Reviewed, UniProtKB/Swiss-Prot Q12792 (TWF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Twinfilin-1
Alternative name(s):
    Protein A6
    Protein tyrosine kinase 9

Gene names

Name:	TWF1
Synonyms:	PTK9

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	368 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 By similarity.
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 By similarity.
Subcellular location	Cytoplasm. Cytoplasm › cytoskeletonBy similarity. Note= Diffuse cytoplasmic localization with perinuclear and G-actin-rich cortical actin structures sublocalization. Also found at membrane ruffles and cell-cell contacts By similarity.
Tissue specificity	Expressed at high levels in the colon, testis, ovary, prostate and lung. Expressed at lower levels in the brain, bladder and heart. Not detected in liver. Ref.1
Post-translational modification	Phosphorylated on serine and threonine residues. Ref.1 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the actin-binding proteins ADF family. Twinfilin subfamily. Contains 2 ADF-H domains.
Caution	Was originally (Ref.1) thought to have protein tyrosine kinase activity.
Sequence caution	The sequence AAH22344.1 differs from that shown. Reason: Frameshift at position 26.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Actin-binding
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	actin cytoskeleton Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	actin binding Inferred from electronic annotation. Source: InterPro protein tyrosine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q12792-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Notes: Peptide 177-189 identified and sequenced in Ref.7.

Isoform 1 (identifier: Q12792-2)

The sequence of this isoform differs from the canonical sequence as follows:
     9-26: Missing.

Notes: Peptides 2-19 and 159-171 identified and sequenced in Ref.7.

Isoform 3 (identifier: Q12792-3)

The sequence of this isoform differs from the canonical sequence as follows:
     9-26: Missing.
     179-179: E → ESPEDHIG

Notes: Peptide 2-19 identified and sequenced in Ref.7.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 368	367	Twinfilin-1		PRO_0000214950
Regions
	Domain	19 – 157	139	ADF-H 1
	Domain	193 – 331	139	ADF-H 2
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.7
	Modified residue	161	1	Phosphoserine Ref.9
	Modified residue	327	1	Phosphotyrosine Ref.8
	Modified residue	367	1	Phosphothreonine Ref.10
Natural variations
	Alternative sequence	9 – 26	18	Missing in isoform 1 and isoform 3.		VSP_050508
	Alternative sequence	179	1	E → ESPEDHIG in isoform 3.		VSP_017899
Experimental info
	Sequence conflict	30	1	D → Y in CAG46561. Ref.3
	Sequence conflict	287	1	R → W in CAG46536. Ref.3
	Sequence conflict	320	1	E → G in BAF83912. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified June 1, 2003. Version 2. Checksum: 4DBBA2F66E750998	FASTA	368	42,209
	10 20 30 40 50 60 MSHQTGIQGK SWDSGGDWGF STLSRTASED VKEIFARARN GKYRLLKISI ENEQLVIGSY 70 80 90 100 110 120 SQPSDSWDKD YDSFVLPLLE DKQPCYILFR LDSQNAQGYE WIFIAWSPDH SHVRQKMLYA 130 140 150 160 170 180 ATRATLKKEF GGGHIKDEVF GTVKEDVSLH GYKKYLLSQS SPAPLTAAEE ELRQIKINEV 190 200 210 220 230 240 QTDVGVDTKH QTLQGVAFPI SREAFQALEK LNNRQLNYVQ LEIDIKNEII ILANTTNTEL 250 260 270 280 290 300 KDLPKRIPKD SARYHFFLYK HSHEGDYLES IVFIYSMPGY TCSIRERMLY SSCKSRLLEI 310 320 330 340 350 360 VERQLQMDVI RKIEIDNGDE LTADFLYEEV HPKQHAHKQS FAKPKGPAGK RGIRRLIRGP AETEATTD
	Isoform 1. Checksum: 5F68A6946E969A80		350	40,283
	10 20 30 40 50 60 MSHQTGIQAS EDVKEIFARA RNGKYRLLKI SIENEQLVIG SYSQPSDSWD KDYDSFVLPL 70 80 90 100 110 120 LEDKQPCYIL FRLDSQNAQG YEWIFIAWSP DHSHVRQKML YAATRATLKK EFGGGHIKDE 130 140 150 160 170 180 VFGTVKEDVS LHGYKKYLLS QSSPAPLTAA EEELRQIKIN EVQTDVGVDT KHQTLQGVAF 190 200 210 220 230 240 PISREAFQAL EKLNNRQLNY VQLEIDIKNE IIILANTTNT ELKDLPKRIP KDSARYHFFL 250 260 270 280 290 300 YKHSHEGDYL ESIVFIYSMP GYTCSIRERM LYSSCKSRLL EIVERQLQMD VIRKIEIDNG 310 320 330 340 350 DELTADFLYE EVHPKQHAHK QSFAKPKGPA GKRGIRRLIR GPAETEATTD
	Isoform 3. Checksum: 826E95A7D995033B		357	41,018
	10 20 30 40 50 60 MSHQTGIQAS EDVKEIFARA RNGKYRLLKI SIENEQLVIG SYSQPSDSWD KDYDSFVLPL 70 80 90 100 110 120 LEDKQPCYIL FRLDSQNAQG YEWIFIAWSP DHSHVRQKML YAATRATLKK EFGGGHIKDE 130 140 150 160 170 180 VFGTVKEDVS LHGYKKYLLS QSSPAPLTAA EEELRQIKIN ESPEDHIGVQ TDVGVDTKHQ 190 200 210 220 230 240 TLQGVAFPIS REAFQALEKL NNRQLNYVQL EIDIKNEIII LANTTNTELK DLPKRIPKDS 250 260 270 280 290 300 ARYHFFLYKH SHEGDYLESI VFIYSMPGYT CSIRERMLYS SCKSRLLEIV ERQLQMDVIR 310 320 330 340 350 KIEIDNGDEL TADFLYEEVH PKQHAHKQSF AKPKGPAGKR GIRRLIRGPA ETEATTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prokaryotic expression cloning of a novel human tyrosine kinase." Beeler J.F., LaRochelle W.J., Chedid M., Tronick S.R., Aaronson S.A. Mol. Cell. Biol. 14:982-988(1994) [PubMed: 7507208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, TISSUE SPECIFICITY, PHOSPHORYLATION. Tissue: Lung fibroblast.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Teratocarcinoma.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Prostate and Testis.
[7]	Bienvenut W.V., Calvo F., Kolch W. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-37 (ISOFORMS 1/3), PROTEIN SEQUENCE OF 83-90; 117-123; 129-173; 190-210; 254-260 AND 297-303 (ISOFORMS 1/2/3), PROTEIN SEQUENCE OF 177-189 (ISOFORM 1/2), CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-327, MASS SPECTROMETRY.
[9]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-367, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Molecular embrace - Issue 73 of August 2006

Cross-references

Sequence databases
EMBLGenBankDDBJ	U02680 mRNA. Translation: AAC50062.1. AK291223 mRNA. Translation: BAF83912.1. BT019691 mRNA. Translation: AAV38497.1. CR541736 mRNA. Translation: CAG46536.1. CR541761 mRNA. Translation: CAG46561.1. AB209302 mRNA. Translation: BAD92539.1. Different initiation. BC022344 mRNA. Translation: AAH22344.1. Frameshift. BC043148 mRNA. Translation: AAH43148.2. Different initiation. BC068548 mRNA. Translation: AAH68548.1. Different initiation.
PIR	A55922.
RefSeq	NP_002813.2.
UniGene	Hs.189075
3D structure databases
HSSP	HSSP built from PDB template 1M4J based on UniProtKB Q91YR1.
SMR	Q12792. Positions 27-157, 179-331.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12792. 2 interactions.
PTM databases
PhosphoSite	Q12792.
2-D gel databases
OGP	Q12792.
Proteomic databases
PRIDE	Q12792.
Genome annotation databases
Ensembl	ENSG00000151239. Homo sapiens. [Contig view]
GeneID	5756.
KEGG	hsa:5756.
Organism-specific databases
GeneCards	GC12M042474.
HGNC	HGNC:9620. TWF1.
HPA	HPA018116.
MIM	610932. gene.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q12792.
Gene expression databases
CleanEx	HS_TWF1.
GermOnline	ENSG00000151239. Homo sapiens.
Family and domain databases
InterPro	IPR002108. Cofilin_actin_bd. [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 Resources
LinkHub	Q12792.
NextBio	22400.
SOURCE	Search...

Entry information

Entry name

TWF1_HUMAN

Accession

Primary (citable) accession number: Q12792
Secondary accession number(s): A8K5A8 , Q59G07, Q5U0B1, Q6FHJ1, Q6FHL6, Q6NUK9, Q86XL6, Q8TCD3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	June 1, 2003
Last modified:	December 16, 2008
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)