Protein-coding gene in the species Homo sapiens
LHX1 |
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Identifiers |
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Aliases | LHX1, LIM-1, LIM1, LIM homeobox 1 |
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External IDs | OMIM: 601999; MGI: 99783; HomoloGene: 4068; GeneCards: LHX1; OMA:LHX1 - orthologs |
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Gene location (Human) |
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![Chromosome 17 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/0/00/Ideogram_human_chromosome_17.svg/300px-Ideogram_human_chromosome_17.svg.png) | Chr. | Chromosome 17 (human)[1] |
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| Band | 17q12 | Start | 36,936,785 bp[1] |
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End | 36,944,612 bp[1] |
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Gene location (Mouse) |
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![Chromosome 11 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/a/a5/Ideogram_house_mouse_chromosome_11.svg/260px-Ideogram_house_mouse_chromosome_11.svg.png) | Chr. | Chromosome 11 (mouse)[2] |
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| Band | 11 C|11 51.31 cM | Start | 84,409,110 bp[2] |
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End | 84,416,361 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - cerebellum
- cerebellar cortex
- cerebellar hemisphere
- right hemisphere of cerebellum
- human kidney
- gonad
- hypothalamus
- right uterine tube
- substantia nigra
- ventricular zone
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| Top expressed in | - hypoblast
- suprachiasmatic nucleus
- connecting tubule
- mesoderm
- Mesorchium
- intermediate mesoderm
- paramesonephric duct
- lobe of cerebellum
- glomerulus
- cerebellar vermis
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| More reference expression data |
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BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/3/3b/PBB_GE_LHX1_206230_at_fs.png/250px-PBB_GE_LHX1_206230_at_fs.png) | More reference expression data |
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Gene ontology |
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Molecular function | - sequence-specific DNA binding
- DNA binding
- transcription corepressor activity
- DNA-binding transcription factor activity
- metal ion binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- cis-regulatory region sequence-specific DNA binding
| Cellular component | - intracellular anatomical structure
- nucleus
- protein-containing complex
- transcription regulator complex
| Biological process | - pattern specification process
- pronephros development
- oviduct epithelium development
- cell differentiation
- renal system development
- ureteric bud development
- positive regulation of branching involved in ureteric bud morphogenesis
- mesonephric tubule development
- regulation of transcription, DNA-templated
- retina layer formation
- comma-shaped body morphogenesis
- spinal cord association neuron differentiation
- embryonic pattern specification
- mesonephric duct development
- uterine epithelium development
- kidney development
- positive regulation of gastrulation
- vagina development
- metanephric glomerulus development
- cell-cell signaling
- somite rostral/caudal axis specification
- anatomical structure morphogenesis
- gastrulation with mouth forming second
- cerebellar Purkinje cell differentiation
- cerebellar Purkinje cell-granule cell precursor cell signaling involved in regulation of granule cell precursor cell proliferation
- anatomical structure formation involved in morphogenesis
- head development
- metanephric renal vesicle morphogenesis
- transcription by RNA polymerase II
- post-embryonic development
- cellular response to fibroblast growth factor stimulus
- renal vesicle morphogenesis
- lateral motor column neuron migration
- cerebellum development
- nervous system development
- transcription, DNA-templated
- nephric duct elongation
- ventral spinal cord development
- cervix development
- uterus development
- positive regulation of transcription, DNA-templated
- epithelium development
- mesonephros development
- multicellular organism development
- metanephric comma-shaped body morphogenesis
- telencephalon development
- branching involved in ureteric bud morphogenesis
- forebrain regionalization
- positive regulation of anterior head development
- metanephric part of ureteric bud development
- S-shaped body morphogenesis
- retina development in camera-type eye
- nephric duct morphogenesis
- oviduct development
- spinal cord development
- embryonic retina morphogenesis in camera-type eye
- animal organ morphogenesis
- regulation of gene expression
- paramesonephric duct development
- urogenital system development
- embryonic viscerocranium morphogenesis
- metanephric S-shaped body morphogenesis
- endoderm formation
- anterior/posterior axis specification
- horizontal cell localization
- positive regulation of embryonic development
- motor neuron axon guidance
- dorsal/ventral pattern formation
- negative regulation of transcription, DNA-templated
- metanephros development
- primitive streak formation
- ectoderm formation
- anterior/posterior pattern specification
- positive regulation of nephron tubule epithelial cell differentiation
- dorsal spinal cord interneuron posterior axon guidance
- regulation of transcription by RNA polymerase II
- neuron differentiation
- positive regulation of transcription by RNA polymerase II
- ureter morphogenesis
- endoderm development
- mesendoderm development
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | |
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ENSG00000273706 ENSG00000274577 |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 17: 36.94 – 36.94 Mb | Chr 11: 84.41 – 84.42 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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LIM homeobox 1 is a protein that in humans is encoded by the LHX1 gene.[5] This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells. It is also key in development of renal and urogenital systems and is required for normal organogenesis.[6] A similar protein in mice is an essential regulator of the vertebrate head organizer.[5]
Function
The Lim gene family is a subfamily of homeobox genes.[7] The homeobox genes are essential in organizing the body plan of an organism and all contain the same conserved homeodomain of amino acids.[8] Evidence that Lim-1 is essential to a developing organism is its conservation throughout evolution and presence in a variety of organisms.[7] The Lim-1 gene encodes a transcription factor which binds to the DNA of specific genes and functions to produce the needed gene product for development of the organism.[9] Lim-1 is important during early molecular development and is required in both primitive streak-derived tissue and visceral endoderm of the early embryo for development of a head.[10] Studies done using mutant organisms without the Lim gene results in organisms that develop no head structure at all support the essential role of the Lim-1 gene in formation of the head.[11] This gene has also been shown to play a crucial role in the formation of the female reproductive tract.[9] The gene is expressed in the developing Müllerian duct of females, and when the gene is knocked out no reproductive tract forms.[9] Recent studies have shown that Lim-1 mutations may be one cause of the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.[12] MRKH is characterized by defective development, or absence, of the uterus and upper part of the vagina in women with normal ovaries and karyotype.[12]
Lim-1’s expression is controlled in part by the sonic hedgehog-Gli signaling pathway.[6] Recent studies in mice have shown that Lim-1 silencing halts tumor growth and impairs tumor cell movement via inhibition of protein expression involved in metastatic spread.[6] Therefore, in tumor cells Lim-1 acts as an oncogene.[6] Thus, targeting Lim-1 can be a potential cancer therapy. In addition, Lim-1 is important in rodent renal development.[13] Lim-1 deficiency results in development of multicystic kidney, whereas, its expression can contribute to pathogenesis of nephroblastomas.[13] Also, Lim-1 plays a role in embryonic retinal development.[14] Lim-1 expression affects differentiation and maintenance of horizontal cells located in the retinal, thus, it could serve as a marker in studies of horizontal cell specification.[14]
Lim-1 (Lhx1) functions as a transcription factor necessary for regulating the production of coupling factors required for proper communication between the neurons located in the part of the brain responsible for regulation of circadian rhythms called the suprachiasmatic nucleus (SCN).[15] In mouse studies where Lim-1 transcription was restricted at some point during development in utero, the individual units within the subject’s molecular clock functioned properly but were unable to work together.[15] Communication of these units is required to match their release of clock proteins which begin a transcription cascade of many other proteins that produce functional responses in tissues.[15] The cyclic pattern of these responses is due to the feedback of the clock proteins and consequent changes to this transcription cascade.[15] Reduced Lim-1 expression leads to inadequate levels of proteins such as Vasoactive Intestinal Polypeptide (VIP) that work to produce the neuron coordination required for a regulated circadian rhythm.[15] The lack of such coupling factors causes the circadian clock to not function properly because the units within the SCN cannot match their release of clock proteins, and therefore their transcriptional cascades of proteins that cause changes in arousal do not align.[15]
References
- ^ a b c ENSG00000274577 GRCh38: Ensembl release 89: ENSG00000273706, ENSG00000274577 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018698 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: LHX1 LIM homeobox 1".
- ^ a b c d Dormoy V, et al. (2011). "LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma". Oncogene. 30 (15): 1753–1763. doi:10.1038/onc.2010.557. PMID 21132009.
- ^ a b Hobert O, Heiner Westphal (February 2000). "Functions of LIM-homeobox genes". Trends in Genetics. 16 (2): 75–83. doi:10.1016/S0168-9525(99)01883-1. PMID 10652534.
- ^ Carlson BM (2009). Human Embryology and Developmental Biology. Philadelphia, PA: Mosby Elsevier. pp. 67–70. ISBN 978-0-323-05385-3.
- ^ a b c Kobayashi A, Shawlot W, Kania A, Behringer RR (Feb 2004). "Requirement of Lim1 for female reproductive tract development". Development. 131 (3): 539–49. doi:10.1242/dev.00951. PMID 14695376.
- ^ Shawlot W, Wakamiya M, Kwan KM, Kania A, Jessell TM, Behringer RR (Nov 1999). "Lim1 is required in both primitive streak-derived tissues and visceral endoderm for head formation in the mouse". Development. 126 (22): 4925–32. doi:10.1242/dev.126.22.4925. PMID 10529411.
- ^ Bally-Cuif L, Boncinelli E (Feb 1997). "Transcription factors and head formation in vertebrates". BioEssays. 19 (2): 127–35. doi:10.1002/bies.950190207. PMID 9046242. S2CID 44679684.
- ^ a b Ledig S, Brucker S, Barresi G, Schomburg J, Rall K, Wieacker P (Sep 2012). "Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome". Human Reproduction. 27 (9): 2872–5. doi:10.1093/humrep/des206. PMID 22740494.
- ^ a b Guertl B, Senanayake U, Nusshold E, Leuschner I, Mannweiler S, Ebner B, Hoefler G (2011). "Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas". Pathobiology. 78 (4): 210–9. doi:10.1159/000326769. PMID 21778788.
- ^ a b Liu W, Wang JH, Xiang M (Mar 2000). "Specific expression of the LIM/homeodomain protein Lim-1 in horizontal cells during retinogenesis". Developmental Dynamics. 217 (3): 320–5. doi:10.1002/(SICI)1097-0177(200003)217:3<320::AID-DVDY10>3.0.CO;2-F. PMID 10741426.
- ^ a b c d e f Hatori M, Gill S, Mure LS, Goulding M, O'Leary DD, Panda S (Jul 2014). "Lhx1 maintains synchrony among circadian oscillator neurons of the SCN". eLife. 3: e03357. doi:10.7554/eLife.03357. PMC 4137275. PMID 25035422.
Further reading
- Shawlot W, Behringer RR (Mar 1995). "Requirement for Lim1 in head-organizer function". Nature. 374 (6521): 425–30. Bibcode:1995Natur.374..425S. doi:10.1038/374425a0. PMID 7700351. S2CID 4353647.
- Bozzi F, Bertuzzi S, Strina D, Giannetto C, Vezzoni P, Villa A (Dec 1996). "The exon-intron structure of human LHX1 gene". Biochemical and Biophysical Research Communications. 229 (2): 494–7. doi:10.1006/bbrc.1996.1832. PMID 8954926.
- Dong WF, Heng HH, Lowsky R, Xu Y, DeCoteau JF, Shi XM, Tsui LC, Minden MD (Jun 1997). "Cloning, expression, and chromosomal localization to 11p12-13 of a human LIM/HOMEOBOX gene, hLim-1". DNA and Cell Biology. 16 (6): 671–8. doi:10.1089/dna.1997.16.671. hdl:10722/44331. PMID 9212161.
- Jurata LW, Pfaff SL, Gill GN (Feb 1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". The Journal of Biological Chemistry. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID 9452425.
- Phillips JC (2003). "Assignment of LHX1 to human chromosome bands 17q11.2-->q12 by use of radiation hybrid mapping and somatic cell hybridization". Cytogenetic and Genome Research. 97 (1–2): 140D. doi:10.1159/000064048. PMID 12438757.