FHL2_HUMAN
ID FHL2_HUMAN Reviewed; 279 AA.
AC Q14192; Q13229; Q13644; Q2I5I4; Q5TM15; Q9P294;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 207.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=9150430; DOI=10.1089/dna.1997.16.433;
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] (ISOFORM 1), 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 protein
RT preferentially expressed in human heart.";
RL Gene 210:345-350(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Leukocyte;
RX PubMed=11001931; DOI=10.1093/oxfordjournals.hmg.a018919;
RA Tanahashi H., Tabira T.;
RT "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-
RT domain protein.";
RL Hum. Mol. Genet. 9:2281-2289(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=15453830; DOI=10.1042/bj20040775;
RA Takahashi K., Matsumoto C., Ra C.;
RT "FHL3 negatively regulates human high-affinity IgE receptor beta-chain gene
RT expression by acting as a transcriptional co-repressor of MZF-1.";
RL Biochem. J. 386:191-200(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 127-279 (ISOFORM 1), 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 [9]
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 [10]
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 may be
RT mediated by DRAL/FHL-2.";
RL J. Cell Sci. 115:4925-4936(2002).
RN [11]
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 [12]
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., Labalette C.,
RA 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [14]
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 regulator
RT FHL2 in a Grb7 phosphorylation-dependent manner.";
RL J. Mol. Recognit. 22:9-17(2009).
RN [15]
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., Buerckstuemmer T.,
RA 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 [16]
RP FUNCTION.
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).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-78; LYS-167 AND LYS-220, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [18]
RP INTERACTION WITH CEFIP.
RX PubMed=28717008; DOI=10.1074/jbc.m117.786764;
RA Dierck F., Kuhn C., Rohr C., Hille S., Braune J., Sossalla S., Molt S.,
RA van der Ven P.F.M., Fuerst D.O., Frey N.;
RT "The novel cardiac z-disc protein CEFIP regulates cardiomyocyte hypertrophy
RT by modulating calcineurin signaling.";
RL J. Biol. Chem. 292:15180-15191(2017).
RN [19]
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 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. Negatively regulates the calcineurin/NFAT signaling
CC pathway in cardiomyocytes (PubMed:28717008).
CC {ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16652157,
CC ECO:0000269|PubMed:18853468, ECO:0000269|PubMed:28717008}.
CC -!- SUBUNIT: Interacts with ZNF638 and TTN/titin (PubMed:11813260,
CC PubMed:12432079). Interacts with E4F1 (PubMed:16652157). Interacts with
CC GRB7 (PubMed:18853468). Interacts with SIRT1 and FOXO1
CC (PubMed:15692560). Interacts with CEFIP (PubMed:28717008). Interacts
CC with calcineurin (By similarity). Interacts with FOXK1 (By similarity).
CC {ECO:0000250|UniProtKB:O70433, ECO:0000269|PubMed:11813260,
CC ECO:0000269|PubMed:12432079, ECO:0000269|PubMed:15692560,
CC ECO:0000269|PubMed:16652157, ECO:0000269|PubMed:18853468,
CC ECO:0000269|PubMed:28717008}.
CC -!- INTERACTION:
CC Q14192; Q9NQ94: A1CF; NbExp=3; IntAct=EBI-701903, EBI-2809489;
CC Q14192; Q8IZP0-5: ABI1; NbExp=3; IntAct=EBI-701903, EBI-11743294;
CC Q14192; O14639-4: ABLIM1; NbExp=3; IntAct=EBI-701903, EBI-11030084;
CC Q14192; Q9NQ31: AKIP1; NbExp=3; IntAct=EBI-701903, EBI-517035;
CC Q14192; A2BDD9: AMOT; NbExp=3; IntAct=EBI-701903, EBI-17286414;
CC Q14192; Q3KP44: ANKRD55; NbExp=3; IntAct=EBI-701903, EBI-14493093;
CC Q14192; Q9BRR9: ARHGAP9; NbExp=3; IntAct=EBI-701903, EBI-750254;
CC Q14192; P18847: ATF3; NbExp=3; IntAct=EBI-701903, EBI-712767;
CC Q14192; A0A0S2Z5G4: BANP; NbExp=3; IntAct=EBI-701903, EBI-16429704;
CC Q14192; B4DE54: BANP; NbExp=4; IntAct=EBI-701903, EBI-16429313;
CC Q14192; Q8N9N5: BANP; NbExp=5; IntAct=EBI-701903, EBI-744695;
CC Q14192; Q8N9N5-2: BANP; NbExp=6; IntAct=EBI-701903, EBI-11524452;
CC Q14192; Q8N9N5-7: BANP; NbExp=3; IntAct=EBI-701903, EBI-16429296;
CC Q14192; Q9UMQ3: BARX2; NbExp=3; IntAct=EBI-701903, EBI-12053927;
CC Q14192; Q9H2G9: BLZF1; NbExp=10; IntAct=EBI-701903, EBI-2548012;
CC Q14192; P38398: BRCA1; NbExp=6; IntAct=EBI-701903, EBI-349905;
CC Q14192; Q9H1P6: C20orf85; NbExp=3; IntAct=EBI-701903, EBI-12155483;
CC Q14192; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-701903, EBI-739879;
CC Q14192; O75155: CAND2; NbExp=3; IntAct=EBI-701903, EBI-5656182;
CC Q14192; E9PSE9: CCDC198; NbExp=3; IntAct=EBI-701903, EBI-11748295;
CC Q14192; Q53HC0: CCDC92; NbExp=10; IntAct=EBI-701903, EBI-719994;
CC Q14192; P05814: CSN2; NbExp=4; IntAct=EBI-701903, EBI-1642112;
CC Q14192; W5RWE1: CSN2; NbExp=3; IntAct=EBI-701903, EBI-10330381;
CC Q14192; A0PJW8: DAPL1; NbExp=3; IntAct=EBI-701903, EBI-12840152;
CC Q14192; Q9NPI6: DCP1A; NbExp=10; IntAct=EBI-701903, EBI-374238;
CC Q14192; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-701903, EBI-742054;
CC Q14192; O75398: DEAF1; NbExp=3; IntAct=EBI-701903, EBI-718185;
CC Q14192; Q6IS01: DLGAP1; NbExp=3; IntAct=EBI-701903, EBI-11961832;
CC Q14192; Q86UW9: DTX2; NbExp=6; IntAct=EBI-701903, EBI-740376;
CC Q14192; Q9H8W3: FAM204A; NbExp=3; IntAct=EBI-701903, EBI-8465160;
CC Q14192; Q7L5A3: FAM214B; NbExp=3; IntAct=EBI-701903, EBI-745689;
CC Q14192; Q14192: FHL2; NbExp=3; IntAct=EBI-701903, EBI-701903;
CC Q14192; Q12778: FOXO1; NbExp=8; IntAct=EBI-701903, EBI-1108782;
CC Q14192; O95995: GAS8; NbExp=3; IntAct=EBI-701903, EBI-1052570;
CC Q14192; Q8WXI9: GATAD2B; NbExp=3; IntAct=EBI-701903, EBI-923440;
CC Q14192; Q49A26: GLYR1; NbExp=4; IntAct=EBI-701903, EBI-2804292;
CC Q14192; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-701903, EBI-12143817;
CC Q14192; Q9UKD1: GMEB2; NbExp=3; IntAct=EBI-701903, EBI-948296;
CC Q14192; Q9UBI6: GNG12; NbExp=11; IntAct=EBI-701903, EBI-358636;
CC Q14192; P50150: GNG4; NbExp=3; IntAct=EBI-701903, EBI-6395970;
CC Q14192; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-701903, EBI-11163335;
CC Q14192; P13984: GTF2F2; NbExp=3; IntAct=EBI-701903, EBI-1030560;
CC Q14192; P32780: GTF2H1; NbExp=3; IntAct=EBI-701903, EBI-715539;
CC Q14192; P51610-1: HCFC1; NbExp=5; IntAct=EBI-701903, EBI-396188;
CC Q14192; A0A024R8L2: hCG_1987119; NbExp=5; IntAct=EBI-701903, EBI-14103818;
CC Q14192; O75031: HSF2BP; NbExp=3; IntAct=EBI-701903, EBI-7116203;
CC Q14192; Q02535: ID3; NbExp=4; IntAct=EBI-701903, EBI-1387094;
CC Q14192; P80217-2: IFI35; NbExp=5; IntAct=EBI-701903, EBI-12823003;
CC Q14192; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-701903, EBI-11522367;
CC Q14192; Q14005-2: IL16; NbExp=3; IntAct=EBI-701903, EBI-17178971;
CC Q14192; Q0VD86: INCA1; NbExp=5; IntAct=EBI-701903, EBI-6509505;
CC Q14192; P14923: JUP; NbExp=7; IntAct=EBI-701903, EBI-702484;
CC Q14192; Q63ZY3: KANK2; NbExp=6; IntAct=EBI-701903, EBI-2556193;
CC Q14192; Q5T5P2-6: KIAA1217; NbExp=3; IntAct=EBI-701903, EBI-10188326;
CC Q14192; P33176: KIF5B; NbExp=3; IntAct=EBI-701903, EBI-355878;
CC Q14192; Q9Y4X4: KLF12; NbExp=3; IntAct=EBI-701903, EBI-750750;
CC Q14192; Q5T749: KPRP; NbExp=3; IntAct=EBI-701903, EBI-10981970;
CC Q14192; Q5SW96: LDLRAP1; NbExp=3; IntAct=EBI-701903, EBI-747813;
CC Q14192; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-701903, EBI-473196;
CC Q14192; Q9UJ55: MAGEL2; NbExp=3; IntAct=EBI-701903, EBI-5668174;
CC Q14192; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-701903, EBI-12516603;
CC Q14192; Q8IVT2: MISP; NbExp=3; IntAct=EBI-701903, EBI-2555085;
CC Q14192; Q9BZQ8: NIBAN1; NbExp=6; IntAct=EBI-701903, EBI-6916466;
CC Q14192; Q16656: NRF1; NbExp=3; IntAct=EBI-701903, EBI-2547810;
CC Q14192; Q16656-4: NRF1; NbExp=3; IntAct=EBI-701903, EBI-11742836;
CC Q14192; O43189: PHF1; NbExp=3; IntAct=EBI-701903, EBI-530034;
CC Q14192; Q96BD5: PHF21A; NbExp=3; IntAct=EBI-701903, EBI-745085;
CC Q14192; Q13492: PICALM; NbExp=8; IntAct=EBI-701903, EBI-2803688;
CC Q14192; P55347: PKNOX1; NbExp=3; IntAct=EBI-701903, EBI-1373569;
CC Q14192; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-701903, EBI-2692890;
CC Q14192; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-701903, EBI-1389308;
CC Q14192; P78424: POU6F2; NbExp=3; IntAct=EBI-701903, EBI-12029004;
CC Q14192; Q7Z5V6-2: PPP1R32; NbExp=3; IntAct=EBI-701903, EBI-12000762;
CC Q14192; Q9NQV5: PRDM11; NbExp=3; IntAct=EBI-701903, EBI-12941246;
CC Q14192; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-701903, EBI-11320284;
CC Q14192; Q6MZQ0: PRR5L; NbExp=3; IntAct=EBI-701903, EBI-1567866;
CC Q14192; Q2TAL8: QRICH1; NbExp=3; IntAct=EBI-701903, EBI-2798044;
CC Q14192; Q9Y5P3: RAI2; NbExp=7; IntAct=EBI-701903, EBI-746228;
CC Q14192; Q9NYN1: RASL12; NbExp=4; IntAct=EBI-701903, EBI-12917066;
CC Q14192; Q04864: REL; NbExp=3; IntAct=EBI-701903, EBI-307352;
CC Q14192; P48380: RFX3; NbExp=10; IntAct=EBI-701903, EBI-742557;
CC Q14192; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-701903, EBI-10226430;
CC Q14192; Q8IYX7: SAXO1; NbExp=4; IntAct=EBI-701903, EBI-3957636;
CC Q14192; Q658L1: SAXO2; NbExp=3; IntAct=EBI-701903, EBI-18394432;
CC Q14192; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-701903, EBI-748391;
CC Q14192; O43699: SIGLEC6; NbExp=3; IntAct=EBI-701903, EBI-2814604;
CC Q14192; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-701903, EBI-1802965;
CC Q14192; Q8ND83: SLAIN1; NbExp=3; IntAct=EBI-701903, EBI-10269374;
CC Q14192; O95863: SNAI1; NbExp=3; IntAct=EBI-701903, EBI-1045459;
CC Q14192; O94993: SOX30; NbExp=3; IntAct=EBI-701903, EBI-742973;
CC Q14192; Q02086: SP2; NbExp=3; IntAct=EBI-701903, EBI-8651703;
CC Q14192; Q02086-2: SP2; NbExp=3; IntAct=EBI-701903, EBI-9088579;
CC Q14192; Q9NYA1: SPHK1; NbExp=7; IntAct=EBI-701903, EBI-985303;
CC Q14192; Q9C004: SPRY4; NbExp=3; IntAct=EBI-701903, EBI-354861;
CC Q14192; Q12772: SREBF2; NbExp=3; IntAct=EBI-701903, EBI-465059;
CC Q14192; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-701903, EBI-3923210;
CC Q14192; Q9C0C2: TNKS1BP1; NbExp=6; IntAct=EBI-701903, EBI-2104458;
CC Q14192; Q86UV6-2: TRIM74; NbExp=3; IntAct=EBI-701903, EBI-10259086;
CC Q14192; Q6F5E7: TXNRD3NB; NbExp=3; IntAct=EBI-701903, EBI-18122152;
CC Q14192; Q8TAG6: VXN; NbExp=3; IntAct=EBI-701903, EBI-12071548;
CC Q14192; P25490: YY1; NbExp=5; IntAct=EBI-701903, EBI-765538;
CC Q14192; Q9NTW7: ZFP64; NbExp=8; IntAct=EBI-701903, EBI-711679;
CC Q14192; Q5VZL5: ZMYM4; NbExp=3; IntAct=EBI-701903, EBI-2514659;
CC Q14192; P52739-2: ZNF131; NbExp=6; IntAct=EBI-701903, EBI-10213055;
CC Q14192; P52747: ZNF143; NbExp=3; IntAct=EBI-701903, EBI-2849334;
CC Q14192; P98182: ZNF200; NbExp=3; IntAct=EBI-701903, EBI-3913354;
CC Q14192; P17027: ZNF23; NbExp=3; IntAct=EBI-701903, EBI-5657766;
CC Q14192; Q9H9D4: ZNF408; NbExp=3; IntAct=EBI-701903, EBI-347633;
CC Q14192; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-701903, EBI-11741890;
CC Q14192; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-701903, EBI-740727;
CC Q14192; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-701903, EBI-4395669;
CC Q14192; Q8N720: ZNF655; NbExp=3; IntAct=EBI-701903, EBI-625509;
CC Q14192; P36508: ZNF76; NbExp=3; IntAct=EBI-701903, EBI-7254550;
CC Q14192; Q49A12: ZNF85; NbExp=3; IntAct=EBI-701903, EBI-18141506;
CC Q14192; O15535: ZSCAN9; NbExp=3; IntAct=EBI-701903, EBI-751531;
CC Q14192; Q9ERP3: Trim54; Xeno; NbExp=2; IntAct=EBI-701903, EBI-15626796;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11813260,
CC ECO:0000269|PubMed:16652157}. Nucleus {ECO:0000269|PubMed:11813260,
CC ECO:0000269|PubMed:16652157}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250|UniProtKB:O35115}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14192-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14192-2; Sequence=VSP_056999, VSP_057000;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle and heart.
CC {ECO:0000269|PubMed:11813260}.
CC -!- DOMAIN: The third LIM zinc-binding mediates interaction with E4F1.
CC {ECO:0000269|PubMed:16652157}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FHL2ID44092ch2q12.html";
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DR EMBL; L42176; AAA85333.1; -; mRNA.
DR EMBL; U29332; AAC52073.1; -; mRNA.
DR EMBL; AB038794; BAA92253.1; -; Genomic_DNA.
DR EMBL; AB158503; BAD69710.1; -; mRNA.
DR EMBL; DQ307067; ABC25549.1; -; mRNA.
DR EMBL; AC012360; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014397; AAH14397.1; -; mRNA.
DR EMBL; U60117; AAC50794.1; -; mRNA.
DR CCDS; CCDS2070.1; -. [Q14192-1]
DR PIR; JC6565; JC6565.
DR RefSeq; NP_001034581.1; NM_001039492.2. [Q14192-1]
DR RefSeq; NP_001305823.1; NM_001318894.1. [Q14192-1]
DR RefSeq; NP_001305824.1; NM_001318895.1. [Q14192-1]
DR RefSeq; NP_001305825.1; NM_001318896.1. [Q14192-1]
DR RefSeq; NP_001305826.1; NM_001318897.1.
DR RefSeq; NP_001441.4; NM_001450.3. [Q14192-1]
DR RefSeq; NP_963849.1; NM_201555.1. [Q14192-1]
DR RefSeq; NP_963851.2; NM_201557.3. [Q14192-1]
DR RefSeq; XP_011509100.1; XM_011510798.2.
DR PDB; 1X4K; NMR; -; A=101-159.
DR PDB; 1X4L; NMR; -; A=221-279.
DR PDB; 2D8Z; NMR; -; A=162-218.
DR PDB; 2MIU; NMR; -; A=1-98.
DR PDBsum; 1X4K; -.
DR PDBsum; 1X4L; -.
DR PDBsum; 2D8Z; -.
DR PDBsum; 2MIU; -.
DR AlphaFoldDB; Q14192; -.
DR SMR; Q14192; -.
DR BioGRID; 108565; 386.
DR CORUM; Q14192; -.
DR DIP; DIP-5980N; -.
DR IntAct; Q14192; 212.
DR MINT; Q14192; -.
DR STRING; 9606.ENSP00000386665; -.
DR GlyGen; Q14192; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14192; -.
DR MetOSite; Q14192; -.
DR PhosphoSitePlus; Q14192; -.
DR SwissPalm; Q14192; -.
DR BioMuta; FHL2; -.
DR DMDM; 116241364; -.
DR UCD-2DPAGE; Q14192; -.
DR EPD; Q14192; -.
DR jPOST; Q14192; -.
DR MassIVE; Q14192; -.
DR PaxDb; Q14192; -.
DR PeptideAtlas; Q14192; -.
DR PRIDE; Q14192; -.
DR ProteomicsDB; 59914; -. [Q14192-1]
DR ProteomicsDB; 65204; -.
DR Antibodypedia; 949; 366 antibodies from 38 providers.
DR DNASU; 2274; -.
DR Ensembl; ENST00000322142.13; ENSP00000322909.8; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000344213.9; ENSP00000344266.5; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000358129.8; ENSP00000350846.5; ENSG00000115641.19. [Q14192-2]
DR Ensembl; ENST00000393352.7; ENSP00000377020.3; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000393353.7; ENSP00000377021.3; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000408995.5; ENSP00000386633.1; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000409177.6; ENSP00000386892.3; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000409807.5; ENSP00000386665.1; ENSG00000115641.19. [Q14192-1]
DR Ensembl; ENST00000530340.6; ENSP00000433567.2; ENSG00000115641.19. [Q14192-1]
DR GeneID; 2274; -.
DR KEGG; hsa:2274; -.
DR MANE-Select; ENST00000530340.6; ENSP00000433567.2; NM_001318895.3; NP_001305824.1.
DR UCSC; uc061mpc.1; human. [Q14192-1]
DR CTD; 2274; -.
DR DisGeNET; 2274; -.
DR GeneCards; FHL2; -.
DR HGNC; HGNC:3703; FHL2.
DR HPA; ENSG00000115641; Group enriched (heart muscle, ovary).
DR MalaCards; FHL2; -.
DR MIM; 602633; gene.
DR neXtProt; NX_Q14192; -.
DR OpenTargets; ENSG00000115641; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR PharmGKB; PA164; -.
DR VEuPathDB; HostDB:ENSG00000115641; -.
DR eggNOG; KOG1704; Eukaryota.
DR GeneTree; ENSGT00950000183028; -.
DR HOGENOM; CLU_001357_2_0_1; -.
DR InParanoid; Q14192; -.
DR OMA; CHYCKET; -.
DR PhylomeDB; Q14192; -.
DR TreeFam; TF321684; -.
DR PathwayCommons; Q14192; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR SignaLink; Q14192; -.
DR SIGNOR; Q14192; -.
DR BioGRID-ORCS; 2274; 12 hits in 1090 CRISPR screens.
DR ChiTaRS; FHL2; human.
DR EvolutionaryTrace; Q14192; -.
DR GeneWiki; FHL2; -.
DR GenomeRNAi; 2274; -.
DR Pharos; Q14192; Tbio.
DR PRO; PR:Q14192; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14192; protein.
DR Bgee; ENSG00000115641; Expressed in left ventricle myocardium and 192 other tissues.
DR ExpressionAtlas; Q14192; baseline and differential.
DR Genevisible; Q14192; HS.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; ISS:BHF-UCL.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0055014; P:atrial cardiac muscle cell development; IEA:Ensembl.
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: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:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0009725; P:response to hormone; IMP:BHF-UCL.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEA:Ensembl.
DR IDEAL; IID00473; -.
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 3D-structure; Alternative splicing; Cytoplasm; Isopeptide bond; LIM domain;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..279
FT /note="Four and a half LIM domains protein 2"
FT /id="PRO_0000075737"
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:0007744|PubMed:18669648"
FT CROSSLNK 78
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 220
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT VAR_SEQ 53..151
FT /note="DLSYKDRHWHEACFHCSQCRNSLVDKPFAAKEDQLLCTDCYSNEYSSKCQEC
FT KKTIMPGTRKMEYKGSSWHETCFICHRCQQPIGTKSFIPKDNQNFCV -> VPARWSTR
FT AAAGMRPASSATAASSQLEPRVSSPKTIRISVCPAMRNNMPCSAFSAKSPSPREGSLTG
FT SSPGTRSASCAPPAGSSCLGSASQLAMTLPTA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15453830"
FT /id="VSP_056999"
FT VAR_SEQ 152..279
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15453830"
FT /id="VSP_057000"
FT VARIANT 167
FT /note="K -> M"
FT /evidence="ECO:0000269|PubMed:8753811,
FT ECO:0000269|PubMed:9573400, ECO:0000269|Ref.5"
FT /id="VAR_067455"
FT TURN 8..10
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:2MIU"
FT HELIX 29..36
FT /evidence="ECO:0007829|PDB:2MIU"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:2MIU"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2MIU"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:2MIU"
FT HELIX 90..97
FT /evidence="ECO:0007829|PDB:2MIU"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:1X4K"
FT TURN 124..127
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:1X4K"
FT HELIX 151..157
FT /evidence="ECO:0007829|PDB:1X4K"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:2D8Z"
FT STRAND 171..182
FT /evidence="ECO:0007829|PDB:2D8Z"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:2D8Z"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:2D8Z"
FT STRAND 201..208
FT /evidence="ECO:0007829|PDB:2D8Z"
FT HELIX 210..216
FT /evidence="ECO:0007829|PDB:2D8Z"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:1X4L"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:1X4L"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:1X4L"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:1X4L"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:1X4L"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:1X4L"
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
