Full text data of TWF1
TWF1
(PTK9)
[Confidence: low (only semi-automatic identification from reviews)]
Twinfilin-1 (Protein A6; Protein tyrosine kinase 9)
Twinfilin-1 (Protein A6; Protein tyrosine kinase 9)
UniProt
Q12792
ID TWF1_HUMAN Reviewed; 350 AA.
AC Q12792; A8K5A8; B3KXS6; B4DLX9; Q59G07; Q5U0B1; Q6FHJ1; Q6FHL6;
read moreAC Q6NUK9; Q86XL6; Q8TCD3;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Twinfilin-1;
DE AltName: Full=Protein A6;
DE AltName: Full=Protein tyrosine kinase 9;
GN Name=TWF1; Synonyms=PTK9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, TISSUE SPECIFICITY,
RP AND PHOSPHORYLATION.
RC TISSUE=Lung fibroblast;
RX PubMed=7507208;
RA Beeler J.F., LaRochelle W.J., Chedid M., Tronick S.R., Aaronson S.A.;
RT "Prokaryotic expression cloning of a novel human tyrosine kinase.";
RL Mol. Cell. Biol. 14:982-988(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Brain, Placenta, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Prostate, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-37 (ISOFORMS 1/3), PROTEIN SEQUENCE OF 65-72;
RP 99-105; 111-155; 172-192; 236-242 AND 279-285 (ISOFORMS 1/3), PROTEIN
RP SEQUENCE OF 159-171 (ISOFORM 1), CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND MASS
RP SPECTROMETRY.
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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-349, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Actin-binding protein involved in motile and
CC morphological processes. Inhibits actin polymerization, likely by
CC sequestering G-actin. By capping the barbed ends of filaments, it
CC also regulates motility. Seems to play an important role in
CC clathrin-mediated endocytosis and distribution of endocytic
CC organelles (By similarity).
CC -!- SUBUNIT: Interacts with G-actin; ADP-actin form and capping
CC protein (CP). May also be able to interact with TWF2 and
CC phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-
CC regulated (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton (By
CC similarity). Note=Diffuse cytoplasmic localization with
CC perinuclear and G-actin-rich cortical actin structures
CC sublocalization. Also found at membrane ruffles and cell-cell
CC contacts (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q12792-2; Sequence=Displayed;
CC Name=3;
CC IsoId=Q12792-3; Sequence=VSP_017899;
CC Name=4;
CC IsoId=Q12792-4; Sequence=VSP_038075;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the colon, testis,
CC ovary, prostate and lung. Expressed at lower levels in the brain,
CC bladder and heart. Not detected in liver.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family.
CC Twinfilin subfamily.
CC -!- SIMILARITY: Contains 2 ADF-H domains.
CC -!- CAUTION: Was originally (PubMed:7507208) thought to have protein
CC tyrosine kinase activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH43148.2; Type=Erroneous initiation;
CC Sequence=AAH68548.1; Type=Erroneous initiation;
CC Sequence=BAD92539.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Molecular embrace -
CC Issue 73 of August 2006;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt073.shtml";
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DR EMBL; U02680; AAC50062.1; -; mRNA.
DR EMBL; AK127868; BAG54588.1; -; mRNA.
DR EMBL; AK291223; BAF83912.1; -; mRNA.
DR EMBL; AK297206; BAG59691.1; -; mRNA.
DR EMBL; CR541736; CAG46536.1; -; mRNA.
DR EMBL; CR541761; CAG46561.1; -; mRNA.
DR EMBL; BT019691; AAV38497.1; -; mRNA.
DR EMBL; AB209302; BAD92539.1; ALT_INIT; mRNA.
DR EMBL; BC022344; AAH22344.1; -; mRNA.
DR EMBL; BC043148; AAH43148.2; ALT_INIT; mRNA.
DR EMBL; BC068548; AAH68548.1; ALT_INIT; mRNA.
DR PIR; A55922; A55922.
DR RefSeq; NP_001229326.1; NM_001242397.1.
DR RefSeq; NP_002813.3; NM_002822.4.
DR UniGene; Hs.189075; -.
DR UniGene; Hs.313056; -.
DR ProteinModelPortal; Q12792; -.
DR SMR; Q12792; 7-139, 176-316.
DR IntAct; Q12792; 3.
DR MINT; MINT-3026525; -.
DR PhosphoSite; Q12792; -.
DR DMDM; 259016376; -.
DR OGP; Q12792; -.
DR PaxDb; Q12792; -.
DR PRIDE; Q12792; -.
DR DNASU; 5756; -.
DR Ensembl; ENST00000325127; ENSP00000321058; ENSG00000151239.
DR Ensembl; ENST00000395510; ENSP00000378886; ENSG00000151239.
DR Ensembl; ENST00000548315; ENSP00000449428; ENSG00000151239.
DR Ensembl; ENST00000552521; ENSP00000448750; ENSG00000151239.
DR GeneID; 5756; -.
DR KEGG; hsa:5756; -.
DR UCSC; uc001roa.4; human.
DR CTD; 5756; -.
DR GeneCards; GC12M044187; -.
DR HGNC; HGNC:9620; TWF1.
DR HPA; HPA018116; -.
DR MIM; 610932; gene.
DR neXtProt; NX_Q12792; -.
DR PharmGKB; PA162407406; -.
DR eggNOG; NOG263290; -.
DR HOVERGEN; HBG000848; -.
DR KO; K08870; -.
DR OrthoDB; EOG79GT6W; -.
DR GeneWiki; TWF1; -.
DR GenomeRNAi; 5756; -.
DR NextBio; 22400; -.
DR PRO; PR:Q12792; -.
DR ArrayExpress; Q12792; -.
DR Bgee; Q12792; -.
DR Genevestigator; Q12792; -.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:BHF-UCL.
DR GO; GO:0030175; C:filopodium; ISS:BHF-UCL.
DR GO; GO:0030016; C:myofibril; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0032587; C:ruffle membrane; IEA:Ensembl.
DR GO; GO:0003785; F:actin monomer binding; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:BHF-UCL.
DR GO; GO:0051016; P:barbed-end actin filament capping; IEA:Ensembl.
DR GO; GO:0043538; P:regulation of actin phosphorylation; IDA:BHF-UCL.
DR GO; GO:0042989; P:sequestering of actin monomers; ISS:BHF-UCL.
DR InterPro; IPR002108; Actin-bd_cofilin/tropomyosin.
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 Acetylation; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 350 Twinfilin-1.
FT /FTId=PRO_0000214950.
FT DOMAIN 2 139 ADF-H 1.
FT DOMAIN 175 313 ADF-H 2.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 143 143 Phosphoserine.
FT MOD_RES 309 309 Phosphotyrosine.
FT MOD_RES 349 349 Phosphothreonine.
FT VAR_SEQ 1 98 Missing (in isoform 4).
FT /FTId=VSP_038075.
FT VAR_SEQ 161 161 E -> ESPEDHIG (in isoform 3).
FT /FTId=VSP_017899.
FT CONFLICT 12 12 D -> Y (in Ref. 3; CAG46561).
FT CONFLICT 246 246 E -> V (in Ref. 2; BAG54588).
FT CONFLICT 269 269 R -> W (in Ref. 3; CAG46536).
FT CONFLICT 302 302 E -> G (in Ref. 2; BAF83912).
FT CONFLICT 329 329 P -> H (in Ref. 2; BAG59691).
SQ SEQUENCE 350 AA; 40283 MW; 5F68A6946E969A80 CRC64;
MSHQTGIQAS EDVKEIFARA RNGKYRLLKI SIENEQLVIG SYSQPSDSWD KDYDSFVLPL
LEDKQPCYIL FRLDSQNAQG YEWIFIAWSP DHSHVRQKML YAATRATLKK EFGGGHIKDE
VFGTVKEDVS LHGYKKYLLS QSSPAPLTAA EEELRQIKIN EVQTDVGVDT KHQTLQGVAF
PISREAFQAL EKLNNRQLNY VQLEIDIKNE IIILANTTNT ELKDLPKRIP KDSARYHFFL
YKHSHEGDYL ESIVFIYSMP GYTCSIRERM LYSSCKSRLL EIVERQLQMD VIRKIEIDNG
DELTADFLYE EVHPKQHAHK QSFAKPKGPA GKRGIRRLIR GPAETEATTD
//
ID TWF1_HUMAN Reviewed; 350 AA.
AC Q12792; A8K5A8; B3KXS6; B4DLX9; Q59G07; Q5U0B1; Q6FHJ1; Q6FHL6;
read moreAC Q6NUK9; Q86XL6; Q8TCD3;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Twinfilin-1;
DE AltName: Full=Protein A6;
DE AltName: Full=Protein tyrosine kinase 9;
GN Name=TWF1; Synonyms=PTK9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), COFACTOR, TISSUE SPECIFICITY,
RP AND PHOSPHORYLATION.
RC TISSUE=Lung fibroblast;
RX PubMed=7507208;
RA Beeler J.F., LaRochelle W.J., Chedid M., Tronick S.R., Aaronson S.A.;
RT "Prokaryotic expression cloning of a novel human tyrosine kinase.";
RL Mol. Cell. Biol. 14:982-988(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Brain, Placenta, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Prostate, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-37 (ISOFORMS 1/3), PROTEIN SEQUENCE OF 65-72;
RP 99-105; 111-155; 172-192; 236-242 AND 279-285 (ISOFORMS 1/3), PROTEIN
RP SEQUENCE OF 159-171 (ISOFORM 1), CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND MASS
RP SPECTROMETRY.
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
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-349, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-309, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Actin-binding protein involved in motile and
CC morphological processes. Inhibits actin polymerization, likely by
CC sequestering G-actin. By capping the barbed ends of filaments, it
CC also regulates motility. Seems to play an important role in
CC clathrin-mediated endocytosis and distribution of endocytic
CC organelles (By similarity).
CC -!- SUBUNIT: Interacts with G-actin; ADP-actin form and capping
CC protein (CP). May also be able to interact with TWF2 and
CC phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-
CC regulated (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton (By
CC similarity). Note=Diffuse cytoplasmic localization with
CC perinuclear and G-actin-rich cortical actin structures
CC sublocalization. Also found at membrane ruffles and cell-cell
CC contacts (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q12792-2; Sequence=Displayed;
CC Name=3;
CC IsoId=Q12792-3; Sequence=VSP_017899;
CC Name=4;
CC IsoId=Q12792-4; Sequence=VSP_038075;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the colon, testis,
CC ovary, prostate and lung. Expressed at lower levels in the brain,
CC bladder and heart. Not detected in liver.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family.
CC Twinfilin subfamily.
CC -!- SIMILARITY: Contains 2 ADF-H domains.
CC -!- CAUTION: Was originally (PubMed:7507208) thought to have protein
CC tyrosine kinase activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH43148.2; Type=Erroneous initiation;
CC Sequence=AAH68548.1; Type=Erroneous initiation;
CC Sequence=BAD92539.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Molecular embrace -
CC Issue 73 of August 2006;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt073.shtml";
CC -----------------------------------------------------------------------
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DR EMBL; U02680; AAC50062.1; -; mRNA.
DR EMBL; AK127868; BAG54588.1; -; mRNA.
DR EMBL; AK291223; BAF83912.1; -; mRNA.
DR EMBL; AK297206; BAG59691.1; -; mRNA.
DR EMBL; CR541736; CAG46536.1; -; mRNA.
DR EMBL; CR541761; CAG46561.1; -; mRNA.
DR EMBL; BT019691; AAV38497.1; -; mRNA.
DR EMBL; AB209302; BAD92539.1; ALT_INIT; mRNA.
DR EMBL; BC022344; AAH22344.1; -; mRNA.
DR EMBL; BC043148; AAH43148.2; ALT_INIT; mRNA.
DR EMBL; BC068548; AAH68548.1; ALT_INIT; mRNA.
DR PIR; A55922; A55922.
DR RefSeq; NP_001229326.1; NM_001242397.1.
DR RefSeq; NP_002813.3; NM_002822.4.
DR UniGene; Hs.189075; -.
DR UniGene; Hs.313056; -.
DR ProteinModelPortal; Q12792; -.
DR SMR; Q12792; 7-139, 176-316.
DR IntAct; Q12792; 3.
DR MINT; MINT-3026525; -.
DR PhosphoSite; Q12792; -.
DR DMDM; 259016376; -.
DR OGP; Q12792; -.
DR PaxDb; Q12792; -.
DR PRIDE; Q12792; -.
DR DNASU; 5756; -.
DR Ensembl; ENST00000325127; ENSP00000321058; ENSG00000151239.
DR Ensembl; ENST00000395510; ENSP00000378886; ENSG00000151239.
DR Ensembl; ENST00000548315; ENSP00000449428; ENSG00000151239.
DR Ensembl; ENST00000552521; ENSP00000448750; ENSG00000151239.
DR GeneID; 5756; -.
DR KEGG; hsa:5756; -.
DR UCSC; uc001roa.4; human.
DR CTD; 5756; -.
DR GeneCards; GC12M044187; -.
DR HGNC; HGNC:9620; TWF1.
DR HPA; HPA018116; -.
DR MIM; 610932; gene.
DR neXtProt; NX_Q12792; -.
DR PharmGKB; PA162407406; -.
DR eggNOG; NOG263290; -.
DR HOVERGEN; HBG000848; -.
DR KO; K08870; -.
DR OrthoDB; EOG79GT6W; -.
DR GeneWiki; TWF1; -.
DR GenomeRNAi; 5756; -.
DR NextBio; 22400; -.
DR PRO; PR:Q12792; -.
DR ArrayExpress; Q12792; -.
DR Bgee; Q12792; -.
DR Genevestigator; Q12792; -.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:BHF-UCL.
DR GO; GO:0030175; C:filopodium; ISS:BHF-UCL.
DR GO; GO:0030016; C:myofibril; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0032587; C:ruffle membrane; IEA:Ensembl.
DR GO; GO:0003785; F:actin monomer binding; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:BHF-UCL.
DR GO; GO:0051016; P:barbed-end actin filament capping; IEA:Ensembl.
DR GO; GO:0043538; P:regulation of actin phosphorylation; IDA:BHF-UCL.
DR GO; GO:0042989; P:sequestering of actin monomers; ISS:BHF-UCL.
DR InterPro; IPR002108; Actin-bd_cofilin/tropomyosin.
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 Acetylation; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Phosphoprotein;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 350 Twinfilin-1.
FT /FTId=PRO_0000214950.
FT DOMAIN 2 139 ADF-H 1.
FT DOMAIN 175 313 ADF-H 2.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 143 143 Phosphoserine.
FT MOD_RES 309 309 Phosphotyrosine.
FT MOD_RES 349 349 Phosphothreonine.
FT VAR_SEQ 1 98 Missing (in isoform 4).
FT /FTId=VSP_038075.
FT VAR_SEQ 161 161 E -> ESPEDHIG (in isoform 3).
FT /FTId=VSP_017899.
FT CONFLICT 12 12 D -> Y (in Ref. 3; CAG46561).
FT CONFLICT 246 246 E -> V (in Ref. 2; BAG54588).
FT CONFLICT 269 269 R -> W (in Ref. 3; CAG46536).
FT CONFLICT 302 302 E -> G (in Ref. 2; BAF83912).
FT CONFLICT 329 329 P -> H (in Ref. 2; BAG59691).
SQ SEQUENCE 350 AA; 40283 MW; 5F68A6946E969A80 CRC64;
MSHQTGIQAS EDVKEIFARA RNGKYRLLKI SIENEQLVIG SYSQPSDSWD KDYDSFVLPL
LEDKQPCYIL FRLDSQNAQG YEWIFIAWSP DHSHVRQKML YAATRATLKK EFGGGHIKDE
VFGTVKEDVS LHGYKKYLLS QSSPAPLTAA EEELRQIKIN EVQTDVGVDT KHQTLQGVAF
PISREAFQAL EKLNNRQLNY VQLEIDIKNE IIILANTTNT ELKDLPKRIP KDSARYHFFL
YKHSHEGDYL ESIVFIYSMP GYTCSIRERM LYSSCKSRLL EIVERQLQMD VIRKIEIDNG
DELTADFLYE EVHPKQHAHK QSFAKPKGPA GKRGIRRLIR GPAETEATTD
//
MIM
610932
*RECORD*
*FIELD* NO
610932
*FIELD* TI
*610932 TWINFILIN, DROSOPHILA, HOMOLOG OF, 1; TWF1
;;PROTEIN TYROSINE KINASE 9; PTK9;;
read moreA6 PROTEIN TYROSINE KINASE
*FIELD* TX
CLONING
By screening a human embryonic lung fibroblast bacteria expression
library with antiphosphotyrosine antibody, Beeler et al. (1994) cloned
TWF1, which they called A6. The deduced 350-amino acid protein has a
calculated molecular mass of 40.3 kD. TWF1 has an N-myristoylation site
and several sites for threonine, serine, and tyrosine phosphorylation,
but it lacks a conserved protein kinase catalytic domain. Northern blot
analysis detected a 3.4-kb transcript that was highly expressed in
colon, testis, uterus, ovary, prostate, and lung. Lower expression was
detected in brain, bladder, and heart, and no expression was detected in
liver. In vitro transcription/translation resulted in a 40-kD TWF1
protein, as determined by SDS-PAGE. Southern blot analysis indicated
that TWF1 is conserved in vertebrates.
By searching databases for homologs of yeast twinfilin, Vartiainen et
al. (2000) identified mouse and human TWF1. The mouse and human TWF1
proteins contain 2 cofilin (see CFL1; 601442)-like repeats called
actin-depolymerizing factor (DSTN; 609114) homology (ADFH) domains.
Immunofluorescence microscopy localized Twf1 in a punctate perinuclear
distribution in mouse fibroblasts and neuroblastoma cells. Twf1 also
localized to globular (G)-actin (see 102610)-rich areas of the actin
cytoskeleton in fibroblasts and to filamentous (F)-actin-rich filopodia
in neuroblastoma cells.
GENE FUNCTION
Beeler et al. (1994) showed that recombinant TWF1 underwent
autophosphorylation on tyrosines and serines in an in vitro kinase
assay, and it phosphorylated exogenous substrates on tyrosines.
Recombinant TWF1 had kinase activity similar to that of recombinant
FGFR2 (176943), with optimal activity over pH 6.5 to 7.4 and a
preference for manganese over magnesium as a divalent cofactor.
In contrast to the findings of Beeler et al. (1994), Vartiainen et al.
(2000) found that recombinant mouse Twf1 lacked tyrosine kinase
activity. They showed that Twf1 bound G-actin in a 1:1 stoichiometry and
prevented F-actin assembly in a concentration-dependent manner.
Overexpression of Twf1 in mouse fibroblasts decreased the amount of
stress fibers and caused the appearance of abnormal cytoplasmic actin
filaments. In mouse fibroblasts, Twf1 colocalized with GTP-bound forms
of Cdc42 (116952) and Rac1 (602048) at membrane ruffles and cell-cell
contacts, respectively, and localization of Twf1 in these cells appeared
to be regulated by Rac1.
Paavilainen et al. (2007) showed that the N- and C-terminal ADFH domains
of mouse Twf1, which they called TWF-N and TWF-C, respectively, were
required for actin barbed-end capping. NMR and mutagenesis analyses,
together with biochemical and motility assays, showed that TWF-C bound
G-actin and interacted with the sides of F-actin like ADF and cofilins,
whereas TWF-N bound only G-actin. During filament barbed-end capping,
TWF-N interacted with the terminal actin subunit, and TWF-C bound
between 2 adjacent subunits at the side of the filament. The domain
requirement for actin filament capping by Twf1 was similar to that of
gelsolin (GSN; 137350)-type proteins, suggesting the existence of a
general barbed-end capping mechanism.
In an adaptation of loss-of-function screening to mouse models of
cancer, Meacham et al. (2009) introduced a library of shRNAs into
individual mice using transplantable E-mu-myc lymphoma cells. This
approach allowed them to screen nearly 1,000 genetic alterations in the
context of a single tumor-bearing mouse. Their experiments identified a
central role for regulators of actin dynamics and cell motility in
lymphoma cell homeostasis in vivo. Validation experiments confirmed that
these proteins represent bona fide lymphoma drug targets. Additionally,
suppression of 2 of these targets, Rac2 (602049) and twinfilin
potentiated the action of the front-line chemotherapeutic vincristine,
suggesting a critical relationship between cell motility and tumor
relapse in hematopoietic malignancies.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TWF1
gene to chromosome 12 (TMAP RH70527).
*FIELD* RF
1. Beeler, J. F.; LaRochelle, W. J.; Chedid, M.; Tronick, S. R.; Aaronson,
S. A.: Prokaryotic expression cloning of a novel human tyrosine kinase. Molec.
Cell. Biol. 14: 982-988, 1994.
2. Meacham, C. E.; Ho, E. E.; Dubrovsky, E.; Gertler, F. B.; Hemann,
M. T.: In vivo RNAi screening identifies regulators of actin dynamics
as key determinants of lymphoma progression. Nature Genet. 41: 1133-1137,
2009.
3. Paavilainen, V. O.; Hellman, M.; Helfer, E.; Bovellan, M.; Annila,
A.; Carlier, M.-F.; Permi, P.; Lappalainen, P.: Structural basis
and evolutionary origin of actin filament capping by twinfilin. Proc.
Nat. Acad. Sci. 104: 3113-3118, 2007.
4. Vartiainen, M.; Ojala, P. J.; Auvinen, P.; Peranen, J.; Lappalainen,
P.: Mouse A6/twinfilin is an actin monomer-binding protein that localizes
to the regions of rapid actin dynamics. Molec. Cell. Biol. 20: 1772-1783,
2000.
*FIELD* CN
Ada Hamosh - updated: 1/12/2010
*FIELD* CD
Patricia A. Hartz: 4/16/2007
*FIELD* ED
alopez: 01/14/2010
terry: 1/12/2010
mgross: 4/16/2007
*RECORD*
*FIELD* NO
610932
*FIELD* TI
*610932 TWINFILIN, DROSOPHILA, HOMOLOG OF, 1; TWF1
;;PROTEIN TYROSINE KINASE 9; PTK9;;
read moreA6 PROTEIN TYROSINE KINASE
*FIELD* TX
CLONING
By screening a human embryonic lung fibroblast bacteria expression
library with antiphosphotyrosine antibody, Beeler et al. (1994) cloned
TWF1, which they called A6. The deduced 350-amino acid protein has a
calculated molecular mass of 40.3 kD. TWF1 has an N-myristoylation site
and several sites for threonine, serine, and tyrosine phosphorylation,
but it lacks a conserved protein kinase catalytic domain. Northern blot
analysis detected a 3.4-kb transcript that was highly expressed in
colon, testis, uterus, ovary, prostate, and lung. Lower expression was
detected in brain, bladder, and heart, and no expression was detected in
liver. In vitro transcription/translation resulted in a 40-kD TWF1
protein, as determined by SDS-PAGE. Southern blot analysis indicated
that TWF1 is conserved in vertebrates.
By searching databases for homologs of yeast twinfilin, Vartiainen et
al. (2000) identified mouse and human TWF1. The mouse and human TWF1
proteins contain 2 cofilin (see CFL1; 601442)-like repeats called
actin-depolymerizing factor (DSTN; 609114) homology (ADFH) domains.
Immunofluorescence microscopy localized Twf1 in a punctate perinuclear
distribution in mouse fibroblasts and neuroblastoma cells. Twf1 also
localized to globular (G)-actin (see 102610)-rich areas of the actin
cytoskeleton in fibroblasts and to filamentous (F)-actin-rich filopodia
in neuroblastoma cells.
GENE FUNCTION
Beeler et al. (1994) showed that recombinant TWF1 underwent
autophosphorylation on tyrosines and serines in an in vitro kinase
assay, and it phosphorylated exogenous substrates on tyrosines.
Recombinant TWF1 had kinase activity similar to that of recombinant
FGFR2 (176943), with optimal activity over pH 6.5 to 7.4 and a
preference for manganese over magnesium as a divalent cofactor.
In contrast to the findings of Beeler et al. (1994), Vartiainen et al.
(2000) found that recombinant mouse Twf1 lacked tyrosine kinase
activity. They showed that Twf1 bound G-actin in a 1:1 stoichiometry and
prevented F-actin assembly in a concentration-dependent manner.
Overexpression of Twf1 in mouse fibroblasts decreased the amount of
stress fibers and caused the appearance of abnormal cytoplasmic actin
filaments. In mouse fibroblasts, Twf1 colocalized with GTP-bound forms
of Cdc42 (116952) and Rac1 (602048) at membrane ruffles and cell-cell
contacts, respectively, and localization of Twf1 in these cells appeared
to be regulated by Rac1.
Paavilainen et al. (2007) showed that the N- and C-terminal ADFH domains
of mouse Twf1, which they called TWF-N and TWF-C, respectively, were
required for actin barbed-end capping. NMR and mutagenesis analyses,
together with biochemical and motility assays, showed that TWF-C bound
G-actin and interacted with the sides of F-actin like ADF and cofilins,
whereas TWF-N bound only G-actin. During filament barbed-end capping,
TWF-N interacted with the terminal actin subunit, and TWF-C bound
between 2 adjacent subunits at the side of the filament. The domain
requirement for actin filament capping by Twf1 was similar to that of
gelsolin (GSN; 137350)-type proteins, suggesting the existence of a
general barbed-end capping mechanism.
In an adaptation of loss-of-function screening to mouse models of
cancer, Meacham et al. (2009) introduced a library of shRNAs into
individual mice using transplantable E-mu-myc lymphoma cells. This
approach allowed them to screen nearly 1,000 genetic alterations in the
context of a single tumor-bearing mouse. Their experiments identified a
central role for regulators of actin dynamics and cell motility in
lymphoma cell homeostasis in vivo. Validation experiments confirmed that
these proteins represent bona fide lymphoma drug targets. Additionally,
suppression of 2 of these targets, Rac2 (602049) and twinfilin
potentiated the action of the front-line chemotherapeutic vincristine,
suggesting a critical relationship between cell motility and tumor
relapse in hematopoietic malignancies.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the TWF1
gene to chromosome 12 (TMAP RH70527).
*FIELD* RF
1. Beeler, J. F.; LaRochelle, W. J.; Chedid, M.; Tronick, S. R.; Aaronson,
S. A.: Prokaryotic expression cloning of a novel human tyrosine kinase. Molec.
Cell. Biol. 14: 982-988, 1994.
2. Meacham, C. E.; Ho, E. E.; Dubrovsky, E.; Gertler, F. B.; Hemann,
M. T.: In vivo RNAi screening identifies regulators of actin dynamics
as key determinants of lymphoma progression. Nature Genet. 41: 1133-1137,
2009.
3. Paavilainen, V. O.; Hellman, M.; Helfer, E.; Bovellan, M.; Annila,
A.; Carlier, M.-F.; Permi, P.; Lappalainen, P.: Structural basis
and evolutionary origin of actin filament capping by twinfilin. Proc.
Nat. Acad. Sci. 104: 3113-3118, 2007.
4. Vartiainen, M.; Ojala, P. J.; Auvinen, P.; Peranen, J.; Lappalainen,
P.: Mouse A6/twinfilin is an actin monomer-binding protein that localizes
to the regions of rapid actin dynamics. Molec. Cell. Biol. 20: 1772-1783,
2000.
*FIELD* CN
Ada Hamosh - updated: 1/12/2010
*FIELD* CD
Patricia A. Hartz: 4/16/2007
*FIELD* ED
alopez: 01/14/2010
terry: 1/12/2010
mgross: 4/16/2007