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Protein

Heart- and neural crest derivatives-expressed protein 2

Gene

Hand2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processAngiogenesis, 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:103580 Hand2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271921 – 217Heart- and neural crest derivatives-expressed protein 2Add BLAST217

Proteomic databases

MaxQBiQ61039
PaxDbiQ61039
PRIDEiQ61039

PTM databases

iPTMnetiQ61039
PhosphoSitePlusiQ61039

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

BgeeiENSMUSG00000038193 Expressed in 171 organ(s), highest expression level in decidua
GenevisibleiQ61039 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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200205, 6 interactors
IntActiQ61039, 7 interactors
STRINGi10090.ENSMUSP00000044983

Structurei

3D structure databases

ProteinModelPortaliQ61039
SMRiQ61039
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini99 – 151bHLHPROSITE-ProRule annotationAdd BLAST53

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi21 – 32Poly-AlaAdd BLAST12

Phylogenomic databases

eggNOGiKOG4029 Eukaryota
ENOG411227D LUCA
GeneTreeiENSGT00760000119097
HOGENOMiHOG000232082
HOVERGENiHBG051880
InParanoidiQ61039
KOiK18486
OMAiYLMDILD
OrthoDBiEOG091G0MSL
PhylomeDBiQ61039
TreeFamiTF315153

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit

Sequencei

Sequence statusi: Complete.

Q61039-1 [UniParc]FASTAAdd 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti92 – 93LG → TA in AAA86274 (PubMed:7671815).Curated2
Sequence conflicti156A → P in AAC52338 (PubMed:8533092).Curated1
Sequence conflicti166A → G in AAA86274 (PubMed:7671815).Curated1

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.
CCDSiCCDS22315.1
RefSeqiNP_034532.3, NM_010402.4
UniGeneiMm.430844

Genome annotation databases

EnsembliENSMUST00000040104; ENSMUSP00000044983; ENSMUSG00000038193
GeneIDi15111
KEGGimmu:15111
UCSCiuc009lss.2 mouse

Similar proteinsi

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.
CCDSiCCDS22315.1
RefSeqiNP_034532.3, NM_010402.4
UniGeneiMm.430844

3D structure databases

ProteinModelPortaliQ61039
SMRiQ61039
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200205, 6 interactors
IntActiQ61039, 7 interactors
STRINGi10090.ENSMUSP00000044983

PTM databases

iPTMnetiQ61039
PhosphoSitePlusiQ61039

Proteomic databases

MaxQBiQ61039
PaxDbiQ61039
PRIDEiQ61039

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000040104; ENSMUSP00000044983; ENSMUSG00000038193
GeneIDi15111
KEGGimmu:15111
UCSCiuc009lss.2 mouse

Organism-specific databases

CTDi9464
MGIiMGI:103580 Hand2

Phylogenomic databases

eggNOGiKOG4029 Eukaryota
ENOG411227D LUCA
GeneTreeiENSGT00760000119097
HOGENOMiHOG000232082
HOVERGENiHBG051880
InParanoidiQ61039
KOiK18486
OMAiYLMDILD
OrthoDBiEOG091G0MSL
PhylomeDBiQ61039
TreeFamiTF315153

Miscellaneous databases

ChiTaRSiHand2 mouse
PROiPR:Q61039
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038193 Expressed in 171 organ(s), highest expression level in decidua
GenevisibleiQ61039 MM

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
PfamiView protein in Pfam
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHAND2_MOUSE
AccessioniPrimary (citable) accession number: Q61039
Secondary accession number(s): Q61100
Entry historyiIntegrated 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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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