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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 basic helix-loop-helix (bHLH) 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 heart looping Inferred from sequence or structural similarity. Source: BHF-UCL in utero embryonic development Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of cardiac muscle cell apoptosis Inferred from sequence or structural similarity. Source: BHF-UCL noradrenergic neuron differentiation Non-traceable author statement. Source: BHF-UCL positive regulation of transcription regulatory region DNA binding Inferred from direct assay. Source: BHF-UCL regulation of secondary heart field cardioblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL thymus development Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	nuclear chromatin Inferred from direct assay. Source: BHF-UCL transcription factor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	AT DNA binding Inferred from direct assay. Source: UniProtKB E-box binding Inferred from direct assay. 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. Source: UniProtKB RNA polymerase II regulatory region sequence-specific DNA binding Inferred from direct assay. 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	112 – 155	44	Helix-loop-helix motif
	DNA binding	99 – 111	13	Basic motif
	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

[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: 9878849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Embryonic heart.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF087940 mRNA. Translation: AAD13185.1. AF087941 Genomic DNA. Translation: AAD13186.1.
IPI	IPI00029953.
RefSeq	NP_068808.1. NM_021973.2.
UniGene	Hs.388245.
3D structure databases
ProteinModelPortal	P61296.
SMR	P61296. Positions 100-156.
ModBase	Search...
Protein-protein interaction databases
STRING	P61296.
Polymorphism databases
DMDM	47117699.
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.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12455.
HOGENOM	HBG717563.
HOVERGEN	HBG051880.
InParanoid	P61296.
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
InterPro	IPR011598. HLH_DNA-bd. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K09071.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. HLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	35460.
SOURCE	Search...

Entry information

Entry name

HAND2_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	January 25, 2012
This is version 70 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.