LHX1_XENLA
ID LHX1_XENLA Reviewed; 403 AA.
AC P29674; Q9PSU2;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=LIM/homeobox protein Lhx1;
DE Short=LIM homeobox protein 1;
DE AltName: Full=Homeobox protein Lim-1;
DE Short=Xlim1;
DE Short=x-Lhx1;
DE Short=xLIM-1;
GN Name=lhx1; Synonyms=lim-1, lim1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RX PubMed=1347750; DOI=10.1101/gad.6.3.356;
RA Taira M., Jamrich M., Good P.J., Dawid I.B.;
RT "The LIM domain-containing homeo box gene Xlim-1 is expressed specifically
RT in the organizer region of Xenopus gastrula embryos.";
RL Genes Dev. 6:356-366(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112, AND INDUCTION.
RX PubMed=9275190; DOI=10.1073/pnas.94.18.9717;
RA Rebbert M.L., Dawid I.B.;
RT "Transcriptional regulation of the Xlim-1 gene by activin is mediated by an
RT element in intron I.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9717-9722(1997).
RN [3]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=7914163; DOI=10.1242/dev.120.6.1525;
RA Taira M., Otani H., Jamrich M., Dawid I.B.;
RT "Expression of the LIM class homeobox gene Xlim-1 in pronephros and CNS
RT cell lineages of Xenopus embryos is affected by retinoic acid and
RT exogastrulation.";
RL Development 120:1525-1536(1994).
RN [4]
RP FUNCTION.
RX PubMed=7990959; DOI=10.1038/372677a0;
RA Taira M., Otani H., Saint-Jeannet J.P., Dawid I.B.;
RT "Role of the LIM class homeodomain protein Xlim-1 in neural and muscle
RT induction by the Spemann organizer in Xenopus.";
RL Nature 372:677-679(1994).
RN [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=8793615;
RA Karavanov A.A., Saint-Jeannet J.P., Karavanova I., Taira M., Dawid I.B.;
RT "The LIM homeodomain protein Lim-1 is widely expressed in neural, neural
RT crest and mesoderm derivatives in vertebrate development.";
RL Int. J. Dev. Biol. 40:453-461(1996).
RN [6]
RP FUNCTION, INTERACTION WITH LDB1, AND MUTAGENESIS OF CYS-28 AND CYS-88.
RX PubMed=8918878; DOI=10.1038/384270a0;
RA Agulnick A.D., Taira M., Breen J.J., Tanaka T., Dawid I.B., Westphal H.;
RT "Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain
RT proteins.";
RL Nature 384:270-272(1996).
RN [7]
RP FUNCTION, INDUCTION, AND MUTAGENESIS OF ILE-223.
RX PubMed=9023353; DOI=10.1073/pnas.94.3.895;
RA Taira M., Saint-Jeannet J.P., Dawid I.B.;
RT "Role of the Xlim-1 and Xbra genes in anteroposterior patterning of neural
RT tissue by the head and trunk organizer.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:895-900(1997).
RN [8]
RP INTERACTION WITH LDB1, DOMAIN, AND MUTAGENESIS OF CYS-28 AND CYS-88.
RX PubMed=9468533; DOI=10.1074/jbc.273.8.4712;
RA Breen J.J., Agulnick A.D., Westphal H., Dawid I.B.;
RT "Interactions between LIM domains and the LIM domain-binding protein
RT Ldb1.";
RL J. Biol. Chem. 273:4712-4717(1998).
RN [9]
RP INDUCTION.
RX PubMed=10068640; DOI=10.1242/dev.126.7.1467;
RA Sun B.I., Bush S.M., Collins-Racie L.A., LaVallie E.R.,
RA DiBlasio-Smith E.A., Wolfman N.M., McCoy J.M., Sive H.L.;
RT "derriere: a TGF-beta family member required for posterior development in
RT Xenopus.";
RL Development 126:1467-1482(1999).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10491256; DOI=10.1006/dbio.1999.9414;
RA Carroll T.J., Vize P.D.;
RT "Synergism between Pax-8 and lim-1 in embryonic kidney development.";
RL Dev. Biol. 214:46-59(1999).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=10322628;
RX DOI=10.1002/(sici)1520-6408(1999)24:3/4<199::aid-dvg3>3.0.co;2-d;
RA Carroll T.J., Wallingford J.B., Vize P.D.;
RT "Dynamic patterns of gene expression in the developing pronephros of
RT Xenopus laevis.";
RL Dev. Genet. 24:199-207(1999).
RN [12]
RP FUNCTION.
RX PubMed=10913356; DOI=10.1006/bbrc.2000.3178;
RA Nakano H., Amemiya S., Shiokawa K., Taira M.;
RT "RNA interference for the organizer-specific gene Xlim-1 in Xenopus
RT embryos.";
RL Biochem. Biophys. Res. Commun. 274:434-439(2000).
RN [13]
RP FUNCTION.
RX PubMed=10926781; DOI=10.1006/dbio.2000.9778;
RA Mochizuki T., Karavanov A.A., Curtiss P.E., Ault K.T., Sugimoto N.,
RA Watabe T., Shiokawa K., Jamrich M., Cho K.W.Y., Dawid I.B., Taira M.;
RT "Xlim-1 and LIM domain binding protein 1 cooperate with various
RT transcription factors in the regulation of the goosecoid promoter.";
RL Dev. Biol. 224:470-485(2000).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11112328; DOI=10.1006/dbio.2000.9951;
RA Chan T.-C., Takahashi S., Asashima M.;
RT "A role for Xlim-1 in pronephros development in Xenopus laevis.";
RL Dev. Biol. 228:256-269(2000).
RN [15]
RP DOMAIN, AND MUTAGENESIS OF TYR-278; TYR-281; TYR-285; TYR-286 AND TYR-292.
RX PubMed=11203702; DOI=10.1006/dbio.2000.9986;
RA Hiratani I., Mochizuki T., Tochimoto N., Taira M.;
RT "Functional domains of the LIM homeodomain protein Xlim-1 involved in
RT negative regulation, transactivation, and axis formation in Xenopus
RT embryos.";
RL Dev. Biol. 229:456-467(2001).
RN [16]
RP FUNCTION.
RX PubMed=11291848;
RA Kodjabachian L., Karavanov A.A., Hikasa H., Hukriede N.A., Aoki T.,
RA Taira M., Dawid I.B.;
RT "A study of Xlim1 function in the Spemann-Mangold organizer.";
RL Int. J. Dev. Biol. 45:209-218(2001).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=11567052; DOI=10.1523/jneurosci.21-19-07620.2001;
RA Bachy I., Vernier P., Retaux S.;
RT "The LIM-homeodomain gene family in the developing Xenopus brain:
RT conservation and divergences with the mouse related to the evolution of the
RT forebrain.";
RL J. Neurosci. 21:7620-7629(2001).
RN [18]
RP FUNCTION.
RX PubMed=12381786; DOI=10.1073/pnas.212532399;
RA Chen L., Segal D., Hukriede N.A., Podtelejnikov A.V., Bayarsaihan D.,
RA Kennison J.A., Ogryzko V.V., Dawid I.B., Westphal H.;
RT "Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to
RT regulate development.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14320-14325(2002).
RN [19]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH LDB1 AND RNF12.
RX PubMed=12874135; DOI=10.1242/dev.00621;
RA Hiratani I., Yamamoto N., Mochizuki T., Ohmori S.-Y., Taira M.;
RT "Selective degradation of excess Ldb1 by Rnf12/RLIM confers proper Ldb1
RT expression levels and Xlim-1/Ldb1 stoichiometry in Xenopus organizer
RT functions.";
RL Development 130:4161-4175(2003).
RN [20]
RP FUNCTION.
RX PubMed=12710967; DOI=10.1016/s0012-1606(03)00034-4;
RA Yamamoto S., Hikasa H., Ono H., Taira M.;
RT "Molecular link in the sequential induction of the Spemann organizer:
RT direct activation of the cerberus gene by Xlim-1, Xotx2, Mix.1, and
RT Siamois, immediately downstream from Nodal and Wnt signaling.";
RL Dev. Biol. 257:190-204(2003).
RN [21]
RP FUNCTION.
RX PubMed=12530965; DOI=10.1016/s1534-5807(02)00398-2;
RA Hukriede N.A., Tsang T.E., Habas R., Khoo P.L., Steiner K., Weeks D.L.,
RA Tam P.P., Dawid I.B.;
RT "Conserved requirement of Lim1 function for cell movements during
RT gastrulation.";
RL Dev. Cell 4:83-94(2003).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=15024752; DOI=10.1002/cne.20046;
RA Moreno N., Bachy I., Retaux S., Gonzalez A.;
RT "LIM-homeodomain genes as developmental and adult genetic markers of
RT Xenopus forebrain functional subdivisions.";
RL J. Comp. Neurol. 472:52-72(2004).
RN [23]
RP TISSUE SPECIFICITY.
RX PubMed=15791640; DOI=10.1002/cne.20498;
RA Moreno N., Bachy I., Retaux S., Gonzalez A.;
RT "LIM-homeodomain genes as territory markers in the brainstem of adult and
RT developing Xenopus laevis.";
RL J. Comp. Neurol. 485:240-254(2005).
CC -!- FUNCTION: Involved in the establishment of the body plan via the
CC Spemann organizer during gastrulation. Transcriptional activator
CC required to induce organizer gene expression downstream of siamois.
CC Promotes head formation by binding to 5'-TAAT'-3' elements in the
CC promoters of head organizer genes cer1 and gsc to stimulate expression.
CC Binds as a complex with siamois and mix-A/mix.1 to the cer1 promoter,
CC and with ldb1 and otx2 to the gsc promoter. Also involved in neural
CC induction via the organizer, including a role in notochord formation.
CC Acts synergistically with ldb1 and ssbp in subsequent axis formation.
CC Involved in kidney development, acting synergistically with pax8 to
CC establish the pronephric primordium in late gastrulae/early neurulae
CC and with pax2 during pronephric morphogenesis in tailbud stages. Has a
CC later role in mediating the activity of inhibitors of ventralization.
CC {ECO:0000269|PubMed:10491256, ECO:0000269|PubMed:10913356,
CC ECO:0000269|PubMed:10926781, ECO:0000269|PubMed:11112328,
CC ECO:0000269|PubMed:11291848, ECO:0000269|PubMed:12381786,
CC ECO:0000269|PubMed:12530965, ECO:0000269|PubMed:12710967,
CC ECO:0000269|PubMed:12874135, ECO:0000269|PubMed:1347750,
CC ECO:0000269|PubMed:7990959, ECO:0000269|PubMed:8918878,
CC ECO:0000269|PubMed:9023353}.
CC -!- SUBUNIT: Interacts with ldb1 via the tandem LIM domains. Both LIM
CC domains are required for optimal binding and binding relieves the
CC inhibitory effect of the LIM domains and activates lhx1. Binding to
CC ldb1 also prevents degradation of ldb1 by rnf12. The stoichiometry of
CC lhx1 and ldb1 is important for their function and an excess of ldb1 can
CC inhibit lhx1 function. Interacts with the N-terminal region of rnf12 by
CC a homeobox-dependent mechanism. {ECO:0000269|PubMed:12874135,
CC ECO:0000269|PubMed:8918878, ECO:0000269|PubMed:9468533}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:8793615}.
CC -!- TISSUE SPECIFICITY: Exhibits a biphasic expression pattern. Initially
CC localized to the Spemann organizer region of gastrulae, leading to
CC expression in prechordal mesoderm and notochord. In the second phase,
CC expressed in the lateral mesoderm and neural plate, eventually
CC concentrating in the pronephros and the CNS. Expressed in the
CC pronephros primordium by late gastrula (stage 12.5) and becomes
CC restricted to the tips of the tubules and ducts as kidney development
CC progresses. In the CNS, becomes progressively recognizable in
CC anatomically distinct structures during larval development. Within the
CC forebrain, shows almost identical expression to lhx5 in the
CC diencephalon, being expressed in alternating stripes to lhx2 and lhx9.
CC Expressed in the diencephalic pretectum within prosomere 1,
CC hypothalamus, ventral thalamus and zona limitans intrathalamica. In the
CC telencephalon, the expression pattern is distinct from lhx5, being
CC localized in the pallium and subpallium. Also expressed in the ventral
CC territories of midbrain (mesencephalon) and hindbrain
CC (rhombencephalon), being expressed in the mesencephalic tegmentum and
CC hindbrain reticular formation. Also shows intense expression in the
CC cerebellum including Purkinje cells. {ECO:0000269|PubMed:10322628,
CC ECO:0000269|PubMed:10491256, ECO:0000269|PubMed:11112328,
CC ECO:0000269|PubMed:11567052, ECO:0000269|PubMed:12874135,
CC ECO:0000269|PubMed:1347750, ECO:0000269|PubMed:15024752,
CC ECO:0000269|PubMed:15791640, ECO:0000269|PubMed:7914163,
CC ECO:0000269|PubMed:8793615}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed at a low level in the unfertilized egg. Expression is highest
CC at the gastrula stage, then declines before rising again during the
CC tadpole stage. {ECO:0000269|PubMed:1347750}.
CC -!- INDUCTION: By retinoic acid and by dorsal mesoderm-inducers including
CC activin, derriere, dvr1/vg-1 and nodal. {ECO:0000269|PubMed:10068640,
CC ECO:0000269|PubMed:11112328, ECO:0000269|PubMed:1347750,
CC ECO:0000269|PubMed:7914163, ECO:0000269|PubMed:9023353,
CC ECO:0000269|PubMed:9275190}.
CC -!- DOMAIN: The LIM domains exert a negative regulatory function and
CC disruption of the LIM domains produces an activated form. In addition,
CC two activation domains and a negative regulatory domain exist C-
CC terminally to the homeobox. {ECO:0000269|PubMed:11203702,
CC ECO:0000269|PubMed:9468533}.
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DR EMBL; X63889; CAA45353.1; -; mRNA.
DR EMBL; AF013242; AAB70190.1; -; Genomic_DNA.
DR PIR; S23802; S23802.
DR RefSeq; NP_001084128.1; NM_001090659.1.
DR AlphaFoldDB; P29674; -.
DR SMR; P29674; -.
DR GeneID; 399323; -.
DR KEGG; xla:399323; -.
DR CTD; 399323; -.
DR Xenbase; XB-GENE-856460; lhx1.L.
DR OMA; SPMTETC; -.
DR OrthoDB; 1070389at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 399323; Expressed in gastrula and 8 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:UniProtKB.
DR GO; GO:0009798; P:axis specification; IMP:UniProtKB.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IMP:UniProtKB.
DR GO; GO:0043009; P:chordate embryonic development; IMP:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IMP:UniProtKB.
DR GO; GO:0072080; P:nephron tubule development; IGI:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IMP:UniProtKB.
DR GO; GO:0030903; P:notochord development; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0039003; P:pronephric field specification; IGI:UniProtKB.
DR GO; GO:0039020; P:pronephric nephron tubule development; IGI:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
DR GO; GO:0003002; P:regionalization; IMP:UniProtKB.
DR GO; GO:0035565; P:regulation of pronephros size; IGI:UniProtKB.
DR GO; GO:0032526; P:response to retinoic acid; TAS:AgBase.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00412; LIM; 2.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00132; LIM; 2.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; Differentiation; DNA-binding;
KW Gastrulation; Homeobox; LIM domain; Metal-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..403
FT /note="LIM/homeobox protein Lhx1"
FT /id="PRO_0000075777"
FT DOMAIN 4..54
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 63..117
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 179..238
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 130..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..178
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 28
FT /note="C->G: Disrupts ldb1-binding. Produces an active
FT form; when associated with G-88."
FT /evidence="ECO:0000269|PubMed:8918878,
FT ECO:0000269|PubMed:9468533"
FT MUTAGEN 88
FT /note="C->G: Disrupts ldb1-binding. Produces an active
FT form; when associated with G-28."
FT /evidence="ECO:0000269|PubMed:8918878,
FT ECO:0000269|PubMed:9468533"
FT MUTAGEN 223
FT /note="I->P: Fails to induce chrd."
FT /evidence="ECO:0000269|PubMed:9023353"
FT MUTAGEN 278
FT /note="Y->A: Abolishes transcriptional activity and axis-
FT inducing activity; when associated with A-281; A-285; A-286
FT and A-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 278
FT /note="Y->F: No effect on axis-inducing activity; when
FT associated with F-281; F-285; F-286 and F-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 281
FT /note="Y->A: Abolishes transcriptional activity and axis-
FT inducing activity; when associated with A-278; A-285; A-286
FT and A-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 281
FT /note="Y->F: No effect on axis-inducing activity; when
FT associated with F-278; F-285; F-286 and F-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 285
FT /note="Y->A: Abolishes transcriptional activity and axis-
FT inducing activity; when associated with A-278; A-281; A-286
FT and A-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 285
FT /note="Y->F: No effect on axis-inducing activity; when
FT associated with F-278; F-281; F-286 and F-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 286
FT /note="Y->A: Abolishes transcriptional activity and axis-
FT inducing activity; when associated with A-278; A-281; A-285
FT and A-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 286
FT /note="Y->F: No effect on axis-inducing activity; when
FT associated with F-278; F-281; F-285 and F-292."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 292
FT /note="Y->A: Abolishes transcriptional activity and axis-
FT inducing activity; when associated with A-278; A-281; A-285
FT and A-286."
FT /evidence="ECO:0000269|PubMed:11203702"
FT MUTAGEN 292
FT /note="Y->F: No effect on axis-inducing activity; when
FT associated with F-278; F-281; F-285 and F-286."
FT /evidence="ECO:0000269|PubMed:11203702"
SQ SEQUENCE 403 AA; 44935 MW; 4147EB3A2774C110 CRC64;
MVHCAGCERP ILDRFLLNVL DRAWHVKCVQ CCECKCNLTE KCFSREGKLY CKNDFFRRFG
TKCAGCAQGI SPSDLVRRAR SKVFHLNCFT CMMCNKQLST GEELYIIDEN KFVCKEDYLN
NNNAAKENSF ISVTGSDPSL SPESQDPLQD DAKDSESANV SDKEAGINEN DDQNLGAKRR
GPRTTIKAKQ LETLKAAFAA TPKPTRHIRE QLAQETGLNM RVIQVWFQNR RSKERRMKQL
SALGARRHAF FRSPRRMRPL VDRLEPGELI PNGPFAFYGD YQSEYYGPGS NYDFFPQGPP
SSQAQTPVDL PFVPSSVPAG TPLGAMDHPI PGHHPSSDAQ RFTDIMSHPP GDSPSPEPNL
PGSMHSMSAE VFGQSPPFSS LSVNGGYGNH LSHPPEMNET AVW
