Hand2

Functionⁱ

Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries. Required for vascular development and regulation of angiogenesis, possibly through a VEGF signaling pathway. Plays also an important role in limb development, particularly in the establishment of anterior-posterior polarization, acting as an upstream regulator of sonic hedgehog (SHH) induction in the limb bud. Is involved in the development of branchial arches, which give rise to unique structures in the head and neck. Binds DNA on E-box consensus sequence 5'-CANNTG-3'.4 Publications

GO - Molecular functionⁱ

activating transcription factor binding Source: BHF-UCL
AT DNA binding Source: MGI
E-box binding
Source: MGI
Inferred from direct assayⁱ
- 20144608
protein heterodimerization activity
Source: MGI
Inferred from physical interactionⁱ
- 12392994
protein homodimerization activity
Source: BHF-UCL
Inferred from physical interactionⁱ
- 11812799
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
sequence-specific DNA binding
Source: MGI
Inferred from genetic interactionⁱ
- 12070084
transcription coactivator activity Source: BHF-UCL
transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 11812799

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

adult heart development
Source: MGI
Inferred from mutant phenotypeⁱ
- 9171826
angiogenesis Source: UniProtKB-KW
apoptotic process involved in heart morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 11784028
cardiac neural crest cell development involved in outflow tract morphogenesis
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
cardiac neural crest cell migration involved in outflow tract morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 20144608
cardiac right ventricle formation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 11076755
cartilage morphogenesis
Source: MGI
Inferred from genetic interactionⁱ
- 17764670
cell proliferation involved in outflow tract morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 20144608
coronary artery morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 21350214
determination of heart left/right asymmetry
Source: MGI
Inferred from mutant phenotypeⁱ
- 9576835
embryonic digit morphogenesis
Source: MGI
Inferred from direct assayⁱ
- 12070084
heart development
Source: MGI
Inferred from genetic interactionⁱ
- 15576406
heart looping
Source: MGI
Inferred from mutant phenotypeⁱ
- 9171826
heart morphogenesis
Source: MGI
Inferred from mutant phenotypeⁱ
- 11784028
in utero embryonic development
Source: MGI
Inferred from mutant phenotypeⁱ
- 9171826
mesenchymal cell proliferation
Source: MGI
Inferred from mutant phenotypeⁱ
- 19341725
mesenchyme development
Source: MGI
Inferred from genetic interactionⁱ
- 17764670
negative regulation of apoptotic process
Source: MGI
Inferred from mutant phenotypeⁱ
- 19341725
negative regulation of cardiac muscle cell apoptotic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
negative regulation of DNA binding
Source: MGI
Inferred from direct assayⁱ
- 19144722
negative regulation of DNA-binding transcription factor activity
Source: MGI
Inferred from direct assayⁱ
- 19144722
negative regulation of gene expression Source: MGI
negative regulation of osteoblast differentiation
Source: MGI
Inferred from direct assayⁱ
- 19144722
neural crest cell development
Source: MGI
Inferred from mutant phenotypeⁱ
- 9671575
odontogenesis of dentin-containing tooth
Source: MGI
Inferred from genetic interactionⁱ
- 17764670
peripheral nervous system neuron development
Source: MGI
Inferred from direct assayⁱ
- 16145670
positive regulation of cardiac muscle hypertrophy Source: MGI
positive regulation of ERK1 and ERK2 cascade Source: MGI
positive regulation of gene expression Source: MGI
positive regulation of p38MAPK cascade Source: MGI
positive regulation of semaphorin-plexin signaling pathway involved in outflow tract morphogenesis
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
positive regulation of transcription, DNA-templated
Source: BHF-UCL
Inferred from direct assayⁱ
- 11812799
positive regulation of transcription by RNA polymerase II
Source: BHF-UCL
Inferred from direct assayⁱ
- 11812799
positive regulation of transcription from RNA polymerase II promoter involved in norepinephrine biosynthetic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
positive regulation of transcription regulatory region DNA binding Source: MGI
primary palate development
Source: MGI
Inferred from mutant phenotypeⁱ
- 17531968
regulation of secondary heart field cardioblast proliferation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
regulation of tissue remodeling Source: MGI
regulation of transcription, DNA-templated
Source: MGI
Inferred from direct assayⁱ
- 15351717
roof of mouth development
Source: MGI
Inferred from mutant phenotypeⁱ
- 17531968
- 19341725
suckling behavior
Source: MGI
Inferred from mutant phenotypeⁱ
- 17531968
sympathetic nervous system development
Source: MGI
Inferred from direct assayⁱ
- 16145670
thymus development
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19008477
tongue development
Source: MGI
Inferred from mutant phenotypeⁱ
- 17531968
visceral serous pericardium development
Source: MGI
Inferred from mutant phenotypeⁱ
- 21350214

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding
Biological process	Angiogenesis, Differentiation, Transcription, Transcription regulation

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Heart- and neural crest derivatives-expressed protein 2 Alternative name(s): Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 Short name: dHAND Helix-loop-helix transcription factor expressed in embryo and deciduum Thing-2
Gene namesⁱ	Name:Hand2 Synonyms:Dhand, Hed, Thing2
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 8

Organism-specific databases

MGIⁱ	MGI:103580 Hand2

Keywords - Cellular componentⁱ

Nucleus

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000127192	1 – 217	Heart- and neural crest derivatives-expressed protein 2Add BLAST		217

Proteomic databases

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q61039
PaxDbⁱ	Q61039
PRIDEⁱ	Q61039

PTM databases

iPTMnetⁱ	Q61039
PhosphoSitePlusⁱ	Q61039

Expressionⁱ

Tissue specificityⁱ

Heart and aorta.

Developmental stageⁱ

High extraembryonic expression is detected at 7.5 dpc in the maternally derived deciduum. Also detected along the yolk sac vessels during the process of remodeling at 9.5-10.0 dpc. Within the embryo, detected at 7.5 dpc in the lateral mesoderm including the precardiac mesoderm. On day 8.5 pc expressed throughout the straight heart tube. In the caudal region of the embryo, expressed in the lateral mesoderm at the level of separation of the somatic and splanchnic mesoderm. On day 9.5 pc expressed throughout the developing cardiovascular region, most abundant in the outflow tract and in the first and second aortic arch arteries, and in pharyngeal arches. As the heart loops, the expression becomes restricted to the conotruncus and future right ventricle (endocardium and myocardium). At 10.5 dpc, highly expressed in the branchial arches, as well as in the truncus arteriosus, aortic sac, and the vascular mesenchyme between the third and fourth aortic arch arteries, which later gives rise to vascular smooth muscle cells and to the mesenchyme of the pharyngeal arch. At 13.5 dpc, barely detectable in the heart, but apparent in the neural crest-derived sympathetic trunk and adrenal medulla, a pattern similar to that of HAND1. In the developing limbs, expression is detected in the posterior mesoderm of the buds at 9.5 dpc. It is then progressively down-regulated at the anterior of the limb buds so that a gradient expression along the anterior-posterior axis of the bud is established with higher expression at the posterior border. At later stages of limb development, expression is restricted to the posterior border of the zeugopod and to the posterior autopod. In the autopod, dynamic expression of HAND2 affects the interdigital regions, the lateral borders of the digits and eventually the developing ventral tendons. After 16 dpc, expression decreases throughout the embryo.3 Publications

Gene expression databases

Bgeeⁱ	ENSMUSG00000038193 Expressed in 171 organ(s), highest expression level in decidua
Genevisibleⁱ	Q61039 MM

Interactionⁱ

Subunit structureⁱ

Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND1 and HEY1, HEY2 and HEYL (hairy-related transcription factors).1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
Hand1	Q64279	3	EBI-81388,EBI-81361
Mcf2	Q99N72	3	EBI-81388,EBI-641874
Tcf3	P15806	2	EBI-81388,EBI-81370

GO - Molecular functionⁱ

activating transcription factor binding Source: BHF-UCL
protein heterodimerization activity
Source: MGI
Inferred from physical interactionⁱ
- 12392994
protein homodimerization activity
Source: BHF-UCL
Inferred from physical interactionⁱ
- 11812799
transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 11812799

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	200205, 6 interactors
IntActⁱ	Q61039, 7 interactors
STRINGⁱ	10090.ENSMUSP00000044983

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q61039
SMRⁱ	Q61039
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	99 – 151	bHLHPROSITE-ProRule annotationAdd BLAST		53

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	21 – 32	Poly-AlaAdd BLAST		12

Phylogenomic databases

eggNOGⁱ	KOG4029 Eukaryota ENOG411227D LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119097
HOGENOMⁱ	HOG000232082
HOVERGENⁱ	HBG051880
InParanoidⁱ	Q61039
KEGG Orthology (KO) More...KOⁱ	K18486
OMAⁱ	YLMDILD
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0MSL
PhylomeDBⁱ	Q61039
TreeFamⁱ	TF315153

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q61039-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MSLVGGFPHH PVVHHEGYPF AAAAAAAAAA AASRCSHEEN PYFHGWLIGH 
        60         70         80         90        100
PEMSPPDYSM ALSYSPEYAS GAAGLDHSHY GGVPPGAGPP GLGGPRPVKR 
       110        120        130        140        150
RGTANRKERR RTQSINSAFA ELRECIPNVP ADTKLSKIKT LRLATSYIAY 
       160        170        180        190        200
LMDLLAKDDQ NGEAEAFKAE IKKTDVKEEK RKKELNEILK STVSSNDKKT 
       210 
KGRTGWPQHV WALELKQ

Length:217

Mass (Da):23,666

Last modified:May 10, 2004 - v3

Checksum:ⁱ528F541BB2173F1E

GO

Sequence cautionⁱ

The sequence AAA86274 differs from that shown. Reason: Frameshift at position 183.Curated

The sequence AAC52338 differs from that shown. Reason: Frameshift at positions 20 and 43.Curated

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	92 – 93	LG → TA in AAA86274 (PubMed:7671815).Curated	2
Sequence conflictⁱ	156	A → P in AAC52338 (PubMed:8533092).Curated	1
Sequence conflictⁱ	166	A → G in AAA86274 (PubMed:7671815).Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U40039 Genomic DNA Translation: AAC52338.1 Frameshift. AK035160 mRNA Translation: BAC28965.1 U43715 mRNA Translation: AAA86274.1 Frameshift.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS22315.1
NCBI Reference Sequences More...RefSeqⁱ	NP_034532.3, NM_010402.4
UniGeneⁱ	Mm.430844

Genome annotation databases

Ensemblⁱ	ENSMUST00000040104; ENSMUSP00000044983; ENSMUSG00000038193
GeneIDⁱ	15111
KEGGⁱ	mmu:15111
UCSC genome browser More...UCSCⁱ	uc009lss.2 mouse

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q61039	Heart- and neural crest derivatives-expressed protein 2		HUMAN		217	UniRef100_P61296
Heart- and neural crest derivatives-expressed protein 2		RAT		217
HAND2 isoform 2		PANTR		217
Uncharacterized protein		PROCO		217
Uncharacterized protein		MACMU		217
+18

Protein	Similar proteins		Species	Score	Length	Source
Q61039	Heart- and neural crest derivatives-expressed protein 2		HUMAN		217	UniRef90_P61296
Heart- and neural crest derivatives-expressed protein 2		RAT		217
Heart- and neural crest derivatives-expressed protein 2		XENLA		210
HAND2 isoform 2		PANTR		217
Uncharacterized protein		PROCO		217
+73

Protein	Similar proteins		Species	Score	Length	Source
Q61039	Heart- and neural crest derivatives-expressed protein 2		HUMAN		217	UniRef50_P61296
Heart- and neural crest derivatives-expressed protein 2		RAT		217
Heart- and neural crest derivatives-expressed protein 2		XENLA		210
HAND2 isoform 2		PANTR		217
Uncharacterized protein		PROCO		217
+111

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U40039 Genomic DNA Translation: AAC52338.1 Frameshift. AK035160 mRNA Translation: BAC28965.1 U43715 mRNA Translation: AAA86274.1 Frameshift.
CCDSⁱ	CCDS22315.1
RefSeqⁱ	NP_034532.3, NM_010402.4
UniGeneⁱ	Mm.430844

3D structure databases

ProteinModelPortalⁱ	Q61039
SMRⁱ	Q61039
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	200205, 6 interactors
IntActⁱ	Q61039, 7 interactors
STRINGⁱ	10090.ENSMUSP00000044983

PTM databases

iPTMnetⁱ	Q61039
PhosphoSitePlusⁱ	Q61039

Proteomic databases

MaxQBⁱ	Q61039
PaxDbⁱ	Q61039
PRIDEⁱ	Q61039

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000040104; ENSMUSP00000044983; ENSMUSG00000038193
GeneIDⁱ	15111
KEGGⁱ	mmu:15111
UCSCⁱ	uc009lss.2 mouse

Organism-specific databases

CTDⁱ	9464
MGIⁱ	MGI:103580 Hand2

Phylogenomic databases

eggNOGⁱ	KOG4029 Eukaryota ENOG411227D LUCA
GeneTreeⁱ	ENSGT00760000119097
HOGENOMⁱ	HOG000232082
HOVERGENⁱ	HBG051880
InParanoidⁱ	Q61039
KOⁱ	K18486
OMAⁱ	YLMDILD
OrthoDBⁱ	EOG091G0MSL
PhylomeDBⁱ	Q61039
TreeFamⁱ	TF315153

Miscellaneous databases

ChiTaRSⁱ	Hand2 mouse
Protein Ontology More...PROⁱ	PR:Q61039
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000038193 Expressed in 171 organ(s), highest expression level in decidua
Genevisibleⁱ	Q61039 MM

Family and domain databases

CDDⁱ	cd00083 HLH, 1 hit
Gene3Dⁱ	4.10.280.10, 1 hit
InterProⁱ	View protein in InterPro IPR011598 bHLH_dom IPR036638 HLH_DNA-bd_sf
Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit
SUPFAMⁱ	SSF47459 SSF47459, 1 hit
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	HAND2_MOUSE
Accessionⁱ	Q61039Primary (citable) accession number: Q61039 Secondary accession number(s): Q61100
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
	Last sequence update:	May 10, 2004
	Last modified:	November 7, 2018
	This is version 172 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q61039 (HAND2_MOUSE)

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Heart- and neural crest derivatives-expressed protein 2

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Compositional bias

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ