ID FHL2_HUMAN Reviewed; 279 AA. AC Q14192; Q13229; Q13644; Q2I5I4; Q9P294; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 19-FEB-2014, entry version 134. DE RecName: Full=Four and a half LIM domains protein 2; DE Short=FHL-2; DE AltName: Full=LIM domain protein DRAL; DE AltName: Full=Skeletal muscle LIM-protein 3; DE Short=SLIM-3; GN Name=FHL2; Synonyms=DRAL, SLIM3; 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]. RC TISSUE=Skeletal muscle; RX PubMed=9150430; RA Genini M., Schwalbe P., Scholl F.A., Remppis A., Mattei M.-G., RA Schaefer B.W.; RT "Subtractive cloning and characterization of DRAL, a novel LIM-domain RT protein down-regulated in rhabdomyosarcoma."; RL DNA Cell Biol. 16:433-442(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MET-167. RC TISSUE=Heart; RX PubMed=9573400; DOI=10.1016/S0378-1119(97)00644-6; RA Chan K.K., Tsui S.K.W., Lee S.M.Y., Luk S.C.W., Liew C.C., Fung K.P., RA Waye M.M.Y., Lee C.Y.; RT "Molecular cloning and characterization of FHL2, a novel LIM domain RT protein preferentially expressed in human heart."; RL Gene 210:345-350(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Leukocyte; RX PubMed=11001931; RA Tanahashi H., Tabira T.; RT "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an RT LIM-domain protein."; RL Hum. Mol. Genet. 9:2281-2289(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MET-167. RC TISSUE=Bone marrow; RA Qian Z., Mao L., Fernald A., Yu H., Luo R., Anastasi J., Le Beau M.M.; RT "The FHL2 LIM-domain protein is implicated in hematopoiesis and RT leukemogenesis."; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 127-279, AND VARIANT MET-167. RC TISSUE=Heart muscle; RX PubMed=8753811; DOI=10.1006/bbrc.1996.1222; RA Morgan M.J., Madgwick A.J.A.; RT "Slim defines a novel family of LIM-proteins expressed in skeletal RT muscle."; RL Biochem. Biophys. Res. Commun. 225:632-638(1996). RN [7] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH ZNF638. RX PubMed=11813260; DOI=10.1002/jcb.10041.abs; RA Ng E.K.O., Chan K.K., Wong C.H., Tsui S.K.W., Ngai S.M., Lee S.M.Y., RA Kotaka M., Lee C.Y., Waye M.M.Y., Fung K.P.; RT "Interaction of the heart-specific LIM domain protein, FHL2, with DNA- RT binding nuclear protein, hNP220."; RL J. Cell. Biochem. 84:556-566(2002). RN [8] RP INTERACTION WITH TTN. RX PubMed=12432079; DOI=10.1242/jcs.00181; RA Lange S., Auerbach D., McLoughlin P., Perriard E., Schafer B.W., RA Perriard J.-C., Ehler E.; RT "Subcellular targeting of metabolic enzymes to titin in heart muscle RT may be mediated by DRAL/FHL-2."; RL J. Cell Sci. 115:4925-4936(2002). RN [9] RP FUNCTION, AND INTERACTION WITH SIRT1 AND FOXO1. RX PubMed=15692560; DOI=10.1038/sj.emboj.7600570; RA Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W.; RT "Suppression of FOXO1 activity by FHL2 through SIRT1-mediated RT deacetylation."; RL EMBO J. 24:1021-1032(2005). RN [10] RP FUNCTION, INTERACTION WITH E4F1, AND SUBCELLULAR LOCATION. RX PubMed=16652157; DOI=10.1038/sj.onc.1209567; RA Paul C., Lacroix M., Iankova I., Julien E., Schaefer B.W., RA Labalette C., Wei Y., Le Cam A., Le Cam L., Sardet C.; RT "The LIM-only protein FHL2 is a negative regulator of E4F1."; RL Oncogene 25:5475-5484(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, AND MASS RP 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 [12] RP FUNCTION, AND INTERACTION WITH GRB7. RX PubMed=18853468; DOI=10.1002/jmr.916; RA Siamakpour-Reihani S., Argiros H.J., Wilmeth L.J., Haas L.L., RA Peterson T.A., Johnson D.L., Shuster C.B., Lyons B.A.; RT "The cell migration protein Grb7 associates with transcriptional RT regulator FHL2 in a Grb7 phosphorylation-dependent manner."; RL J. Mol. Recognit. 22:9-17(2009). RN [13] 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). RN [14] RP STRUCTURE BY NMR OF 98-279. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of LIM domains in LIM-protein 3."; RL Submitted (JUN-2006) to the PDB data bank. CC -!- FUNCTION: May function as a molecular transmitter linking various CC signaling pathways to transcriptional regulation. Negatively CC regulates the transcriptional repressor E4F1 and may function in CC cell growth. Inhibits the transcriptional activity of FOXO1 and CC its apoptotic function by enhancing the interaction of FOXO1 with CC SIRT1 and FOXO1 deacetylation. CC -!- SUBUNIT: Interacts with ZNF638 and TTN/titin. Interacts with E4F1. CC Interacts with GRB7. Interacts with SIRT1 and FOXO1. CC -!- INTERACTION: CC Self; NbExp=3; IntAct=EBI-701903, EBI-701903; CC P18847:ATF3; NbExp=3; IntAct=EBI-701903, EBI-712767; CC P38398:BRCA1; NbExp=6; IntAct=EBI-701903, EBI-349905; CC Q12778:FOXO1; NbExp=8; IntAct=EBI-701903, EBI-1108782; CC Q96EB6:SIRT1; NbExp=2; IntAct=EBI-701903, EBI-1802965; CC Q9NYA1:SPHK1; NbExp=7; IntAct=EBI-701903, EBI-985303; CC Q9H9D4:ZNF408; NbExp=3; IntAct=EBI-701903, EBI-347633; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and heart. CC -!- DOMAIN: The third LIM zinc-binding mediates interaction with E4F1. CC -!- SIMILARITY: Contains 4 LIM zinc-binding domains. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/FHL2ID44092ch2q12.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L42176; AAA85333.1; -; mRNA. DR EMBL; U29332; AAC52073.1; -; mRNA. DR EMBL; AB038794; BAA92253.1; -; Genomic_DNA. DR EMBL; DQ307067; ABC25549.1; -; mRNA. DR EMBL; BC014397; AAH14397.1; -; mRNA. DR EMBL; U60117; AAC50794.1; -; mRNA. DR PIR; JC6565; JC6565. DR RefSeq; NP_001034581.1; NM_001039492.2. DR RefSeq; NP_001441.4; NM_001450.3. DR RefSeq; NP_963849.1; NM_201555.1. DR RefSeq; NP_963851.2; NM_201557.3. DR RefSeq; XP_005263961.1; XM_005263904.1. DR RefSeq; XP_005263963.1; XM_005263906.1. DR UniGene; Hs.443687; -. DR PDB; 1X4K; NMR; -; A=98-159. DR PDB; 1X4L; NMR; -; A=221-279. DR PDB; 2D8Z; NMR; -; A=162-218. DR PDBsum; 1X4K; -. DR PDBsum; 1X4L; -. DR PDBsum; 2D8Z; -. DR ProteinModelPortal; Q14192; -. DR SMR; Q14192; 3-279. DR BioGrid; 108565; 61. DR DIP; DIP-5980N; -. DR IntAct; Q14192; 60. DR MINT; MINT-120725; -. DR STRING; 9606.ENSP00000322909; -. DR PhosphoSite; Q14192; -. DR DMDM; 116241364; -. DR UCD-2DPAGE; Q14192; -. DR PaxDb; Q14192; -. DR PRIDE; Q14192; -. DR DNASU; 2274; -. DR Ensembl; ENST00000322142; ENSP00000322909; ENSG00000115641. DR Ensembl; ENST00000358129; ENSP00000350846; ENSG00000115641. DR Ensembl; ENST00000393352; ENSP00000377020; ENSG00000115641. DR Ensembl; ENST00000393353; ENSP00000377021; ENSG00000115641. DR Ensembl; ENST00000408995; ENSP00000386633; ENSG00000115641. DR Ensembl; ENST00000409807; ENSP00000386665; ENSG00000115641. DR GeneID; 2274; -. DR KEGG; hsa:2274; -. DR UCSC; uc002tct.3; human. DR CTD; 2274; -. DR GeneCards; GC02M105974; -. DR HGNC; HGNC:3703; FHL2. DR HPA; CAB008368; -. DR HPA; HPA005922; -. DR HPA; HPA006028; -. DR MIM; 602633; gene. DR neXtProt; NX_Q14192; -. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR PharmGKB; PA164; -. DR eggNOG; NOG314122; -. DR HOGENOM; HOG000231075; -. DR HOVERGEN; HBG074526; -. DR InParanoid; Q14192; -. DR KO; K14380; -. DR OrthoDB; EOG7P8P7M; -. DR TreeFam; TF321684; -. DR Reactome; REACT_111217; Metabolism. DR ChiTaRS; FHL2; human. DR EvolutionaryTrace; Q14192; -. DR GeneWiki; FHL2; -. DR GenomeRNAi; 2274; -. DR NextBio; 9247; -. DR PRO; PR:Q14192; -. DR ArrayExpress; Q14192; -. DR Bgee; Q14192; -. DR CleanEx; HS_FHL2; -. DR Genevestigator; Q14192; -. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:HPA. DR GO; GO:0031430; C:M band; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0030018; C:Z disc; IEA:Ensembl. DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0055014; P:atrial cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome. DR GO; GO:0060347; P:heart trabecula formation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0009725; P:response to hormone; IMP:BHF-UCL. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEA:Ensembl. DR Gene3D; 2.10.110.10; -; 5. DR InterPro; IPR001781; Znf_LIM. 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 3D-structure; Complete proteome; Cytoplasm; LIM domain; Metal-binding; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 279 Four and a half LIM domains protein 2. FT /FTId=PRO_0000075737. FT DOMAIN 40 92 LIM zinc-binding 1. FT DOMAIN 101 153 LIM zinc-binding 2. FT DOMAIN 162 212 LIM zinc-binding 3. FT DOMAIN 221 275 LIM zinc-binding 4. FT ZN_FING 7 31 C4-type (Potential). FT MOD_RES 238 238 Phosphoserine. FT VARIANT 167 167 K -> M (in dbSNP:rs1127588). FT /FTId=VAR_067455. FT STRAND 101 104 FT STRAND 110 112 FT STRAND 114 117 FT STRAND 120 123 FT TURN 124 127 FT STRAND 130 132 FT STRAND 138 144 FT STRAND 147 150 FT HELIX 151 157 FT STRAND 163 165 FT STRAND 171 182 FT TURN 183 185 FT STRAND 189 191 FT STRAND 201 208 FT HELIX 210 216 FT TURN 222 225 FT STRAND 231 233 FT TURN 246 248 FT STRAND 252 254 FT STRAND 267 271 FT HELIX 273 277 SQ SEQUENCE 279 AA; 32193 MW; E94E3A7F6601F9F3 CRC64; MTERFDCHHC NESLFGKKYI LREESPYCVV CFETLFANTC EECGKPIGCD CKDLSYKDRH WHEACFHCSQ CRNSLVDKPF AAKEDQLLCT DCYSNEYSSK CQECKKTIMP GTRKMEYKGS SWHETCFICH RCQQPIGTKS FIPKDNQNFC VPCYEKQHAM QCVQCKKPIT TGGVTYREQP WHKECFVCTA CRKQLSGQRF TARDDFAYCL NCFCDLYAKK CAGCTNPISG LGGTKYISFE ERQWHNDCFN CKKCSLSLVG RGFLTERDDI LCPDCGKDI //