Q64279 (HAND1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 123. History...
Names and origin
|Protein names||Recommended name:|
Heart- and neural crest derivatives-expressed protein 1
Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1
Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||216 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. In the adult, could be required for ongoing expression of cardiac-specific genes. Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box). Ref.4
Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription factors). Interacts with MDFIC. Ref.5 Ref.6
Nucleus › nucleoplasm. Nucleus › nucleolus. Note: Interaction with MDFIC sequesters it into the nucleolus, preventing the transcription factor activity. Phosphorylation by PLK4 disrupts the interaction with MDFIC and releases it from the nucleolus, leading to transcription factor activity. Ref.6
Smooth muscle cells of the gut and adrenal tissue.
Present as a maternal transcript in the egg as well as during cleavage development before blastocyst formation. At 7.5 dpc, strongly expressed in all trophoblast cells. Expression seen in the ectoplacental cone and extraembryonic mesodermal components of the amnion, allantois and visceral yolk sac. This high extraembryonic expression persists in the embryonic component of the placenta throughout development. In the embryo, expressed at 7.75 dpc in the lateral mesoderm along the entire length of the embryo as well as throughout the precardiogenic mesoderm. At 8.0 dpc, in the developing heart, expression becomes restricted to the rostral and caudal regions of the straight heart tube, which are fated to form the conotruncus and left ventricle, respectively. Symmetric expression is observed along the left-right axis in the caudal heart tube and lateral mesoderm. As cardiac looping occurs, the interrupted anterior-posterior patterning is maintained with expression in the future left, but not right ventricle. Expressed in the myocardium, but not in the endocardium, and specifically on the greater curvature of the looping heart which is opposed to the pericardium. After day 10.5 dpc, the high cardiac expression level declines abruptly. By 13.5 dpc, expression in the heart is restricted to the regions of valve formation. Besides the heart, expression becomes detectable in the gut at 9.0 dpc. At 10.0 dpc, expressed also in the lateral mesoderm and in the neural crest-derived branchial arches. At 10.5 dpc prominent expression in the gut, pharyngeal arches and in sympathetic ganglion primordia. At that stage, a low level of transient expression is seen in the distal posterior region of the limb bud. By 13.5 dpc, the neural crest derivatives, especially the autonomic nervous system and adrenal medulla. Are the prominent sites of expression, with expression in the other sites still detectable. Ref.2 Ref.4
Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to tranlocation into the nucleoplasm, allowing dimerization and transcription factor activity.
Contains 1 bHLH (basic helix-loop-helix) domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 216||216||Heart- and neural crest derivatives-expressed protein 1||PRO_0000127185|
|Domain||94 – 146||53||bHLH|
|Compositional bias||9 – 17||9||Poly-His|
|Compositional bias||66 – 71||6||Poly-Ala|
Amino acid modifications
|Modified residue||107||1||Phosphothreonine; by PLK4 Ref.6|
|Modified residue||109||1||Phosphoserine; by PLK4 Ref.6|
|Mutagenesis||107||1||T → A: Remains exclusively in the nucleolus; when associated with A-109. Ref.6|
|Mutagenesis||107||1||T → D: Adopts a nucleus-wide distribution; when associated with D-109. Ref.6|
|Mutagenesis||109||1||S → A: Remains exclusively in the nucleolus; when associated with A-107. Ref.6|
|Mutagenesis||109||1||S → D: Adopts a nucleus-wide distribution; when associated with D-107. Ref.6|
|Sequence conflict||6||1||S → R in AAA86273. Ref.3|
|Sequence conflict||19||1||P → A in AAA86273. Ref.3|
|Sequence conflict||131||1||S → P in AAA86273. Ref.3|
|Sequence conflict||149||1||V → A in AAA86273. Ref.3|
|Sequence conflict||164||1||A → V in AAA86273. Ref.3|
|Sequence conflict||187||1||S → G in AAA86273. Ref.3|
|Sequence conflict||208||1||Q → K in AAA86273. Ref.3|
|||"Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system."|
Hollenberg S.M., Sternglanz R., Cheng P.F., Weintraub H.
Mol. Cell. Biol. 15:3813-3822(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NIH Swiss.
|||"Expression of the novel basic helix-loop-helix gene eHAND in neural crest derivatives and extraembryonic membranes during mouse development."|
Cserjesi P., Brown D., Lyons G.E., Olson E.N.
Dev. Biol. 170:664-678(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
|||"Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development."|
Cross J.C., Flannery M.L., Blanar M.A., Steingrimsson E., Jenkins N.A., Copeland N.G., Rutter W.J., Werb Z.
Development 121:2513-2523(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Embryoid bodies.
|||"The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis."|
Riley P., Anson-Cartwright L., Cross J.C.
Nat. Genet. 18:271-275(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
|||"The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function."|
Firulli B.A., Hadzic D.B., McDaid J.R., Firulli A.B.
J. Biol. Chem. 275:33567-33573(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
|||"Nucleolar release of Hand1 acts as a molecular switch to determine cell fate."|
Martindill D.M.J., Risebro C.A., Smart N., Franco-Viseras Mdel M., Rosario C.O., Swallow C.J., Dennis J.W., Riley P.R.
Nat. Cell Biol. 9:1131-1141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MDFIC, PHOSPHORYLATION AT THR-107 AND SER-109, MUTAGENESIS OF THR-107 AND SER-109.
|+||Additional computationally mapped references.|
|U21226 mRNA. Translation: AAA86887.1.|
S79216 mRNA. Translation: AAB35104.1.
U43714 mRNA. Translation: AAA86273.1.
|RefSeq||NP_032239.1. NM_008213.2. |
3D structure databases
|SMR||Q64279. Positions 102-150. |
Protein-protein interaction databases
|BioGrid||200204. 7 interactions.|
|IntAct||Q64279. 5 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335. |
ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335.
|UCSC||uc007jaf.1. mouse. |
|MGI||MGI:103577. Hand1. |
Gene expression databases
Family and domain databases
|Gene3D||4.10.280.10. 1 hit. |
|InterPro||IPR011598. bHLH_dom. |
|Pfam||PF00010. HLH. 1 hit. |
|SMART||SM00353. HLH. 1 hit. |
|SUPFAM||SSF47459. SSF47459. 1 hit. |
|PROSITE||PS50888. BHLH. 1 hit. |
|Accession||Primary (citable) accession number: Q64279|
Secondary accession number(s): Q61099
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|