Q91YR1 (TWF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Twinfilin-1

Alternative name(s):
Protein A6

Gene names

Name:	Twf1
Synonyms:	Ptk9

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	350 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with G-actin; ADP-actin form and capping protein (CP). May also be able to interact with TWF2 and phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-regulated. Ref.2 Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Note: Diffuse cytoplasmic localization with perinuclear and G-actin-rich cortical actin structures sublocalization. Also found at membrane ruffles and cell-cell contacts. Ref.5
Tissue specificity	Widely expressed with highest levels in brain, liver and kidney. Also expressed in heart, lung and testis. Not detected in spleen or skeletal muscle. Ref.1 Ref.2 Ref.5
Developmental stage	Expression was widespread throughout the embryonic stages analyzed; E10.5, E12.5, E14.5 and E18.5. At E14.5, strongest expression was observed in the developing central and peripheral nervous system (CNS and PNS, respectively) and in the olfactory sensory epithelium. In the CNS, the proliferating neuronal precursors in the ventricular zone expressed it more than the postmitotic neurons. At E18.5, highest expression levels were detected in the mechanosensory hair cells of the inner ear and in the differentiated keratinocytes of the skin. Ref.2
Post-translational modification	Phosphorylated on serine and threonine residues By similarity. UniProtKB Q12792
Sequence similarities	Belongs to the actin-binding proteins ADF family. Twinfilin subfamily. Contains 2 ADF-H domains.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Actin-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	barbed-end actin filament capping Inferred from direct assay PubMed 18837697. Source: BHF-UCL regulation of actin phosphorylation Inferred from electronic annotation. Source: Compara sequestering of actin monomers Inferred from direct assay PubMed 18837697. Source: BHF-UCL
Cellular_component	actin cytoskeleton Inferred from direct assay Ref.5. Source: UniProtKB cell-cell junction Inferred from direct assay Ref.2. Source: BHF-UCL filopodium Inferred from direct assay Ref.2. Source: BHF-UCL myofibril Inferred from direct assay PubMed 18837697. Source: BHF-UCL perinuclear region of cytoplasm Inferred from direct assay Ref.2. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: Compara actin monomer binding Inferred from direct assay Ref.2PubMed 18837697. Source: BHF-UCL phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay Ref.2. Source: BHF-UCL protein tyrosine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 350

349

Twinfilin-1

PRO_0000214951

Regions

Domain

2 – 139

138

ADF-H 1

Domain

175 – 313

139

ADF-H 2

Amino acid modifications

Modified residue

2

1

N-acetylserine By similarity

Modified residue

143

1

Phosphoserine By similarity

Modified residue

309

1

Phosphotyrosine Ref.8

Modified residue

349

1

Phosphothreonine Ref.9

Natural variations

Natural variant

51

1

Q → H. Ref.4

Experimental info

Sequence conflict

345

1

A → R in AAB66592. Ref.1

Sequence conflict

345

1

A → R in AAP31404. Ref.2

Secondary structure

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350

Helix Strand Turn

Details...

Helix

11 – 21

11

Turn

22 – 24

3

Beta strand

26 – 32

7

Beta strand

34 – 43

10

Helix

49 – 57

9

Helix

58 – 60

3

Beta strand

67 – 77

11

Beta strand

80 – 88

9

Helix

95 – 112

18

Helix

114 – 116

3

Beta strand

117 – 125

9

Helix

126 – 129

4

Helix

131 – 138

8

Helix

184 – 194

11

Beta strand

199 – 206

8

Turn

207 – 210

4

Beta strand

211 – 216

6

Helix

222 – 224

3

Helix

226 – 228

3

Beta strand

231 – 233

3

Beta strand

235 – 245

11

Beta strand

248 – 258

11

Beta strand

262 – 264

3

Helix

266 – 274

9

Helix

276 – 287

12

Beta strand

291 – 302

12

Helix

305 – 312

8

Sequences

	Sequence		Length	Mass (Da)
	Q91YR1 [UniParc]. Last modified April 4, 2006. Version 2. Checksum: 643CBBA18D38D4E0	FASTA	350	40,079
	10 20 30 40 50 60 MSHQTGIQAS EDVKEIFARA RNGKYRLLKI SIENEQLVVG SCSPPSDSWE QDYDSFVLPL 70 80 90 100 110 120 LEDKQPCYVL FRLDSQNAQG YEWIFIAWSP DHSHVRQKML YAATRATLKK EFGGGHIKDE 130 140 150 160 170 180 VFGTVKEDVS LHGYKKYLLS QSSPAPLTAA EEELRQIKIN EVQTDVSVDT KHQTLQGVAF 190 200 210 220 230 240 PISRDAFQAL EKLSKKQLNY VQLEIDIKNE TIILANTENT ELRDLPKRIP KDSARYHFFL 250 260 270 280 290 300 YKHSHEGDYL ESVVFIYSMP GYTCSIRERM LYSSCKSPLL EIVERQLQMD VIRKIEIDNG 310 320 330 340 350 DELTADFLYD EVHPKQHAHK QSFAKPKGPA GKRGIRRLIR GPAEAEATTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the mouse homolog of the human A6 gene." Beeler J.F., Patel B.K.R., Chedid M., LaRochelle W.J. Gene 193:31-37(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[2]	"Mammals have two twinfilin isoforms whose subcellular localizations and tissue distributions are differentially regulated." Vartiainen M.K., Sarkkinen E.M., Matilainen T., Salminen M., Lappalainen P. J. Biol. Chem. 278:34347-34355(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH TWF2 AND PHOSPHOINOSITIDE, DEVELOPMENTAL STAGE.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Bone marrow.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-51. Strain: NMRI. Tissue: Mammary gland and Mammary tumor.
[5]	"Mouse A6/twinfilin is an actin monomer-binding protein that localizes to the regions of rapid actin dynamics." Vartiainen M., Ojala P.J., Auvinen P., Peranen J., Lappalainen P. Mol. Cell. Biol. 20:1772-1783(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"Biological role and structural mechanism of twinfilin-capping protein interaction." Falck S., Paavilainen V.O., Wear M.A., Grossmann J.G., Cooper J.A., Lappalainen P. EMBO J. 23:3010-3019(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH G-ACTIN AND CAPPING PROTEINS.
[7]	"Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility." Helfer E., Nevalainen E.M., Naumanen P., Romero S., Didry D., Pantaloni D., Lappalainen P., Carlier M.-F. EMBO J. 25:1184-1195(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH G-ACTIN AND CAPPING PROTEINS.
[8]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-349, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[10]	"Structural conservation between the actin monomer-binding sites of twinfilin and actin-depolymerizing factor (ADF)/cofilin." Paavilainen V.O., Merckel M.C., Falck S., Ojala P.J., Pohl E., Wilmanns M., Lappalainen P. J. Biol. Chem. 277:43089-43095(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-142.
[11]	"NMR solution structures of actin depolymerizing factor homology domains." Goroncy A.K., Koshiba S., Tochio N., Tomizawa T., Sato M., Inoue M., Watanabe S., Hayashizaki Y., Tanaka A., Kigawa T., Yokoyama S. Protein Sci. 18:2384-2392(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 161-313.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Molecular embrace - Issue 73 of August 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U82324 mRNA. Translation: AAB66592.1.
AY267188 mRNA. Translation: AAP31404.1.
AK147990 mRNA. Translation: BAE28272.1.
AK150852 mRNA. Translation: BAE29908.1.
BC015081 mRNA. Translation: AAH15081.1.
BC094034 mRNA. Translation: AAH94034.1.

IPI

IPI00314844.

RefSeq

NP_032997.3. NM_008971.4.

UniGene

Mm.490250.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M4J	X-ray	1.60	A/B	1-142	[»]
2D8B	NMR	-	A	161-313	[»]
2HD7	NMR	-	A	176-316	[»]
3DAW	X-ray	2.55	B	169-322	[»]

ProteinModelPortal

Q91YR1.

SMR

Q91YR1. Positions 7-139, 161-313.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q91YR1. 1 interaction.

PTM databases

PhosphoSite

Q91YR1.

Proteomic databases

PaxDb

Q91YR1.

PRIDE

Q91YR1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000023087; ENSMUSP00000023087; ENSMUSG00000022451.

GeneID

19230.

KEGG

mmu:19230.

UCSC

uc007xjl.1. mouse.

Organism-specific databases

CTD

5756.

MGI

MGI:1100520. Twf1.

Phylogenomic databases

eggNOG

NOG263290.

GeneTree

ENSGT00530000063868.

HOGENOM

HOG000168296.

HOVERGEN

HBG000848.

InParanoid

Q91YR1.

KO

K08870.

OMA

VIRKIEI.

OrthoDB

EOG4TTGJJ.

Gene expression databases

ArrayExpress

Q91YR1.

Bgee

Q91YR1.

Genevestigator

Q91YR1.

GermOnline

ENSMUSG00000022451. Mus musculus.

Family and domain databases

InterPro

IPR002108. Actin-bd_cofilin/tropomyosin.
[Graphical view]

Pfam

PF00241. Cofilin_ADF. 2 hits.
[Graphical view]

SMART

SM00102. ADF. 2 hits.
[Graphical view]

PROSITE

PS51263. ADF_H. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TWF1. mouse.

EvolutionaryTrace

Q91YR1.

NextBio

296036.

SOURCE

Search...

Entry information

Entry name

TWF1_MOUSE

Accession

Primary (citable) accession number: Q91YR1
Secondary accession number(s): O09132, Q52L77, Q80X09

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	April 4, 2006
Last modified:	April 3, 2013
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program