Full text data of CFL2
CFL2
[Confidence: low (only semi-automatic identification from reviews)]
Cofilin-2 (Cofilin, muscle isoform)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cofilin-2 (Cofilin, muscle isoform)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y281
ID COF2_HUMAN Reviewed; 166 AA.
AC Q9Y281; G3V5P4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Cofilin-2;
DE AltName: Full=Cofilin, muscle isoform;
GN Name=CFL2;
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] (ISOFORMS CFL2A AND CFL2B).
RA Jin J., Li G., Hu S., Li W., Yuan J., Qiang B.;
RT "Isolation of two isoforms of human cofilin cDNA.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11422377; DOI=10.1046/j.1432-1327.2001.02247.x;
RA Thirion C., Stucka R., Mendel B., Gruhler A., Jaksch M., Nowak K.J.,
RA Binz N., Laing N.G., Lochmuller H.;
RT "Characterization of human muscle type cofilin (CFL2) in normal and
RT regenerating muscle.";
RL Eur. J. Biochem. 268:3473-3482(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CFL2A AND CFL2B).
RC TISSUE=Bone marrow, Placenta, and Skeletal muscle;
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 [6]
RP PROTEIN SEQUENCE OF 2-21; 35-92; 96-112; 115-125 AND 153-166, CLEAVAGE
RP OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-3, AND MASS 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 [10]
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).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] MET-47.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [13]
RP VARIANT NEM7 THR-35, AND CHARACTERIZATION OF VARIANT NEM7 THR-35.
RX PubMed=17160903; DOI=10.1086/510402;
RA Agrawal P.B., Greenleaf R.S., Tomczak K.K., Lehtokari V.-L.,
RA Wallgren-Pettersson C., Wallefeld W., Laing N.G., Darras B.T.,
RA Maciver S.K., Dormitzer P.R., Beggs A.H.;
RT "Nemaline myopathy with minicores caused by mutation of the CFL2 gene
RT encoding the skeletal muscle actin-binding protein, cofilin-2.";
RL Am. J. Hum. Genet. 80:162-167(2007).
CC -!- FUNCTION: Controls reversibly actin polymerization and
CC depolymerization in a pH-sensitive manner. It has the ability to
CC bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the
CC major component of intranuclear and cytoplasmic actin rods (By
CC similarity).
CC -!- INTERACTION:
CC P60709:ACTB; NbExp=3; IntAct=EBI-351218, EBI-353944;
CC P63261:ACTG1; NbExp=2; IntAct=EBI-351218, EBI-351292;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix (By similarity). Cytoplasm,
CC cytoskeleton (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Isoforms are identical at the level of the protein
CC sequence;
CC Name=CFL2b;
CC IsoId=Q9Y281-1; Sequence=Displayed;
CC Name=CFL2a;
CC IsoId=Q9Y281-2; Sequence=Not described;
CC Name=3;
CC IsoId=Q9Y281-3; Sequence=VSP_046831;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Isoform CFL2b is expressed predominantly in
CC skeletal muscle and heart. Isoform CFL2a is expressed in various
CC tissues.
CC -!- PTM: The phosphorylation of Ser-24 may prevent recognition of the
CC nuclear localization signal.
CC -!- DISEASE: Nemaline myopathy 7 (NEM7) [MIM:610687]: A form of
CC nemaline myopathy. Nemaline myopathies are muscular disorders
CC characterized by muscle weakness of varying severity and onset,
CC and abnormal thread-like or rod-shaped structures in muscle fibers
CC on histologic examination. Nemaline myopathy type 7 presents at
CC birth with hypotonia and generalized weakness. Major motor
CC milestones are delayed, but independent ambulation is achieved.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family.
CC -!- SIMILARITY: Contains 1 ADF-H domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cofilin entry;
CC URL="http://en.wikipedia.org/wiki/Cofilin";
CC -----------------------------------------------------------------------
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DR EMBL; AF134802; AAD31280.1; -; mRNA.
DR EMBL; AF134803; AAD31281.1; -; mRNA.
DR EMBL; AF283513; AAF97934.1; -; Genomic_DNA.
DR EMBL; AF242299; AAF64498.1; -; Genomic_DNA.
DR EMBL; AL355885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65912.1; -; Genomic_DNA.
DR EMBL; BC011444; AAH11444.1; -; mRNA.
DR EMBL; BC022364; AAH22364.1; -; mRNA.
DR EMBL; BC022876; AAH22876.1; -; mRNA.
DR RefSeq; NP_001230574.1; NM_001243645.1.
DR RefSeq; NP_068733.1; NM_021914.7.
DR RefSeq; NP_619579.1; NM_138638.4.
DR UniGene; Hs.180141; -.
DR ProteinModelPortal; Q9Y281; -.
DR SMR; Q9Y281; 1-166.
DR DIP; DIP-33178N; -.
DR IntAct; Q9Y281; 4.
DR MINT; MINT-1161448; -.
DR STRING; 9606.ENSP00000298159; -.
DR PhosphoSite; Q9Y281; -.
DR DMDM; 6831517; -.
DR PaxDb; Q9Y281; -.
DR PRIDE; Q9Y281; -.
DR DNASU; 1073; -.
DR Ensembl; ENST00000298159; ENSP00000298159; ENSG00000165410.
DR Ensembl; ENST00000341223; ENSP00000340635; ENSG00000165410.
DR Ensembl; ENST00000555765; ENSP00000452451; ENSG00000165410.
DR Ensembl; ENST00000556161; ENSP00000452188; ENSG00000165410.
DR GeneID; 1073; -.
DR KEGG; hsa:1073; -.
DR UCSC; uc001wsg.3; human.
DR CTD; 1073; -.
DR GeneCards; GC14M035179; -.
DR HGNC; HGNC:1875; CFL2.
DR HPA; CAB037078; -.
DR MIM; 601443; gene.
DR MIM; 610687; phenotype.
DR neXtProt; NX_Q9Y281; -.
DR Orphanet; 171436; Typical nemaline myopathy.
DR PharmGKB; PA26424; -.
DR eggNOG; NOG303866; -.
DR HOGENOM; HOG000039697; -.
DR HOVERGEN; HBG000381; -.
DR InParanoid; Q9Y281; -.
DR KO; K05765; -.
DR OMA; GLYDATY; -.
DR OrthoDB; EOG7353Z9; -.
DR PhylomeDB; Q9Y281; -.
DR GeneWiki; CFL2_(gene); -.
DR GenomeRNAi; 1073; -.
DR NextBio; 4480; -.
DR PRO; PR:Q9Y281; -.
DR ArrayExpress; Q9Y281; -.
DR Bgee; Q9Y281; -.
DR CleanEx; HS_CFL2; -.
DR Genevestigator; Q9Y281; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0030042; P:actin filament depolymerization; IEA:InterPro.
DR InterPro; IPR002108; Actin-bd_cofilin/tropomyosin.
DR InterPro; IPR017904; ADF/Cofilin/Destrin.
DR PANTHER; PTHR11913; PTHR11913; 1.
DR Pfam; PF00241; Cofilin_ADF; 1.
DR PRINTS; PR00006; COFILIN.
DR SMART; SM00102; ADF; 1.
DR PROSITE; PS51263; ADF_H; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Nemaline myopathy; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 166 Cofilin-2.
FT /FTId=PRO_0000214907.
FT DOMAIN 4 153 ADF-H.
FT MOTIF 30 34 Nuclear localization signal (Potential).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 3 3 Phosphoserine.
FT MOD_RES 6 6 Phosphothreonine (By similarity).
FT VAR_SEQ 1 17 Missing (in isoform 3).
FT /FTId=VSP_046831.
FT VARIANT 35 35 A -> T (in NEM7; protein is less soluble
FT when expressed in Escherichia coli).
FT /FTId=VAR_031989.
FT VARIANT 47 47 I -> M (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036458.
SQ SEQUENCE 166 AA; 18737 MW; 48B6CDCCAE9FE1CC CRC64;
MASGVTVNDE VIKVFNDMKV RKSSTQEEIK KRKKAVLFCL SDDKRQIIVE EAKQILVGDI
GDTVEDPYTS FVKLLPLNDC RYALYDATYE TKESKKEDLV FIFWAPESAP LKSKMIYASS
KDAIKKKFTG IKHEWQVNGL DDIKDRSTLG EKLGGNVVVS LEGKPL
//
ID COF2_HUMAN Reviewed; 166 AA.
AC Q9Y281; G3V5P4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Cofilin-2;
DE AltName: Full=Cofilin, muscle isoform;
GN Name=CFL2;
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] (ISOFORMS CFL2A AND CFL2B).
RA Jin J., Li G., Hu S., Li W., Yuan J., Qiang B.;
RT "Isolation of two isoforms of human cofilin cDNA.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11422377; DOI=10.1046/j.1432-1327.2001.02247.x;
RA Thirion C., Stucka R., Mendel B., Gruhler A., Jaksch M., Nowak K.J.,
RA Binz N., Laing N.G., Lochmuller H.;
RT "Characterization of human muscle type cofilin (CFL2) in normal and
RT regenerating muscle.";
RL Eur. J. Biochem. 268:3473-3482(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS CFL2A AND CFL2B).
RC TISSUE=Bone marrow, Placenta, and Skeletal muscle;
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 [6]
RP PROTEIN SEQUENCE OF 2-21; 35-92; 96-112; 115-125 AND 153-166, CLEAVAGE
RP OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-3, AND MASS 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 [10]
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).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] MET-47.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [13]
RP VARIANT NEM7 THR-35, AND CHARACTERIZATION OF VARIANT NEM7 THR-35.
RX PubMed=17160903; DOI=10.1086/510402;
RA Agrawal P.B., Greenleaf R.S., Tomczak K.K., Lehtokari V.-L.,
RA Wallgren-Pettersson C., Wallefeld W., Laing N.G., Darras B.T.,
RA Maciver S.K., Dormitzer P.R., Beggs A.H.;
RT "Nemaline myopathy with minicores caused by mutation of the CFL2 gene
RT encoding the skeletal muscle actin-binding protein, cofilin-2.";
RL Am. J. Hum. Genet. 80:162-167(2007).
CC -!- FUNCTION: Controls reversibly actin polymerization and
CC depolymerization in a pH-sensitive manner. It has the ability to
CC bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the
CC major component of intranuclear and cytoplasmic actin rods (By
CC similarity).
CC -!- INTERACTION:
CC P60709:ACTB; NbExp=3; IntAct=EBI-351218, EBI-353944;
CC P63261:ACTG1; NbExp=2; IntAct=EBI-351218, EBI-351292;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix (By similarity). Cytoplasm,
CC cytoskeleton (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Isoforms are identical at the level of the protein
CC sequence;
CC Name=CFL2b;
CC IsoId=Q9Y281-1; Sequence=Displayed;
CC Name=CFL2a;
CC IsoId=Q9Y281-2; Sequence=Not described;
CC Name=3;
CC IsoId=Q9Y281-3; Sequence=VSP_046831;
CC Note=Gene prediction based on EST data;
CC -!- TISSUE SPECIFICITY: Isoform CFL2b is expressed predominantly in
CC skeletal muscle and heart. Isoform CFL2a is expressed in various
CC tissues.
CC -!- PTM: The phosphorylation of Ser-24 may prevent recognition of the
CC nuclear localization signal.
CC -!- DISEASE: Nemaline myopathy 7 (NEM7) [MIM:610687]: A form of
CC nemaline myopathy. Nemaline myopathies are muscular disorders
CC characterized by muscle weakness of varying severity and onset,
CC and abnormal thread-like or rod-shaped structures in muscle fibers
CC on histologic examination. Nemaline myopathy type 7 presents at
CC birth with hypotonia and generalized weakness. Major motor
CC milestones are delayed, but independent ambulation is achieved.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family.
CC -!- SIMILARITY: Contains 1 ADF-H domain.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cofilin entry;
CC URL="http://en.wikipedia.org/wiki/Cofilin";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF134802; AAD31280.1; -; mRNA.
DR EMBL; AF134803; AAD31281.1; -; mRNA.
DR EMBL; AF283513; AAF97934.1; -; Genomic_DNA.
DR EMBL; AF242299; AAF64498.1; -; Genomic_DNA.
DR EMBL; AL355885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65912.1; -; Genomic_DNA.
DR EMBL; BC011444; AAH11444.1; -; mRNA.
DR EMBL; BC022364; AAH22364.1; -; mRNA.
DR EMBL; BC022876; AAH22876.1; -; mRNA.
DR RefSeq; NP_001230574.1; NM_001243645.1.
DR RefSeq; NP_068733.1; NM_021914.7.
DR RefSeq; NP_619579.1; NM_138638.4.
DR UniGene; Hs.180141; -.
DR ProteinModelPortal; Q9Y281; -.
DR SMR; Q9Y281; 1-166.
DR DIP; DIP-33178N; -.
DR IntAct; Q9Y281; 4.
DR MINT; MINT-1161448; -.
DR STRING; 9606.ENSP00000298159; -.
DR PhosphoSite; Q9Y281; -.
DR DMDM; 6831517; -.
DR PaxDb; Q9Y281; -.
DR PRIDE; Q9Y281; -.
DR DNASU; 1073; -.
DR Ensembl; ENST00000298159; ENSP00000298159; ENSG00000165410.
DR Ensembl; ENST00000341223; ENSP00000340635; ENSG00000165410.
DR Ensembl; ENST00000555765; ENSP00000452451; ENSG00000165410.
DR Ensembl; ENST00000556161; ENSP00000452188; ENSG00000165410.
DR GeneID; 1073; -.
DR KEGG; hsa:1073; -.
DR UCSC; uc001wsg.3; human.
DR CTD; 1073; -.
DR GeneCards; GC14M035179; -.
DR HGNC; HGNC:1875; CFL2.
DR HPA; CAB037078; -.
DR MIM; 601443; gene.
DR MIM; 610687; phenotype.
DR neXtProt; NX_Q9Y281; -.
DR Orphanet; 171436; Typical nemaline myopathy.
DR PharmGKB; PA26424; -.
DR eggNOG; NOG303866; -.
DR HOGENOM; HOG000039697; -.
DR HOVERGEN; HBG000381; -.
DR InParanoid; Q9Y281; -.
DR KO; K05765; -.
DR OMA; GLYDATY; -.
DR OrthoDB; EOG7353Z9; -.
DR PhylomeDB; Q9Y281; -.
DR GeneWiki; CFL2_(gene); -.
DR GenomeRNAi; 1073; -.
DR NextBio; 4480; -.
DR PRO; PR:Q9Y281; -.
DR ArrayExpress; Q9Y281; -.
DR Bgee; Q9Y281; -.
DR CleanEx; HS_CFL2; -.
DR Genevestigator; Q9Y281; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0030042; P:actin filament depolymerization; IEA:InterPro.
DR InterPro; IPR002108; Actin-bd_cofilin/tropomyosin.
DR InterPro; IPR017904; ADF/Cofilin/Destrin.
DR PANTHER; PTHR11913; PTHR11913; 1.
DR Pfam; PF00241; Cofilin_ADF; 1.
DR PRINTS; PR00006; COFILIN.
DR SMART; SM00102; ADF; 1.
DR PROSITE; PS51263; ADF_H; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Nemaline myopathy; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 166 Cofilin-2.
FT /FTId=PRO_0000214907.
FT DOMAIN 4 153 ADF-H.
FT MOTIF 30 34 Nuclear localization signal (Potential).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 3 3 Phosphoserine.
FT MOD_RES 6 6 Phosphothreonine (By similarity).
FT VAR_SEQ 1 17 Missing (in isoform 3).
FT /FTId=VSP_046831.
FT VARIANT 35 35 A -> T (in NEM7; protein is less soluble
FT when expressed in Escherichia coli).
FT /FTId=VAR_031989.
FT VARIANT 47 47 I -> M (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036458.
SQ SEQUENCE 166 AA; 18737 MW; 48B6CDCCAE9FE1CC CRC64;
MASGVTVNDE VIKVFNDMKV RKSSTQEEIK KRKKAVLFCL SDDKRQIIVE EAKQILVGDI
GDTVEDPYTS FVKLLPLNDC RYALYDATYE TKESKKEDLV FIFWAPESAP LKSKMIYASS
KDAIKKKFTG IKHEWQVNGL DDIKDRSTLG EKLGGNVVVS LEGKPL
//
MIM
601443
*RECORD*
*FIELD* NO
601443
*FIELD* TI
*601443 COFILIN 2; CFL2
;;COFILIN, MUSCLE
*FIELD* TX
DESCRIPTION
Cofilin is a widely distributed intracellular actin-modulating protein
read morethat binds and depolymerizes filamentous F-actin and inhibits the
polymerization of monomeric G-actin in a pH-dependent manner. (Gillett
et al., 1996). Cofilin-2 is a member of the AC group of proteins that
also includes cofilin-1 (CFL1) and destrin (DSTN; 609114), all of which
regulate actin-filament dynamics (Bamburg et al., 1999; Maciver and
Hussey, 2002). The CFL2 gene encodes a skeletal muscle-specific isoform
(Vartiainen et al., 2002) localized to the thin filaments, where it
exerts its effect on actin, in part through interactions with
tropomyosins (Ono and Ono, 2002).
CLONING
By RT-PCR using primers based on murine Cfl2, Thirion et al. (2001)
cloned 4 CFL2 variants from human fetal and adult myoblasts. The
transcripts differ in their 5-prime and 3-prime ends, but have identical
coding regions, due to alternative splicing of the first exon and the
use of alternative polyadenylation signals. The deduced 166-amino acid
CFL2 protein has a calculated molecular mass of 19 kD and shares 99% and
81% identity with mouse Cfl2 and human CFL1 (601442), respectively.
Northern blot analysis detected 2 major CLF2 transcripts that were
highly expressed in heart and skeletal muscle, with weaker expression in
all other tissues examined. Primary human myoblasts and myotubes
expressed transcripts of 1.55, 1.65, and 3.2 kb. Immunohistochemical
analysis of murine and human skeletal muscle localized CFL2 in a uniform
cytoplasmic distribution characteristic of sarcomeric proteins. Western
blot analysis of healthy mouse muscle showed that 30 to 50% of Cfl2 was
phosphorylated.
Agrawal et al. (2012) stated that mouse Cfl2 is expressed as 1.8- and
3.0-kb transcripts that differ in their 3-prime UTRs only and are
alternately expressed during striated muscle development. The 1.8-kb
transcript is expressed at embryonic day 13, peaks in skeletal and
cardiac muscle at birth, and decreases thereafter. The 3.0-kb transcript
is expressed in skeletal muscle only, and its expression increases as
expression of the 1.8-kb transcript decreases.
GENE STRUCTURE
Thirion et al. (2001) determined that the CFL2 gene contains 5 exons,
including alternative first exons (exons 1a and 1b) that encode the
initiating methionine only. Identification of transcription
factor-binding sites upstream of exons 1a and 1b suggested the presence
of 2 promoters. CFL2 has 2 polyadenylation signals.
MAPPING
Gillett et al. (1996) mapped CFL2, the human muscle-type (M-type)
cofilin, to chromosome 14 by analysis of a somatic cell hybrid panel
using an expressed sequence tag (EST) with homology to the mouse
muscle-type cofilin and chicken cofilin.
Agrawal et al. (2012) stated that the CFL2 gene maps to chromosome
14q12.
GENE FUNCTION
By Western blot analysis of 2-dimensional gels, Thirion et al. (2001)
found that expression of Clf2 decreased sharply and that phosphorylated
Cfl2 became undetectable following acute muscle damage in mice. Skeletal
muscle of Duchenne muscular dystrophy (310200) patients and dystrophin
(DMD; 300377)-deficient mdx mice, where continuous muscle degeneration
and regeneration occurs, showed a similar phenomenon.
MOLECULAR GENETICS
Agrawal et al. (2007) used genomic PCR and DNA sequencing to screen the
CFL2 gene in 113 unrelated patients with nemaline myopathy and 58
patients with clinical pathologic diagnoses of other congenital
myopathies. None of the patients had known mutations in previously
identified genes. In 2 sibs with nemaline myopathy (NEM7; 610687) in a
large family of Middle Eastern origin, Agrawal et al. (2007) identified
a homozygous mutation in the CFL2 gene (A35T; 601443.0001). The
proband's muscle contained characteristic nemaline bodies, as well as
occasional fibers with minicores, concentric laminated bodies, and areas
of F-actin accumulation. Cofilin-2 levels were significantly lower in
the proband's muscle, and the mutant protein was less soluble when
expressed in Escherichia coli, suggesting that deficiency of cofilin-2
may result in reduced depolymerization of actin filaments, causing their
accumulation in nemaline bodies, minicores, and, possibly concentric
laminated bodies.
In 2 Iraqi sisters, born of consanguineous parents, with nemaline
myopathy-7, Ockeloen et al. (2012) identified a homozygous missense
mutation in the CFL2 gene (V7M; 601443.0002). The mutation was found by
homozygosity mapping followed by candidate gene sequencing.
ANIMAL MODEL
Agrawal et al. (2012) found that Cfl2 -/- mice were indistinguishable
from wildtype at birth. However, by postnatal day 3, Cfl2 -/- mice
showed reduced size and activity, followed by rapid deterioration and
death by postnatal day 8. Presence of milk in stomachs of Cfl2 -/- mice
at postnatal day 3, but not at postnatal day 7, suggested that the older
animals had lost the ability to suckle. Targeted disruption of Cfl2 to
skeletal or cardiac muscle resulted in a phenotype that was only
modestly less severe. Electron microscopic analysis revealed ballooning
degeneration of skeletal muscle fibers, core-like lesions, extensive
sarcomeric disruption, nemaline bodies, and actin accumulation. Cardiac
muscle fibers did not show evidence of degeneration. Muscle degeneration
and weakness in Cfl2 -/- mice coincided with normal developmental
depletion of Cfl1 in myofibers. Agrawal et al. (2012) hypothesized that
Cfl1 may initiate myofibrillogenesis, whereas Cfl2 is required for
myofiber maintenance.
*FIELD* AV
.0001
NEMALINE MYOPATHY 7
CFL2, ALA35THR
In 2 sisters in a family of Middle Eastern origin, Agrawal et al. (2007)
found that nemaline myopathy with some unusual histopathologic and
clinical features (NEM7; 610687) was related to homozygous mutation of
the CFL2 gene, 103G-A, predicted to result in an alanine-to-threonine
substitution at residue 35 (A35T). An unaffected sib, both unaffected
parents, and a number of other members of the extended family were
heterozygous for this change. Extensive intermarriage, with multiple
consanguinity loops, strongly suggested identity by descent for the 2
mutant alleles, a supposition that was supported by linkage studies
using flanking markers. The mutation was ruled out in 282 unaffected
control individuals, including 91 originating from the same geographic
region and ethnic group as the family.
.0002
NEMALINE MYOPATHY 7
CFL2, VAL7MET
In 2 Iraqi sisters, born of consanguineous parents, with nemaline
myopathy-7 (610687), Ockeloen et al. (2012) identified a homozygous
c.19G-A transition in exon 2 of the CFL2 gene, resulting in a
val7-to-met (V7M) substitution at a highly conserved residue. The
mutation was found by homozygosity mapping followed by candidate gene
sequencing, and each unaffected parent was heterozygous for the
mutation, which was not found in 250 controls or in dbSNP. Functional
studies were not performed. The girls had delayed walking and proximal
and axial muscle weakness; muscle biopsy showed nemaline rods and
abnormal protein aggregates.
*FIELD* RF
1. Agrawal, P. B.; Greenleaf, R. S.; Tomczak, K. K.; Lehtokari, V.-L.;
Wallgren-Pettersson, C.; Wallefeld, W.; Laing, N. G.; Darras, B. T.;
Maciver, S. K.; Dormitzer, P. R.; Beggs, A. H.: Nemaline myopathy
with minicores caused by mutation of the CFL2 gene encoding the skeletal
muscle actin-binding protein, cofilin-2. Am. J. Hum. Genet. 80:
162-167, 2007.
2. Agrawal, P. B.; Joshi, M.; Savic, T.; Chen, Z.; Beggs, A. H.:
Normal myofibrillar development followed by progressive sarcomeric
disruption with actin accumulations in a mouse Cfl2 knockout demonstrates
requirement of cofilin-2 for muscle maintenance. Hum. Molec. Genet. 21:
2341-2356, 2012.
3. Bamburg, J. R.; McGough, A.; Ono, S.: Putting a new twist on actin:
ADF/cofilins modulate actin dynamics. Trends Cell Biol. 9: 364-370,
1999.
4. Gillett, G. T.; Fox, M. F.; Rowe, P. S. N.; Casimir, C. M.; Povey,
S.: Mapping of human non-muscle type cofilin (CFL1) to chromosome
11q13 and muscle-type cofilin (CFL2) to chromosome 14. Ann. Hum.
Genet. 60: 201-211, 1996.
5. Maciver, M. K.; Hussey, P. J.: The ADF/cofilin family: actin-remodeling
proteins. Genome Biol. 3: , 2002. Note: reviews3007.
6. Ockeloen, C. W.; Gilhuis, H. J.; Pfundt, R.; Kamsteeg, E. J.; Agrawal,
P. B.; Beggs, A. H.; Dara Hama-Amin, A.; Diekstra, A.; Knoers, N.
V. A. M.; Lammens, M.; van Alfen, N.: Congenital myopathy caused
by a novel missense mutation in the CFL2 gene. Neuromusc. Disord. 22:
632-639, 2012.
7. Ono, S.; Ono, K.: Tropomyosin inhibits ADF/cofilin-dependent actin
filament dynamics. J. Cell Biol. 156: 1065-1076, 2002. Note: Erratum:
J. Cell Biol. 157: 727 only, 2002.
8. Thirion, C.; Stucka, R.; Mendel, B.; Gruhler, A.; Jaksch, M.; Nowak,
K. J.; Binz, N.; Laing, N. G.; Lochmuller, H.: Characterization of
human muscle type cofilin (CFL2) in normal and regenerating muscle. Europ.
J. Biochem. 268: 3473-3482, 2001.
9. Vartiainen, M. K.; Mustonen, T.; Mattila, P. K.; Ojala, P. J.;
Thesleff, I.; Partanen, J.; Lappalainen, P.: The three mouse actin-depolymerizing
factor/cofilins evolved to fulfill cell-type-specific requirements
for actin dynamics. Molec. Biol. Cell 13: 183-194, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 8/5/2013
Patricia A. Hartz - updated: 7/10/2013
Victor A. McKusick - updated: 1/3/2007
*FIELD* CD
Lori M. Kelman: 9/23/1996
*FIELD* ED
tpirozzi: 08/07/2013
tpirozzi: 8/7/2013
ckniffin: 8/5/2013
mgross: 7/10/2013
terry: 12/19/2012
alopez: 1/5/2007
terry: 1/3/2007
mark: 4/10/1997
mark: 9/24/1996
mark: 9/23/1996
*RECORD*
*FIELD* NO
601443
*FIELD* TI
*601443 COFILIN 2; CFL2
;;COFILIN, MUSCLE
*FIELD* TX
DESCRIPTION
Cofilin is a widely distributed intracellular actin-modulating protein
read morethat binds and depolymerizes filamentous F-actin and inhibits the
polymerization of monomeric G-actin in a pH-dependent manner. (Gillett
et al., 1996). Cofilin-2 is a member of the AC group of proteins that
also includes cofilin-1 (CFL1) and destrin (DSTN; 609114), all of which
regulate actin-filament dynamics (Bamburg et al., 1999; Maciver and
Hussey, 2002). The CFL2 gene encodes a skeletal muscle-specific isoform
(Vartiainen et al., 2002) localized to the thin filaments, where it
exerts its effect on actin, in part through interactions with
tropomyosins (Ono and Ono, 2002).
CLONING
By RT-PCR using primers based on murine Cfl2, Thirion et al. (2001)
cloned 4 CFL2 variants from human fetal and adult myoblasts. The
transcripts differ in their 5-prime and 3-prime ends, but have identical
coding regions, due to alternative splicing of the first exon and the
use of alternative polyadenylation signals. The deduced 166-amino acid
CFL2 protein has a calculated molecular mass of 19 kD and shares 99% and
81% identity with mouse Cfl2 and human CFL1 (601442), respectively.
Northern blot analysis detected 2 major CLF2 transcripts that were
highly expressed in heart and skeletal muscle, with weaker expression in
all other tissues examined. Primary human myoblasts and myotubes
expressed transcripts of 1.55, 1.65, and 3.2 kb. Immunohistochemical
analysis of murine and human skeletal muscle localized CFL2 in a uniform
cytoplasmic distribution characteristic of sarcomeric proteins. Western
blot analysis of healthy mouse muscle showed that 30 to 50% of Cfl2 was
phosphorylated.
Agrawal et al. (2012) stated that mouse Cfl2 is expressed as 1.8- and
3.0-kb transcripts that differ in their 3-prime UTRs only and are
alternately expressed during striated muscle development. The 1.8-kb
transcript is expressed at embryonic day 13, peaks in skeletal and
cardiac muscle at birth, and decreases thereafter. The 3.0-kb transcript
is expressed in skeletal muscle only, and its expression increases as
expression of the 1.8-kb transcript decreases.
GENE STRUCTURE
Thirion et al. (2001) determined that the CFL2 gene contains 5 exons,
including alternative first exons (exons 1a and 1b) that encode the
initiating methionine only. Identification of transcription
factor-binding sites upstream of exons 1a and 1b suggested the presence
of 2 promoters. CFL2 has 2 polyadenylation signals.
MAPPING
Gillett et al. (1996) mapped CFL2, the human muscle-type (M-type)
cofilin, to chromosome 14 by analysis of a somatic cell hybrid panel
using an expressed sequence tag (EST) with homology to the mouse
muscle-type cofilin and chicken cofilin.
Agrawal et al. (2012) stated that the CFL2 gene maps to chromosome
14q12.
GENE FUNCTION
By Western blot analysis of 2-dimensional gels, Thirion et al. (2001)
found that expression of Clf2 decreased sharply and that phosphorylated
Cfl2 became undetectable following acute muscle damage in mice. Skeletal
muscle of Duchenne muscular dystrophy (310200) patients and dystrophin
(DMD; 300377)-deficient mdx mice, where continuous muscle degeneration
and regeneration occurs, showed a similar phenomenon.
MOLECULAR GENETICS
Agrawal et al. (2007) used genomic PCR and DNA sequencing to screen the
CFL2 gene in 113 unrelated patients with nemaline myopathy and 58
patients with clinical pathologic diagnoses of other congenital
myopathies. None of the patients had known mutations in previously
identified genes. In 2 sibs with nemaline myopathy (NEM7; 610687) in a
large family of Middle Eastern origin, Agrawal et al. (2007) identified
a homozygous mutation in the CFL2 gene (A35T; 601443.0001). The
proband's muscle contained characteristic nemaline bodies, as well as
occasional fibers with minicores, concentric laminated bodies, and areas
of F-actin accumulation. Cofilin-2 levels were significantly lower in
the proband's muscle, and the mutant protein was less soluble when
expressed in Escherichia coli, suggesting that deficiency of cofilin-2
may result in reduced depolymerization of actin filaments, causing their
accumulation in nemaline bodies, minicores, and, possibly concentric
laminated bodies.
In 2 Iraqi sisters, born of consanguineous parents, with nemaline
myopathy-7, Ockeloen et al. (2012) identified a homozygous missense
mutation in the CFL2 gene (V7M; 601443.0002). The mutation was found by
homozygosity mapping followed by candidate gene sequencing.
ANIMAL MODEL
Agrawal et al. (2012) found that Cfl2 -/- mice were indistinguishable
from wildtype at birth. However, by postnatal day 3, Cfl2 -/- mice
showed reduced size and activity, followed by rapid deterioration and
death by postnatal day 8. Presence of milk in stomachs of Cfl2 -/- mice
at postnatal day 3, but not at postnatal day 7, suggested that the older
animals had lost the ability to suckle. Targeted disruption of Cfl2 to
skeletal or cardiac muscle resulted in a phenotype that was only
modestly less severe. Electron microscopic analysis revealed ballooning
degeneration of skeletal muscle fibers, core-like lesions, extensive
sarcomeric disruption, nemaline bodies, and actin accumulation. Cardiac
muscle fibers did not show evidence of degeneration. Muscle degeneration
and weakness in Cfl2 -/- mice coincided with normal developmental
depletion of Cfl1 in myofibers. Agrawal et al. (2012) hypothesized that
Cfl1 may initiate myofibrillogenesis, whereas Cfl2 is required for
myofiber maintenance.
*FIELD* AV
.0001
NEMALINE MYOPATHY 7
CFL2, ALA35THR
In 2 sisters in a family of Middle Eastern origin, Agrawal et al. (2007)
found that nemaline myopathy with some unusual histopathologic and
clinical features (NEM7; 610687) was related to homozygous mutation of
the CFL2 gene, 103G-A, predicted to result in an alanine-to-threonine
substitution at residue 35 (A35T). An unaffected sib, both unaffected
parents, and a number of other members of the extended family were
heterozygous for this change. Extensive intermarriage, with multiple
consanguinity loops, strongly suggested identity by descent for the 2
mutant alleles, a supposition that was supported by linkage studies
using flanking markers. The mutation was ruled out in 282 unaffected
control individuals, including 91 originating from the same geographic
region and ethnic group as the family.
.0002
NEMALINE MYOPATHY 7
CFL2, VAL7MET
In 2 Iraqi sisters, born of consanguineous parents, with nemaline
myopathy-7 (610687), Ockeloen et al. (2012) identified a homozygous
c.19G-A transition in exon 2 of the CFL2 gene, resulting in a
val7-to-met (V7M) substitution at a highly conserved residue. The
mutation was found by homozygosity mapping followed by candidate gene
sequencing, and each unaffected parent was heterozygous for the
mutation, which was not found in 250 controls or in dbSNP. Functional
studies were not performed. The girls had delayed walking and proximal
and axial muscle weakness; muscle biopsy showed nemaline rods and
abnormal protein aggregates.
*FIELD* RF
1. Agrawal, P. B.; Greenleaf, R. S.; Tomczak, K. K.; Lehtokari, V.-L.;
Wallgren-Pettersson, C.; Wallefeld, W.; Laing, N. G.; Darras, B. T.;
Maciver, S. K.; Dormitzer, P. R.; Beggs, A. H.: Nemaline myopathy
with minicores caused by mutation of the CFL2 gene encoding the skeletal
muscle actin-binding protein, cofilin-2. Am. J. Hum. Genet. 80:
162-167, 2007.
2. Agrawal, P. B.; Joshi, M.; Savic, T.; Chen, Z.; Beggs, A. H.:
Normal myofibrillar development followed by progressive sarcomeric
disruption with actin accumulations in a mouse Cfl2 knockout demonstrates
requirement of cofilin-2 for muscle maintenance. Hum. Molec. Genet. 21:
2341-2356, 2012.
3. Bamburg, J. R.; McGough, A.; Ono, S.: Putting a new twist on actin:
ADF/cofilins modulate actin dynamics. Trends Cell Biol. 9: 364-370,
1999.
4. Gillett, G. T.; Fox, M. F.; Rowe, P. S. N.; Casimir, C. M.; Povey,
S.: Mapping of human non-muscle type cofilin (CFL1) to chromosome
11q13 and muscle-type cofilin (CFL2) to chromosome 14. Ann. Hum.
Genet. 60: 201-211, 1996.
5. Maciver, M. K.; Hussey, P. J.: The ADF/cofilin family: actin-remodeling
proteins. Genome Biol. 3: , 2002. Note: reviews3007.
6. Ockeloen, C. W.; Gilhuis, H. J.; Pfundt, R.; Kamsteeg, E. J.; Agrawal,
P. B.; Beggs, A. H.; Dara Hama-Amin, A.; Diekstra, A.; Knoers, N.
V. A. M.; Lammens, M.; van Alfen, N.: Congenital myopathy caused
by a novel missense mutation in the CFL2 gene. Neuromusc. Disord. 22:
632-639, 2012.
7. Ono, S.; Ono, K.: Tropomyosin inhibits ADF/cofilin-dependent actin
filament dynamics. J. Cell Biol. 156: 1065-1076, 2002. Note: Erratum:
J. Cell Biol. 157: 727 only, 2002.
8. Thirion, C.; Stucka, R.; Mendel, B.; Gruhler, A.; Jaksch, M.; Nowak,
K. J.; Binz, N.; Laing, N. G.; Lochmuller, H.: Characterization of
human muscle type cofilin (CFL2) in normal and regenerating muscle. Europ.
J. Biochem. 268: 3473-3482, 2001.
9. Vartiainen, M. K.; Mustonen, T.; Mattila, P. K.; Ojala, P. J.;
Thesleff, I.; Partanen, J.; Lappalainen, P.: The three mouse actin-depolymerizing
factor/cofilins evolved to fulfill cell-type-specific requirements
for actin dynamics. Molec. Biol. Cell 13: 183-194, 2002.
*FIELD* CN
Cassandra L. Kniffin - updated: 8/5/2013
Patricia A. Hartz - updated: 7/10/2013
Victor A. McKusick - updated: 1/3/2007
*FIELD* CD
Lori M. Kelman: 9/23/1996
*FIELD* ED
tpirozzi: 08/07/2013
tpirozzi: 8/7/2013
ckniffin: 8/5/2013
mgross: 7/10/2013
terry: 12/19/2012
alopez: 1/5/2007
terry: 1/3/2007
mark: 4/10/1997
mark: 9/24/1996
mark: 9/23/1996
MIM
610687
*RECORD*
*FIELD* NO
610687
*FIELD* TI
#610687 NEMALINE MYOPATHY 7; NEM7
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morenemaline myopathy-7 (NEM7) is caused by homozygous mutation in the CFL2
gene (601443) on chromosome 14q13.
DESCRIPTION
Nemaline myopathy-7 is an autosomal recessive congenital myopathy
characterized by very early onset of hypotonia and delayed motor
development. Affected individuals have difficulty walking and running
due to proximal muscle weakness. The disorder is slowly progressive, and
patients may lose independent ambulation. Muscle biopsy shows nemaline
rods and may later show minicores, abnormal protein aggregates, and
dystrophic changes (summary by Ockeloen et al., 2012).
For a discussion of genetic heterogeneity of nemaline myopathy, see
161800.
CLINICAL FEATURES
Agrawal et al. (2007) described 2 sibs from a large consanguineous
Middle Eastern family, identified in a screen of patients with
congenital myopathies, with nemaline myopathy. Both patients had similar
clinical presentations, with hypotonia noted at birth, delayed early
motor milestones, frequent falls, and inability to run. The elder sister
at age 16 years could walk short distances but used a wheelchair outside
the house. Muscle biopsy showed nonspecific myopathic changes. The
younger sib at age 9 years was ambulant. Muscle biopsy showed
characteristic nemaline bodies as well as occasional fibers with
minicores, concentric laminated bodies, and areas of F-actin
accumulation. The course of the disease in both sibs was like that of
typical nemaline myopathy, but the distribution of weakness was
distinct, without significant facial weakness or foot drop.
Ockeloen et al. (2012) reported 2 sisters, born of consanguineous Iraqi
parents, with congenital myopathy. The proband was a 21-year-old woman
who had delayed walking at age 2 years, 6 months, and slowly progressive
muscle weakness affecting the neck muscles, shoulder girdle muscles, and
legs. She had a high-arched palate, mild facial muscle weakness, severe
kyphoscoliosis, areflexia, and chronic respiratory insufficiency due to
muscle weakness; she was wheelchair-bound. Her 5-year-old sister, who
was also affected, showed delayed walking, hypotonia, occasional head
drop, Gowers sign, waddling gait, and hyperextension of the knees and
elbows. Both patients had normal cognition. Skeletal muscle biopsy
showed a dystrophic pattern with increased fiber variability.
Immunohistochemical staining showed some irregular cytoplasmic
aggregates and the presence of nemaline rods. Enzyme histochemistry with
ATPase showed 'rubbed out' areas in some muscle fibers. Electron
microscopy of 1 biopsy showed areas with Z-band streaming and rods,
often in large aggregates. The aggregates were accompanied by
osmiophilic granular material, degenerating membranous organelles, and
cytoplasmic bodies.
INHERITANCE
The transmission patterns in the families with nemaline myopathy
reported by Agrawal et al. (2007) and Ockeloen et al. (2012) were
consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
On the basis of the role of cofilin-2 in regulation of sarcomeric actin
filaments, Agrawal et al. (2007) screened 113 unrelated patients with
nemaline myopathy and 58 patients with clinicopathologic diagnoses of
other congenital myopathies for mutations in the CFL2 gene. They found a
homozygous missense mutation (601443.0001) in 2 sibs from a large
consanguineous Middle Eastern family with nemaline myopathy. Agrawal et
al. (2007) estimated that the frequency of CFL2 mutations in patients
with nemaline myopathy is well below 0.6%.
In 2 Iraqi sisters with nemaline myopathy and features of myofibrillar
myopathy, Ockeloen et al. (2012) identified a homozygous mutation in the
CFL2 gene (601443.0002). The mutation was found by homozygosity mapping
followed by candidate gene sequencing.
*FIELD* RF
1. Agrawal, P. B.; Greenleaf, R. S.; Tomczak, K. K.; Lehtokari, V.-L.;
Wallgren-Pettersson, C.; Wallefeld, W.; Laing, N. G.; Darras, B. T.;
Maciver, S. K.; Dormitzer, P. R.; Beggs, A. H.: Nemaline myopathy
with minicores caused by mutation of the CFL2 gene encoding the skeletal
muscle actin-binding protein, cofilin-2. Am. J. Hum. Genet. 80:
162-167, 2007.
2. Ockeloen, C. W.; Gilhuis, H. J.; Pfundt, R.; Kamsteeg, E. J.; Agrawal,
P. B.; Beggs, A. H.; Dara Hama-Amin, A.; Diekstra, A.; Knoers, N.
V. A. M.; Lammens, M.; van Alfen, N.: Congenital myopathy caused
by a novel missense mutation in the CFL2 gene. Neuromusc. Disord. 22:
632-639, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Mouth];
High-arched palate;
[Neck];
Neck muscle weakness
RESPIRATORY:
Respiratory insufficiency due to muscle weakness (in some patients)
SKELETAL:
Joint hypermobility;
[Spine]
MUSCLE, SOFT TISSUE:
Muscle weakness, mainly proximal and axial;
Hypotonia;
Gower sign;
Fiber type variation seen on biopsy;
Type 1 fiber predominance;
Nemaline rods;
Muscle biopsy shows dystrophic features (later in disease course);
Protein aggregates resembling myofibrillar myopathy may be present;
Minicores or core-like regions may be present
NEUROLOGIC:
[Central nervous system];
Delayed motor development;
Abnormal gait;
Loss of independent ambulation (in some patients);
[Peripheral nervous system];
Areflexia
MISCELLANEOUS:
Two unrelated families have been reported (last curated August 2013);
Onset in early childhood;
Slowly progressive
MOLECULAR BASIS:
Caused by mutation in the cofilin 2 gene (CFL2, 601443.0001)
*FIELD* CD
Cassandra L. Kniffin: 8/5/2013
*FIELD* ED
joanna: 10/01/2013
ckniffin: 8/5/2013
*FIELD* CN
Cassandra L. Kniffin - updated: 8/5/2013
*FIELD* CD
Victor A. McKusick: 1/5/2007
*FIELD* ED
carol: 08/08/2013
tpirozzi: 8/7/2013
ckniffin: 8/5/2013
carol: 8/2/2013
alopez: 1/5/2007
*RECORD*
*FIELD* NO
610687
*FIELD* TI
#610687 NEMALINE MYOPATHY 7; NEM7
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morenemaline myopathy-7 (NEM7) is caused by homozygous mutation in the CFL2
gene (601443) on chromosome 14q13.
DESCRIPTION
Nemaline myopathy-7 is an autosomal recessive congenital myopathy
characterized by very early onset of hypotonia and delayed motor
development. Affected individuals have difficulty walking and running
due to proximal muscle weakness. The disorder is slowly progressive, and
patients may lose independent ambulation. Muscle biopsy shows nemaline
rods and may later show minicores, abnormal protein aggregates, and
dystrophic changes (summary by Ockeloen et al., 2012).
For a discussion of genetic heterogeneity of nemaline myopathy, see
161800.
CLINICAL FEATURES
Agrawal et al. (2007) described 2 sibs from a large consanguineous
Middle Eastern family, identified in a screen of patients with
congenital myopathies, with nemaline myopathy. Both patients had similar
clinical presentations, with hypotonia noted at birth, delayed early
motor milestones, frequent falls, and inability to run. The elder sister
at age 16 years could walk short distances but used a wheelchair outside
the house. Muscle biopsy showed nonspecific myopathic changes. The
younger sib at age 9 years was ambulant. Muscle biopsy showed
characteristic nemaline bodies as well as occasional fibers with
minicores, concentric laminated bodies, and areas of F-actin
accumulation. The course of the disease in both sibs was like that of
typical nemaline myopathy, but the distribution of weakness was
distinct, without significant facial weakness or foot drop.
Ockeloen et al. (2012) reported 2 sisters, born of consanguineous Iraqi
parents, with congenital myopathy. The proband was a 21-year-old woman
who had delayed walking at age 2 years, 6 months, and slowly progressive
muscle weakness affecting the neck muscles, shoulder girdle muscles, and
legs. She had a high-arched palate, mild facial muscle weakness, severe
kyphoscoliosis, areflexia, and chronic respiratory insufficiency due to
muscle weakness; she was wheelchair-bound. Her 5-year-old sister, who
was also affected, showed delayed walking, hypotonia, occasional head
drop, Gowers sign, waddling gait, and hyperextension of the knees and
elbows. Both patients had normal cognition. Skeletal muscle biopsy
showed a dystrophic pattern with increased fiber variability.
Immunohistochemical staining showed some irregular cytoplasmic
aggregates and the presence of nemaline rods. Enzyme histochemistry with
ATPase showed 'rubbed out' areas in some muscle fibers. Electron
microscopy of 1 biopsy showed areas with Z-band streaming and rods,
often in large aggregates. The aggregates were accompanied by
osmiophilic granular material, degenerating membranous organelles, and
cytoplasmic bodies.
INHERITANCE
The transmission patterns in the families with nemaline myopathy
reported by Agrawal et al. (2007) and Ockeloen et al. (2012) were
consistent with autosomal recessive inheritance.
MOLECULAR GENETICS
On the basis of the role of cofilin-2 in regulation of sarcomeric actin
filaments, Agrawal et al. (2007) screened 113 unrelated patients with
nemaline myopathy and 58 patients with clinicopathologic diagnoses of
other congenital myopathies for mutations in the CFL2 gene. They found a
homozygous missense mutation (601443.0001) in 2 sibs from a large
consanguineous Middle Eastern family with nemaline myopathy. Agrawal et
al. (2007) estimated that the frequency of CFL2 mutations in patients
with nemaline myopathy is well below 0.6%.
In 2 Iraqi sisters with nemaline myopathy and features of myofibrillar
myopathy, Ockeloen et al. (2012) identified a homozygous mutation in the
CFL2 gene (601443.0002). The mutation was found by homozygosity mapping
followed by candidate gene sequencing.
*FIELD* RF
1. Agrawal, P. B.; Greenleaf, R. S.; Tomczak, K. K.; Lehtokari, V.-L.;
Wallgren-Pettersson, C.; Wallefeld, W.; Laing, N. G.; Darras, B. T.;
Maciver, S. K.; Dormitzer, P. R.; Beggs, A. H.: Nemaline myopathy
with minicores caused by mutation of the CFL2 gene encoding the skeletal
muscle actin-binding protein, cofilin-2. Am. J. Hum. Genet. 80:
162-167, 2007.
2. Ockeloen, C. W.; Gilhuis, H. J.; Pfundt, R.; Kamsteeg, E. J.; Agrawal,
P. B.; Beggs, A. H.; Dara Hama-Amin, A.; Diekstra, A.; Knoers, N.
V. A. M.; Lammens, M.; van Alfen, N.: Congenital myopathy caused
by a novel missense mutation in the CFL2 gene. Neuromusc. Disord. 22:
632-639, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Mouth];
High-arched palate;
[Neck];
Neck muscle weakness
RESPIRATORY:
Respiratory insufficiency due to muscle weakness (in some patients)
SKELETAL:
Joint hypermobility;
[Spine]
MUSCLE, SOFT TISSUE:
Muscle weakness, mainly proximal and axial;
Hypotonia;
Gower sign;
Fiber type variation seen on biopsy;
Type 1 fiber predominance;
Nemaline rods;
Muscle biopsy shows dystrophic features (later in disease course);
Protein aggregates resembling myofibrillar myopathy may be present;
Minicores or core-like regions may be present
NEUROLOGIC:
[Central nervous system];
Delayed motor development;
Abnormal gait;
Loss of independent ambulation (in some patients);
[Peripheral nervous system];
Areflexia
MISCELLANEOUS:
Two unrelated families have been reported (last curated August 2013);
Onset in early childhood;
Slowly progressive
MOLECULAR BASIS:
Caused by mutation in the cofilin 2 gene (CFL2, 601443.0001)
*FIELD* CD
Cassandra L. Kniffin: 8/5/2013
*FIELD* ED
joanna: 10/01/2013
ckniffin: 8/5/2013
*FIELD* CN
Cassandra L. Kniffin - updated: 8/5/2013
*FIELD* CD
Victor A. McKusick: 1/5/2007
*FIELD* ED
carol: 08/08/2013
tpirozzi: 8/7/2013
ckniffin: 8/5/2013
carol: 8/2/2013
alopez: 1/5/2007