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Q61039

- HAND2_MOUSE

UniProt

Q61039 - HAND2_MOUSE

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Protein

Heart- and neural crest derivatives-expressed protein 2

Gene
Hand2, Dhand, Hed, Thing2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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

  1. activating transcription factor binding Source: BHF-UCL
  2. AT DNA binding Source: Ensembl
  3. E-box binding Source: MGI
  4. protein binding Source: IntAct
  5. protein heterodimerization activity Source: MGI
  6. protein homodimerization activity Source: BHF-UCL
  7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  8. RNA polymerase II regulatory region sequence-specific DNA binding Source: Ensembl
  9. sequence-specific DNA binding Source: MGI
  10. transcription coactivator activity Source: BHF-UCL
  11. transcription factor binding Source: BHF-UCL

GO - Biological processi

  1. adult heart development Source: MGI
  2. angiogenesis Source: UniProtKB-KW
  3. apoptotic process involved in heart morphogenesis Source: MGI
  4. cardiac neural crest cell development involved in outflow tract morphogenesis Source: BHF-UCL
  5. cardiac neural crest cell migration involved in outflow tract morphogenesis Source: MGI
  6. cardiac right ventricle formation Source: BHF-UCL
  7. cartilage morphogenesis Source: MGI
  8. cell proliferation involved in outflow tract morphogenesis Source: MGI
  9. coronary artery morphogenesis Source: MGI
  10. determination of heart left/right asymmetry Source: MGI
  11. embryonic digit morphogenesis Source: MGI
  12. heart development Source: MGI
  13. heart looping Source: MGI
  14. heart morphogenesis Source: MGI
  15. in utero embryonic development Source: MGI
  16. mesenchymal cell proliferation Source: MGI
  17. mesenchyme development Source: MGI
  18. negative regulation of apoptotic process Source: MGI
  19. negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
  20. negative regulation of DNA binding Source: MGI
  21. negative regulation of osteoblast differentiation Source: MGI
  22. negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  23. neural crest cell development Source: MGI
  24. odontogenesis of dentin-containing tooth Source: MGI
  25. palate development Source: MGI
  26. peripheral nervous system neuron development Source: MGI
  27. positive regulation of semaphorin-plexin signaling pathway involved in outflow tract morphogenesis Source: BHF-UCL
  28. positive regulation of transcription, DNA-templated Source: BHF-UCL
  29. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  30. positive regulation of transcription from RNA polymerase II promoter involved in norepinephrine biosynthetic process Source: BHF-UCL
  31. positive regulation of transcription regulatory region DNA binding Source: Ensembl
  32. regulation of secondary heart field cardioblast proliferation Source: BHF-UCL
  33. regulation of transcription, DNA-templated Source: MGI
  34. suckling behavior Source: MGI
  35. sympathetic nervous system development Source: MGI
  36. thymus development Source: BHF-UCL
  37. tongue development Source: MGI
  38. visceral serous pericardium development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:103580. Hand2.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. nuclear chromatin Source: Ensembl
  2. nucleus Source: MGI
  3. transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 217217Heart- and neural crest derivatives-expressed protein 2PRO_0000127192Add
BLAST

Proteomic databases

PRIDEiQ61039.

PTM databases

PhosphoSiteiQ61039.

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

BgeeiQ61039.
GenevestigatoriQ61039.

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

WithEntry#Exp.IntActNotes
Hand1Q642793EBI-81388,EBI-81361
Mcf2Q99N723EBI-81388,EBI-641874
Tcf3P158062EBI-81388,EBI-81370

Protein-protein interaction databases

BioGridi200205. 6 interactions.
IntActiQ61039. 6 interactions.
MINTiMINT-1666727.

Structurei

3D structure databases

ProteinModelPortaliQ61039.
SMRiQ61039. Positions 94-155.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini99 – 15153bHLHAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi21 – 3212Poly-AlaAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG259520.
GeneTreeiENSGT00730000110394.
HOGENOMiHOG000232082.
HOVERGENiHBG051880.
InParanoidiQ61039.
KOiK09071.
OMAiATRCGHE.
OrthoDBiEOG7G1V82.
PhylomeDBiQ61039.
TreeFamiTF315153.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61039-1 [UniParc]FASTAAdd to Basket

« Hide

MSLVGGFPHH PVVHHEGYPF AAAAAAAAAA AASRCSHEEN PYFHGWLIGH    50
PEMSPPDYSM ALSYSPEYAS GAAGLDHSHY GGVPPGAGPP GLGGPRPVKR 100
RGTANRKERR RTQSINSAFA ELRECIPNVP ADTKLSKIKT LRLATSYIAY 150
LMDLLAKDDQ NGEAEAFKAE IKKTDVKEEK RKKELNEILK STVSSNDKKT 200
KGRTGWPQHV WALELKQ 217
Length:217
Mass (Da):23,666
Last modified:May 10, 2004 - v3
Checksum:i528F541BB2173F1E
GO

Sequence cautioni

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.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti92 – 932LG → TA in AAA86274. 1 Publication
Sequence conflicti156 – 1561A → P in AAC52338. 1 Publication
Sequence conflicti166 – 1661A → G in AAA86274. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U40039 Genomic DNA. Translation: AAC52338.1 . Frameshift.
AK035160 mRNA. Translation: BAC28965.1 .
U43715 mRNA. Translation: AAA86274.1 . Frameshift.
CCDSi CCDS22315.1.
RefSeqi NP_034532.3. NM_010402.4.
UniGenei Mm.430844.

3D structure databases

ProteinModelPortali Q61039.
SMRi Q61039. Positions 94-155.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200205. 6 interactions.
IntActi Q61039. 6 interactions.
MINTi MINT-1666727.

PTM databases

PhosphoSitei Q61039.

Proteomic databases

PRIDEi Q61039.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000040104 ; ENSMUSP00000044983 ; ENSMUSG00000038193 .
GeneIDi 15111.
KEGGi mmu:15111.
UCSCi uc009lss.2. mouse.

Organism-specific databases

CTDi 9464.
MGIi MGI:103580. Hand2.

Phylogenomic databases

eggNOGi NOG259520.
GeneTreei ENSGT00730000110394.
HOGENOMi HOG000232082.
HOVERGENi HBG051880.
InParanoidi Q61039.
KOi K09071.
OMAi ATRCGHE.
OrthoDBi EOG7G1V82.
PhylomeDBi Q61039.
TreeFami TF315153.

Miscellaneous databases

ChiTaRSi HAND2. mouse.
NextBioi 287514.
PROi Q61039.
SOURCEi Search...

Gene expression databases

Bgeei Q61039.
Genevestigatori Q61039.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
[Graphical view ]
Pfami PF00010. HLH. 1 hit.
[Graphical view ]
SMARTi SM00353. HLH. 1 hit.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiHAND2_MOUSE
AccessioniPrimary (citable) accession number: Q61039
Secondary accession number(s): Q61100
Entry historyi
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 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
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi