P61296 (HAND2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Angiogenesis Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult 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 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: Compara cardiac right ventricle formation Inferred from electronic annotation. Source: Compara cartilage morphogenesis Inferred from electronic annotation. Source: Compara cell proliferation involved in outflow tract morphogenesis Inferred from electronic annotation. Source: Compara coronary artery morphogenesis Inferred from electronic annotation. Source: Compara embryonic digit morphogenesis Inferred from electronic annotation. Source: Compara heart looping 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: Compara negative regulation of DNA binding Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara noradrenergic neuron differentiation Non-traceable author statement PubMed 16280598. Source: BHF-UCL odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara palate development Inferred from electronic annotation. Source: Compara peripheral nervous system neuron development Inferred from electronic annotation. Source: Compara 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 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 regulation of secondary heart field cardioblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL suckling behavior Inferred from electronic annotation. Source: Compara sympathetic nervous system development Inferred from electronic annotation. Source: Compara thymus development Inferred from sequence or structural similarity. Source: BHF-UCL tongue development Inferred from electronic annotation. Source: Compara visceral serous pericardium development Inferred from electronic annotation. Source: Compara
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 16280598. Source: BHF-UCL transcription factor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	AT 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 217	217	Heart- and neural crest derivatives-expressed protein 2		PRO_0000127191
Regions
	Domain	99 – 151	53	bHLH
	Compositional bias	21 – 32	12	Poly-Ala

Sequences

	Sequence		Length	Mass (Da)
	P61296 [UniParc]. Last modified May 10, 2004. Version 1. Checksum: 528F541BB2173F1E	FASTA	217	23,666
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00029953.
RefSeq	NP_068808.1. NM_021973.2.
UniGene	Hs.388245.
3D structure databases
ProteinModelPortal	P61296.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000352565.
PTM databases
PhosphoSite	P61296.
Polymorphism databases
DMDM	47117699.
Proteomic databases
PaxDb	P61296.
PRIDE	P61296.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359562; ENSP00000352565; ENSG00000164107.
GeneID	9464.
KEGG	hsa:9464.
UCSC	uc003ith.1. human.
Organism-specific databases
CTD	9464.
GeneCards	GC04M174447.
HGNC	HGNC:4808. HAND2.
HPA	CAB025576.
MIM	602407. gene.
neXtProt	NX_P61296.
PharmGKB	PA29184.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG259520.
HOGENOM	HOG000232082.
HOVERGEN	HBG051880.
InParanoid	P61296.
KO	K09071.
OMA	ATRCGHE.
OrthoDB	EOG4FTW1T.
PhylomeDB	P61296.
Gene expression databases
ArrayExpress	P61296.
Bgee	P61296.
CleanEx	HS_HAND2.
Genevestigator	P61296.
GermOnline	ENSG00000164107. Homo sapiens.
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
GenomeRNAi	9464.
NextBio	35460.
SOURCE	Search...

Entry information

Entry name

HAND2_HUMAN

Accession

Primary (citable) accession number: P61296
Secondary accession number(s): B6ECG9 , O95300, O95301, P97833

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	May 1, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.