Twinfilin-1 (TWF1)

The protein contains 350 amino acids for an estimated molecular weight of 40283 Da.

 

Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles (By similarity). (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 77%
Model score: 87

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VariantDescription
Found in a patient with isolated coloboma, increases interaction with ACTG1

The reference OMIM entry for this protein is 610932

Twinfilin, drosophila, homolog of, 1; twf1
Protein tyrosine kinase 9; ptk9
A6 protein tyrosine kinase

CLONING

By screening a human embryonic lung fibroblast bacteria expression library with antiphosphotyrosine antibody, Beeler et al. (1994) cloned TWF1, which they called A6. The deduced 350-amino acid protein has a calculated molecular mass of 40.3 kD. TWF1 has an N-myristoylation site and several sites for threonine, serine, and tyrosine phosphorylation, but it lacks a conserved protein kinase catalytic domain. Northern blot analysis detected a 3.4-kb transcript that was highly expressed in colon, testis, uterus, ovary, prostate, and lung. Lower expression was detected in brain, bladder, and heart, and no expression was detected in liver. In vitro transcription/translation resulted in a 40-kD TWF1 protein, as determined by SDS-PAGE. Southern blot analysis indicated that TWF1 is conserved in vertebrates. By searching databases for homologs of yeast twinfilin, Vartiainen et al. (2000) identified mouse and human TWF1. The mouse and human TWF1 proteins contain 2 cofilin (see CFL1; 601442)-like repeats called actin-depolymerizing factor (DSTN; 609114) homology (ADFH) domains. Immunofluorescence microscopy localized Twf1 in a punctate perinuclear distribution in mouse fibroblasts and neuroblastoma cells. Twf1 also localized to globular (G)-actin (see 102610)-rich areas of the actin cytoskeleton in fibroblasts and to filamentous (F)-actin-rich filopodia in neuroblastoma cells.

GENE FUNCTION

Beeler et al. (1994) showed that recombinant TWF1 underwent autophosphorylation on tyrosines and serines in an in vitro kinase assay, and it phosphorylated exogenous substrates on tyrosines. Recombinant TWF1 had kinase activity similar to that of recombinant FGFR2 (176943), with optimal activity over pH 6.5 to 7.4 and a preference for manganese over magnesium as a divalent cofactor. In contrast to the findings of Beeler et al. (1994), Vartiainen et al. (2000) found that recombinant mouse Twf1 lacked tyrosine kinase activity. They showed that Twf1 bound G-actin in a 1:1 stoichiometry and prevented F-actin assembly in a concentration-dependent manner. Overexpression of Twf1 in mouse fibroblasts decreased the amount of stress fibers and caused the appearance of abnormal cytoplasmic actin filaments. In mouse fibroblasts, Twf1 colocalized with GTP-bound forms of Cdc42 (116952) and Rac1 (602048) at membrane ruffles and cell-cell contacts, respectively, and localization of Twf1 in these cells appeared to be regulated by Rac1. Paavilainen et al. (2007) showed that the N- and C-terminal ADFH domains of mouse Twf1, which they called TWF-N and TWF-C, respectively, were required for actin barbed-end capping. NMR and mutagenesis analyses, together with biochemical and motility assays, showed that TWF-C bound G-actin and interacted with the sides of F-actin like ADF and cofilins, whereas TWF-N bound only G-actin. During filament barbed-end capping, TWF-N interacted with the terminal actin subunit, and TWF-C bound between 2 adjacent subunits at the side of the filament. The domain requirement for actin filament capping by Twf1 was similar to that of gelsolin (GSN; 137350)-type proteins, suggesting the existence of a general barbed-end capping mechanism. In an adaptation of loss-of-function screening to mouse models of cancer, Meacham et al. (2009) introduced a library of shRNAs into individual mice using transplantable E-mu-myc lymphoma cells. This approach allowed them to screen nearly 1,000 genetic alterations in the context of a single tumor-bear ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610932 was added.