ID   FHL2_MOUSE              Reviewed;         279 AA.
AC   O70433; P97448;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   27-MAR-2024, entry version 175.
DE   RecName: Full=Four and a half LIM domains protein 2;
DE            Short=FHL-2;
DE   AltName: Full=Skeletal muscle LIM-protein 3;
DE            Short=SLIM-3;
GN   Name=Fhl2;
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].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Chan K.K., Tsui S.K.W., Lee C.Y., Fung K.P., Waye M.M.Y.;
RT   "The cloning, sequencing and characterization of a mouse FHL2, which
RT   contains four and a half LIM domains.";
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Skeletal muscle;
RX   PubMed=10049693; DOI=10.1006/bbrc.1999.0179;
RA   Morgan M.J., Madgwick A.J.A.;
RT   "The LIM proteins FHL1 and FHL3 are expressed differently in skeletal
RT   muscle.";
RL   Biochem. Biophys. Res. Commun. 255:245-250(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=10906474; DOI=10.1016/s0925-4773(00)00341-5;
RA   Chu P.-H., Ruiz-Lozano P., Zhou Q., Cai C., Chen J.;
RT   "Expression patterns of FHL/SLIM family members suggest important
RT   functional roles in skeletal muscle and cardiovascular system.";
RL   Mech. Dev. 95:259-265(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RA   Starzinski-Powitz A., Martin B., Eckerdt F.;
RT   "Isolation of the mouse homolog mDRAL from skeletal muscle derived
RT   myoblasts.";
RL   Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, and Testis;
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   [6]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH FOXK1.
RX   PubMed=20013826; DOI=10.1002/stem.274;
RA   Shi X., Bowlin K.M., Garry D.J.;
RT   "Fhl2 interacts with Foxk1 and corepresses Foxo4 activity in myogenic
RT   progenitors.";
RL   Stem Cells 28:462-469(2010).
RN   [7]
RP   FUNCTION, INDUCTION, INTERACTION WITH CALCINEURIN, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=22851699; DOI=10.1128/mcb.05948-11;
RA   Hojayev B., Rothermel B.A., Gillette T.G., Hill J.A.;
RT   "FHL2 binds calcineurin and represses pathological cardiac growth.";
RL   Mol. Cell. Biol. 32:4025-4034(2012).
CC   -!- FUNCTION: May function as a molecular transmitter linking various
CC       signaling pathways to transcriptional regulation. Negatively regulates
CC       the transcriptional repressor E4F1 and may function in cell growth.
CC       Inhibits the transcriptional activity of FOXO1 and its apoptotic
CC       function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1
CC       deacetylation (By similarity). Negatively regulates the
CC       calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:22851699).
CC       {ECO:0000250|UniProtKB:Q14192, ECO:0000269|PubMed:22851699}.
CC   -!- SUBUNIT: Interacts with ZNF638 and TTN/titin. Interacts with E4F1.
CC       Interacts with GRB7. Interacts with SIRT1 and FOXO1. Interacts with
CC       CEFIP (By similarity). Interacts with calcineurin (PubMed:22851699).
CC       Interacts with FOXK1 (PubMed:20013826). {ECO:0000250|UniProtKB:Q14192,
CC       ECO:0000269|PubMed:20013826, ECO:0000269|PubMed:22851699}.
CC   -!- INTERACTION:
CC       O70433; Q8CIH5: Plcg2; NbExp=3; IntAct=EBI-299379, EBI-617954;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14192}. Nucleus
CC       {ECO:0000269|PubMed:20013826}. Cytoplasm, myofibril, sarcomere, Z line
CC       {ECO:0000269|PubMed:22851699}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in heart but also detectable in
CC       brain and skeletal muscle. {ECO:0000269|PubMed:10906474}.
CC   -!- INDUCTION: Up-regulated in hearts exposed to isoproterenol (at protein
CC       level). {ECO:0000269|PubMed:22851699}.
CC   -!- DOMAIN: The third LIM zinc-binding mediates interaction with E4F1.
CC       {ECO:0000250|UniProtKB:Q14192}.
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DR   EMBL; AF055889; AAC12770.1; -; mRNA.
DR   EMBL; U77040; AAB19211.2; -; mRNA.
DR   EMBL; AF114381; AAD53230.1; -; mRNA.
DR   EMBL; AF153340; AAD34170.1; -; mRNA.
DR   CCDS; CCDS14922.1; -.
DR   RefSeq; NP_001276462.1; NM_001289533.1.
DR   RefSeq; NP_034342.1; NM_010212.4.
DR   RefSeq; XP_011236736.1; XM_011238434.2.
DR   AlphaFoldDB; O70433; -.
DR   SMR; O70433; -.
DR   BioGRID; 199669; 10.
DR   IntAct; O70433; 6.
DR   MINT; O70433; -.
DR   STRING; 10090.ENSMUSP00000008280; -.
DR   GlyGen; O70433; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O70433; -.
DR   PhosphoSitePlus; O70433; -.
DR   SwissPalm; O70433; -.
DR   EPD; O70433; -.
DR   jPOST; O70433; -.
DR   PaxDb; 10090-ENSMUSP00000008280; -.
DR   PeptideAtlas; O70433; -.
DR   ProteomicsDB; 270988; -.
DR   Pumba; O70433; -.
DR   Antibodypedia; 949; 408 antibodies from 38 providers.
DR   DNASU; 14200; -.
DR   Ensembl; ENSMUST00000008280.14; ENSMUSP00000008280.8; ENSMUSG00000008136.15.
DR   Ensembl; ENSMUST00000185893.2; ENSMUSP00000141170.2; ENSMUSG00000008136.15.
DR   GeneID; 14200; -.
DR   KEGG; mmu:14200; -.
DR   UCSC; uc007avk.2; mouse.
DR   AGR; MGI:1338762; -.
DR   CTD; 2274; -.
DR   MGI; MGI:1338762; Fhl2.
DR   VEuPathDB; HostDB:ENSMUSG00000008136; -.
DR   eggNOG; KOG1704; Eukaryota.
DR   GeneTree; ENSGT00950000183028; -.
DR   HOGENOM; CLU_001357_2_0_1; -.
DR   InParanoid; O70433; -.
DR   OMA; CAKCYED; -.
DR   OrthoDB; 370973at2759; -.
DR   PhylomeDB; O70433; -.
DR   TreeFam; TF321684; -.
DR   BioGRID-ORCS; 14200; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Fhl2; mouse.
DR   PRO; PR:O70433; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; O70433; Protein.
DR   Bgee; ENSMUSG00000008136; Expressed in heart right ventricle and 246 other cell types or tissues.
DR   ExpressionAtlas; O70433; baseline and differential.
DR   GO; GO:0031430; C:M band; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR   GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR   GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR   GO; GO:0008134; F:transcription factor binding; ISS:UniProtKB.
DR   GO; GO:0055014; P:atrial cardiac muscle cell development; IEP:BHF-UCL.
DR   GO; GO:0060347; P:heart trabecula formation; IEP:BHF-UCL.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0001649; P:osteoblast differentiation; IEP:BHF-UCL.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0009725; P:response to hormone; ISO:MGI.
DR   GO; GO:0055015; P:ventricular cardiac muscle cell development; IEP:BHF-UCL.
DR   CDD; cd09433; LIM4_FHL2; 1.
DR   Gene3D; 2.10.110.10; Cysteine Rich Protein; 4.
DR   InterPro; IPR001781; Znf_LIM.
DR   PANTHER; PTHR24205; FOUR AND A HALF LIM DOMAINS PROTEIN; 1.
DR   PANTHER; PTHR24205:SF3; FOUR AND A HALF LIM DOMAINS PROTEIN 2; 1.
DR   Pfam; PF00412; LIM; 4.
DR   SMART; SM00132; LIM; 4.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 5.
DR   PROSITE; PS00478; LIM_DOMAIN_1; 4.
DR   PROSITE; PS50023; LIM_DOMAIN_2; 4.
DR   Genevisible; O70433; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Isopeptide bond; LIM domain; Metal-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..279
FT                   /note="Four and a half LIM domains protein 2"
FT                   /id="PRO_0000075738"
FT   DOMAIN          40..92
FT                   /note="LIM zinc-binding 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DOMAIN          101..153
FT                   /note="LIM zinc-binding 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DOMAIN          162..212
FT                   /note="LIM zinc-binding 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DOMAIN          221..275
FT                   /note="LIM zinc-binding 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   ZN_FING         7..31
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         238
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14192"
FT   CROSSLNK        78
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q14192"
FT   CROSSLNK        167
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q14192"
FT   CROSSLNK        220
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q14192"
SQ   SEQUENCE   279 AA;  32073 MW;  6D8CBC4B4424BFF2 CRC64;
     MTERFDCHHC NESLYGKKYI LKEENPHCVA CFEELYANTC EECGTPIGCD CKDLSYKDRH
     WHEGCFHCSR CGSSLVDKPF AAKEEQLLCT DCYSNEYSSK CQECKKTIMP GTRKMEYKGS
     SWHETCFTCQ RCQQPIGTKS FIPKENQNFC VPCYEKQYAL QCVQCKKPIT TGGVTYREQP
     WHKECFVCTA CKKQLSGQRF TARDEFPYCL TCFCDLYAKK CAGCTNPISG LGGTKYISFE
     ERQWHNDCFN CKKCSLSLVG RGFLTERDDI LCPDCGKDI
//