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Q64279 (HAND1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Heart- and neural crest derivatives-expressed protein 1
Alternative name(s):
Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1
Short name=eHAND
Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast
Thing-1
Short name=Th1
Gene names
Name:Hand1
Synonyms:Ehand, Hxt, Thing1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length216 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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). Ref.4

Subunit structure

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

Subcellular location

Nucleusnucleoplasm. Nucleusnucleolus. 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

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. Ref.2 Ref.4

Post-translational modification

Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to tranlocation into the nucleoplasm, allowing dimerization and transcription factor activity.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from mutant phenotype PubMed 15073150. Source: MGI

cardiac left ventricle formation

Inferred from electronic annotation. Source: Ensembl

cardiac right ventricle formation

Inferred from electronic annotation. Source: Ensembl

cardiac septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

cartilage morphogenesis

Inferred from genetic interaction PubMed 17764670. Source: MGI

cell differentiation

Inferred from genetic interaction PubMed 16759287. Source: MGI

cell fate determination

Non-traceable author statement Ref.6. Source: UniProtKB

determination of heart left/right asymmetry

Inferred from mutant phenotype PubMed 11076684. Source: MGI

embryonic heart tube development

Inferred from mutant phenotype Ref.4. Source: MGI

embryonic heart tube formation

Inferred from mutant phenotype PubMed 11076684. Source: MGI

heart development

Inferred from mutant phenotype PubMed 15576406PubMed 9500550. Source: MGI

heart looping

Inferred from mutant phenotype Ref.4. Source: MGI

heart morphogenesis

Non-traceable author statement Ref.6. Source: UniProtKB

in utero embryonic development

Inferred from mutant phenotype Ref.4. Source: MGI

mesenchyme development

Inferred from genetic interaction PubMed 17764670. Source: MGI

mesoderm formation

Inferred from mutant phenotype PubMed 9500550. Source: MGI

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19144722. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 16759287. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from genetic interaction PubMed 17764670. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15509787PubMed 16759287. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15509787. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

trophectodermal cell differentiation

Inferred from electronic annotation. Source: Ensembl

trophoblast giant cell differentiation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype Ref.4. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay Ref.6. Source: UniProtKB

nucleoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15509787. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from direct assay PubMed 15509787. Source: MGI

bHLH transcription factor binding

Inferred from physical interaction PubMed 15509787. Source: BHF-UCL

enzyme binding

Inferred from physical interaction Ref.6. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.5. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 15509787. Source: MGI

protein homodimerization activity

Inferred from physical interaction Ref.5. Source: BHF-UCL

sequence-specific DNA binding

Inferred from genetic interaction PubMed 12070084. Source: MGI

transcription coactivator activity

Inferred from direct assay PubMed 15509787. Source: BHF-UCL

transcription factor binding

Inferred from physical interaction PubMed 19144722PubMed 7814632. Source: MGI

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 216216Heart- and neural crest derivatives-expressed protein 1
PRO_0000127185

Regions

Domain94 – 14653bHLH
Compositional bias9 – 179Poly-His
Compositional bias66 – 716Poly-Ala

Amino acid modifications

Modified residue1071Phosphothreonine; by PLK4 Ref.6
Modified residue1091Phosphoserine; by PLK4 Ref.6

Experimental info

Mutagenesis1071T → A: Remains exclusively in the nucleolus; when associated with A-109. Ref.6
Mutagenesis1071T → D: Adopts a nucleus-wide distribution; when associated with D-109. Ref.6
Mutagenesis1091S → A: Remains exclusively in the nucleolus; when associated with A-107. Ref.6
Mutagenesis1091S → D: Adopts a nucleus-wide distribution; when associated with D-107. Ref.6
Sequence conflict61S → R in AAA86273. Ref.3
Sequence conflict191P → A in AAA86273. Ref.3
Sequence conflict1311S → P in AAA86273. Ref.3
Sequence conflict1491V → A in AAA86273. Ref.3
Sequence conflict1641A → V in AAA86273. Ref.3
Sequence conflict1871S → G in AAA86273. Ref.3
Sequence conflict2081Q → K in AAA86273. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q64279 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 307B14BB835833F1

FASTA21623,806
        10         20         30         40         50         60 
MNLVGSYAHH HHHHHSHPPH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPAGG 

        70         80         90        100        110        120 
PPPTTAVAAA AYGPDARPSQ SPGRLEALGS RLPKRKGSGP KKERRRTESI NSAFAELREC 

       130        140        150        160        170        180 
IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQAGDPE AFKAELKKTD GGRESKRKRE 

       190        200        210 
LPQQPESFPP ASGPGEKRIK GRTGWPQQVW ALELNQ 

« Hide

References

[1]"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.
Tissue: Embryo.
[2]"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.
Tissue: Embryo.
[3]"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].
Strain: 129/Sv.
Tissue: Embryoid bodies.
[4]"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.
[5]"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.
[6]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U21226 mRNA. Translation: AAA86887.1.
S79216 mRNA. Translation: AAB35104.1.
U43714 mRNA. Translation: AAA86273.1.
RefSeqNP_032239.1. NM_008213.2.
UniGeneMm.4746.

3D structure databases

ProteinModelPortalQ64279.
SMRQ64279. Positions 102-150.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200204. 7 interactions.
DIPDIP-455N.
IntActQ64279. 5 interactions.
STRING10090.ENSMUSP00000046999.

PTM databases

PhosphoSiteQ64279.

Proteomic databases

PRIDEQ64279.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335.
ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335.
GeneID15110.
KEGGmmu:15110.
UCSCuc007jaf.1. mouse.

Organism-specific databases

CTD9421.
MGIMGI:103577. Hand1.

Phylogenomic databases

eggNOGNOG259520.
GeneTreeENSGT00730000110394.
HOGENOMHOG000232082.
HOVERGENHBG051880.
InParanoidQ64279.
KOK09071.
OMARPYFQSW.
OrthoDBEOG7G1V82.
PhylomeDBQ64279.
TreeFamTF315153.

Gene expression databases

BgeeQ64279.
GenevestigatorQ64279.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio287510.
PROQ64279.
SOURCESearch...

Entry information

Entry nameHAND1_MOUSE
AccessionPrimary (citable) accession number: Q64279
Secondary accession number(s): Q61099
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot