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   24-JAN-2024, entry version 185.
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   SwissPalm; O54785; -.
DR   EPD; O54785; -.
DR   PaxDb; 10090-ENSMUSP00000099162; -.
DR   PeptideAtlas; O54785; -.
DR   ProteomicsDB; 286201; -. [O54785-1]
DR   ProteomicsDB; 286202; -. [O54785-2]
DR   ProteomicsDB; 286203; -. [O54785-3]
DR   Pumba; O54785; -.
DR   Antibodypedia; 2106; 682 antibodies from 38 providers.
DR   DNASU; 16886; -.
DR   Ensembl; ENSMUST00000101638.4; ENSMUSP00000099162.4; ENSMUSG00000020451.18. [O54785-1]
DR   Ensembl; ENSMUST00000101642.10; ENSMUSP00000099165.4; ENSMUSG00000020451.18. [O54785-2]
DR   Ensembl; ENSMUST00000110029.9; ENSMUSP00000105656.3; ENSMUSG00000020451.18. [O54785-3]
DR   GeneID; 16886; -.
DR   KEGG; mmu:16886; -.
DR   UCSC; uc007hss.1; mouse. [O54785-1]
DR   UCSC; uc007hst.1; mouse. [O54785-2]
DR   AGR; MGI:1197517; -.
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; RMHISSN; -.
DR   OrthoDB; 5474815at2759; -.
DR   PhylomeDB; O54785; -.
DR   TreeFam; TF318014; -.
DR   BioGRID-ORCS; 16886; 4 hits in 79 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 261 other cell types or tissues.
DR   ExpressionAtlas; O54785; baseline and differential.
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; ISS:UniProtKB.
DR   GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR   CDD; cd09465; LIM2_LIMK2; 1.
DR   CDD; cd00992; PDZ_signaling; 1.
DR   CDD; cd14222; STKc_LIMK2; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 2.10.110.10; Cysteine Rich Protein; 2.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR46485; LIM DOMAIN KINASE 1; 1.
DR   PANTHER; PTHR46485:SF1; LIM DOMAIN KINASE 2; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 2.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; O54785; MM.
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
//