Alpha-actinin-1 (ACTN1)
The protein contains 892 amino acids for an estimated molecular weight of 103058 Da.
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| BDPLT15 | |
| BDPLT15 | |
| BDPLT15 | |
| dbSNP:rs904887313 | |
| BDPLT15 | |
| dbSNP:rs7157661 | |
| BDPLT15 | |
| BDPLT15 | |
| dbSNP:rs11557769 |
Biological Process
Actin crosslink formation
Actin filament bundle assembly
Actin filament network formation
Actin filament organization
Blood coagulation
Cell junction assembly
Extracellular matrix organization
Focal adhesion assembly
Negative regulation of cellular component movement
Platelet activation
Platelet degranulation
Platelet formation
Platelet morphogenesis
Regulation of apoptotic process
Regulation of nucleic acid-templated transcription
Cellular Component
Brush border
Cell projection
Cell-cell junction
Cortical actin cytoskeleton
Cytoplasm
Cytosol
Dendritic spine
Extracellular exosome
Extracellular region
Extracellular space
Fascia adherens
Focal adhesion
Glutamatergic synapse
Intracellular anatomical structure
Nucleus
Plasma membrane
Platelet alpha granule lumen
Pseudopodium
Ruffle
Stress fiber
Z disc
The reference OMIM entry for this protein is 102575
Actinin, alpha-1; actn1
DESCRIPTION
Alpha-actinin was initially isolated from rabbit skeletal muscle as a factor that induces the gelation of F-actin and promotes the superprecipitation of actomyosin. Subsequently, a number of different isoforms were isolated from both muscle and nonmuscle cells and from a wide variety of organisms. The native molecule is thought to be a homodimer of 97-kD subunits arranged in antiparallel fashion. In myofibrillar cells, alpha-actinin constitutes a major component of Z discs in striated muscle and of the functionally analogous dense bodies and dense plaques in smooth muscle. In nonmuscle cells, it is distributed along microfilament bundles and is thought to mediate their attachment to the membrane at adherens-type junctions (Youssoufian et al., 1990).CLONING
Youssoufian et al. (1990) cloned and characterized a full-length cDNA encoding the human cytoskeletal isoform. The gene encodes 891 amino acids with 96 to 98% sequence identity at the amino acid level to chicken nonskeletal muscle alpha-actinin. Transient expression in COS cells produced a protein of about 104 kD.GENE FUNCTION
Kanchanawong et al. (2010) used 3-dimensional super-resolution fluorescence microscopy to map nanoscale protein organization in focal adhesions. Their results revealed that integrins and actin are vertically separated by an approximately 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signaling layer containing integrin cytoplasmic tails (see 193210), focal adhesion kinase (600758), and paxillin (602505); an intermediate force-transduction layer containing talin (186745) and vinculin (193065); and an uppermost actin-regulatory layer containing zyxin (602002), vasodilator-stimulated phosphoprotein (601703), and alpha-actinin. By localizing amino- and carboxy-terminally tagged talins, Kanchanawong et al. (2010) revealed talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. Kanchanawong et al. (2010) concluded that their composite multilaminar protein architecture provided a molecular blueprint for understanding focal adhesion functions.MAPPING
By analysis of somatic cell hybrids and by in situ hybridization, Youssoufian et al. (1990) mapped the gene to 14q22-q24. Pulsed-field gel analysis of genomic DNA showed that the ACTN1 gene and that for erythroid beta-spectrin (SPTB; 182870) are located in the same restriction fragment. This finding is of great interest because of the structural homology between spectrin and actinin.MOLECULAR GENETICS
In affected members from 6 unrelated Japanese families with autosomal dominant platelet-type bleeding disorder-15 (BDPLT15; 615193), manifest mainly as macrothrombocytopenia with little bleeding, Kunishima et al. (2013) identified 6 different heterozygous missense mutations in the ACTN1 gene (102575.0001-102575.0006). Three of the mutations were identified by exome sequencing. ACTN1 mutations were found in 5.5% of the dominant forms of congenital macrothrombocytopenia in their cohort, and represented the fourth most common cause of the disorder in Japanese individuals. Expression of the mutations in Chinese hamster ovary (CHO) cells showed that the mutant proteins caused varying degrees of disorganization of the actin filaments, with mutant ACTN1 colocalized with less fine, shortened actin filaments, and unbound ACTN1 coarsely distributed within the cytoplasm. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 16, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 102575 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed