BioPAX pathway converted from "Association of profilin with monomeric actin" in the Reactome database. LEFT-TO-RIGHT Association of profilin with monomeric actin Profilins PFN1 and PFN2 bind to monomeric actin (G-actin), forming a 1:1 complex and subsequently regulate actin filament barbed end assembly downstream of various signaling pathways (Pring et al. 1992, Korenbaum et al. 1998, Nodelman et al. 1999) Authored: Pollard, T, 2007-09-30 10:07:47 Reviewed: Rivero Crespo, Francisco, 2014-12-26 Edited: Orlic-Milacic, Marija, 2015-02-02 G-actin actin:ATP Reactome DB_ID: 201857 cytosol GENE ONTOLOGY GO:0005829 Converted from EntitySet in Reactome actin Reactome DB_ID: 201859 ACTB ACTB(1-375) beta-actin cytoplasmic actin 1 Reactome DB_ID: 201861 UniProt:P60709 ACTB ACTB FUNCTION Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947).SUBUNIT Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (PubMed:28604741, PubMed:16685646). Each actin can bind to 4 others (PubMed:28604741, PubMed:16685646). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:18765789). In muscle cells, the BAF complex also contains DPF3 (PubMed:18765789). Found in a complex with XPO6, Ran, ACTB and PFN1 (PubMed:14592989). Interacts with XPO6 and EMD (PubMed:15328537). Interacts with ERBB2 (PubMed:21555369). Interacts with GCSAM (PubMed:17823310). Interacts with TBC1D21 (By similarity). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (By similarity). Interacts with DHX9 (via C-terminus); this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (PubMed:11687588). Interacts with FAM107A (PubMed:21969592, PubMed:28604741).PTM ISGylated.PTM Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.PTM Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes (PubMed:23673617). Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (PubMed:23673617).PTM Methylated at His-73 by SETD3 (PubMed:30526847, PubMed:30626964, PubMed:30785395, PubMed:31388018). Methylation at His-73 is required for smooth muscle contraction of the laboring uterus during delivery (By similarity).PTM (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).MISCELLANEOUS In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.SIMILARITY Belongs to the actin family.CAUTION Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203). Homo sapiens NCBI Taxonomy 9606 UniProt P60709 1 EQUAL 375 EQUAL Reactome Database ID Release 81 201861 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201861 Reactome R-HSA-201861 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201861.1 Reactome http://www.reactome.org ACTG1 cytoplasmic actin 2 Reactome DB_ID: 201858 UniProt:P63261 ACTG1 ACTG1 ACTG FUNCTION Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.SUBUNIT Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin (PubMed:28493397).PTM Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.PTM Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.PTM Methylated at His-73 by SETD3.PTM (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).DISEASE Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.MISCELLANEOUS In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.SIMILARITY Belongs to the actin family. UniProt P63261 1 EQUAL 375 EQUAL Reactome Database ID Release 81 201858 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201858 Reactome R-HSA-201858 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201858.1 Reactome Database ID Release 81 201859 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201859 Reactome R-HSA-201859 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201859.1 1 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 81 113592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.5 COMPOUND C00002 additional information MI MI:0361 1 Reactome Database ID Release 81 201857 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201857 Reactome R-HSA-201857 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201857.3 Converted from EntitySet in Reactome PFN Profilin (PFN1,PFN2) Reactome DB_ID: 203077 PFN1 Profilin I Reactome DB_ID: 203081 UniProt:P07737 PFN1 PFN1 FUNCTION Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.SUBUNIT Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio. Found in a complex with XPO6, Ran, ACTB and PFN1. Interacts with VASP. Interacts with HTT.TISSUE SPECIFICITY Expressed in epididymis (at protein level).PTM Phosphorylation at Ser-138 reduces its affinity for G-actin and blocks its interaction with HTT, reducing its ability to inhibit androgen receptor (AR) and HTT aggregation.SIMILARITY Belongs to the profilin family. UniProt P07737 2 EQUAL 140 EQUAL Reactome Database ID Release 81 203081 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203081 Reactome R-HSA-203081 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203081.1 PFN2 Profilin-2 PROF2_HUMAN Reactome DB_ID: 3009037 UniProt:P35080 PFN2 PFN2 FUNCTION Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.SUBUNIT Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio (PubMed:7758455). Interacts with PFN2 (By similarity).TISSUE SPECIFICITY Highly expressed in brain, skeletal muscle and kidney and less strongly in heart, placenta, lung and liver.SIMILARITY Belongs to the profilin family. UniProt P35080 1 EQUAL 140 EQUAL Reactome Database ID Release 81 3009037 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3009037 Reactome R-HSA-3009037 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-3009037.1 Reactome Database ID Release 81 203077 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203077 Reactome R-HSA-203077 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203077.2 Profilin:G-actin PFN1,PFN2:G-actin Profilin:monomeric actin Reactome DB_ID: 203080 1 1 Reactome Database ID Release 81 203080 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203080 Reactome R-HSA-203080 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203080.1 Reactome Database ID Release 81 203070 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203070 Reactome R-HSA-203070 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203070.1 9649308 Pubmed 1998 The role of profilin in actin polymerization and nucleotide exchange Korenbaum, E Nordberg, P Björkegren-Sjögren, C Schutt, C E Lindberg, U Karlsson, R Biochemistry 37:9274-83 1737036 Pubmed 1992 Profilin-actin complexes directly elongate actin filaments at the barbed end Pring, M Weber, A Bubb, M R Biochemistry 31:1827-36 10600384 Pubmed 1999 X-ray structure determination of human profilin II: A comparative structural analysis of human profilins Nodelman, IM Bowman, GD Lindberg, U Schutt, CE J Mol Biol 294:1271-85