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FLASH GENE
Symbol HAND2 contributors: mct/npt/pgu/shn - updated : 06-12-2013
HGNC name heart and neural crest derivatives expressed 2
HGNC id 4808
Location 4q34.1      Physical location : 174.447.651 - 174.451.378
Synonym name
  • deciduum, heart, autonomic nervous system and neural crest
  • derivatives-expressed protein 2
  • basic helix-loop-helix transcription factor HAND2
  • class A basic helix-loop-helix protein 26
  • heart- and neural crest derivatives-expressed protein 2
  • Synonym symbol(s) DHAND, HED, DHAND2, THING2, FLJ16260, Hed, MGC125303, MGC125304, bHLHa26
    DNA
    TYPE functioning gene
    STRUCTURE 3.73 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D4S1595 - D4S2992 - HAND2 - D4S2991 - D4S2431 - qter
    Physical map
    KIAA0626 4q32.3 KIAA0626 gene product AADAT 4q32.2 aminoadipate aminotransferase LOC132604 4q34.1 GalNAc transferase 10 isoform-like GALNT7 4q31.1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GalNAc-T7) HMGB2 4q31 high-mobility group box 2 SAP30 4q34.1 sin3-associated polypeptide, 30kDa SCRG1 4q31-q32 sin3-associated polypeptide, 30kDa LOC391716 4 similar to 60S ribosomal protein L5 LOC389242 4 LOC389242 HAND2 4q33 heart and neural crest derivatives expressed 2 FLJ11539 4q34.1 hypothetical protein FLJ11539 MORF4 4q33-q34.1 mortality factor 4 LOC391717 4 similar to RAN protein LOC389243 4 LOC389243 FBXO8 4q34.1 F-box only protein 8 KIAA1712 4q34 KIAA1712 HPGD 4q34-q35 hydroxyprostaglandin dehydrogenase 15-(NAD) GLRA3 4q33-q34 glycine receptor, alpha 3 ADAM29 4q34 a disintegrin and metalloproteinase domain 29 LOC391718 4 similar to hypothetical protein MGC2776 GPM6A 4q34 glycoprotein M6A WDR17 4q34 WD repeat domain 17 TSARG2 4q34.2 testis and spermatogenesis cell related protein 2 ASB5 4q34.1 ankyrin repeat and SOCS box-containing 5 FLJ22649 4q34.2 hypothetical protein FLJ22649 similar to signal peptidase SPC22/23 VEGFC 4q34 vascular endothelial growth factor C
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2368 - 217 - 2006 16467358
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiensAdultNM_021973
     heartventricle    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • heart and neural crest derivates, developing right ventricules, vascular smooth muscle cells
  • expressed in numerous cell lineages that contribute to the developing heart
  • cardiac expression is largely limited to cells of the primary heart field, overlapping little with HAND2 expression
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic helix-loop-helix (HLH) protein
  • a strong transcriptional activation domain in the amino-terminal third of the protein
  • HOMOLOGY
    interspecies ortholog to Hand2, Mus musculus
    ortholog to hand2, Danio rerio
    ortholog to Hand2, Rattus norvegicus
    ortholog to HAND2, Pan troglodytes
    Homologene
    FAMILY
  • Hand family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • required for vascular development and regulates angiogenesis
  • activating UFD1L in neural crest mesenchyme
  • functions as a transcription activator by binding a subset of E-boxes as a heterodimer with E-proteins
  • acting in a complementary fashion with HAND1 in the formation of right ventricles and aortic arches and in regulation of angiogenesis
  • maybe involved in breaking of symetry (conversion)
  • having an essential and selective function for the noradrenergic differentiation of sympathetic neurons
  • playing an essential role for the differentiation of noradrenergic neurons
  • implicated in the maintenance of TH and DBH expression in autonomic neurons
  • have a crucial function in sustaining the survival of neonatal sympathetic neurons with NGF by a feed-forward loop that maintains the expression of NTRK1
  • acts as a novel inhibitor of the RUNX2-DNA interaction and thereby regulates osteoblast differentiation in branchial arch development
  • plays a key role in maintaining noradrenergic properties in differentiated neurons
  • HAND2 acts with PBX in early myocardial differentiation
  • strongly inhibited chondrogenesis in the axial and cranial base skeleton
  • the HAND2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of FN1 levels
  • essential for survival of second heart field progenitors and the graded loss of HAND2 function in this cardiac progenitor pool can cause a spectrum of congenital heart malformation
  • HAND2 and GATA3 are transcription factors that induce noradrenergic genes during development and are present in mature sympathetic neurons
  • cardiac HAND1 expression is largely limited to cells of the primary heart field, overlapping little with HAND2 expression
  • appears to establish a distal mandibular arch domain that is conducive for lower jaw development, including the initiation of tongue mesenchyme morphogenesis
  • essential for neurogenesis, neurotransmitter specification and neural network patterning in the developing enteric nervous system
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text involved in development of the branchial arches, heart, limb, vasculature, and nervous system
    PATHWAY
    metabolism
    signaling
  • HAND2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of FN1 levels
  • a component
  • heterodimering with TWIST1 (coexpressed in distinct regions of the developing limb)
  • HAND2 formed a complex with TCF3, and bound to the E-box in the target gene promoter region
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • GATA4
  • heterodimerizes with the broadly expressed bHLH factors, the E-proteins
  • Arix
  • PP2A targeting-subunit B56delta
  • TCF3
  • can activate the SNS differentiation program by induction of SNS-related genes, including PHOX2B, ASCL1, DBH and TH
  • cell & other
    REGULATION
    induced by the activation of canonical Wnt signaling, which strongly represses chondrogenesis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    represses chondrogenesis and the expression of chondrocytic genes, SOX9, type II collagen and aggrecan
    constitutional   amplification    
    recurring copy-number variants in congenital heart disease
    Susceptibility to Saethre-Chotzen syndrome and limb abnormalities
    Variant & Polymorphism
    Candidate gene
  • may be a potential candidate gene of stenosis of the right ventricle, outflow tract
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Targeted deletion of the dHAND gene in mice revealed severe defects of embryonic and yolk sac vascular development by embryonic day 9.5
  • Hand2 deletion in mouse nestin-expressing neural precursor cells impacts development of the enteric nervous system resulting in a marked disruption of the developing neural network, exemplified by lack of a myenteric plexus and extensive overgrowth of fibers