ID COF1_RAT Reviewed; 166 AA. AC P45592; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 192. DE RecName: Full=Cofilin-1; DE AltName: Full=Cofilin, non-muscle isoform; GN Name=Cfl1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Wistar; TISSUE=Brain; RA Shirasawa T., Takahashi H., Sakamoto K., Kawashima A., Akashi T.; RL Submitted (OCT-1991) to the EMBL/GenBank/DDBJ databases. RN [2] RP PROTEIN SEQUENCE OF 2-166, ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-3, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Parotid gland; RX PubMed=9877327; DOI=10.1016/s0003-9969(98)00083-1; RA Kanamori T., Suzuki M., Titani K.; RT "Complete amino acid sequences and phosphorylation sites, determined by RT Edman degradation and mass spectrometry, of rat parotid destrin- and RT cofilin-like proteins."; RL Arch. Oral Biol. 43:955-967(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary, and Pituitary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 35-73; 82-92; 96-112; 133-146 AND 153-166, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.; RL Submitted (JUL-2007) to UniProtKB. RN [5] RP ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-3, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RA Lubec G., Chen W.-Q.; RL Submitted (FEB-2007) to UniProtKB. CC -!- FUNCTION: Binds to F-actin and exhibits pH-sensitive F-actin CC depolymerizing activity (By similarity). Important for normal progress CC through mitosis and normal cytokinesis (By similarity). In conjunction CC with the subcortical maternal complex (SCMC), plays an essential role CC for zygotes to progress beyond the first embryonic cell divisions via CC regulation of actin dynamics (By similarity). Required for the CC centralization of the mitotic spindle and symmetric division of zygotes CC (By similarity). Plays a role in the regulation of cell morphology and CC cytoskeletal organization in epithelial cells (By similarity). Required CC for the up-regulation of atypical chemokine receptor ACKR2 from CC endosomal compartment to cell membrane, increasing its efficiency in CC chemokine uptake and degradation (By similarity). Required for neural CC tube morphogenesis and neural crest cell migration (By similarity). CC {ECO:0000250|UniProtKB:P18760, ECO:0000250|UniProtKB:P23528}. CC -!- SUBUNIT: Can bind G- and F-actin in a 1:1 ratio of cofilin to actin (By CC similarity). It is a major component of intranuclear and cytoplasmic CC actin rods (By similarity). Interacts with the subcortical maternal CC complex (SCMC) via interaction with TLE6 and NLRP5 (By similarity). CC Interacts with C9orf72 (By similarity). {ECO:0000250|UniProtKB:P10668, CC ECO:0000250|UniProtKB:P18760}. CC -!- INTERACTION: CC P45592; Q66HL2: Cttn; NbExp=4; IntAct=EBI-917556, EBI-6273816; CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:P10668}. CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P10668}. Cell CC projection, ruffle membrane {ECO:0000250}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P10668}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P10668}. Cell projection, lamellipodium membrane CC {ECO:0000250|UniProtKB:P10668}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P10668}; Cytoplasmic side CC {ECO:0000250|UniProtKB:P10668}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:P18760}. Cell projection, growth cone CC {ECO:0000250|UniProtKB:P18760}. Cell projection, axon CC {ECO:0000250|UniProtKB:P18760}. Note=Colocalizes with the actin CC cytoskeleton in membrane ruffles and lamellipodia. Detected at the CC cleavage furrow and contractile ring during cytokinesis. Almost CC completely in nucleus in cells exposed to heat shock or 10% dimethyl CC sulfoxide. {ECO:0000250|UniProtKB:P10668, CC ECO:0000250|UniProtKB:P23528}. CC -!- PTM: Inactivated by phosphorylation on Ser-3. Phosphorylated on Ser-3 CC in resting cells. Dephosphorylated by PDXP/chronophin; this restores CC its activity in promoting actin filament depolymerization. The CC phosphorylation of Ser-24 may prevent recognition of the nuclear CC localization signal (By similarity). Phosphorylated via a ARRB1-RAC1- CC LIMK1-PAK1 cascade upon active ligand stimulation of atypical chemokine CC receptor ACKR2 (By similarity). {ECO:0000250|UniProtKB:P45695}. CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X62908; CAA44694.1; -; mRNA. DR EMBL; BC059143; AAH59143.1; -; mRNA. DR EMBL; BC086533; AAH86533.1; -; mRNA. DR PIR; S49101; S49101. DR RefSeq; NP_058843.1; NM_017147.2. DR AlphaFoldDB; P45592; -. DR BMRB; P45592; -. DR SMR; P45592; -. DR BioGRID; 247942; 12. DR IntAct; P45592; 6. DR MINT; P45592; -. DR STRING; 10116.ENSRNOP00000059624; -. DR GlyGen; P45592; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P45592; -. DR PhosphoSitePlus; P45592; -. DR jPOST; P45592; -. DR PaxDb; 10116-ENSRNOP00000059624; -. DR Ensembl; ENSRNOT00000117088.1; ENSRNOP00000093902.1; ENSRNOG00000020660.8. DR GeneID; 29271; -. DR KEGG; rno:29271; -. DR UCSC; RGD:69285; rat. DR AGR; RGD:69285; -. DR CTD; 1072; -. DR RGD; 69285; Cfl1. DR eggNOG; KOG1735; Eukaryota. DR GeneTree; ENSGT00950000183000; -. DR HOGENOM; CLU_094004_0_0_1; -. DR InParanoid; P45592; -. DR OMA; WSMIYAT; -. DR OrthoDB; 3380386at2759; -. DR PhylomeDB; P45592; -. DR PRO; PR:P45592; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000020660; Expressed in cerebellum and 19 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central. DR GO; GO:0031252; C:cell leading edge; IDA:RGD. DR GO; GO:0005911; C:cell-cell junction; ISO:RGD. DR GO; GO:0090732; C:cofilin-actin rod; IDA:RGD. DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0030175; C:filopodium; IDA:RGD. DR GO; GO:0005925; C:focal adhesion; ISO:RGD. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0030426; C:growth cone; IDA:RGD. DR GO; GO:0030027; C:lamellipodium; IDA:RGD. DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031966; C:mitochondrial membrane; IDA:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0097060; C:synaptic membrane; IDA:RGD. DR GO; GO:0003779; F:actin binding; IMP:RGD. DR GO; GO:0051015; F:actin filament binding; IDA:RGD. DR GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; IPI:RGD. DR GO; GO:0019903; F:protein phosphatase binding; IPI:RGD. DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD. DR GO; GO:0030042; P:actin filament depolymerization; ISO:RGD. DR GO; GO:0030043; P:actin filament fragmentation; ISO:RGD. DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB. DR GO; GO:0051014; P:actin filament severing; IBA:GO_Central. DR GO; GO:0048870; P:cell motility; ISO:RGD. DR GO; GO:0030030; P:cell projection organization; IDA:MGI. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IMP:RGD. DR GO; GO:0071362; P:cellular response to ether; IEP:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:RGD. DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IDA:RGD. DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:RGD. DR GO; GO:0071354; P:cellular response to interleukin-6; IDA:RGD. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:RGD. DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0030010; P:establishment of cell polarity; ISO:RGD. DR GO; GO:0051293; P:establishment of spindle localization; ISS:UniProtKB. DR GO; GO:0021766; P:hippocampus development; IEP:RGD. DR GO; GO:0000281; P:mitotic cytokinesis; ISO:RGD. DR GO; GO:0098885; P:modification of postsynaptic actin cytoskeleton; IDA:SynGO. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:SynGO. DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; IMP:RGD. DR GO; GO:0030835; P:negative regulation of actin filament depolymerization; IMP:RGD. DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:RGD. DR GO; GO:2000146; P:negative regulation of cell motility; IMP:RGD. DR GO; GO:0045792; P:negative regulation of cell size; IDA:MGI. DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IMP:RGD. DR GO; GO:0010593; P:negative regulation of lamellipodium assembly; IMP:RGD. DR GO; GO:1905875; P:negative regulation of postsynaptic density organization; IMP:RGD. DR GO; GO:0051511; P:negative regulation of unidimensional cell growth; IMP:RGD. DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD. DR GO; GO:0001842; P:neural fold formation; ISO:RGD. DR GO; GO:0044794; P:positive regulation by host of viral process; ISO:RGD. DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; ISO:RGD. DR GO; GO:2000814; P:positive regulation of barbed-end actin filament capping; IMP:RGD. DR GO; GO:0030307; P:positive regulation of cell growth; IMP:RGD. DR GO; GO:2000147; P:positive regulation of cell motility; IMP:RGD. DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD. DR GO; GO:0040019; P:positive regulation of embryonic development; ISS:UniProtKB. DR GO; GO:2000784; P:positive regulation of establishment of cell polarity regulating cell shape; IMP:RGD. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IMP:RGD. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:RGD. DR GO; GO:1905873; P:positive regulation of protein localization to cell leading edge; IMP:RGD. DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:RGD. DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IMP:RGD. DR GO; GO:0006606; P:protein import into nucleus; IMP:RGD. DR GO; GO:0022604; P:regulation of cell morphogenesis; ISS:UniProtKB. DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:ParkinsonsUK-UCL. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR GO; GO:0043200; P:response to amino acid; ISO:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0009615; P:response to virus; ISO:RGD. DR CDD; cd11286; ADF_cofilin_like; 1. DR Gene3D; 3.40.20.10; Severin; 1. DR InterPro; IPR002108; ADF-H. DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf. DR InterPro; IPR017904; ADF/Cofilin. DR PANTHER; PTHR11913:SF17; COFILIN-1; 1. DR PANTHER; PTHR11913; COFILIN-RELATED; 1. DR Pfam; PF00241; Cofilin_ADF; 1. DR PRINTS; PR00006; COFILIN. DR SMART; SM00102; ADF; 1. DR SUPFAM; SSF55753; Actin depolymerizing proteins; 1. DR PROSITE; PS51263; ADF_H; 1. DR World-2DPAGE; 0004:P45592; -. DR Genevisible; P45592; RN. PE 1: Evidence at protein level; KW Acetylation; Actin-binding; Cell membrane; Cell projection; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Isopeptide bond; Membrane; KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9877327, ECO:0000269|Ref.5" FT CHAIN 2..166 FT /note="Cofilin-1" FT /id="PRO_0000214902" FT DOMAIN 4..153 FT /note="ADF-H" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00599" FT MOTIF 30..34 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:9877327, ECO:0000269|Ref.5" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:9877327, ECO:0000269|Ref.5" FT MOD_RES 8 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P18760" FT MOD_RES 13 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 25 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 41 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 68 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 73 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 140 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 144 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT MOD_RES 156 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P23528" FT CROSSLNK 132 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P23528" SQ SEQUENCE 166 AA; 18533 MW; 19835391A81A5AB2 CRC64; MASGVAVSDG VIKVFNDMKV RKSSTPEEVK KRKKAVLFCL SEDKKNIILE EGKEILVGDV GQTVDDPYTT FVKMLPDKDC RYALYDATYE TKESKKEDLV FIFWAPESAP LKSKMIYASS KDAIKKKLTG IKHELQANCY EEVKDRCTLA EKLGGSAVIS LEGKPL //