UniProtKB - Q64279 (HAND1_MOUSE)
Protein
Heart- and neural crest derivatives-expressed protein 1
Gene
Hand1
Organism
Mus musculus (Mouse)
Status
Functioni
Transcription factor that plays an essential role in both trophoblast giant cell differentiation and in cardiac morphogenesis (PubMed:9500551, PubMed:16759287). Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (PubMed:7791788). Acts as a transcriptional repressor of SOX15 (PubMed:16759287). In the adult, could be required for ongoing expression of cardiac-specific genes (By similarity).By similarity3 Publications
GO - Molecular functioni
- bHLH transcription factor binding Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: BHF-UCL
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: MGI
- enzyme binding Source: UniProtKB
- identical protein binding Source: MGI
- protein homodimerization activity Source: BHF-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific DNA binding Source: MGI
- transcription coregulator binding Source: BHF-UCL
- transcription factor binding Source: MGI
GO - Biological processi
- angiogenesis Source: MGI
- cardiac left ventricle formation Source: MGI
- cardiac right ventricle formation Source: MGI
- cardiac septum morphogenesis Source: MGI
- cartilage morphogenesis Source: MGI
- cell differentiation Source: MGI
- cell fate determination Source: UniProtKB
- determination of heart left/right asymmetry Source: MGI
- developmental process Source: GO_Central
- embryonic heart tube development Source: MGI
- embryonic heart tube formation Source: MGI
- heart development Source: MGI
- heart looping Source: MGI
- heart morphogenesis Source: BHF-UCL
- in utero embryonic development Source: MGI
- mesenchyme development Source: MGI
- mesoderm formation Source: MGI
- negative regulation of DNA-binding transcription factor activity Source: MGI
- negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- odontogenesis of dentin-containing tooth Source: MGI
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- regulation of transcription by RNA polymerase II Source: GO_Central
- trophectodermal cell differentiation Source: Ensembl
- trophoblast giant cell differentiation Source: MGI
- ventricular cardiac muscle tissue morphogenesis Source: MGI
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Heart- and neural crest derivatives-expressed protein 1Alternative name(s): Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 Short name: eHAND Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast Thing-1 Short name: Th1 |
Gene namesi | Name:Hand1 Synonyms:Ehand, Hxt, Thing1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:103577, Hand1 |
Subcellular locationi
Nucleus
- nucleoplasm 1 Publication
- nucleolus 1 Publication
Note: Interaction with MDFIC sequesters it into the nucleolus, preventing the transcription factor activity. Phosphorylation by PLK4 disrupts the interaction with MDFIC and releases it from the nucleolus, leading to transcription factor activity.
Nucleus
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: MGI
- RNA polymerase II transcription regulator complex Source: MGI
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 107 | T → A: Remains exclusively in the nucleolus; when associated with A-109. 1 Publication | 1 | |
Mutagenesisi | 107 | T → D: Adopts a nucleus-wide distribution; when associated with D-109. 1 Publication | 1 | |
Mutagenesisi | 109 | S → A: Remains exclusively in the nucleolus; when associated with A-107. 1 Publication | 1 | |
Mutagenesisi | 109 | S → D: Adopts a nucleus-wide distribution; when associated with D-107. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127185 | 1 – 216 | Heart- and neural crest derivatives-expressed protein 1Add BLAST | 216 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 107 | Phosphothreonine; by PLK41 Publication | 1 | |
Modified residuei | 109 | Phosphoserine; by PLK41 Publication | 1 |
Post-translational modificationi
Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to translocation into the nucleoplasm, allowing dimerization and transcription factor activity.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q64279 |
PRIDEi | Q64279 |
ProteomicsDBi | 271389 |
PTM databases
iPTMneti | Q64279 |
PhosphoSitePlusi | Q64279 |
Expressioni
Tissue specificityi
Smooth muscle cells of the gut and adrenal tissue.
Developmental stagei
Present as a maternal transcript in the egg as well as during cleavage development before blastocyst formation. At 7.5 dpc, strongly expressed in all trophoblast cells (PubMed:16759287). Expression seen in the ectoplacental cone and extraembryonic mesodermal components of the amnion, allantois and visceral yolk sac. This high extraembryonic expression persists in the embryonic component of the placenta throughout development. In the embryo, expressed at 7.75 dpc in the lateral mesoderm along the entire length of the embryo as well as throughout the precardiogenic mesoderm. At 8.0 dpc, in the developing heart, expression becomes restricted to the rostral and caudal regions of the straight heart tube, which are fated to form the conotruncus and left ventricle, respectively. Symmetric expression is observed along the left-right axis in the caudal heart tube and lateral mesoderm. As cardiac looping occurs, the interrupted anterior-posterior patterning is maintained with expression in the future left, but not right ventricle. Expressed in the myocardium, but not in the endocardium, and specifically on the greater curvature of the looping heart which is opposed to the pericardium. After day 10.5 dpc, the high cardiac expression level declines abruptly. By 13.5 dpc, expression in the heart is restricted to the regions of valve formation. Besides the heart, expression becomes detectable in the gut at 9.0 dpc. At 10.0 dpc, expressed also in the lateral mesoderm and in the neural crest-derived branchial arches. At 10.5 dpc prominent expression in the gut, pharyngeal arches and in sympathetic ganglion primordia. At that stage, a low level of transient expression is seen in the distal posterior region of the limb bud. At 12 dpc expressed in the conceptus trophoblast giant cell layer in the placenta (PubMed:16759287). At 13.5 dpc expressed in neural crest derivatives, with abundant expression in the autonomic nervous system and adrenal medulla.3 Publications
Gene expression databases
Bgeei | ENSMUSG00000037335, Expressed in ectoplacental cone and 177 other tissues |
ExpressionAtlasi | Q64279, baseline and differential |
Genevisiblei | Q64279, MM |
Interactioni
Subunit structurei
Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription factors).
Interacts with MDFIC.
Interacts with SOX15; the interaction enhances HAND1-induced differentiation of trophoblast giant cells (PubMed:16759287).
3 PublicationsBinary interactionsi
Hide detailsQ64279
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-81361,EBI-81361 |
Hand2 [Q61039] | 3 | EBI-81361,EBI-81388 |
Tcf3 [P15806] | 2 | EBI-81361,EBI-81370 |
GO - Molecular functioni
- bHLH transcription factor binding Source: MGI
- enzyme binding Source: UniProtKB
- identical protein binding Source: MGI
- protein homodimerization activity Source: BHF-UCL
- transcription coregulator binding Source: BHF-UCL
- transcription factor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 200204, 7 interactors |
DIPi | DIP-455N |
IntActi | Q64279, 6 interactors |
STRINGi | 10090.ENSMUSP00000046999 |
Miscellaneous databases
RNActi | Q64279, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 94 – 146 | bHLHPROSITE-ProRule annotationAdd BLAST | 53 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 9 – 17 | Poly-His | 9 | |
Compositional biasi | 66 – 71 | Poly-Ala | 6 |
Phylogenomic databases
eggNOGi | KOG4029, Eukaryota |
GeneTreei | ENSGT00940000161111 |
HOGENOMi | CLU_119591_0_0_1 |
InParanoidi | Q64279 |
OMAi | YFQSWVL |
OrthoDBi | 1449816at2759 |
PhylomeDBi | Q64279 |
TreeFami | TF315153 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf |
Pfami | View protein in Pfam PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q64279-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MNLVGSYAHH HHHHHSHPPH PMLHEPFLFG PASRCHQERP YFQSWLLSPA
60 70 80 90 100
DAAPDFPAGG PPPTTAVAAA AYGPDARPSQ SPGRLEALGS RLPKRKGSGP
110 120 130 140 150
KKERRRTESI NSAFAELREC IPNVPADTKL SKIKTLRLAT SYIAYLMDVL
160 170 180 190 200
AKDAQAGDPE AFKAELKKTD GGRESKRKRE LPQQPESFPP ASGPGEKRIK
210
GRTGWPQQVW ALELNQ
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ5SQG0 | Q5SQG0_MOUSE | Heart- and neural crest derivatives... | Hand1 | 31 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 6 | S → R in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 19 | P → A in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 131 | S → P in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 149 | V → A in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 164 | A → V in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 187 | S → G in AAA86273 (PubMed:7671815).Curated | 1 | |
Sequence conflicti | 208 | Q → K in AAA86273 (PubMed:7671815).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U21226 mRNA Translation: AAA86887.1 S79216 mRNA Translation: AAB35104.1 U43714 mRNA Translation: AAA86273.1 |
CCDSi | CCDS24721.1 |
RefSeqi | NP_032239.1, NM_008213.2 |
Genome annotation databases
Ensembli | ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335 ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335 |
GeneIDi | 15110 |
KEGGi | mmu:15110 |
UCSCi | uc007jaf.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U21226 mRNA Translation: AAA86887.1 S79216 mRNA Translation: AAB35104.1 U43714 mRNA Translation: AAA86273.1 |
CCDSi | CCDS24721.1 |
RefSeqi | NP_032239.1, NM_008213.2 |
3D structure databases
SMRi | Q64279 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200204, 7 interactors |
DIPi | DIP-455N |
IntActi | Q64279, 6 interactors |
STRINGi | 10090.ENSMUSP00000046999 |
PTM databases
iPTMneti | Q64279 |
PhosphoSitePlusi | Q64279 |
Proteomic databases
PaxDbi | Q64279 |
PRIDEi | Q64279 |
ProteomicsDBi | 271389 |
Protocols and materials databases
Antibodypediai | 16446, 367 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000036917; ENSMUSP00000046999; ENSMUSG00000037335 ENSMUST00000160392; ENSMUSP00000124951; ENSMUSG00000037335 |
GeneIDi | 15110 |
KEGGi | mmu:15110 |
UCSCi | uc007jaf.1, mouse |
Organism-specific databases
CTDi | 9421 |
MGIi | MGI:103577, Hand1 |
Phylogenomic databases
eggNOGi | KOG4029, Eukaryota |
GeneTreei | ENSGT00940000161111 |
HOGENOMi | CLU_119591_0_0_1 |
InParanoidi | Q64279 |
OMAi | YFQSWVL |
OrthoDBi | 1449816at2759 |
PhylomeDBi | Q64279 |
TreeFami | TF315153 |
Miscellaneous databases
BioGRID-ORCSi | 15110, 1 hit in 53 CRISPR screens |
ChiTaRSi | Hand1, mouse |
PROi | PR:Q64279 |
RNActi | Q64279, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000037335, Expressed in ectoplacental cone and 177 other tissues |
ExpressionAtlasi | Q64279, baseline and differential |
Genevisiblei | Q64279, MM |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf |
Pfami | View protein in Pfam PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HAND1_MOUSE | |
Accessioni | Q64279Primary (citable) accession number: Q64279 Secondary accession number(s): Q61099 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | November 1, 1996 | |
Last modified: | April 7, 2021 | |
This is version 165 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot