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Q61039

- HAND2_MOUSE

UniProt

Q61039 - HAND2_MOUSE

Protein

Heart- and neural crest derivatives-expressed protein 2

Gene

Hand2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 3 (10 May 2004)
      Previous versions | rss
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    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

    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 PROSITE-ProRule annotation

    GO - Cellular componenti

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

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini99 – 15153bHLHPROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

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

    Sequence similaritiesi

    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti92 – 932LG → TA in AAA86274. (PubMed:7671815)Curated
    Sequence conflicti156 – 1561A → P in AAC52338. (PubMed:8533092)Curated
    Sequence conflicti166 – 1661A → G in AAA86274. (PubMed:7671815)Curated

    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

    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: October 1, 2014
    This is version 144 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