Interacts with sarcoglycans SGCD and SGCG. Interacts (via filament repeats 17-18, 20-21 and 24) with USP25 (isoform USP25m only). Interacts with FBLIM1. Interacts with XIRP1; this interaction is mediated by filamin 20 repeat. Interacts with KY. Interacts with IGFN1 (By similarity). Interacts with MICALL2 (By similarity). Interacts with ANK3. Interacts with SYNPO2. {ECO:0000250, ECO:0000269|PubMed:10629222, ECO:0000269|PubMed:10984498, ECO:0000269|PubMed:11038172, ECO:0000269|PubMed:11102480, ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:11739414, ECO:0000269|PubMed:11842093, ECO:0000269|PubMed:12525170, ECO:0000269|PubMed:16076904, ECO:0000269|PubMed:16501887, ECO:0000269|PubMed:16631741, ECO:0000269|PubMed:17379241, ECO:0000269|PubMed:19074766, ECO:0000269|PubMed:20554076, ECO:0000269|PubMed:21223964}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:11038172, ECO:0000269|PubMed:25351925}. Membrane {ECO:0000269|PubMed:11038172}; Peripheral membrane protein {ECO:0000269|PubMed:11038172}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11038172}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:11038172}. Note=A small amount localizes at membranes. In striated muscle cells, it predominantly localizes in myofibrillar Z lines, while a minor fraction localizes with subsarcolemme. Targeting to developing and mature Z lines is mediated by the intradomain insert.

Tissue specificity: Highly expressed in striated muscles. Weakly expressed in thyroid, fetal brain, fetal lung, retina, spinal cord and bone marrow. Not expressed in testis, pancreas, adrenal gland, placenta, liver and kidney. {ECO:0000269|PubMed:11038172, ECO:0000269|PubMed:7689010, ECO:0000269|PubMed:9791010}.

Developmental stage: Expressed in both differentiating and adult muscles.

Ptm: Ubiquitinated by FBXL22, leading to proteasomal degradation. {ECO:0000269|PubMed:22972877}.

Disease: Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction. {ECO:0000269|PubMed:15929027}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation. {ECO:0000269|PubMed:21620354}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cardiomyopathy, familial hypertrophic 26 (CMH26) [MIM:617047]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:25351925}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cardiomyopathy, familial restrictive 5 (RCM5) [MIM:617047]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:26666891}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Silenced in MKN28 and MKN74 gastric cancer cell lines due to aberrant methylation of the gene.

Similarity: Belongs to the filamin family. {ECO:0000305}.

Sequence caution: Sequence=AAD12245.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF68195.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF80245.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA49688.1; Type=Frameshift; 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:		Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.


Subunit:		Homodimer; the filamin repeat 24 and the second hinge domain are important for dimer formation. Interacts with FLNB, INPPL1, ITGB1A, KCND2, MYOT, MYOZ1 and MYOZ3. Interacts with sarcoglycans SGCD and SGCG. Interacts (via filament repeats 17-18, 20-21 and 24) with USP25 (isoform USP25m only). Interacts with FBLIM1. Interacts with XIRP1; this interaction is mediated by filamin 20 repeat. Interacts with KY. Interacts with IGFN1 (By similarity). Interacts with MICALL2 (By similarity). Interacts with ANK3. Interacts with SYNPO2. {ECO:0000250, ECO:0000269\|PubMed:10629222, ECO:0000269\|PubMed:10984498, ECO:0000269\|PubMed:11038172, ECO:0000269\|PubMed:11102480, ECO:0000269\|PubMed:11171996, ECO:0000269\|PubMed:11739414, ECO:0000269\|PubMed:11842093, ECO:0000269\|PubMed:12525170, ECO:0000269\|PubMed:16076904, ECO:0000269\|PubMed:16501887, ECO:0000269\|PubMed:16631741, ECO:0000269\|PubMed:17379241, ECO:0000269\|PubMed:19074766, ECO:0000269\|PubMed:20554076, ECO:0000269\|PubMed:21223964}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:11038172, ECO:0000269\|PubMed:25351925}. Membrane {ECO:0000269\|PubMed:11038172}; Peripheral membrane protein {ECO:0000269\|PubMed:11038172}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:11038172}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269\|PubMed:11038172}. Note=A small amount localizes at membranes. In striated muscle cells, it predominantly localizes in myofibrillar Z lines, while a minor fraction localizes with subsarcolemme. Targeting to developing and mature Z lines is mediated by the intradomain insert.
Tissue specificity:		Highly expressed in striated muscles. Weakly expressed in thyroid, fetal brain, fetal lung, retina, spinal cord and bone marrow. Not expressed in testis, pancreas, adrenal gland, placenta, liver and kidney. {ECO:0000269\|PubMed:11038172, ECO:0000269\|PubMed:7689010, ECO:0000269\|PubMed:9791010}.
Developmental stage:		Expressed in both differentiating and adult muscles.
Ptm:		Ubiquitinated by FBXL22, leading to proteasomal degradation. {ECO:0000269\|PubMed:22972877}.
Disease:		Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction. {ECO:0000269\|PubMed:15929027}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation. {ECO:0000269\|PubMed:21620354}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cardiomyopathy, familial hypertrophic 26 (CMH26) [MIM:617047]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269\|PubMed:25351925}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cardiomyopathy, familial restrictive 5 (RCM5) [MIM:617047]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269\|PubMed:26666891}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Silenced in MKN28 and MKN74 gastric cancer cell lines due to aberrant methylation of the gene.
Similarity:		Belongs to the filamin family. {ECO:0000305}.
Sequence caution:		Sequence=AAD12245.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF68195.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAF80245.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA49688.1; Type=Frameshift; Evidence={ECO:0000305};