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Q61039 (HAND2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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):
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 names
Name:Hand2
Synonyms:Dhand, Hed, Thing2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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'. Ref.4 Ref.5 Ref.7 Ref.8

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). Ref.6

Subcellular location

Nucleus By similarity.

Tissue specificity

Heart and aorta.

Developmental stage

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. Ref.4 Ref.7 Ref.8

Sequence similarities

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

Sequence caution

The sequence AAA86274.1 differs from that shown. Reason: Frameshift at position 183.

The sequence AAC52338.1 differs from that shown. Reason: Frameshift at positions 20 and 43.

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 mutant phenotype Ref.4. Source: MGI

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process involved in heart morphogenesis

Inferred from mutant phenotype PubMed 11784028. Source: MGI

cardiac neural crest cell development involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

cardiac neural crest cell migration involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 20144608. Source: MGI

cardiac right ventricle formation

Inferred from mutant phenotype PubMed 11076755. Source: BHF-UCL

cartilage morphogenesis

Inferred from genetic interaction PubMed 17764670. Source: MGI

cell proliferation involved in outflow tract morphogenesis

Inferred from mutant phenotype PubMed 20144608. Source: MGI

coronary artery morphogenesis

Inferred from mutant phenotype PubMed 21350214. Source: MGI

determination of heart left/right asymmetry

Inferred from mutant phenotype PubMed 9576835. Source: MGI

embryonic digit morphogenesis

Inferred from direct assay PubMed 12070084. Source: MGI

heart development

Inferred from genetic interaction PubMed 15576406. Source: MGI

heart looping

Inferred from mutant phenotype Ref.4. Source: MGI

heart morphogenesis

Inferred from mutant phenotype PubMed 11784028. Source: MGI

in utero embryonic development

Inferred from mutant phenotype Ref.4. Source: MGI

mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 19341725. Source: MGI

mesenchyme development

Inferred from genetic interaction PubMed 17764670. Source: MGI

negative regulation of DNA binding

Inferred from direct assay PubMed 19144722. Source: MGI

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 19341725. Source: MGI

negative regulation of cardiac muscle cell apoptotic process

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

negative regulation of osteoblast differentiation

Inferred from direct assay PubMed 19144722. Source: MGI

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19144722. Source: MGI

neural crest cell development

Inferred from mutant phenotype Ref.5. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from genetic interaction PubMed 17764670. Source: MGI

palate development

Inferred from mutant phenotype PubMed 17531968PubMed 19341725. Source: MGI

peripheral nervous system neuron development

Inferred from direct assay PubMed 16145670. Source: MGI

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

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11812799. Source: BHF-UCL

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

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

positive regulation of transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11812799. Source: BHF-UCL

regulation of secondary heart field cardioblast proliferation

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15351717. Source: MGI

suckling behavior

Inferred from mutant phenotype PubMed 17531968. Source: MGI

sympathetic nervous system development

Inferred from direct assay PubMed 16145670. Source: MGI

thymus development

Inferred from mutant phenotype PubMed 19008477. Source: BHF-UCL

tongue development

Inferred from mutant phenotype PubMed 17531968. Source: MGI

visceral serous pericardium development

Inferred from mutant phenotype PubMed 21350214. Source: MGI

   Cellular_componentnuclear chromatin

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 19144722. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 11812799. Source: BHF-UCL

   Molecular_functionAT DNA binding

Inferred from electronic annotation. Source: Ensembl

E-box binding

Inferred from direct assay PubMed 20144608. Source: MGI

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

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II regulatory region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

activating transcription factor binding

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

protein binding

Inferred from physical interaction Ref.6PubMed 15102471. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 12392994. Source: MGI

protein homodimerization activity

Inferred from physical interaction PubMed 11812799. Source: BHF-UCL

sequence-specific DNA binding

Inferred from genetic interaction PubMed 12070084. Source: MGI

transcription coactivator activity

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

transcription factor binding

Inferred from physical interaction PubMed 11812799. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 217217Heart- and neural crest derivatives-expressed protein 2
PRO_0000127192

Regions

Domain99 – 15153bHLH
Compositional bias21 – 3212Poly-Ala

Experimental info

Sequence conflict92 – 932LG → TA in AAA86274. Ref.3
Sequence conflict1561A → P in AAC52338. Ref.1
Sequence conflict1661A → G in AAA86274. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q61039 [UniParc].

Last modified May 10, 2004. Version 3.
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]"A subclass of bHLH proteins required for cardiac morphogenesis."
Srivastava D., Cserjesi P., Olson E.N.
Science 270:1995-1998(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Embryo.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
[3]"Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development."
Cross J.C., Flannery M.L., Blanar M.A., Steingrimsson E., Jenkins N.A., Copeland N.G., Rutter W.J., Werb Z.
Development 121:2513-2523(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 92-203.
Strain: 129/Sv.
Tissue: Embryoid bodies.
[4]"Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND."
Srivastava D., Thomas T., Lin Q., Kirby M.L., Brown D., Olson E.N.
Nat. Genet. 16:154-160(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[5]"A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme."
Thomas T., Kurihara H., Yamagishi H., Kurihara Y., Yazaki Y., Olson E.N., Srivastava D.
Development 125:3005-3014(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function."
Firulli B.A., Hadzic D.B., McDaid J.R., Firulli A.B.
J. Biol. Chem. 275:33567-33573(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"The bHLH transcription factor dHAND controls Sonic hedgehog expression and establishment of the zone of polarizing activity during limb development."
Charite J., McFadden D.G., Olson E.N.
Development 127:2461-2470(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[8]"Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway."
Fernandez-Teran M., Piedra M.E., Kathiriya I.S., Srivastava D., Rodriguez-Rey J.C., Ros M.A.
Development 127:2133-2142(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U40039 Genomic DNA. Translation: AAC52338.1. Frameshift.
AK035160 mRNA. Translation: BAC28965.1.
U43715 mRNA. Translation: AAA86274.1. Frameshift.
CCDSCCDS22315.1.
RefSeqNP_034532.3. NM_010402.4.
UniGeneMm.430844.

3D structure databases

ProteinModelPortalQ61039.
SMRQ61039. Positions 94-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200205. 6 interactions.
IntActQ61039. 6 interactions.
MINTMINT-1666727.

PTM databases

PhosphoSiteQ61039.

Proteomic databases

PRIDEQ61039.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000040104; ENSMUSP00000044983; ENSMUSG00000038193.
GeneID15111.
KEGGmmu:15111.
UCSCuc009lss.2. mouse.

Organism-specific databases

CTD9464.
MGIMGI:103580. Hand2.

Phylogenomic databases

eggNOGNOG259520.
GeneTreeENSGT00730000110394.
HOGENOMHOG000232082.
HOVERGENHBG051880.
InParanoidQ61039.
KOK09071.
OMAATRCGHE.
OrthoDBEOG7G1V82.
PhylomeDBQ61039.
TreeFamTF315153.

Gene expression databases

BgeeQ61039.
GenevestigatorQ61039.

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

ChiTaRSHAND2. mouse.
NextBio287514.
PROQ61039.
SOURCESearch...

Entry information

Entry nameHAND2_MOUSE
AccessionPrimary (citable) accession number: Q61039
Secondary accession number(s): Q61100
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 10, 2004
Last modified: July 9, 2014
This is version 143 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot