LIMK2_MOUSE
ID LIMK2_MOUSE Reviewed; 638 AA.
AC O54785; O54776; O55238; Q9QUL4;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=LIM domain kinase 2;
DE Short=LIMK-2;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P53671};
GN Name=Limk2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (LIMK2A).
RC STRAIN=ICR; TISSUE=Embryo;
RX PubMed=9425257; DOI=10.1006/bbrc.1997.7795;
RA Koshimizu U., Takahashi H., Yoshida M.C., Nakamura T.;
RT "cDNA cloning, genomic organization, and chromosomal localization of the
RT mouse LIM motif-containing kinase gene, Limk2.";
RL Biochem. Biophys. Res. Commun. 241:243-250(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (LIMK2A AND LIMK2B).
RC STRAIN=129/Sv; TISSUE=Kidney;
RX PubMed=9441759; DOI=10.1006/geno.1997.5060;
RA Ikebe C., Ohashi K., Fujimori T., Bernard O., Noda T., Robertson E.J.,
RA Mizuno K.;
RT "Mouse LIM-kinase 2 gene: cDNA cloning, genomic organization, and tissue-
RT specific expression of two alternatively initiated transcripts.";
RL Genomics 46:504-508(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9705845; DOI=10.1006/bbrc.1998.9094;
RA Takahashi H., Koshimizu U., Nakamura T.;
RT "A novel transcript encoding truncated LIM kinase 2 is specifically
RT expressed in male germ cells undergoing meiosis.";
RL Biochem. Biophys. Res. Commun. 249:138-145(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=9610354; DOI=10.1006/bbrc.1998.8609;
RA Ikebe C., Ohashi K., Mizuno K.;
RT "Identification of testis-specific (LimK2t) and brain-specific (LimK2c)
RT isoforms of mouse LIM-kinase 2 gene transcripts.";
RL Biochem. Biophys. Res. Commun. 246:307-312(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (LIMK2A).
RC TISSUE=Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH NISCH.
RX PubMed=18332102; DOI=10.1128/mcb.01832-07;
RA Ding Y., Milosavljevic T., Alahari S.K.;
RT "Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell
RT invasion.";
RL Mol. Cell. Biol. 28:3742-3756(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP STRUCTURE BY NMR OF 139-246.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain from mouse LIM domain kinase.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: Serine/threonine-protein kinase that plays an essential role
CC in the regulation of actin filament dynamics. Acts downstream of
CC several Rho family GTPase signal transduction pathways. Involved in
CC astral microtubule organization and mitotic spindle orientation during
CC early stages of mitosis by mediating phosphorylation of TPPP. Displays
CC serine/threonine-specific phosphorylation of myelin basic protein and
CC histone (MBP) in vitro. Suppresses ciliogenesis via multiple pathways;
CC phosphorylation of CFL1, suppression of directional trafficking of
CC ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear
CC localization where it acts as a transcriptional corepressor of the
CC TEAD4 target genes AURKA and PLK1 (By similarity).
CC {ECO:0000250|UniProtKB:P53671}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P53671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P53671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P53671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P53671};
CC -!- SUBUNIT: Binds ROCK1 and MARF1 (By similarity). Interacts with NISCH
CC (PubMed:18332102). {ECO:0000250|UniProtKB:P53671,
CC ECO:0000269|PubMed:18332102}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:P53671}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P53671}.
CC -!- SUBCELLULAR LOCATION: [Isoform LIMK2a]: Cytoplasm
CC {ECO:0000250|UniProtKB:P53671}. Nucleus {ECO:0000250|UniProtKB:P53671}.
CC -!- SUBCELLULAR LOCATION: [Isoform LIMK2b]: Cytoplasm
CC {ECO:0000250|UniProtKB:P53671}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P53671}. Nucleus {ECO:0000250|UniProtKB:P53671}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=LIMK2a;
CC IsoId=O54785-1; Sequence=Displayed;
CC Name=LIMK2b;
CC IsoId=O54785-2; Sequence=VSP_010350;
CC Name=3; Synonyms=LIMK2t, tLIMK2;
CC IsoId=O54785-3; Sequence=VSP_010351;
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Specifically expressed in the testes.
CC {ECO:0000269|PubMed:9705845}.
CC -!- PTM: Phosphorylated on serine and/or threonine residues by ROCK1.
CC {ECO:0000250|UniProtKB:P53671}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AB008117; BAA29035.1; -; mRNA.
DR EMBL; AB005140; BAA24491.1; -; Genomic_DNA.
DR EMBL; AB005131; BAA24488.1; -; mRNA.
DR EMBL; AB005132; BAA24489.1; -; mRNA.
DR EMBL; AB005134; BAA24490.1; -; Genomic_DNA.
DR EMBL; U88618; AAC39947.1; -; mRNA.
DR EMBL; AB012291; BAA32437.1; -; mRNA.
DR EMBL; AB012092; BAA31147.1; -; mRNA.
DR EMBL; BC007129; AAH07129.1; -; mRNA.
DR CCDS; CCDS24358.1; -. [O54785-1]
DR CCDS; CCDS24359.1; -. [O54785-2]
DR CCDS; CCDS24360.1; -. [O54785-3]
DR PIR; JC5813; JC5813.
DR PIR; JC5814; JC5814.
DR PIR; JE0240; JE0240.
DR RefSeq; NP_001029202.1; NM_001034030.2. [O54785-3]
DR RefSeq; NP_034848.1; NM_010718.4. [O54785-1]
DR RefSeq; NP_774958.1; NM_173053.1. [O54785-2]
DR PDB; 2YUB; NMR; -; A=142-246.
DR PDBsum; 2YUB; -.
DR AlphaFoldDB; O54785; -.
DR BMRB; O54785; -.
DR SMR; O54785; -.
DR BioGRID; 201167; 2.
DR STRING; 10090.ENSMUSP00000099162; -.
DR iPTMnet; O54785; -.
DR PhosphoSitePlus; O54785; -.
DR EPD; O54785; -.
DR PaxDb; O54785; -.
DR PeptideAtlas; O54785; -.
DR PRIDE; O54785; -.
DR ProteomicsDB; 286201; -. [O54785-1]
DR ProteomicsDB; 286202; -. [O54785-2]
DR ProteomicsDB; 286203; -. [O54785-3]
DR Antibodypedia; 2106; 584 antibodies from 38 providers.
DR DNASU; 16886; -.
DR Ensembl; ENSMUST00000101638; ENSMUSP00000099162; ENSMUSG00000020451. [O54785-1]
DR Ensembl; ENSMUST00000101642; ENSMUSP00000099165; ENSMUSG00000020451. [O54785-2]
DR Ensembl; ENSMUST00000110029; ENSMUSP00000105656; ENSMUSG00000020451. [O54785-3]
DR GeneID; 16886; -.
DR KEGG; mmu:16886; -.
DR UCSC; uc007hss.1; mouse. [O54785-1]
DR UCSC; uc007hst.1; mouse. [O54785-2]
DR CTD; 3985; -.
DR MGI; MGI:1197517; Limk2.
DR VEuPathDB; HostDB:ENSMUSG00000020451; -.
DR eggNOG; KOG1187; Eukaryota.
DR GeneTree; ENSGT00940000159133; -.
DR HOGENOM; CLU_000288_7_23_1; -.
DR InParanoid; O54785; -.
DR OMA; NAGHSPT; -.
DR OrthoDB; 988822at2759; -.
DR PhylomeDB; O54785; -.
DR TreeFam; TF318014; -.
DR BioGRID-ORCS; 16886; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Limk2; mouse.
DR EvolutionaryTrace; O54785; -.
DR PRO; PR:O54785; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O54785; protein.
DR Bgee; ENSMUSG00000020451; Expressed in lip and 259 other tissues.
DR ExpressionAtlas; O54785; baseline and differential.
DR Genevisible; O54785; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005801; C:cis-Golgi network; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IMP:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0030953; P:astral microtubule organization; ISS:UniProtKB.
DR GO; GO:0061303; P:cornea development in camera-type eye; IMP:MGI.
DR GO; GO:0051650; P:establishment of vesicle localization; ISS:UniProtKB.
DR GO; GO:0060322; P:head development; IMP:MGI.
DR GO; GO:1902018; P:negative regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 2.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00132; LIM; 2.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Cytoskeleton;
KW Kinase; LIM domain; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc.
FT CHAIN 1..638
FT /note="LIM domain kinase 2"
FT /id="PRO_0000075810"
FT DOMAIN 12..63
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 72..124
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 152..239
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 331..608
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 255..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 451
FT /evidence="ECO:0000250|UniProtKB:P53671"
FT BINDING 337..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 360
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 210
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53671"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53671"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53671"
FT MOD_RES 505
FT /note="Phosphothreonine; by ROCK1 and CDC42BP"
FT /evidence="ECO:0000250|UniProtKB:P53671"
FT VAR_SEQ 1..187
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9610354,
FT ECO:0000303|PubMed:9705845"
FT /id="VSP_010351"
FT VAR_SEQ 1..37
FT /note="MAALAGDEAWRCRGCGTYVPLSQRLYRTANEAWHGSC -> MGSYLSVPAYF
FT TSRDP (in isoform LIMK2b)"
FT /evidence="ECO:0000303|PubMed:9441759"
FT /id="VSP_010350"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:2YUB"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:2YUB"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:2YUB"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:2YUB"
FT HELIX 217..225
FT /evidence="ECO:0007829|PDB:2YUB"
FT STRAND 231..237
FT /evidence="ECO:0007829|PDB:2YUB"
SQ SEQUENCE 638 AA; 72202 MW; 54CFA5E7A6A79C39 CRC64;
MAALAGDEAW RCRGCGTYVP LSQRLYRTAN EAWHGSCFRC SECQESLTNW YYEKDGKLYC
HKDYWAKFGE FCHGCSLLMT GPAMVAGEFK YHPECFACMS CKVIIEDGDA YALVQHATLY
CGKCHNEVVL APMFERLSTE SVQDQLPYSV TLISMPATTE CRRGFSVTVE SASSNYATTV
QVKEVNRMHI SPNNRNAIHP GDRILEINGT PVRTLRVEEV EDAIKQTSQT LQLLIEHDPV
PQRLDQLRLD ARLPPHMQST GHTLMLSTLD TKENQEGTLR RRSLRRSNSI SKSPGPSSPK
EPLLLSRDIS RSESLRCSSS YSQQIFRPCD LIHGEVLGKG FFGQAIKVTH KATGKVMVMK
ELIRCDEETQ KTFLTEVKVM RSLDHPNVLK FIGVLYKDKK LNLLTEYIEG GTLKDFLRSV
DPFPWQQKVR FAKGISSGMA YLHSMCIIHR DLNSHNCLIK LDKTVVVADF GLSRLIVEER
KRPPVEKATT KKRTLRKSDR KKRYTVVGNP YWMAPEMLNG KSYDETVDVF SFGIVLCEII
GQVYADPDCL PRTLDFGLNV KLFWEKFVPT DCPPAFFPLA AICCKLEPES RPAFSKLEDS
FEALSLFLGE LAIPLPAELE DLDHTVSMEY GLTRDSPP
