Full text data of LASP1
LASP1
(MLN50)
[Confidence: low (only semi-automatic identification from reviews)]
LIM and SH3 domain protein 1; LASP-1 (Metastatic lymph node gene 50 protein; MLN 50)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
LIM and SH3 domain protein 1; LASP-1 (Metastatic lymph node gene 50 protein; MLN 50)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14847
ID LASP1_HUMAN Reviewed; 261 AA.
AC Q14847; Q96ED2; Q96IG0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 2.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=LIM and SH3 domain protein 1;
DE Short=LASP-1;
DE AltName: Full=Metastatic lymph node gene 50 protein;
DE Short=MLN 50;
GN Name=LASP1; Synonyms=MLN50;
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).
RC TISSUE=Mammary carcinoma;
RX PubMed=7490069; DOI=10.1006/geno.1995.1163;
RA Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G.,
RA Chenard M.-P., Lidereau R., Basset P., Rio M.-C.;
RT "Identification of four novel human genes amplified and overexpressed
RT in breast carcinoma and localized to the q11-q21.3 region of
RT chromosome 17.";
RL Genomics 28:367-376(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver, and Skin;
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 [3]
RP PROTEIN SEQUENCE OF 1-7, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [4]
RP DOMAINS.
RX PubMed=7589475; DOI=10.1016/0014-5793(95)01040-L;
RA Tomasetto C., Moog-Lutz C., Regnier C.H., Schreiber V., Basset P.,
RA Rio M.-C.;
RT "Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by
RT the association of LIM and SH3 domains.";
RL FEBS Lett. 373:245-249(1995).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-104, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-146, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68; THR-104 AND SER-146,
RP AND MASS 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 [8]
RP INTERACTION WITH KBTBD10.
RX PubMed=19726686; DOI=10.1074/jbc.M109.023259;
RA Gray C.H., McGarry L.C., Spence H.J., Riboldi-Tunnicliffe A.,
RA Ozanne B.W.;
RT "Novel beta-propeller of the BTB-Kelch protein Krp1 provides a binding
RT site for Lasp-1 that is necessary for pseudopodial extension.";
RL J. Biol. Chem. 284:30498-30507(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68 AND THR-104, 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68; THR-104; SER-118 AND
RP SER-146, 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 [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: Plays an important role in the regulation of dynamic
CC actin-based, cytoskeletal activities. Agonist-dependent changes in
CC LASP1 phosphorylation may also serve to regulate actin-associated
CC ion transport activities, not only in the parietal cell but also
CC in certain other F-actin-rich secretory epithelial cell types (By
CC similarity).
CC -!- SUBUNIT: Interacts with F-actin (By similarity). Interacts with
CC ANKRD54 (By similarity). Interacts with KBTBD10.
CC -!- INTERACTION:
CC Q93052:LPP; NbExp=3; IntAct=EBI-742828, EBI-718388;
CC Q99750:MDFI; NbExp=3; IntAct=EBI-742828, EBI-724076;
CC Q9UDY2:TJP2; NbExp=9; IntAct=EBI-742828, EBI-1042602;
CC Q15645:TRIP13; NbExp=4; IntAct=EBI-742828, EBI-358993;
CC Q15942:ZYX; NbExp=5; IntAct=EBI-742828, EBI-444225;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Note=Associated with the
CC F-actin rich cortical cytoskeleton (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14847-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14847-2; Sequence=VSP_016554;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 LIM zinc-binding domain.
CC -!- SIMILARITY: Contains 2 nebulin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/Lasp1ID203.html";
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; X82456; CAA57833.1; -; mRNA.
DR EMBL; BC007560; AAH07560.1; -; mRNA.
DR EMBL; BC012460; AAH12460.1; -; mRNA.
DR PIR; S68234; S68234.
DR RefSeq; NP_001258537.1; NM_001271608.1.
DR RefSeq; NP_006139.1; NM_006148.3.
DR UniGene; Hs.741156; -.
DR PDB; 3I35; X-ray; 1.40 A; A=202-261.
DR PDBsum; 3I35; -.
DR ProteinModelPortal; Q14847; -.
DR SMR; Q14847; 1-54, 205-261.
DR IntAct; Q14847; 14.
DR MINT; MINT-5001286; -.
DR STRING; 9606.ENSP00000325240; -.
DR PhosphoSite; Q14847; -.
DR DMDM; 3122342; -.
DR OGP; Q14847; -.
DR SWISS-2DPAGE; Q14847; -.
DR PaxDb; Q14847; -.
DR PRIDE; Q14847; -.
DR DNASU; 3927; -.
DR Ensembl; ENST00000318008; ENSP00000325240; ENSG00000002834.
DR Ensembl; ENST00000435347; ENSP00000392853; ENSG00000002834.
DR GeneID; 3927; -.
DR KEGG; hsa:3927; -.
DR UCSC; uc002hra.3; human.
DR CTD; 3927; -.
DR GeneCards; GC17P037026; -.
DR HGNC; HGNC:6513; LASP1.
DR HPA; CAB022049; -.
DR HPA; HPA012072; -.
DR MIM; 602920; gene.
DR neXtProt; NX_Q14847; -.
DR PharmGKB; PA30298; -.
DR eggNOG; NOG259964; -.
DR HOGENOM; HOG000006616; -.
DR HOVERGEN; HBG054636; -.
DR InParanoid; Q14847; -.
DR OMA; YWHKACF; -.
DR OrthoDB; EOG771280; -.
DR ChiTaRS; LASP1; human.
DR EvolutionaryTrace; Q14847; -.
DR GeneWiki; LASP1; -.
DR GenomeRNAi; 3927; -.
DR NextBio; 15423; -.
DR PRO; PR:Q14847; -.
DR ArrayExpress; Q14847; -.
DR Bgee; Q14847; -.
DR CleanEx; HS_LASP1; -.
DR Genevestigator; Q14847; -.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0015075; F:ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 2.10.110.10; -; 1.
DR InterPro; IPR000900; Nebulin_repeat.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 1.
DR Pfam; PF00880; Nebulin; 2.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00132; LIM; 1.
DR SMART; SM00227; NEBU; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 1.
DR PROSITE; PS50023; LIM_DOMAIN_2; 1.
DR PROSITE; PS51216; NEBULIN; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Ion transport; LIM domain; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Transport; Zinc.
FT CHAIN 1 261 LIM and SH3 domain protein 1.
FT /FTId=PRO_0000075761.
FT DOMAIN 5 56 LIM zinc-binding.
FT REPEAT 61 95 Nebulin 1.
FT REPEAT 97 131 Nebulin 2.
FT DOMAIN 202 261 SH3.
FT COMPBIAS 201 204 Poly-Gly.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 42 42 N6-acetyllysine.
FT MOD_RES 68 68 Phosphothreonine.
FT MOD_RES 104 104 Phosphothreonine.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 146 146 Phosphoserine.
FT VAR_SEQ 201 261 GGGGKRYRAVYDYSAADEDEVSFQDGDTIVNVQQIDDGWMY
FT GTVERTGDTGMLPANYVEAI -> ICLQHIPRHRIRPGRDP
FT SILQCLCFLKPATACDSYPSSSFFCQLKPSSATSAGSLLWQ
FT ASPLIDFLVFSLDGTGMGLSGGGRGPWGRAGMGDLLACGPH
FT LPLCSLPSHPPAQLLTYPHIPGLG (in isoform 2).
FT /FTId=VSP_016554.
FT CONFLICT 79 79 E -> R (in Ref. 2; AAH12460).
FT CONFLICT 210 210 V -> A (in Ref. 2; AAH12460).
FT CONFLICT 220 220 E -> A (in Ref. 2; AAH12460).
FT STRAND 207 211
FT STRAND 228 236
FT STRAND 239 244
FT TURN 245 248
FT STRAND 249 254
FT HELIX 255 257
FT STRAND 258 260
SQ SEQUENCE 261 AA; 29717 MW; 3B89B988605B3639 CRC64;
MNPNCARCGK IVYPTEKVNC LDKFWHKACF HCETCKMTLN MKNYKGYEKK PYCNAHYPKQ
SFTMVADTPE NLRLKQQSEL QSQVRYKEEF EKNKGKGFSV VADTPELQRI KKTQDQISNI
KYHEEFEKSR MGPSGGEGME PERRDSQDGS SYRRPLEQQQ PHHIPTSAPV YQQPQQQPVA
QSYGGYKEPA APVSIQRSAP GGGGKRYRAV YDYSAADEDE VSFQDGDTIV NVQQIDDGWM
YGTVERTGDT GMLPANYVEA I
//
ID LASP1_HUMAN Reviewed; 261 AA.
AC Q14847; Q96ED2; Q96IG0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 2.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=LIM and SH3 domain protein 1;
DE Short=LASP-1;
DE AltName: Full=Metastatic lymph node gene 50 protein;
DE Short=MLN 50;
GN Name=LASP1; Synonyms=MLN50;
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).
RC TISSUE=Mammary carcinoma;
RX PubMed=7490069; DOI=10.1006/geno.1995.1163;
RA Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G.,
RA Chenard M.-P., Lidereau R., Basset P., Rio M.-C.;
RT "Identification of four novel human genes amplified and overexpressed
RT in breast carcinoma and localized to the q11-q21.3 region of
RT chromosome 17.";
RL Genomics 28:367-376(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver, and Skin;
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 [3]
RP PROTEIN SEQUENCE OF 1-7, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [4]
RP DOMAINS.
RX PubMed=7589475; DOI=10.1016/0014-5793(95)01040-L;
RA Tomasetto C., Moog-Lutz C., Regnier C.H., Schreiber V., Basset P.,
RA Rio M.-C.;
RT "Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by
RT the association of LIM and SH3 domains.";
RL FEBS Lett. 373:245-249(1995).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-104, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-146, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68; THR-104 AND SER-146,
RP AND MASS 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 [8]
RP INTERACTION WITH KBTBD10.
RX PubMed=19726686; DOI=10.1074/jbc.M109.023259;
RA Gray C.H., McGarry L.C., Spence H.J., Riboldi-Tunnicliffe A.,
RA Ozanne B.W.;
RT "Novel beta-propeller of the BTB-Kelch protein Krp1 provides a binding
RT site for Lasp-1 that is necessary for pseudopodial extension.";
RL J. Biol. Chem. 284:30498-30507(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68 AND THR-104, 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-68; THR-104; SER-118 AND
RP SER-146, 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 [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: Plays an important role in the regulation of dynamic
CC actin-based, cytoskeletal activities. Agonist-dependent changes in
CC LASP1 phosphorylation may also serve to regulate actin-associated
CC ion transport activities, not only in the parietal cell but also
CC in certain other F-actin-rich secretory epithelial cell types (By
CC similarity).
CC -!- SUBUNIT: Interacts with F-actin (By similarity). Interacts with
CC ANKRD54 (By similarity). Interacts with KBTBD10.
CC -!- INTERACTION:
CC Q93052:LPP; NbExp=3; IntAct=EBI-742828, EBI-718388;
CC Q99750:MDFI; NbExp=3; IntAct=EBI-742828, EBI-724076;
CC Q9UDY2:TJP2; NbExp=9; IntAct=EBI-742828, EBI-1042602;
CC Q15645:TRIP13; NbExp=4; IntAct=EBI-742828, EBI-358993;
CC Q15942:ZYX; NbExp=5; IntAct=EBI-742828, EBI-444225;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Note=Associated with the
CC F-actin rich cortical cytoskeleton (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14847-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14847-2; Sequence=VSP_016554;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 LIM zinc-binding domain.
CC -!- SIMILARITY: Contains 2 nebulin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/Lasp1ID203.html";
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; X82456; CAA57833.1; -; mRNA.
DR EMBL; BC007560; AAH07560.1; -; mRNA.
DR EMBL; BC012460; AAH12460.1; -; mRNA.
DR PIR; S68234; S68234.
DR RefSeq; NP_001258537.1; NM_001271608.1.
DR RefSeq; NP_006139.1; NM_006148.3.
DR UniGene; Hs.741156; -.
DR PDB; 3I35; X-ray; 1.40 A; A=202-261.
DR PDBsum; 3I35; -.
DR ProteinModelPortal; Q14847; -.
DR SMR; Q14847; 1-54, 205-261.
DR IntAct; Q14847; 14.
DR MINT; MINT-5001286; -.
DR STRING; 9606.ENSP00000325240; -.
DR PhosphoSite; Q14847; -.
DR DMDM; 3122342; -.
DR OGP; Q14847; -.
DR SWISS-2DPAGE; Q14847; -.
DR PaxDb; Q14847; -.
DR PRIDE; Q14847; -.
DR DNASU; 3927; -.
DR Ensembl; ENST00000318008; ENSP00000325240; ENSG00000002834.
DR Ensembl; ENST00000435347; ENSP00000392853; ENSG00000002834.
DR GeneID; 3927; -.
DR KEGG; hsa:3927; -.
DR UCSC; uc002hra.3; human.
DR CTD; 3927; -.
DR GeneCards; GC17P037026; -.
DR HGNC; HGNC:6513; LASP1.
DR HPA; CAB022049; -.
DR HPA; HPA012072; -.
DR MIM; 602920; gene.
DR neXtProt; NX_Q14847; -.
DR PharmGKB; PA30298; -.
DR eggNOG; NOG259964; -.
DR HOGENOM; HOG000006616; -.
DR HOVERGEN; HBG054636; -.
DR InParanoid; Q14847; -.
DR OMA; YWHKACF; -.
DR OrthoDB; EOG771280; -.
DR ChiTaRS; LASP1; human.
DR EvolutionaryTrace; Q14847; -.
DR GeneWiki; LASP1; -.
DR GenomeRNAi; 3927; -.
DR NextBio; 15423; -.
DR PRO; PR:Q14847; -.
DR ArrayExpress; Q14847; -.
DR Bgee; Q14847; -.
DR CleanEx; HS_LASP1; -.
DR Genevestigator; Q14847; -.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR GO; GO:0015075; F:ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 2.10.110.10; -; 1.
DR InterPro; IPR000900; Nebulin_repeat.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 1.
DR Pfam; PF00880; Nebulin; 2.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00132; LIM; 1.
DR SMART; SM00227; NEBU; 2.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 1.
DR PROSITE; PS50023; LIM_DOMAIN_2; 1.
DR PROSITE; PS51216; NEBULIN; 2.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Ion transport; LIM domain; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Transport; Zinc.
FT CHAIN 1 261 LIM and SH3 domain protein 1.
FT /FTId=PRO_0000075761.
FT DOMAIN 5 56 LIM zinc-binding.
FT REPEAT 61 95 Nebulin 1.
FT REPEAT 97 131 Nebulin 2.
FT DOMAIN 202 261 SH3.
FT COMPBIAS 201 204 Poly-Gly.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 42 42 N6-acetyllysine.
FT MOD_RES 68 68 Phosphothreonine.
FT MOD_RES 104 104 Phosphothreonine.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 146 146 Phosphoserine.
FT VAR_SEQ 201 261 GGGGKRYRAVYDYSAADEDEVSFQDGDTIVNVQQIDDGWMY
FT GTVERTGDTGMLPANYVEAI -> ICLQHIPRHRIRPGRDP
FT SILQCLCFLKPATACDSYPSSSFFCQLKPSSATSAGSLLWQ
FT ASPLIDFLVFSLDGTGMGLSGGGRGPWGRAGMGDLLACGPH
FT LPLCSLPSHPPAQLLTYPHIPGLG (in isoform 2).
FT /FTId=VSP_016554.
FT CONFLICT 79 79 E -> R (in Ref. 2; AAH12460).
FT CONFLICT 210 210 V -> A (in Ref. 2; AAH12460).
FT CONFLICT 220 220 E -> A (in Ref. 2; AAH12460).
FT STRAND 207 211
FT STRAND 228 236
FT STRAND 239 244
FT TURN 245 248
FT STRAND 249 254
FT HELIX 255 257
FT STRAND 258 260
SQ SEQUENCE 261 AA; 29717 MW; 3B89B988605B3639 CRC64;
MNPNCARCGK IVYPTEKVNC LDKFWHKACF HCETCKMTLN MKNYKGYEKK PYCNAHYPKQ
SFTMVADTPE NLRLKQQSEL QSQVRYKEEF EKNKGKGFSV VADTPELQRI KKTQDQISNI
KYHEEFEKSR MGPSGGEGME PERRDSQDGS SYRRPLEQQQ PHHIPTSAPV YQQPQQQPVA
QSYGGYKEPA APVSIQRSAP GGGGKRYRAV YDYSAADEDE VSFQDGDTIV NVQQIDDGWM
YGTVERTGDT GMLPANYVEA I
//
MIM
602920
*RECORD*
*FIELD* NO
602920
*FIELD* TI
*602920 LIM AND SH3 PROTEIN 1; LASP1
;;MLN50
LASP1/MLL FUSION GENE, INCLUDED
*FIELD* TX
read more
CLONING
By differential screening of cDNAs from breast cancer-derived metastatic
axillary lymph nodes, Tomasetto et al. (1995) identified TRAF4 (602464)
and 3 other novel genes that are overexpressed in breast cancer. They
designated one of these genes, which mapped to chromosome 17q, MLN50. In
breast cancer cell lines, overexpression of the 4-kb MLN50 mRNA was
correlated with amplification of the gene and with amplification and
overexpression of ERBB2 (164870), which maps to the same region. The
authors suggested that the 2 genes belong to the same amplicon.
Amplification of chromosomal region 17q11-q21 is one of the most common
events occurring in human breast cancers (Tomasetto et al., 1995).
Tomasetto et al. (1995) reported that the predicted 261-amino acid MLN50
protein contains an N-terminal LIM domain and a C-terminal SH3 domain.
They renamed the protein LASP1, for 'LIM and SH3 protein.' Northern blot
analysis revealed that LASP1 mRNA was expressed at a basal level in all
normal tissues examined and overexpressed in 8% of primary breast
cancers. In most of these cancers, LASP1 and ERBB2 were simultaneously
overexpressed.
Schreiber et al. (1998) isolated cDNAs encoding mouse Lasp1. They
determined that both human and mouse LASP1 contain an actin-binding
domain.
MAPPING
Tomasetto et al. (1995) mapped the LASP1 gene to chromosome 17q11-q21.3
by radioactive in situ hybridization.
Using in situ hybridization, Schreiber et al. (1998) mapped the mouse
Lasp1 gene to the 11C-11D region of chromosome 11.
GENE FUNCTION
By yeast 2-hybrid, truncation, and pull-down analyses, Li et al. (2004)
found that an N-terminal motif of zyxin (ZYX; 602002) interacted with
the C-terminal SH3 domains of LIM-nebulette (605491), nebulin (NEB;
161650), and LASP1, but not with the SH3 domains of other proteins
examined. Zyxin, LIM-nebulette, and LASP1 colocalized at focal adhesions
in transfected HeLa and HT1080 cells.
Traenka et al. (2010) stated that LASP1 is frequently overexpressed in
metastatic human breast cancer and ovarian cancer. Using expression
profiling, quantitative real-time PCR, and immunohistochemical analysis,
they found that LASP1 mRNA and protein were overexpressed in
medulloblastomas and that LASP1 overexpression correlated with
chromosome 17q gain, metastatic dissemination, and unfavorable outcome.
LASP1 protein expression was strong in 2 of 5 recurrent medulloblastomas
in which no LASP1 expression was detected in patient-matched primary
tumors. In 2 adherent medulloblastoma cell lines, LASP1 expression was
associated with focal adhesion contacts, with intense colocalization
with filamentous actin. In an adherent/suspension medulloblastoma cell
line with isochromosome 17q and abnormal neurofilament expression, LASP1
localization with filamentous actin was less definite but present at the
leading edges of cells. Knockdown of LASP1 expression in all 3
medulloblastoma cell lines reduced cell proliferation and migratory
potential and enhanced cell adhesion. Differential display analysis
showed that knockdown of LASP1 resulted in upregulation of genes
involved in cell adhesion and downregulation of genes involved in
invasion and migration.
CYTOGENETICS
- LASP1/MLL Fusion Gene
The MLL gene (159555), located on chromosome 11q23, is frequently
rearranged in acute leukemia. Strehl et al. (2003) identified a new MLL
fusion partner on chromosome 17q in the case of an infant with AML-M4
(see 601626) and a t(11;17)(q23;q21) translocation. FISH and RT-PCR
analyses indicated a rearrangement of the MLL gene, but no fusion with
previously identified MLL fusion partners at 17q, such as AF17 (600328)
or MSF (604061). RACE revealed an in-frame fusion of MLL to LASP1. The
authors stated that retroviral transduction of myeloid progenitors
demonstrated that LASP1/MLL was the fourth known fusion of MLL with a
cytoplasmic protein that has no in vitro transformation capability, the
others being GRAF (605370), FBP17 (606193), and ABI1 (603050).
*FIELD* RF
1. Li, B.; Zhuang, L.; Trueb, B.: Zyxin interacts with the SH3 domains
of the cytoskeletal proteins LIM-nebulette and Lasp-1. J. Biol. Chem. 279:
20401-20410, 2004.
2. Schreiber, V.; Masson, R.; Linares, J. L.; Mattei, M. G.; Tomasetto,
C.; Rio, M. C.: Chromosomal assignment and expression pattern of
the murine Lasp-1 gene. Gene 207: 171-175, 1998.
3. Strehl, S.; Borkhardt, A.; Slany, R.; Fuchs, U. E.; Konig, M.;
Haas, O. A.: The human LASP1 gene is fused to MLL in an acute myeloid
leukemia with t(11;17)(q23;q21). Oncogene 22: 157-160, 2003.
4. Tomasetto, C.; Moog-Lutz, C.; Regnier, C. H.; Schreiber, V.; Basset,
P.; Rio, M.-C.: Lasp-1 (MLN 50) defines a new LIM protein subfamily
characterized by the association of LIM and SH3 domains. FEBS Lett. 373:
245-249, 1995.
5. Tomasetto, C.; Regnier, C.; Moog-Lutz, C.; Mattei, M. G.; Chenard,
M. P.; Lidereau, R.; Basset, P.; Rio, M. C.: Identification of four
novel human genes amplified and overexpressed in breast carcinoma
and localized to the q11-q21.3 region of chromosome 17. Genomics 28:
367-376, 1995.
6. Traenka, C.; Remke, M.; Korshunov, A.; Bender, S.; Hielscher, T.;
Northcott, P. A.; Witt, H.; Ryzhova, M.; Felsberg, J.; Benner, A.;
Riester, S.; Scheurlen, W.; Grunewald, T. G. P.; von Deimling, A.;
Kulozik, A. E.; Reifenberger, G.; Taylor, M. D.; Lichter, P.; Butt,
E.; Pfister, S. M.: Role of LIM and SH3 protein 1 (LASP1) in the
metastatic dissemination of medulloblastoma. Cancer Res. 70: 8003-8014,
2010.
*FIELD* CN
Patricia A. Hartz - updated: 10/08/2012
Patricia A. Hartz - updated: 9/26/2012
Victor A. McKusick - updated: 3/25/2003
*FIELD* CD
Rebekah S. Rasooly: 8/3/1998
*FIELD* ED
mgross: 10/08/2012
mgross: 9/28/2012
terry: 9/26/2012
carol: 6/13/2012
tkritzer: 3/27/2003
tkritzer: 3/26/2003
terry: 3/25/2003
alopez: 8/3/1998
*RECORD*
*FIELD* NO
602920
*FIELD* TI
*602920 LIM AND SH3 PROTEIN 1; LASP1
;;MLN50
LASP1/MLL FUSION GENE, INCLUDED
*FIELD* TX
read more
CLONING
By differential screening of cDNAs from breast cancer-derived metastatic
axillary lymph nodes, Tomasetto et al. (1995) identified TRAF4 (602464)
and 3 other novel genes that are overexpressed in breast cancer. They
designated one of these genes, which mapped to chromosome 17q, MLN50. In
breast cancer cell lines, overexpression of the 4-kb MLN50 mRNA was
correlated with amplification of the gene and with amplification and
overexpression of ERBB2 (164870), which maps to the same region. The
authors suggested that the 2 genes belong to the same amplicon.
Amplification of chromosomal region 17q11-q21 is one of the most common
events occurring in human breast cancers (Tomasetto et al., 1995).
Tomasetto et al. (1995) reported that the predicted 261-amino acid MLN50
protein contains an N-terminal LIM domain and a C-terminal SH3 domain.
They renamed the protein LASP1, for 'LIM and SH3 protein.' Northern blot
analysis revealed that LASP1 mRNA was expressed at a basal level in all
normal tissues examined and overexpressed in 8% of primary breast
cancers. In most of these cancers, LASP1 and ERBB2 were simultaneously
overexpressed.
Schreiber et al. (1998) isolated cDNAs encoding mouse Lasp1. They
determined that both human and mouse LASP1 contain an actin-binding
domain.
MAPPING
Tomasetto et al. (1995) mapped the LASP1 gene to chromosome 17q11-q21.3
by radioactive in situ hybridization.
Using in situ hybridization, Schreiber et al. (1998) mapped the mouse
Lasp1 gene to the 11C-11D region of chromosome 11.
GENE FUNCTION
By yeast 2-hybrid, truncation, and pull-down analyses, Li et al. (2004)
found that an N-terminal motif of zyxin (ZYX; 602002) interacted with
the C-terminal SH3 domains of LIM-nebulette (605491), nebulin (NEB;
161650), and LASP1, but not with the SH3 domains of other proteins
examined. Zyxin, LIM-nebulette, and LASP1 colocalized at focal adhesions
in transfected HeLa and HT1080 cells.
Traenka et al. (2010) stated that LASP1 is frequently overexpressed in
metastatic human breast cancer and ovarian cancer. Using expression
profiling, quantitative real-time PCR, and immunohistochemical analysis,
they found that LASP1 mRNA and protein were overexpressed in
medulloblastomas and that LASP1 overexpression correlated with
chromosome 17q gain, metastatic dissemination, and unfavorable outcome.
LASP1 protein expression was strong in 2 of 5 recurrent medulloblastomas
in which no LASP1 expression was detected in patient-matched primary
tumors. In 2 adherent medulloblastoma cell lines, LASP1 expression was
associated with focal adhesion contacts, with intense colocalization
with filamentous actin. In an adherent/suspension medulloblastoma cell
line with isochromosome 17q and abnormal neurofilament expression, LASP1
localization with filamentous actin was less definite but present at the
leading edges of cells. Knockdown of LASP1 expression in all 3
medulloblastoma cell lines reduced cell proliferation and migratory
potential and enhanced cell adhesion. Differential display analysis
showed that knockdown of LASP1 resulted in upregulation of genes
involved in cell adhesion and downregulation of genes involved in
invasion and migration.
CYTOGENETICS
- LASP1/MLL Fusion Gene
The MLL gene (159555), located on chromosome 11q23, is frequently
rearranged in acute leukemia. Strehl et al. (2003) identified a new MLL
fusion partner on chromosome 17q in the case of an infant with AML-M4
(see 601626) and a t(11;17)(q23;q21) translocation. FISH and RT-PCR
analyses indicated a rearrangement of the MLL gene, but no fusion with
previously identified MLL fusion partners at 17q, such as AF17 (600328)
or MSF (604061). RACE revealed an in-frame fusion of MLL to LASP1. The
authors stated that retroviral transduction of myeloid progenitors
demonstrated that LASP1/MLL was the fourth known fusion of MLL with a
cytoplasmic protein that has no in vitro transformation capability, the
others being GRAF (605370), FBP17 (606193), and ABI1 (603050).
*FIELD* RF
1. Li, B.; Zhuang, L.; Trueb, B.: Zyxin interacts with the SH3 domains
of the cytoskeletal proteins LIM-nebulette and Lasp-1. J. Biol. Chem. 279:
20401-20410, 2004.
2. Schreiber, V.; Masson, R.; Linares, J. L.; Mattei, M. G.; Tomasetto,
C.; Rio, M. C.: Chromosomal assignment and expression pattern of
the murine Lasp-1 gene. Gene 207: 171-175, 1998.
3. Strehl, S.; Borkhardt, A.; Slany, R.; Fuchs, U. E.; Konig, M.;
Haas, O. A.: The human LASP1 gene is fused to MLL in an acute myeloid
leukemia with t(11;17)(q23;q21). Oncogene 22: 157-160, 2003.
4. Tomasetto, C.; Moog-Lutz, C.; Regnier, C. H.; Schreiber, V.; Basset,
P.; Rio, M.-C.: Lasp-1 (MLN 50) defines a new LIM protein subfamily
characterized by the association of LIM and SH3 domains. FEBS Lett. 373:
245-249, 1995.
5. Tomasetto, C.; Regnier, C.; Moog-Lutz, C.; Mattei, M. G.; Chenard,
M. P.; Lidereau, R.; Basset, P.; Rio, M. C.: Identification of four
novel human genes amplified and overexpressed in breast carcinoma
and localized to the q11-q21.3 region of chromosome 17. Genomics 28:
367-376, 1995.
6. Traenka, C.; Remke, M.; Korshunov, A.; Bender, S.; Hielscher, T.;
Northcott, P. A.; Witt, H.; Ryzhova, M.; Felsberg, J.; Benner, A.;
Riester, S.; Scheurlen, W.; Grunewald, T. G. P.; von Deimling, A.;
Kulozik, A. E.; Reifenberger, G.; Taylor, M. D.; Lichter, P.; Butt,
E.; Pfister, S. M.: Role of LIM and SH3 protein 1 (LASP1) in the
metastatic dissemination of medulloblastoma. Cancer Res. 70: 8003-8014,
2010.
*FIELD* CN
Patricia A. Hartz - updated: 10/08/2012
Patricia A. Hartz - updated: 9/26/2012
Victor A. McKusick - updated: 3/25/2003
*FIELD* CD
Rebekah S. Rasooly: 8/3/1998
*FIELD* ED
mgross: 10/08/2012
mgross: 9/28/2012
terry: 9/26/2012
carol: 6/13/2012
tkritzer: 3/27/2003
tkritzer: 3/26/2003
terry: 3/25/2003
alopez: 8/3/1998