Q6IBS0 (TWF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Twinfilin-2

Alternative name(s):
A6-related protein
Short name=hA6RP
Protein tyrosine kinase 9-like
Twinfilin-1-like protein

Gene names

Name:	TWF2
Synonyms:	PTK9L
ORF Names:	MSTP011

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	349 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. May play a role in regulating the mature length of the middle and short rows of stereocilia By similarity.
Subunit structure	Interacts with G-actin; ADP-actin form and capping protein (CP). May also be able to interact with TWF1 and phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-regulated. Interacts with MYO7A By similarity.
Subcellular location	Cytoplasm › cytoskeleton. Cytoplasm › perinuclear region. Cell projection › stereocilium By similarity. Note: Perinuclear and G-actin-rich cortical actin structure sublocalization. Ref.1
Tissue specificity	Ubiquitously expressed (at protein level). Ref.1
Post-translational modification	In vitro, phosphorylated by PRKCZ, CK2 and SRC. Ref.1
Sequence similarities	Belongs to the actin-binding proteins ADF family. Twinfilin subfamily. Contains 2 ADF-H domains.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Actin-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	barbed-end actin filament capping Inferred from sequence or structural similarity PubMed 18837697. Source: BHF-UCL cell projection organization Inferred from electronic annotation. Source: UniProtKB-KW cellular response to growth factor stimulus Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL cellular response to retinoic acid Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL positive regulation of axon extension Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL positive regulation of lamellipodium assembly Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL positive regulation of neuron projection development Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL regulation of microvillus length Inferred by curator PubMed 19955359. Source: BHF-UCL sequestering of actin monomers Inferred from sequence or structural similarity PubMed 18837697. Source: BHF-UCL
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell filopodium Inferred from sequence or structural similarity PubMed 12807912. Source: BHF-UCL growth cone Inferred from direct assay PubMed 17910947. Source: BHF-UCL lamellipodium Inferred from sequence or structural similarity PubMed 12807912. Source: BHF-UCL myofibril Inferred from sequence or structural similarity PubMed 18837697. Source: BHF-UCL perinuclear region of cytoplasm Inferred from sequence or structural similarity PubMed 12807912. Source: BHF-UCL stereocilium Inferred from sequence or structural similarity PubMed 19955359. Source: BHF-UCL
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB actin monomer binding Inferred from sequence or structural similarity PubMed 12807912PubMed 18837697. Source: BHF-UCL phosphatidylinositol-4,5-bisphosphate binding Inferred from sequence or structural similarity PubMed 12807912. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 349

348

Twinfilin-2

PRO_0000233136

Regions

Domain

4 – 139

136

ADF-H 1

Domain

177 – 313

137

ADF-H 2

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6 Ref.10

Modified residue

14

1

N6-acetyllysine Ref.10

Modified residue

309

1

Phosphotyrosine Ref.7 Ref.9

Modified residue

349

1

Phosphoserine Ref.9 Ref.12

Natural variations

Natural variant

72

1

R → C. Ref.13
Corresponds to variant rs35114109 [ dbSNP | Ensembl ].

VAR_042407

Natural variant

76

1

Q → R. Ref.13
Corresponds to variant rs35711542 [ dbSNP | Ensembl ].

VAR_042408

Natural variant

103

1

A → T in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.13

VAR_042409

Experimental info

Sequence conflict

110

1

K → R in CAG33013. Ref.4

Secondary structure

1

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349

Helix Strand Turn

Details...

Helix

11 – 22

12

Beta strand

26 – 33

8

Beta strand

36 – 43

8

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 – 136

6

Helix

184 – 194

11

Beta strand

199 – 206

8

Turn

207 – 210

4

Beta strand

211 – 216

6

Helix

222 – 228

7

Beta strand

231 – 233

3

Beta strand

235 – 245

11

Beta strand

248 – 258

11

Helix

261 – 263

3

Helix

266 – 285

20

Beta strand

291 – 298

8

Helix

300 – 302

3

Helix

305 – 312

8

Sequences

	Sequence		Length	Mass (Da)
	Q6IBS0 [UniParc]. Last modified May 2, 2006. Version 2. Checksum: 635EF8C04EFCE92B	FASTA	349	39,548
	10 20 30 40 50 60 MAHQTGIHAT EELKEFFAKA RAGSVRLIKV VIEDEQLVLG ASQEPVGRWD QDYDRAVLPL 70 80 90 100 110 120 LDAQQPCYLL YRLDSQNAQG FEWLFLAWSP DNSPVRLKML YAATRATVKK EFGGGHIKDE 130 140 150 160 170 180 LFGTVKDDLS FAGYQKHLSS CAAPAPLTSA ERELQQIRIN EVKTEISVES KHQTLQGLAF 190 200 210 220 230 240 PLQPEAQRAL QQLKQKMVNY IQMKLDLERE TIELVHTEPT DVAQLPSRVP RDAARYHFFL 250 260 270 280 290 300 YKHTHEGDPL ESVVFIYSMP GYKCSIKERM LYSSCKSRLL DSVEQDFHLE IAKKIEIGDG 310 320 330 340 AELTAEFLYD EVHPKQHAFK QAFAKPKGPG GKRGHKRLIR GPGENGDDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and characterization of an A6 related protein." Rohwer A., Kittstein W., Marks F., Gschwendt M. Eur. J. Biochem. 263:518-525(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PHOSPHORYLATION. Tissue: Keratinocyte.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	Hui R.T., Liu Y.Q., Liu B., Zhao B., Meng X.M., Sheng H., Xu Y.Y., Wang X.Y., Ye J., Song L., Gao Y., Wei Y.J., Zhang C.L., Zhang J., Chai M.Q., Chen J.Z., Sun Y.H., Zhou X.L. , Jiang Y.X., Zhao X.W., Liu S., Cao H.Q., Zhao Y., Liu D.Q., Ding J.F., Liu L.S., Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C., Zhao M.S. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Aorta.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: Kidney, Lung and Placenta.
[6]	Bienvenut W.V., Vousden K.H., Lukashchuk N. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-19 AND 279-293, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, MASS SPECTROMETRY.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309 AND SER-349, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-14, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, MASS SPECTROMETRY.
[13]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-72; ARG-76 AND THR-103.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Molecular embrace - Issue 73 of August 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y17169 mRNA. Translation: CAB38055.1.
AL136773 mRNA. Translation: CAB66707.1.
AF109365 mRNA. Translation: AAQ13513.1.
CR456732 mRNA. Translation: CAG33013.1.
CR533520 mRNA. Translation: CAG38551.1.
BC000327 mRNA. Translation: AAH00327.1.
BC003161 mRNA. Translation: AAH03161.1.
BC016452 mRNA. Translation: AAH16452.1.

IPI

IPI00550917.

PIR

T46362.

RefSeq

NP_009215.1. NM_007284.3.

UniGene

Hs.436439.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VAC	X-ray	1.70	A	6-137	[»]
2W0I	X-ray	1.80	A	181-313	[»]

ProteinModelPortal

Q6IBS0.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6IBS0. 5 interactions.

MINT

MINT-1414584.

STRING

9606.ENSP00000303908.

PTM databases

PhosphoSite

Q6IBS0.

Polymorphism databases

DMDM

94730596.

2D gel databases

OGP

Q9Y3F5.

Proteomic databases

PaxDb

Q6IBS0.

PeptideAtlas

Q6IBS0.

PRIDE

Q6IBS0.

Protocols and materials databases

DNASU

11344.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305533; ENSP00000303908; ENSG00000247596.

GeneID

11344.

KEGG

hsa:11344.

UCSC

uc003ddd.3. human.

Organism-specific databases

CTD

11344.

GeneCards

GC03M052262.

HGNC

HGNC:9621. TWF2.

HPA

HPA053874.

MIM

607433. gene.

neXtProt

NX_Q6IBS0.

PharmGKB

PA162407429.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG263290.

HOGENOM

HOG000168296.

HOVERGEN

HBG000848.

InParanoid

Q6IBS0.

KO

K08870.

OMA

SHNAQGF.

Gene expression databases

ArrayExpress

Q6IBS0.

Bgee

Q6IBS0.

CleanEx

HS_TWF2.

Genevestigator

Q6IBS0.

GermOnline

ENSG00000173366. Homo sapiens.

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

EvolutionaryTrace

Q6IBS0.

GenomeRNAi

11344.

NextBio

43112.

SOURCE

Search...

Entry information

Entry name

TWF2_HUMAN

Accession

Primary (citable) accession number: Q6IBS0
Secondary accession number(s): Q9Y3F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 2, 2006
Last sequence update:	May 2, 2006
Last modified:	May 1, 2013
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.