HAND1

HAND1
Identifiers
Aliases	HAND1, Hxt, Thing1, bHLHa27, eHand, heart and neural crest derivatives expressed 1
External IDs	OMIM: 602406; MGI: 103577; HomoloGene: 3545; GeneCards: HAND1; OMA:HAND1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q33.2 Start 154,474,972 bp End 154,478,227 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B1.3|11 35.27 cM Start 57,719,531 bp End 57,723,644 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle layer of sigmoid colon gonad apex of heart left ventricle amniotic fluid right ventricle myocardium myocardium of left ventricle buccal mucosa cell appendix Top expressed in primordial ventricle yolk sac thoracic ganglia trophoblast giant cell placenta embryo morula urethra male urethra mesothelium of parietal serous pericardium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding protein dimerization activity protein homodimerization activity transcription corepressor activity transcription coactivator activity transcription factor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific bHLH transcription factor binding protein binding identical protein binding protein heterodimerization activity enzyme binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm nucleoplasm RNA polymerase II transcription regulator complex nucleolus nucleus Biological process trophoblast giant cell differentiation cell differentiation determination of heart left/right asymmetry regulation of transcription, DNA-templated cardiac septum morphogenesis cardiac left ventricle formation cardiac right ventricle formation mesenchyme development mesoderm formation in utero embryonic development negative regulation of transcription by RNA polymerase II embryonic heart tube formation transcription by RNA polymerase II negative regulation of DNA-binding transcription factor activity transcription, DNA-templated embryonic heart tube development multicellular organism development heart looping odontogenesis of dentin-containing tooth ventricular cardiac muscle tissue morphogenesis positive regulation of transcription, DNA-templated heart development negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding trophectodermal cell differentiation angiogenesis cartilage morphogenesis negative regulation of transcription, DNA-templated blastocyst development positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9421 15110 Ensembl ENSG00000113196 ENSMUSG00000037335 UniProt O96004 Q64279 RefSeq (mRNA) NM_004821 NM_008213 RefSeq (protein) NP_004812 NP_032239 Location (UCSC) Chr 5: 154.47 – 154.48 Mb Chr 11: 57.72 – 57.72 Mb PubMed search
Wikidata
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Heart- and neural crest derivatives-expressed protein 1 is a protein that in humans is encoded by the HAND1 gene.

Function

The protein encoded by this gene belongs to the basic helix-loop-helix family of transcription factors. This gene product is one of two closely related family members, the HAND proteins are expressed within the developing ventricular chambers, cardiac neural crest, endocardium (HAND2 only) and epicardium (HAND2 only) . HAND1 is expressed with myocardium of the primary heart field and plays an essential but poorly understood role in cardiac morphogenesis.

HAND1 works jointly with HAND2 in cardiac development of embryos based on a crucial HAND gene dosage system. If HAND1 is over or under expressed then morphological abnormalities can form; most notable are cleft lips and palates. Expression was modeled with a knock-in of phosphorylation to turn on and off gene expression which induced the craniofacial abnormalities. Knock-out experimentation on mice caused death and severe cardiac malformations such as failed cardiac looping, impaired ventricular development and defective chamber septation. This aids in the implication that HAND1 expression is a factor to patients suffering from congenital heart disease. However, a lack of HAND1 in the distal regions of the Neural Crest has no effect on cranial feature formation. Mutation of HAND1 has been shown to hinder the effect of GATA4, another vital cardiac transcription factor, and is associated with congenital heart disease. The lack of HAND1 detection in the developing embryo leads to many of the structural defects that causes heart disease and facial deformities while the dosage of HAND1 relates to the severity of these maladies.

HAND factors function in the formation of the right ventricle, left ventricle, aortic arch arteries, epicardium, and endocardium implicating them as mediators of congenital heart disease. In addition, HAND1 is uniquely expressed in trophoblasts and is essential for early trophoblast differentiation.

Further reading

• Srivastava D (1999). "HAND proteins: molecular mediators of cardiac development and congenital heart disease". Trends in Cardiovascular Medicine. 9 (1–2): 11–8. doi:10.1016/S1050-1738(98)00033-4. PMID 10189962.
• Weber MC, de Clarke V, Harwin RM, Shiff CJ (Sep 1975). "An extended field trial of pyrimethamine combined with dapsone in the prophylaxis of malaria". The Central African Journal of Medicine. 21 (9): 187–92. PMID 1182795.
• Cross SH, Charlton JA, Nan X, Bird AP (Mar 1994). "Purification of CpG islands using a methylated DNA binding column". Nature Genetics. 6 (3): 236–44. doi:10.1038/ng0394-236. PMID 8012384.
• Scott IC, Anson-Cartwright L, Riley P, Reda D, Cross JC (Jan 2000). "The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms". Molecular and Cellular Biology. 20 (2): 530–41. doi:10.1128/MCB.20.2.530-541.2000. PMC 85124. PMID 10611232.
• Bounpheng MA, Morrish TA, Dodds SG, Christy BA (Jun 2000). "Negative regulation of selected bHLH proteins by eHAND". Experimental Cell Research. 257 (2): 320–31. doi:10.1006/excr.2000.4898. PMID 10837146.
• Firulli BA, Hadzic DB, McDaid JR, Firulli AB (Oct 2000). "The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function". The Journal of Biological Chemistry. 275 (43): 33567–73. doi:10.1074/jbc.M005888200. PMC 2561327. PMID 10924525.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Knöfler M, Meinhardt G, Bauer S, Loregger T, Vasicek R, Bloor DJ, Kimber SJ, Husslein P (Feb 2002). "Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains". The Biochemical Journal. 361 (Pt 3): 641–51. doi:10.1042/0264-6021:3610641. PMC 1222348. PMID 11802795.
• Dai YS, Cserjesi P (Apr 2002). "The basic helix-loop-helix factor, HAND2, functions as a transcriptional activator by binding to E-boxes as a heterodimer". The Journal of Biological Chemistry. 277 (15): 12604–12. doi:10.1074/jbc.M200283200. PMID 11812799.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Srivastava D, Gottlieb PD, Olson EN (2003). "Molecular mechanisms of ventricular hypoplasia". Cold Spring Harbor Symposia on Quantitative Biology. 67: 121–5. doi:10.1101/sqb.2002.67.121. PMID 12858532.
• Firulli BA, Howard MJ, McDaid JR, McIlreavey L, Dionne KM, Centonze VE, Cserjesi P, Virshup DM, Firulli AB (Nov 2003). "PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation". Molecular Cell. 12 (5): 1225–37. doi:10.1016/S1097-2765(03)00425-8. PMID 14636580.
• Hill AA, Riley PR (Nov 2004). "Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2". Molecular and Cellular Biology. 24 (22): 9835–47. doi:10.1128/MCB.24.22.9835-9847.2004. PMC 525463. PMID 15509787.
• Morin S, Pozzulo G, Robitaille L, Cross J, Nemer M (Sep 2005). "MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters". The Journal of Biological Chemistry. 280 (37): 32272–8. doi:10.1074/jbc.M507640200. PMID 16043483.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

• HAND1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.