Protein:ACTN2 |
Protein Summary |
 Gene summary |
| Gene name: ACTN2 | ASpdb.0 ID: 88 | Gene | Gene symbol | ACTN2 | Gene ID | 88 |
| Gene name | actinin alpha 2 |
| Synonyms | CMD1AA|CMH23|CMYP8|MPD6|MYOCOZ |
| Cytomap | 1q43 |
| Type of gene | protein-coding |
| Description | alpha-actinin-2F-actin cross-linking proteinalpha-actinin skeletal muscle |
| Modification date | 20240331 |
| UniProtAcc | P35609 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ACTN2 | GO:0005546 | phosphatidylinositol-4,5-bisphosphate binding | 25433700 |
| Gene | ACTN2 | GO:0005886 | plasma membrane | 19815520 |
| Gene | ACTN2 | GO:0008092 | cytoskeletal protein binding | 10427098|11699871 |
| Gene | ACTN2 | GO:0030018 | Z disc | 19932097|19943616|25433700 |
| Gene | ACTN2 | GO:0030035 | microspike assembly | 12356918 |
| Gene | ACTN2 | GO:0030175 | filopodium | 12356918 |
| Gene | ACTN2 | GO:0043268 | positive regulation of potassium ion transport | 17110593 |
| Gene | ACTN2 | GO:0051373 | FATZ binding | 11699871 |
| Gene | ACTN2 | GO:1901018 | positive regulation of potassium ion transmembrane transporter activity | 17110593 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P35609-1 | P35609-1_4d1e_A.pdb | 4D1E | X-ray | 3.5 | A | 34 | 892 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P35609 | ACTN2 | P35609-1 | P35609-2 | 894 | 894 | 234 | 261 | Substitution | IVNTPKPDERAIMTYVSCFYHAFAGAEQ | LVYTARPDERAIMTYVSCYYHAFAGAQK | 234 | 261 |
| Multiple sequence alignment of our canonical and alternatively spliced ACTN2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ACTN2 |
| UniProt-id | ENSG | ENST | ENSP |
| P35609-1 | ENSG00000077522.15 | ENST00000366578.6 | ENSP00000355537.4 |
| P35609-2 | ENSG00000077522.15 | ENST00000542672.7 | ENSP00000443495.1 |
| UniProt-id | NM ID | NP ID |
| P35609-1 | NM_001103.3 | NP_001094.1 |
| P35609-2 | NM_001278343.1 | NP_001265272.1 |
| Amino acid sequences of our canonical and alternatively spliced ACTN2 |
| accession_id | Protein sequence |
| P35609-1 | MNQIEPGVQYNYVYDEDEYMIQEEEWDRDLLLDPAWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRNGLKLMLLLEVISGERLPKPDRG KMRFHKIANVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIILRFAIQDISVEETSAKEGLLLWCQRKTAPYRNVNIQNFHTSW KDGLGLCALIHRHRPDLIDYSKLNKDDPIGNINLAMEIAEKHLDIPKMLDAEDIVNTPKPDERAIMTYVSCFYHAFAGAEQAETAANRIC KVLAVNQENERLMEEYERLASELLEWIRRTIPWLENRTPEKTMQAMQKKLEDFRDYRRKHKPPKVQEKCQLEINFNTLQTKLRISNRPAF MPSEGKMVSDIAGAWQRLEQAEKGYEEWLLNEIRRLERLEHLAEKFRQKASTHETWAYGKEQILLQKDYESASLTEVRALLRKHEAFESD LAAHQDRVEQIAAIAQELNELDYHDAVNVNDRCQKICDQWDRLGTLTQKRREALERMEKLLETIDQLHLEFAKRAAPFNNWMEGAMEDLQ DMFIVHSIEEIQSLITAHEQFKATLPEADGERQSIMAIQNEVEKVIQSYNIRISSSNPYSTVTMDELRTKWDKVKQLVPIRDQSLQEELA RQHANERLRRQFAAQANAIGPWIQNKMEEIARSSIQITGALEDQMNQLKQYEHNIINYKNNIDKLEGDHQLIQEALVFDNKHTNYTMEHI RVGWELLLTTIARTINEVETQILTRDAKGITQEQMNEFRASFNHFDRRKNGLMDHEDFRACLISMGYDLGEAEFARIMTLVDPNGQGTVT |
| P35609-2 | MNQIEPGVQYNYVYDEDEYMIQEEEWDRDLLLDPAWEKQQRKTFTAWCNSHLRKAGTQIENIEEDFRNGLKLMLLLEVISGERLPKPDRG KMRFHKIANVNKALDYIASKGVKLVSIGAEEIVDGNVKMTLGMIWTIILRFAIQDISVEETSAKEGLLLWCQRKTAPYRNVNIQNFHTSW KDGLGLCALIHRHRPDLIDYSKLNKDDPIGNINLAMEIAEKHLDIPKMLDAEDLVYTARPDERAIMTYVSCYYHAFAGAQKAETAANRIC KVLAVNQENERLMEEYERLASELLEWIRRTIPWLENRTPEKTMQAMQKKLEDFRDYRRKHKPPKVQEKCQLEINFNTLQTKLRISNRPAF MPSEGKMVSDIAGAWQRLEQAEKGYEEWLLNEIRRLERLEHLAEKFRQKASTHETWAYGKEQILLQKDYESASLTEVRALLRKHEAFESD LAAHQDRVEQIAAIAQELNELDYHDAVNVNDRCQKICDQWDRLGTLTQKRREALERMEKLLETIDQLHLEFAKRAAPFNNWMEGAMEDLQ DMFIVHSIEEIQSLITAHEQFKATLPEADGERQSIMAIQNEVEKVIQSYNIRISSSNPYSTVTMDELRTKWDKVKQLVPIRDQSLQEELA RQHANERLRRQFAAQANAIGPWIQNKMEEIARSSIQITGALEDQMNQLKQYEHNIINYKNNIDKLEGDHQLIQEALVFDNKHTNYTMEHI RVGWELLLTTIARTINEVETQILTRDAKGITQEQMNEFRASFNHFDRRKNGLMDHEDFRACLISMGYDLGEAEFARIMTLVDPNGQGTVT |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ACTN2 (go to UniProt):P35609 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P35609 | Domain | 151 | 257 | Note=Calponin-homology (CH) 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00044 | Type=Substitution;Start=234;End=261 |
| P35609 | Region | 1 | 254 | Note=Actin-binding | Type=Substitution;Start=234;End=261 |
Gene Isoform Structures and Expression Levels for ACTN2 |
| Gene structures of our canonical and alternative spliced genes of ACTN2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P35609-1 |
| 3D view using mol* of P35609-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P35609-1 |
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| pLDDT distribution across the protein length of P35609-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P35609-1 |
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| Ramachandran plot of P35609-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P35609-1 | 1.068 | 121 | 1.1 | 284.69 | 0.506 | 0.762 | 0.98 | 1.098 | 0.911 | 1.205 | 1.043 | 324,327,328,329,331,332,335,336,343,679,682,685,68 6,689,692,693,696,717,721,724,725,728,731,732,735, 736,739 |
| P35609-2 | 1.037 | 183 | 1.091 | 585.158 | 0.636 | 0.683 | 0.866 | 0.785 | 0.793 | 0.99 | 0.979 | 401,405,408,409,412,415,416,420,423,428,440,442,44 3,444,445,446,447,449,450,454,457,519,522,523,525, 526,527,529,530,533,536,537,539,540,541,542,543,60 0,601,602,606,610,613,617,620,621,624 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P35609-1_P35609-1_4d1e_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P35609-1_4d1e_A_P35609-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P35609-1_P35609-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P35609-1_vs_P35609-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P35609-1_vs_P35609-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ACTN2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to ACTN2 |
| Previous studies relating to the alternative splicing of ACTN2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ACTN2 | 24860983 | Muscle lim protein isoform negatively regulates striated muscle actin dynamics and differentiation. | Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including α-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity. | D009468 | Neuromuscular Diseases |
Clinically important variants in ACTN2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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