Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P61296 (HAND2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Heart- and neural crest derivatives-expressed protein 2
Alternative name(s):
Class A basic helix-loop-helix protein 26
Short name=bHLHa26
Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2
Short name=dHAND
Gene names
Name:HAND2
Synonyms:BHLHA26, DHAND
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length217 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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' By similarity.

Subunit structure

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) By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Heart.

Developmental stage

Expressed in the fetal heart.

Sequence similarities

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

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult heart development

Inferred from expression pattern Ref.1. Source: BHF-UCL

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

apoptotic process involved in heart morphogenesis

Inferred from electronic annotation. Source: Ensembl

cardiac neural crest cell development involved in outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac neural crest cell migration involved in outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

cardiac right ventricle formation

Inferred from electronic annotation. Source: Ensembl

cartilage morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell proliferation involved in outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

coronary artery morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Inferred from electronic annotation. Source: Ensembl

heart development

Non-traceable author statement PubMed 15486975. Source: UniProtKB

heart looping

Inferred from sequence or structural similarity. Source: BHF-UCL

heart morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

in utero embryonic development

Inferred from sequence or structural similarity. Source: BHF-UCL

mesenchymal cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of cardiac muscle cell apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

neural crest cell development

Inferred from sequence or structural similarity. Source: BHF-UCL

noradrenergic neuron differentiation

Non-traceable author statement PubMed 16280598. Source: BHF-UCL

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

peripheral nervous system neuron development

Inferred from electronic annotation. Source: Ensembl

positive regulation of semaphorin-plexin signaling pathway involved in outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15486975. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter involved in norepinephrine biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription regulatory region DNA binding

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of secondary heart field cardioblast proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: BHF-UCL

suckling behavior

Inferred from electronic annotation. Source: Ensembl

sympathetic nervous system development

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from sequence or structural similarity. Source: BHF-UCL

tongue development

Inferred from electronic annotation. Source: Ensembl

visceral serous pericardium development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

protein complex

Inferred from direct assay PubMed 15486975. Source: UniProtKB

transcription factor complex

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionAT DNA binding

Inferred from direct assay PubMed 15486975. Source: UniProtKB

E-box binding

Inferred from direct assay PubMed 15486975. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 15486975. Source: UniProtKB

RNA polymerase II regulatory region sequence-specific DNA binding

Inferred from direct assay PubMed 16280598. Source: BHF-UCL

activating transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein homodimerization activity

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription coactivator activity

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 217217Heart- and neural crest derivatives-expressed protein 2
PRO_0000127191

Regions

Domain99 – 15153bHLH
Compositional bias21 – 3212Poly-Ala

Sequences

Sequence LengthMass (Da)Tools
P61296 [UniParc].

Last modified May 10, 2004. Version 1.
Checksum: 528F541BB2173F1E

FASTA21723,666
        10         20         30         40         50         60 
MSLVGGFPHH PVVHHEGYPF AAAAAAAAAA AASRCSHEEN PYFHGWLIGH PEMSPPDYSM 

        70         80         90        100        110        120 
ALSYSPEYAS GAAGLDHSHY GGVPPGAGPP GLGGPRPVKR RGTANRKERR RTQSINSAFA 

       130        140        150        160        170        180 
ELRECIPNVP ADTKLSKIKT LRLATSYIAY LMDLLAKDDQ NGEAEAFKAE IKKTDVKEEK 

       190        200        210 
RKKELNEILK STVSSNDKKT KGRTGWPQHV WALELKQ 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the human HAND2 gene."
Russell M.W., Kemp P., Wang L., Brody L.C., Izumo S.
Biochim. Biophys. Acta 1443:393-399(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Embryonic heart.
[2]"Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma."
Voth H., Oberthuer A., Simon T., Kahlert Y., Berthold F., Fischer M.
BMC Mol. Biol. 10:28-28(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Neuroblastoma.
[3]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF087940 mRNA. Translation: AAD13185.1.
AF087941 Genomic DNA. Translation: AAD13186.1.
FJ226608 mRNA. Translation: ACI42790.1.
CH471056 Genomic DNA. Translation: EAX04749.1.
RefSeqNP_068808.1. NM_021973.2.
UniGeneHs.388245.

3D structure databases

ProteinModelPortalP61296.
SMRP61296. Positions 94-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114850. 13 interactions.
STRING9606.ENSP00000352565.

PTM databases

PhosphoSiteP61296.

Polymorphism databases

DMDM47117699.

Proteomic databases

PaxDbP61296.
PRIDEP61296.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359562; ENSP00000352565; ENSG00000164107.
GeneID9464.
KEGGhsa:9464.
UCSCuc003ith.1. human.

Organism-specific databases

CTD9464.
GeneCardsGC04M174447.
HGNCHGNC:4808. HAND2.
HPACAB025576.
MIM602407. gene.
neXtProtNX_P61296.
PharmGKBPA29184.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259520.
HOGENOMHOG000232082.
HOVERGENHBG051880.
InParanoidP61296.
KOK09071.
OMAATRCGHE.
PhylomeDBP61296.
TreeFamTF315153.

Gene expression databases

ArrayExpressP61296.
BgeeP61296.
CleanExHS_HAND2.
GenevestigatorP61296.

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

GeneWikiHAND2.
GenomeRNAi9464.
NextBio35460.
PROP61296.
SOURCESearch...

Entry information

Entry nameHAND2_HUMAN
AccessionPrimary (citable) accession number: P61296
Secondary accession number(s): B6ECG9 expand/collapse secondary AC list , O95300, O95301, P97833
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: April 16, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM