HAND1

Heart and neural crest derivatives expressed 1
Identifiers
Symbols	HAND1 ; Hxt; Thing1; bHLHa27; eHand
External IDs	OMIM: 602406 MGI: 103577 HomoloGene: 3545 GeneCards: HAND1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription coactivator activity • transcription corepressor activity • protein binding • transcription factor binding • enzyme binding • identical protein binding • protein homodimerization activity • bHLH transcription factor binding • transcription regulatory region DNA binding • protein heterodimerization activity Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • RNA polymerase II transcription factor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • angiogenesis • mesoderm formation • blastocyst development • trophectodermal cell differentiation • heart looping • embryonic heart tube formation • cardiac left ventricle formation • cardiac right ventricle formation • transcription from RNA polymerase II promoter • heart development • embryonic heart tube development • odontogenesis of dentin-containing tooth • negative regulation of sequence-specific DNA binding transcription factor activity • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • ventricular cardiac muscle tissue morphogenesis • cardiac septum morphogenesis • mesenchyme development • cartilage morphogenesis • trophoblast giant cell differentiation • negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
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: 57.83 – 57.83 Mb
PubMed search

Heart- and neural crest derivatives-expressed protein 1 is a protein that in humans is encoded by the HAND1 gene.^[1][2][3]

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.^[4] 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.^[5] However, a lack of HAND1 in the distal regions of the Neural Crest has no effect on cranial feature formation.^[4] Mutation of HAND1 has been shown to hinder the effect of GATA4, another vital cardiac transcription factor, and is associated with congenital heart disease.^[6] 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.^[4]

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.^[3]

References

1. Russell MW, Baker P, Izumo S (Jan 1998). "Cloning, chromosomal mapping, and expression of the human eHAND gene". Mammalian Genome 8 (11): 863–5. doi:10.1007/s003359900596. PMID 9337404.
2. Knöfler M, Meinhardt G, Vasicek R, Husslein P, Egarter C (Dec 1998). "Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart". Gene 224 (1-2): 77–86. doi:10.1016/S0378-1119(98)00511-3. PMID 9931445.
3. "Entrez Gene: HAND1 heart and neural crest derivatives expressed 1".
4. Firulli, Beth A.; Fuchs, Robyn K.; Vincentz, Joshua W.; Clouthier, David E.; Firulli, Anthony B. (2014-08-01). "Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis". Development 141 (15): 3050–3061. doi:10.1242/dev.107680. ISSN 0950-1991. PMC 4197675. PMID 25053435.
5. Reamon-Buettner, Stella Marie; Ciribilli, Yari; Traverso, Ilaria; Kuhls, Beate; Inga, Alberto; Borlak, Juergen (2009-10-01). "A functional genetic study identifies HAND1 mutations in septation defects of the human heart". Human Molecular Genetics 18 (19): 3567–3578. doi:10.1093/hmg/ddp305. ISSN 0964-6906. PMID 19586923.
6. Zhou, Yi-Meng; Dai, Xiao-Yong; Qiu, Xing-Biao; Yuan, Fang; Li, Ruo-Gu; Xu, Ying-Jia; Qu, Xin-Kai; Huang, Ri-Tai; Xue, Song. "HAND1 loss-of-function mutation associated with familial dilated cardiomyopathy". Clinical Chemistry and Laboratory Medicine (CCLM) 0 (0). doi:10.1515/cclm-2015-0766.

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.
• 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.
• 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.

External links

• HAND1 protein, human at the US 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.