UniProt functional annotation for P11532



	UniProt functional annotation for P11532

UniProt code: P11532.

Organism: Homo sapiens (Human).

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

Function: Anchors the extracellular matrix to the cytoskeleton via F- actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission. {ECO:0000250|UniProtKB:P11531, ECO:0000269|PubMed:16710609}.

Subunit: Interacts with SYNM (By similarity). Interacts with the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2 (PubMed:7844150, PubMed:8576247). Interacts with KRT19 (PubMed:16000376). Component of the dystrophin-associated glycoprotein complex which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan- sarcospan complex. Interacts with DAG1 (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif of DAG1 (PubMed:7592992, PubMed:11495720, PubMed:10932245). Interacts with CMYA5 (By similarity). Directly interacts with ANK2 and ANK3; these interactions do not interfere with betaDAG1-binding and are necessary for proper localization in muscle cells (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By similarity). Interacts with DTNB (By similarity). {ECO:0000250|UniProtKB:P11530, ECO:0000250|UniProtKB:P11531, ECO:0000269|PubMed:10932245, ECO:0000269|PubMed:11495720, ECO:0000269|PubMed:16000376, ECO:0000269|PubMed:7592992, ECO:0000269|PubMed:7844150, ECO:0000269|PubMed:8576247}.

Subcellular location: Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P11531}; Peripheral membrane protein {ECO:0000250|UniProtKB:P11531}; Cytoplasmic side {ECO:0000250|UniProtKB:P11531}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P11531}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250|UniProtKB:P11531}. Note=In muscle cells, sarcolemma localization requires the presence of ANK2, while localization to costameres requires the presence of ANK3. Localizes to neuromuscular junctions (NMJs). In adult muscle, NMJ localization depends upon ANK2 presence, but not in newborn animals. {ECO:0000250|UniProtKB:P11531}.

Tissue specificity: Expressed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma. Expressed in brain, muscle, kidney, lung and testis. Most tissues contain transcripts of multiple isoforms. Isoform 15: Only isoform to be detected in heart and liver and is also expressed in brain, testis and hepatoma cells. {ECO:0000269|PubMed:1319059, ECO:0000269|PubMed:16000376, ECO:0000269|PubMed:8541829}.

Developmental stage: Isoform 15: Expressed in embryonic neural tissue from the sixth week of development. Isoform 16: Detected in all embryonic tissues examined. {ECO:0000269|PubMed:9370062}.

Disease: Duchenne muscular dystrophy (DMD) [MIM:310200]: Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment. {ECO:0000269|PubMed:12632325, ECO:0000269|PubMed:24302611, ECO:0000269|PubMed:7981690, ECO:0000269|PubMed:8401582, ECO:0000269|PubMed:8817332, ECO:0000269|PubMed:9851445}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Becker muscular dystrophy (BMD) [MIM:300376]: A neuromuscular disorder characterized by dystrophin deficiency. It appears between the age of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Becker muscular dystrophy has a more benign course than Duchenne muscular dystrophy. {ECO:0000269|PubMed:10573008}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Cardiomyopathy, dilated, X-linked 3B (CMD3B) [MIM:302045]: 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:12359139, ECO:0000269|PubMed:25340340, ECO:0000269|PubMed:9170407}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: The DMD gene is the largest known gene in humans. It is 2.4 million base-pairs in size, comprises 79 exons and takes over 16 hours to be transcribed and cotranscriptionally spliced.

Miscellaneous: [Isoform 1]: Produced by alternative promoter usage.

Miscellaneous: [Isoform 2]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 3]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 4]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 5]: Produced by alternative splicing of isoform 4. {ECO:0000305}.

Miscellaneous: [Isoform 6]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 7]: Produced by alternative splicing of isoform 6. {ECO:0000305}.

Miscellaneous: [Isoform 8]: Produced by alternative splicing of isoform 6. {ECO:0000305}.

Miscellaneous: [Isoform 9]: Produced by alternative splicing of isoform 6. {ECO:0000305}.

Miscellaneous: [Isoform 10]: Produced by alternative splicing of isoform 6. {ECO:0000305}.

Miscellaneous: [Isoform 11]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 12]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform 13]: Produced by alternative splicing of isoform 12. {ECO:0000305}.

Miscellaneous: [Isoform 14]: Produced by alternative splicing of isoform 12. {ECO:0000305}.

Miscellaneous: [Isoform 15]: Produced by alternative splicing of isoform 12. {ECO:0000305}.

Miscellaneous: [Isoform 16]: Produced by alternative splicing of isoform 12. {ECO:0000305}.

Miscellaneous: [Isoform 17]: Produced by alternative splicing of isoform 12. {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:		Anchors the extracellular matrix to the cytoskeleton via F- actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission. {ECO:0000250\|UniProtKB:P11531, ECO:0000269\|PubMed:16710609}.


Subunit:		Interacts with SYNM (By similarity). Interacts with the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2 (PubMed:7844150, PubMed:8576247). Interacts with KRT19 (PubMed:16000376). Component of the dystrophin-associated glycoprotein complex which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan- sarcospan complex. Interacts with DAG1 (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif of DAG1 (PubMed:7592992, PubMed:11495720, PubMed:10932245). Interacts with CMYA5 (By similarity). Directly interacts with ANK2 and ANK3; these interactions do not interfere with betaDAG1-binding and are necessary for proper localization in muscle cells (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By similarity). Interacts with DTNB (By similarity). {ECO:0000250\|UniProtKB:P11530, ECO:0000250\|UniProtKB:P11531, ECO:0000269\|PubMed:10932245, ECO:0000269\|PubMed:11495720, ECO:0000269\|PubMed:16000376, ECO:0000269\|PubMed:7592992, ECO:0000269\|PubMed:7844150, ECO:0000269\|PubMed:8576247}.
Subcellular location:		Cell membrane, sarcolemma {ECO:0000250\|UniProtKB:P11531}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P11531}; Cytoplasmic side {ECO:0000250\|UniProtKB:P11531}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:P11531}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250\|UniProtKB:P11531}. Note=In muscle cells, sarcolemma localization requires the presence of ANK2, while localization to costameres requires the presence of ANK3. Localizes to neuromuscular junctions (NMJs). In adult muscle, NMJ localization depends upon ANK2 presence, but not in newborn animals. {ECO:0000250\|UniProtKB:P11531}.
Tissue specificity:		Expressed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma. Expressed in brain, muscle, kidney, lung and testis. Most tissues contain transcripts of multiple isoforms. Isoform 15: Only isoform to be detected in heart and liver and is also expressed in brain, testis and hepatoma cells. {ECO:0000269\|PubMed:1319059, ECO:0000269\|PubMed:16000376, ECO:0000269\|PubMed:8541829}.
Developmental stage:		Isoform 15: Expressed in embryonic neural tissue from the sixth week of development. Isoform 16: Detected in all embryonic tissues examined. {ECO:0000269\|PubMed:9370062}.
Disease:		Duchenne muscular dystrophy (DMD) [MIM:310200]: Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment. {ECO:0000269\|PubMed:12632325, ECO:0000269\|PubMed:24302611, ECO:0000269\|PubMed:7981690, ECO:0000269\|PubMed:8401582, ECO:0000269\|PubMed:8817332, ECO:0000269\|PubMed:9851445}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Becker muscular dystrophy (BMD) [MIM:300376]: A neuromuscular disorder characterized by dystrophin deficiency. It appears between the age of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Becker muscular dystrophy has a more benign course than Duchenne muscular dystrophy. {ECO:0000269\|PubMed:10573008}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Cardiomyopathy, dilated, X-linked 3B (CMD3B) [MIM:302045]: 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:12359139, ECO:0000269\|PubMed:25340340, ECO:0000269\|PubMed:9170407}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		The DMD gene is the largest known gene in humans. It is 2.4 million base-pairs in size, comprises 79 exons and takes over 16 hours to be transcribed and cotranscriptionally spliced.
Miscellaneous:		[Isoform 1]: Produced by alternative promoter usage.
Miscellaneous:		[Isoform 2]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 3]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 4]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 5]: Produced by alternative splicing of isoform 4. {ECO:0000305}.
Miscellaneous:		[Isoform 6]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 7]: Produced by alternative splicing of isoform 6. {ECO:0000305}.
Miscellaneous:		[Isoform 8]: Produced by alternative splicing of isoform 6. {ECO:0000305}.
Miscellaneous:		[Isoform 9]: Produced by alternative splicing of isoform 6. {ECO:0000305}.
Miscellaneous:		[Isoform 10]: Produced by alternative splicing of isoform 6. {ECO:0000305}.
Miscellaneous:		[Isoform 11]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 12]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform 13]: Produced by alternative splicing of isoform 12. {ECO:0000305}.
Miscellaneous:		[Isoform 14]: Produced by alternative splicing of isoform 12. {ECO:0000305}.
Miscellaneous:		[Isoform 15]: Produced by alternative splicing of isoform 12. {ECO:0000305}.
Miscellaneous:		[Isoform 16]: Produced by alternative splicing of isoform 12. {ECO:0000305}.
Miscellaneous:		[Isoform 17]: Produced by alternative splicing of isoform 12. {ECO:0000305}.