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Protein

Cofilin/actin-depolymerizing factor homolog

Gene

tsr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Exhibits F-actin depolymerizing activity and regulates actin cytoskeleton dynamics (PubMed:21205790). Required for cytokinesis in both mitotic and meiotic cells and for aster migration and separation (PubMed:8522587). Promotes cell motility during ovary development and oogenesis (PubMed:11175754). During larval development, required for the cell rearrangement needed for formation of terminal filaments which are stacks of somatic cells that are important for the initiation of ovarioles (PubMed:11175754). Also required for border cell migration during oogenesis (PubMed:11175754). During border cell migration, required for actin turnover and lamellipodial protrusion (PubMed:21205790). Required for the establishment of planar cell polarity (PCP) where cells adopt a uniform orientation within the plane of an epithelium (PubMed:16571634). During establishment of PCP, required for the redistribution of the PCP core proteins fz and stan/fmi to the proximodistal cell boundary (PubMed:16571634). During pupal development, required for elongation of the retinal cell body and for rhabdomere morphogenesis (PubMed:18423434). Required for mushroom body neuroblast proliferation and axon growth (PubMed:15572110). Plays a role in the positive regulation of protein secretion (PubMed:20026655). Plays a role in the regulation of nuclear localization of actin (PubMed:22323606). Required for the maintenance of epithelial integrity by controlling cell junctions and is also necessary for cell survival and tissue growth through regulation of JNK and yki signaling (PubMed:27041568).9 Publications

Miscellaneous

The name 'twinstar' derives from the characteristic aberrant arrangement of asters seen in mutants.1 Publication

GO - Molecular functioni

  • actin binding Source: FlyBase

GO - Biological processi

  • actin filament depolymerization Source: UniProtKB
  • actin filament organization Source: FlyBase
  • actin filament polymerization Source: FlyBase
  • actomyosin contractile ring assembly Source: FlyBase
  • axonogenesis Source: FlyBase
  • border follicle cell migration Source: UniProtKB
  • cell morphogenesis Source: FlyBase
  • centrosome separation Source: UniProtKB
  • compound eye development Source: FlyBase
  • compound eye morphogenesis Source: FlyBase
  • epithelial structure maintenance Source: UniProtKB
  • establishment of imaginal disc-derived wing hair orientation Source: FlyBase
  • establishment of ommatidial planar polarity Source: FlyBase
  • establishment of planar polarity Source: FlyBase
  • female gonad development Source: FlyBase
  • imaginal disc-derived leg segmentation Source: FlyBase
  • lamellipodium assembly Source: UniProtKB
  • meiotic cytokinesis Source: UniProtKB
  • mitotic cytokinesis Source: UniProtKB
  • mushroom body development Source: FlyBase
  • positive regulation of protein secretion Source: UniProtKB
  • regulation of lamellipodium assembly Source: FlyBase
  • rhabdomere development Source: FlyBase

Keywordsi

Molecular functionActin-binding
Biological processCell cycle, Cell division

Names & Taxonomyi

Protein namesi
Recommended name:
Cofilin/actin-depolymerizing factor homolog
Alternative name(s):
Protein D61
Protein twinstar1 Publication
Gene namesi
Name:tsr1 PublicationImported
Synonyms:Cadf
ORF Names:CG4254Imported
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2R

Organism-specific databases

FlyBaseiFBgn0011726 tsr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Late larval or pupal lethality with mutants showing defects in cytokinesis in both mitotic and meiotic cells, abnormal accumulation of F-actin in mature primary spermatocytes, and defective aster migration where the asters remain in close proximity to each other rather than separating from each other and migrating around the periphery of the nuclear envelope as in the wild type (PubMed:8522587). Failure of terminal filament formation in the ovary at the third larval instar at 25 degrees Celsius but formation occurs at 18 degrees Celsius (PubMed:11175754). Significantly thinner retina than controls, significantly increased F-actin levels in pupal eye disks and defective rhabdomere morphogenesis (PubMed:18423434). Defective mushroom body neuroblast proliferation with newly hatched larvae containing significantly fewer neurons than controls and severe axon growth defects with mutants failing to extend axons beyond the peduncle (PubMed:15572110). RNAi-mediated knockdown in the wing results in increased F-actin levels, altered subcellular location of the transcriptional coactivator yki, strong expression of the yki target genes wg and ex, cell extrusion from the basement membrane, reduced levels of the junction proteins dlg1, arm and shg, up-regulation of Rho1, apoptosis and JNK signaling (PubMed:27041568).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3S → A: Abolishes in vitro phosphorylation by LIMK1. Partial rescue of both the defective neuroblast proliferation and defective axon growth seen in null mutants. 2 Publications1
Mutagenesisi3S → E: No rescue of the defective neuroblast proliferation seen in null mutants but partial rescue of the defective axon growth. 1 Publication1
Mutagenesisi27V → Q: Defective distal orientation of wing hairs and incorrect localization of the planar cell polarity proteins fz and stan/fmi; when associated with 139-AAALA-143. 1 Publication1
Mutagenesisi139 – 143EEKLR → AAALA: Defective distal orientation of wing hairs and incorrect localization of the planar cell polarity proteins fz and stan/fmi; when associated with Q-27. 1 Publication5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002149161 – 148Cofilin/actin-depolymerizing factor homologAdd BLAST148

Post-translational modificationi

Phosphorylated in vitro by protein kinase LIMK1 (PubMed:20026655). Phosphorylation is required for inactivation of tsr and for cell proliferation and axon growth (PubMed:15572110). Phosphorylation is negatively regulated by the panthothenate kinase fbl which catalyzes the first step in the conversion of panthothenic acid to coenzyme A (PubMed:22912811).3 Publications
Dephosphorylated by protein phosphatase ssh which activates tsr.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP45594
PRIDEiP45594

PTM databases

iPTMnetiP45594

Expressioni

Developmental stagei

Expressed during all stages of development and peaks in late larval and pupal stages. Expressed in both male and female adults.1 Publication

Gene expression databases

BgeeiFBgn0011726
ExpressionAtlasiP45594 baseline and differential
GenevisibleiP45594 DM

Interactioni

GO - Molecular functioni

  • actin binding Source: FlyBase

Protein-protein interaction databases

BioGridi63422, 45 interactors
DIPiDIP-20149N
IntActiP45594, 48 interactors
STRINGi7227.FBpp0072097

Structurei

Secondary structure

1148
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 20Combined sources12
Beta strandi26 – 32Combined sources7
Turni33 – 35Combined sources3
Beta strandi36 – 43Combined sources8
Helixi49 – 59Combined sources11
Beta strandi61 – 63Combined sources3
Beta strandi65 – 77Combined sources13
Beta strandi80 – 94Combined sources15
Helixi101 – 113Combined sources13
Helixi114 – 116Combined sources3
Beta strandi122 – 127Combined sources6
Turni130 – 132Combined sources3
Helixi135 – 144Combined sources10

3D structure databases

ProteinModelPortaliP45594
SMRiP45594
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 143ADF-HPROSITE-ProRule annotationAdd BLAST140

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 23Nuclear localization signalSequence analysis5

Sequence similaritiesi

Belongs to the actin-binding proteins ADF family.Curated

Phylogenomic databases

eggNOGiKOG1735 Eukaryota
ENOG41122P5 LUCA
GeneTreeiENSGT00730000112650
InParanoidiP45594
KOiK05765
OMAiIEIQGTD
OrthoDBiEOG091G0TDH
PhylomeDBiP45594

Family and domain databases

CDDicd11286 ADF_cofilin_like, 1 hit
Gene3Di3.40.20.10, 1 hit
InterProiView protein in InterPro
IPR002108 ADF-H
IPR029006 ADF-H/Gelsolin-like_dom_sf
IPR017904 ADF/Cofilin
PANTHERiPTHR11913 PTHR11913, 1 hit
PfamiView protein in Pfam
PF00241 Cofilin_ADF, 1 hit
SMARTiView protein in SMART
SM00102 ADF, 1 hit
PROSITEiView protein in PROSITE
PS51263 ADF_H, 1 hit

Sequencei

Sequence statusi: Complete.

P45594-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGVTVSDV CKTTYEEIKK DKKHRYVIFY IRDEKQIDVE TVADRNAEYD
60 70 80 90 100
QFLEDIQKCG PGECRYGLFD FEYMHQCQGT SESSKKQKLF LMSWCPDTAK
110 120 130 140
VKKKMLYSSS FDALKKSLVG VQKYIQATDL SEASREAVEE KLRATDRQ
Length:148
Mass (Da):17,153
Last modified:November 1, 1995 - v1
Checksum:i24F7216033859620
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08217 mRNA Translation: AAA19856.1
U24490 mRNA Translation: AAC46962.1
U24676 Genomic DNA Translation: AAC46963.1
AE013599 Genomic DNA Translation: AAF47146.1
BT089017 mRNA Translation: ACT98664.1
PIRiA57569
RefSeqiNP_477034.1, NM_057686.4
UniGeneiDm.763

Genome annotation databases

EnsemblMetazoaiFBtr0072188; FBpp0072097; FBgn0011726
GeneIDi37841
KEGGidme:Dmel_CG4254

Similar proteinsi

Entry informationi

Entry nameiCADF_DROME
AccessioniPrimary (citable) accession number: P45594
Secondary accession number(s): C6SV25, Q9W1C4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 18, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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