UniProt functional annotation for P35609



	UniProt functional annotation for P35609

UniProt code: P35609.

Organism: Homo sapiens (Human).

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

Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.

Subunit: Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C- terminal region with the LDB3 PDZ domain. Interacts with XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts with PARVB. Interacts with SYNPO2. {ECO:0000269|PubMed:10427098, ECO:0000269|PubMed:10984498, ECO:0000269|PubMed:11114196, ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:11842093, ECO:0000269|PubMed:15159419, ECO:0000269|PubMed:17046827, ECO:0000269|PubMed:19932097}.

Subcellular location: Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:11171996, ECO:0000269|PubMed:19932097, ECO:0000269|PubMed:30701273}. Note=Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal muscle.

Tissue specificity: Expressed in both skeletal and cardiac muscle.

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

Disease: Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction (CMH23) [MIM:612158]: 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:20022194, ECO:0000269|PubMed:25173926}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction (CMD1AA) [MIM:612158]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:14567970, ECO:0000269|PubMed:25224718}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Myopathy, congenital, with structured cores and Z-line abnormalities (MYOCOZ) [MIM:618654]: An autosomal dominant muscular disorder characterized by progressive early-onset muscle weakness, gait difficulties, loss of ambulation, and respiratory insufficiency. Morphological and ultrastructural analyses of muscle biopsies reveal type 1 fiber predominance, multiple structured cores forming a circular arrangement beneath the sarcolemma, and jagged Z-lines. {ECO:0000269|PubMed:30701273}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Myopathy, distal, 6, adult onset, autosomal dominant (MPD6) [MIM:618655]: An autosomal dominant muscular disorder characterized by adult onset of asymmetric distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles. {ECO:0000269|PubMed:30900782}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the alpha-actinin 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:		F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.


Subunit:		Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C- terminal region with the LDB3 PDZ domain. Interacts with XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts with PARVB. Interacts with SYNPO2. {ECO:0000269\|PubMed:10427098, ECO:0000269\|PubMed:10984498, ECO:0000269\|PubMed:11114196, ECO:0000269\|PubMed:11171996, ECO:0000269\|PubMed:11842093, ECO:0000269\|PubMed:15159419, ECO:0000269\|PubMed:17046827, ECO:0000269\|PubMed:19932097}.
Subcellular location:		Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269\|PubMed:11171996, ECO:0000269\|PubMed:19932097, ECO:0000269\|PubMed:30701273}. Note=Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal muscle.
Tissue specificity:		Expressed in both skeletal and cardiac muscle.
Ptm:		Ubiquitinated by FBXL22, leading to proteasomal degradation. {ECO:0000269\|PubMed:22972877}.
Disease:		Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction (CMH23) [MIM:612158]: 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:20022194, ECO:0000269\|PubMed:25173926}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction (CMD1AA) [MIM:612158]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269\|PubMed:14567970, ECO:0000269\|PubMed:25224718}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Myopathy, congenital, with structured cores and Z-line abnormalities (MYOCOZ) [MIM:618654]: An autosomal dominant muscular disorder characterized by progressive early-onset muscle weakness, gait difficulties, loss of ambulation, and respiratory insufficiency. Morphological and ultrastructural analyses of muscle biopsies reveal type 1 fiber predominance, multiple structured cores forming a circular arrangement beneath the sarcolemma, and jagged Z-lines. {ECO:0000269\|PubMed:30701273}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Myopathy, distal, 6, adult onset, autosomal dominant (MPD6) [MIM:618655]: An autosomal dominant muscular disorder characterized by adult onset of asymmetric distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles. {ECO:0000269\|PubMed:30900782}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the alpha-actinin family. {ECO:0000305}.