FHL2_MOUSE
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 03-AUG-2022, entry version 166.
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 iPTMnet; O70433; -.
DR PhosphoSitePlus; O70433; -.
DR EPD; O70433; -.
DR jPOST; O70433; -.
DR PaxDb; O70433; -.
DR PeptideAtlas; O70433; -.
DR PRIDE; O70433; -.
DR ProteomicsDB; 270988; -.
DR Antibodypedia; 949; 366 antibodies from 38 providers.
DR DNASU; 14200; -.
DR Ensembl; ENSMUST00000008280; ENSMUSP00000008280; ENSMUSG00000008136.
DR Ensembl; ENSMUST00000185893; ENSMUSP00000141170; ENSMUSG00000008136.
DR GeneID; 14200; -.
DR KEGG; mmu:14200; -.
DR UCSC; uc007avk.2; mouse.
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; CHYCKET; -.
DR OrthoDB; 642235at2759; -.
DR PhylomeDB; O70433; -.
DR TreeFam; TF321684; -.
DR BioGRID-ORCS; 14200; 1 hit in 74 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 242 other tissues.
DR ExpressionAtlas; O70433; baseline and differential.
DR Genevisible; O70433; MM.
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 InterPro; IPR037987; FHL2/3/5.
DR InterPro; IPR001781; Znf_LIM.
DR PANTHER; PTHR24205; PTHR24205; 1.
DR Pfam; PF00412; LIM; 4.
DR SMART; SM00132; LIM; 4.
DR PROSITE; PS00478; LIM_DOMAIN_1; 4.
DR PROSITE; PS50023; LIM_DOMAIN_2; 4.
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
