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Heart- and neural crest derivatives-expressed protein 1 (Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1) (eHAND) (Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast) (Thing-1) (Th1)

 HAND1_MOUSE             Reviewed;         216 AA.
Q64279; Q61099;
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
12-SEP-2018, entry version 151.
RecName: Full=Heart- and neural crest derivatives-expressed protein 1;
AltName: Full=Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1;
Short=eHAND;
AltName: Full=Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast;
AltName: Full=Thing-1;
Short=Th1;
Name=Hand1; Synonyms=Ehand, Hxt, Thing1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=NIH Swiss; TISSUE=Embryo;
PubMed=7791788; DOI=10.1128/MCB.15.7.3813;
Hollenberg S.M., Sternglanz R., Cheng P.F., Weintraub H.;
"Identification of a new family of tissue-specific basic helix-loop-
helix proteins with a two-hybrid system.";
Mol. Cell. Biol. 15:3813-3822(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
TISSUE=Embryo;
PubMed=7649392; DOI=10.1006/dbio.1995.1245;
Cserjesi P., Brown D., Lyons G.E., Olson E.N.;
"Expression of the novel basic helix-loop-helix gene eHAND in neural
crest derivatives and extraembryonic membranes during mouse
development.";
Dev. Biol. 170:664-678(1995).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=129/Sv; TISSUE=Embryoid bodies;
PubMed=7671815;
Cross J.C., Flannery M.L., Blanar M.A., Steingrimsson E.,
Jenkins N.A., Copeland N.G., Rutter W.J., Werb Z.;
"Hxt encodes a basic helix-loop-helix transcription factor that
regulates trophoblast cell development.";
Development 121:2513-2523(1995).
[4]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=9500551; DOI=10.1038/ng0398-271;
Riley P., Anson-Cartwright L., Cross J.C.;
"The Hand1 bHLH transcription factor is essential for placentation and
cardiac morphogenesis.";
Nat. Genet. 18:271-275(1998).
[5]
SUBUNIT.
PubMed=10924525; DOI=10.1074/jbc.M005888200;
Firulli B.A., Hadzic D.B., McDaid J.R., Firulli A.B.;
"The basic helix-loop-helix transcription factors dHAND and eHAND
exhibit dimerization characteristics that suggest complex regulation
of function.";
J. Biol. Chem. 275:33567-33573(2000).
[6]
SUBCELLULAR LOCATION, INTERACTION WITH MDFIC, PHOSPHORYLATION AT
THR-107 AND SER-109, AND MUTAGENESIS OF THR-107 AND SER-109.
PubMed=17891141; DOI=10.1038/ncb1633;
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.;
"Nucleolar release of Hand1 acts as a molecular switch to determine
cell fate.";
Nat. Cell Biol. 9:1131-1141(2007).
-!- FUNCTION: 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). {ECO:0000269|PubMed:9500551}.
-!- SUBUNIT: 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.
{ECO:0000269|PubMed:10924525, ECO:0000269|PubMed:17891141}.
-!- INTERACTION:
Self; NbExp=2; IntAct=EBI-81361, EBI-81361;
Q61039:Hand2; NbExp=3; IntAct=EBI-81361, EBI-81388;
P15806:Tcf3; NbExp=2; IntAct=EBI-81361, EBI-81370;
-!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
{ECO:0000269|PubMed:17891141}. Nucleus, nucleolus
{ECO:0000269|PubMed:17891141}. 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.
-!- TISSUE SPECIFICITY: Smooth muscle cells of the gut and adrenal
tissue.
-!- DEVELOPMENTAL STAGE: 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. {ECO:0000269|PubMed:7649392,
ECO:0000269|PubMed:9500551}.
-!- PTM: Phosphorylation by PLK4 disrupts the interaction with MDFIC
and leads to translocation into the nucleoplasm, allowing
dimerization and transcription factor activity.
{ECO:0000269|PubMed:17891141}.
-----------------------------------------------------------------------
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EMBL; U21226; AAA86887.1; -; mRNA.
EMBL; S79216; AAB35104.1; -; mRNA.
EMBL; U43714; AAA86273.1; -; mRNA.
CCDS; CCDS24721.1; -.
RefSeq; NP_032239.1; NM_008213.2.
UniGene; Mm.4746; -.
ProteinModelPortal; Q64279; -.
BioGrid; 200204; 7.
DIP; DIP-455N; -.
IntAct; Q64279; 6.
STRING; 10090.ENSMUSP00000046999; -.
iPTMnet; Q64279; -.
PhosphoSitePlus; Q64279; -.
PaxDb; Q64279; -.
PRIDE; Q64279; -.
Ensembl; ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335.
Ensembl; ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335.
GeneID; 15110; -.
KEGG; mmu:15110; -.
UCSC; uc007jaf.1; mouse.
CTD; 9421; -.
MGI; MGI:103577; Hand1.
eggNOG; KOG4029; Eukaryota.
eggNOG; ENOG411227D; LUCA.
GeneTree; ENSGT00760000119097; -.
HOGENOM; HOG000232082; -.
HOVERGEN; HBG051880; -.
InParanoid; Q64279; -.
KO; K09071; -.
OMA; RPYFQSW; -.
OrthoDB; EOG091G0MSL; -.
PhylomeDB; Q64279; -.
TreeFam; TF315153; -.
PRO; PR:Q64279; -.
Proteomes; UP000000589; Chromosome 11.
Bgee; ENSMUSG00000037335; Expressed in 165 organ(s), highest expression level in placenta.
ExpressionAtlas; Q64279; baseline and differential.
Genevisible; Q64279; MM.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; ISO:MGI.
GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0046982; F:protein heterodimerization activity; IPI:MGI.
GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IGI:MGI.
GO; GO:0003713; F:transcription coactivator activity; IDA:BHF-UCL.
GO; GO:0008134; F:transcription factor binding; IPI:MGI.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0001525; P:angiogenesis; IMP:MGI.
GO; GO:0003218; P:cardiac left ventricle formation; ISO:MGI.
GO; GO:0003219; P:cardiac right ventricle formation; ISO:MGI.
GO; GO:0060411; P:cardiac septum morphogenesis; ISO:MGI.
GO; GO:0060536; P:cartilage morphogenesis; IGI:MGI.
GO; GO:0030154; P:cell differentiation; IGI:MGI.
GO; GO:0001709; P:cell fate determination; NAS:UniProtKB.
GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:MGI.
GO; GO:0035050; P:embryonic heart tube development; IMP:MGI.
GO; GO:0003144; P:embryonic heart tube formation; IMP:MGI.
GO; GO:0007507; P:heart development; IMP:MGI.
GO; GO:0001947; P:heart looping; IMP:MGI.
GO; GO:0003007; P:heart morphogenesis; TAS:BHF-UCL.
GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
GO; GO:0060485; P:mesenchyme development; IGI:MGI.
GO; GO:0001707; P:mesoderm formation; IMP:MGI.
GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; ISO:MGI.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IGI:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
GO; GO:0060707; P:trophoblast giant cell differentiation; IDA:MGI.
GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:MGI.
CDD; cd00083; HLH; 1.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
Pfam; PF00010; HLH; 1.
SMART; SM00353; HLH; 1.
SUPFAM; SSF47459; SSF47459; 1.
PROSITE; PS50888; BHLH; 1.
1: Evidence at protein level;
Activator; Complete proteome; Developmental protein; DNA-binding;
Nucleus; Phosphoprotein; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 216 Heart- and neural crest derivatives-
expressed protein 1.
/FTId=PRO_0000127185.
DOMAIN 94 146 bHLH. {ECO:0000255|PROSITE-
ProRule:PRU00981}.
COMPBIAS 9 17 Poly-His.
COMPBIAS 66 71 Poly-Ala.
MOD_RES 107 107 Phosphothreonine; by PLK4.
{ECO:0000269|PubMed:17891141}.
MOD_RES 109 109 Phosphoserine; by PLK4.
{ECO:0000269|PubMed:17891141}.
MUTAGEN 107 107 T->A: Remains exclusively in the
nucleolus; when associated with A-109.
{ECO:0000269|PubMed:17891141}.
MUTAGEN 107 107 T->D: Adopts a nucleus-wide distribution;
when associated with D-109.
{ECO:0000269|PubMed:17891141}.
MUTAGEN 109 109 S->A: Remains exclusively in the
nucleolus; when associated with A-107.
{ECO:0000269|PubMed:17891141}.
MUTAGEN 109 109 S->D: Adopts a nucleus-wide distribution;
when associated with D-107.
{ECO:0000269|PubMed:17891141}.
CONFLICT 6 6 S -> R (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 19 19 P -> A (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 131 131 S -> P (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 149 149 V -> A (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 164 164 A -> V (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 187 187 S -> G (in Ref. 3; AAA86273).
{ECO:0000305}.
CONFLICT 208 208 Q -> K (in Ref. 3; AAA86273).
{ECO:0000305}.
SEQUENCE 216 AA; 23806 MW; 307B14BB835833F1 CRC64;
MNLVGSYAHH HHHHHSHPPH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPAGG
PPPTTAVAAA AYGPDARPSQ SPGRLEALGS RLPKRKGSGP KKERRRTESI NSAFAELREC
IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQAGDPE AFKAELKKTD GGRESKRKRE
LPQQPESFPP ASGPGEKRIK GRTGWPQQVW ALELNQ


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