Q64279 (HAND1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Protein existence	Evidence 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	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
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 process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from mutant phenotype PubMed 15073150. Source: MGI cardiac left ventricle formation Inferred from electronic annotation. Source: Compara cardiac right ventricle formation Inferred from electronic annotation. Source: Compara cardiac septum morphogenesis Inferred from electronic annotation. Source: Compara cartilage morphogenesis Inferred from genetic interaction PubMed 17764670. Source: MGI cell fate determination Non-traceable author statement Ref.6. Source: UniProtKB embryonic heart tube formation Inferred from mutant phenotype PubMed 11076684. Source: MGI heart looping 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 transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara trophectodermal cell differentiation Inferred from electronic annotation. Source: Compara 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_component	cytoplasm Inferred from electronic annotation. Source: Compara nucleolus Inferred from direct assay Ref.6. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	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 regulatory region DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-81361,EBI-81361
Hand2	Q61039	3	EBI-81361,EBI-81388
Tcf3	P15806	2	EBI-81361,EBI-81370

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 216	216	Heart- and neural crest derivatives-expressed protein 1		PRO_0000127185
Regions
	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
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Q64279 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 307B14BB835833F1	FASTA	216	23,806
	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

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.
IPI	IPI00132280.
RefSeq	NP_032239.1. NM_008213.2.
UniGene	Mm.4746.
3D structure databases
ProteinModelPortal	Q64279.
SMR	Q64279. Positions 98-152.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-455N.
IntAct	Q64279. 5 interactions.
STRING	10090.ENSMUSP00000046999.
PTM databases
PhosphoSite	Q64279.
Proteomic databases
PRIDE	Q64279.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335. ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335.
GeneID	15110.
KEGG	mmu:15110.
UCSC	uc007jaf.1. mouse.
Organism-specific databases
CTD	9421.
MGI	MGI:103577. Hand1.
Phylogenomic databases
eggNOG	NOG259520.
GeneTree	ENSGT00690000101643.
HOGENOM	HOG000232082.
HOVERGEN	HBG051880.
InParanoid	Q64279.
KO	K09071.
OMA	RPYFQSW.
OrthoDB	EOG4FTW1T.
Gene expression databases
ArrayExpress	Q64279.
Bgee	Q64279.
Genevestigator	Q64279.
GermOnline	ENSMUSG00000037335. Mus musculus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287510.
SOURCE	Search...

Entry information

Entry name

HAND1_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program