TWF2_MOUSE
ID TWF2_MOUSE Reviewed; 349 AA.
AC Q9Z0P5; Q3TD06; Q3TZG2; Q8BN77; Q9DCK8;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Twinfilin-2;
DE AltName: Full=A6-related protein;
DE Short=mA6RP;
DE AltName: Full=Twinfilin-1-like protein;
GN Name=Twf2; Synonyms=Ptk9l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10406962; DOI=10.1046/j.1432-1327.1999.00537.x;
RA Rohwer A., Kittstein W., Marks F., Gschwendt M.;
RT "Cloning, expression and characterization of an A6 related protein.";
RL Eur. J. Biochem. 263:518-525(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TWF1 AND
RP PHOSPHOINOSITIDE, AND DEVELOPMENTAL STAGE.
RC STRAIN=NMRI;
RX PubMed=12807912; DOI=10.1074/jbc.m303642200;
RA Vartiainen M.K., Sarkkinen E.M., Matilainen T., Salminen M.,
RA Lappalainen P.;
RT "Mammals have two twinfilin isoforms whose subcellular localizations and
RT tissue distributions are differentially regulated.";
RL J. Biol. Chem. 278:34347-34355(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE PROMOTER USAGE,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18837697; DOI=10.1042/bj20080608;
RA Nevalainen E.M., Skwarek-Maruszewska A., Braun A., Moser M.,
RA Lappalainen P.;
RT "Two biochemically distinct and tissue-specific twinfilin isoforms are
RT generated from the mouse Twf2 gene by alternative promoter usage.";
RL Biochem. J. 417:593-600(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Eye, Inner ear, Kidney, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=NMRI; TISSUE=Mammary tumor;
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 [6]
RP PROTEIN SEQUENCE OF 30-48; 56-72; 111-136; 172-188; 197-204; 210-228 AND
RP 294-315, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Klug S., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J; TISSUE=Cochlea;
RX PubMed=19955359; DOI=10.1523/jneurosci.2782-09.2009;
RA Peng A.W., Belyantseva I.A., Hsu P.D., Friedman T.B., Heller S.;
RT "Twinfilin 2 regulates actin filament lengths in cochlear stereocilia.";
RL J. Neurosci. 29:15083-15088(2009).
RN [10]
RP INTERACTION WITH MYO7A, AND SUBCELLULAR LOCATION.
RC STRAIN=C3Heb/FeJ; TISSUE=Inner ear;
RX PubMed=19774077; DOI=10.1371/journal.pone.0007097;
RA Rzadzinska A.K., Nevalainen E.M., Prosser H.M., Lappalainen P., Steel K.P.;
RT "MyosinVIIa interacts with Twinfilin-2 at the tips of mechanosensory
RT stereocilia in the inner ear.";
RL PLoS ONE 4:E7097-E7097(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/6J;
RX PubMed=21876732; DOI=10.1371/journal.pone.0022894;
RA Nevalainen E.M., Braun A., Vartiainen M.K., Serlachius M., Andersson L.C.,
RA Moser M., Lappalainen P.;
RT "Twinfilin-2a is dispensable for mouse development.";
RL PLoS ONE 6:E22894-E22894(2011).
CC -!- FUNCTION: Actin-binding protein involved in motile and morphological
CC processes. Inhibits actin polymerization, likely by sequestering G-
CC actin. By capping the barbed ends of filaments, it also regulates
CC motility. Seems to play an important role in clathrin-mediated
CC endocytosis and distribution of endocytic organelles. May play a role
CC in regulating the mature length of the middle and short rows of
CC stereocilia. {ECO:0000269|PubMed:18837697,
CC ECO:0000269|PubMed:19955359}.
CC -!- SUBUNIT: Interacts with G-actin; ADP-actin form and capping protein
CC (CP). Isoform 2 interacts (via its N-terminal ADF-H domain) with G-
CC actin (ADP-bound form) with significantly higher affinity than isoform
CC 1. May also be able to interact with TWF1 and phosphoinositides,
CC PI(4,5)P2. When bound to PI(4,5)P2, it is down-regulated. Interacts
CC with MYO7A. {ECO:0000269|PubMed:12807912, ECO:0000269|PubMed:18837697,
CC ECO:0000269|PubMed:19774077}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:19955359}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:10406962}. Cell projection, stereocilium
CC {ECO:0000269|PubMed:19774077, ECO:0000269|PubMed:19955359}.
CC Note=Perinuclear and G-actin-rich cortical actin structure
CC sublocalization. Isoform 2 found also along myofibrils in
CC cardiomyocytes (PubMed:18837697). Localized in cochlea hair cells to
CC the tips of the middle and short rows of stereocilia (PubMed:19955359).
CC {ECO:0000269|PubMed:18837697, ECO:0000269|PubMed:19955359}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=Twf2a;
CC IsoId=Q9Z0P5-1; Sequence=Displayed;
CC Name=2; Synonyms=Twf2b;
CC IsoId=Q9Z0P5-2; Sequence=VSP_018053;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed (at protein
CC level). Isoform 2 expression is restricted to heart and skeletal muscle
CC where it is the predominant form. {ECO:0000269|PubMed:10406962,
CC ECO:0000269|PubMed:18837697}.
CC -!- DEVELOPMENTAL STAGE: Expression was relatively weak during all of the
CC embryonic stages. At 14.5 dpc, a slight increase in the expression
CC could be observed in heart, CNS, and PNS. At 18.5 dpc, it is strongly
CC expressed in the inner ear, hair cells and in the head muscles. No
CC expression is detected in the nasal epithelium or in the skin
CC keratinocytes. {ECO:0000269|PubMed:12807912}.
CC -!- PTM: Phosphorylated on both serine/threonine and tyrosine.
CC -!- DISRUPTION PHENOTYPE: Mice lacking isoform 1 develop normally to
CC adulthood, are fertile, and do not exhibit obvious morphological or
CC behavioral abnormalities. {ECO:0000269|PubMed:21876732}.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family. Twinfilin
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Molecular embrace - Issue 73
CC of August 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/073";
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DR EMBL; Y17808; CAB38083.1; -; mRNA.
DR EMBL; AY267189; AAP31405.1; -; mRNA.
DR EMBL; AK002699; BAB22293.1; -; mRNA.
DR EMBL; AK084026; BAC39101.1; -; mRNA.
DR EMBL; AK087422; BAC39867.1; -; mRNA.
DR EMBL; AK155204; BAE33117.1; -; mRNA.
DR EMBL; AK157886; BAE34246.1; -; mRNA.
DR EMBL; AK166900; BAE39103.1; -; mRNA.
DR EMBL; AK170441; BAE41799.1; -; mRNA.
DR EMBL; BC003338; AAH03338.1; -; mRNA.
DR CCDS; CCDS23473.1; -. [Q9Z0P5-1]
DR RefSeq; NP_036006.1; NM_011876.3. [Q9Z0P5-1]
DR PDB; 7DS3; X-ray; 2.09 A; C=315-344.
DR PDBsum; 7DS3; -.
DR AlphaFoldDB; Q9Z0P5; -.
DR SMR; Q9Z0P5; -.
DR BioGRID; 204847; 18.
DR DIP; DIP-61549N; -.
DR IntAct; Q9Z0P5; 2.
DR STRING; 10090.ENSMUSP00000024047; -.
DR iPTMnet; Q9Z0P5; -.
DR PhosphoSitePlus; Q9Z0P5; -.
DR SwissPalm; Q9Z0P5; -.
DR EPD; Q9Z0P5; -.
DR MaxQB; Q9Z0P5; -.
DR PaxDb; Q9Z0P5; -.
DR PeptideAtlas; Q9Z0P5; -.
DR PRIDE; Q9Z0P5; -.
DR ProteomicsDB; 300162; -. [Q9Z0P5-1]
DR ProteomicsDB; 300163; -. [Q9Z0P5-2]
DR Antibodypedia; 46152; 243 antibodies from 28 providers.
DR DNASU; 23999; -.
DR Ensembl; ENSMUST00000024047; ENSMUSP00000024047; ENSMUSG00000023277. [Q9Z0P5-1]
DR Ensembl; ENSMUST00000188650; ENSMUSP00000140339; ENSMUSG00000023277. [Q9Z0P5-2]
DR GeneID; 23999; -.
DR KEGG; mmu:23999; -.
DR UCSC; uc009rjf.1; mouse. [Q9Z0P5-1]
DR UCSC; uc009rjg.1; mouse. [Q9Z0P5-2]
DR CTD; 11344; -.
DR MGI; MGI:1346078; Twf2.
DR VEuPathDB; HostDB:ENSMUSG00000023277; -.
DR eggNOG; KOG1747; Eukaryota.
DR GeneTree; ENSGT00530000063868; -.
DR HOGENOM; CLU_031995_1_0_1; -.
DR InParanoid; Q9Z0P5; -.
DR OMA; RWDTDYD; -.
DR OrthoDB; 1578109at2759; -.
DR PhylomeDB; Q9Z0P5; -.
DR TreeFam; TF352598; -.
DR BioGRID-ORCS; 23999; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Twf2; mouse.
DR PRO; PR:Q9Z0P5; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9Z0P5; protein.
DR Bgee; ENSMUSG00000023277; Expressed in intercostal muscle and 250 other tissues.
DR ExpressionAtlas; Q9Z0P5; baseline and differential.
DR Genevisible; Q9Z0P5; MM.
DR GO; GO:0005884; C:actin filament; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:BHF-UCL.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:BHF-UCL.
DR GO; GO:0030016; C:myofibril; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0032420; C:stereocilium; IDA:BHF-UCL.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0003785; F:actin monomer binding; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0030042; P:actin filament depolymerization; IBA:GO_Central.
DR GO; GO:0051016; P:barbed-end actin filament capping; IDA:BHF-UCL.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:BHF-UCL.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IBA:GO_Central.
DR GO; GO:0032532; P:regulation of microvillus length; IC:BHF-UCL.
DR GO; GO:0042989; P:sequestering of actin monomers; IDA:BHF-UCL.
DR Gene3D; 3.40.20.10; -; 2.
DR InterPro; IPR002108; ADF-H.
DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf.
DR InterPro; IPR028458; Twinfilin.
DR PANTHER; PTHR13759; PTHR13759; 1.
DR Pfam; PF00241; Cofilin_ADF; 2.
DR SMART; SM00102; ADF; 2.
DR PROSITE; PS51263; ADF_H; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative promoter usage;
KW Cell projection; Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Developmental protein; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q6IBS0"
FT CHAIN 2..349
FT /note="Twinfilin-2"
FT /id="PRO_0000233137"
FT DOMAIN 4..139
FT /note="ADF-H 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00599"
FT DOMAIN 177..313
FT /note="ADF-H 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00599"
FT REGION 322..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q6IBS0"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q6IBS0"
FT MOD_RES 309
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..8
FT /note="MAHQTGIH -> MFLVLI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:18837697"
FT /id="VSP_018053"
FT CONFLICT 202
FT /note="Q -> R (in Ref. 4; BAE41799)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="P -> L (in Ref. 4; BAB22293)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 349 AA; 39471 MW; A9F20CBD45B8B477 CRC64;
MAHQTGIHAT EELKEFFAKA RAGSIRLIKV IIEDEQLVLG ASQEPVGRWD QDYDRAVLPL
LDAQEPCYLL FRLDSQNAQG FEWLFLAWSP DNSPVRLKML YAATRATVKK EFGGGHIKDE
LFGTVKDDLS LAGYQKHLSS CAAPAPLTSA ERELQQIRIN EVKTEISVES KHQTLQGLAF
PLQPEAQRAL QQLKQKTVNY IQLKLDLERE TIELVHTEPT NVAQLPSRIP RDAARYHFFL
YKHTHEGDAL ESVVFIYSMP GYKCSIKERM LYSSCKSRLL DSVEQDFQLE IAKKIEIGDG
AELTAEFLYD EVHPKQHAFK QAFAKPKGPG GKRGHKRLIR GPGENGEDS
