HAND1_HUMAN
ID HAND1_HUMAN Reviewed; 215 AA.
AC O96004;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Heart- and neural crest derivatives-expressed protein 1;
DE AltName: Full=Class A basic helix-loop-helix protein 27;
DE Short=bHLHa27;
DE AltName: Full=Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1;
DE Short=eHAND;
GN Name=HAND1; Synonyms=BHLHA27, EHAND;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND FUNCTION.
RC TISSUE=Heart;
RX PubMed=9931445; DOI=10.1016/s0378-1119(98)00511-3;
RA Knoefler M., Meinhardt G., Vasicek R., Husslein P., Egarter C.;
RT "Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted
RT expression in cytotrophoblastic cells and heart.";
RL Gene 224:77-86(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Transcription factor that plays an essential role in both
CC trophoblast giant cell differentiation and in cardiac morphogenesis (By
CC similarity). Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box)
CC (By similarity). Acts as a transcriptional repressor of SOX15 (By
CC similarity). In the adult, could be required for ongoing expression of
CC cardiac-specific genes (PubMed:9931445). {ECO:0000250|UniProtKB:Q64279,
CC ECO:0000269|PubMed:9931445}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms homodimers and heterodimers with TCF3 gene products E12
CC and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription
CC factors). Interacts with MDFIC (By similarity). Interacts with SOX15;
CC the interaction enhances HAND1-induced differentiation of trophoblast
CC giant cells (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q64279}.
CC -!- INTERACTION:
CC O96004; G5E9A7: DMWD; NbExp=3; IntAct=EBI-11320290, EBI-10976677;
CC O96004; P60371: KRTAP10-6; NbExp=3; IntAct=EBI-11320290, EBI-12012928;
CC O96004; D3DTS7: PMP22; NbExp=3; IntAct=EBI-11320290, EBI-25882629;
CC O96004; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-11320290, EBI-5235340;
CC O96004; Q99081-3: TCF12; NbExp=3; IntAct=EBI-11320290, EBI-11952764;
CC O96004; P15923-3: TCF3; NbExp=3; IntAct=EBI-11320290, EBI-12000326;
CC O96004; Q86WV8: TSC1; NbExp=3; IntAct=EBI-11320290, EBI-12806590;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000250}. Nucleus,
CC nucleolus {ECO:0000250}. Note=Interaction with MDFIC sequesters it into
CC the nucleolus, preventing the transcription factor activity.
CC Phosphorylation by PLK4 disrupts the interaction with MDFIC and
CC releases it from the nucleolus, leading to transcription factor
CC activity (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Heart.
CC -!- PTM: Phosphorylation by PLK4 disrupts the interaction with MDFIC and
CC leads to translocation into the nucleoplasm, allowing dimerization and
CC transcription factor activity. {ECO:0000250}.
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DR EMBL; AF063012; AAD19283.1; -; Genomic_DNA.
DR EMBL; AF061756; AAD19280.1; -; mRNA.
DR EMBL; BC021190; AAH21190.1; -; mRNA.
DR CCDS; CCDS4327.1; -.
DR RefSeq; NP_004812.1; NM_004821.2.
DR AlphaFoldDB; O96004; -.
DR SMR; O96004; -.
DR BioGRID; 114814; 14.
DR IntAct; O96004; 8.
DR MINT; O96004; -.
DR STRING; 9606.ENSP00000231121; -.
DR iPTMnet; O96004; -.
DR PhosphoSitePlus; O96004; -.
DR BioMuta; HAND1; -.
DR MassIVE; O96004; -.
DR PaxDb; O96004; -.
DR PeptideAtlas; O96004; -.
DR PRIDE; O96004; -.
DR ProteomicsDB; 51183; -.
DR Antibodypedia; 16446; 381 antibodies from 35 providers.
DR DNASU; 9421; -.
DR Ensembl; ENST00000231121.3; ENSP00000231121.2; ENSG00000113196.3.
DR GeneID; 9421; -.
DR KEGG; hsa:9421; -.
DR MANE-Select; ENST00000231121.3; ENSP00000231121.2; NM_004821.3; NP_004812.1.
DR UCSC; uc003lvn.3; human.
DR CTD; 9421; -.
DR DisGeNET; 9421; -.
DR GeneCards; HAND1; -.
DR HGNC; HGNC:4807; HAND1.
DR HPA; ENSG00000113196; Tissue enhanced (heart muscle, intestine, smooth muscle).
DR MIM; 602406; gene.
DR neXtProt; NX_O96004; -.
DR OpenTargets; ENSG00000113196; -.
DR PharmGKB; PA29183; -.
DR VEuPathDB; HostDB:ENSG00000113196; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000161111; -.
DR HOGENOM; CLU_119591_0_0_1; -.
DR InParanoid; O96004; -.
DR OMA; YFQSWVL; -.
DR OrthoDB; 1449816at2759; -.
DR PhylomeDB; O96004; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; O96004; -.
DR SignaLink; O96004; -.
DR SIGNOR; O96004; -.
DR BioGRID-ORCS; 9421; 13 hits in 1094 CRISPR screens.
DR GeneWiki; HAND1; -.
DR GenomeRNAi; 9421; -.
DR Pharos; O96004; Tbio.
DR PRO; PR:O96004; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O96004; protein.
DR Bgee; ENSG00000113196; Expressed in muscle layer of sigmoid colon and 54 other tissues.
DR Genevisible; O96004; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001221; F:transcription coregulator binding; ISS:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; ISS:BHF-UCL.
DR GO; GO:0001824; P:blastocyst development; IEP:BHF-UCL.
DR GO; GO:0003218; P:cardiac left ventricle formation; IMP:BHF-UCL.
DR GO; GO:0003219; P:cardiac right ventricle formation; IMP:BHF-UCL.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060536; P:cartilage morphogenesis; IEA:Ensembl.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0035050; P:embryonic heart tube development; ISS:BHF-UCL.
DR GO; GO:0003144; P:embryonic heart tube formation; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0060485; P:mesenchyme development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEP:BHF-UCL.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; ISS:UniProtKB.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..215
FT /note="Heart- and neural crest derivatives-expressed
FT protein 1"
FT /id="PRO_0000127184"
FT DOMAIN 94..146
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 53..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 166..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 107
FT /note="Phosphothreonine; by PLK4"
FT /evidence="ECO:0000250|UniProtKB:Q64279"
FT MOD_RES 109
FT /note="Phosphoserine; by PLK4"
FT /evidence="ECO:0000250|UniProtKB:Q64279"
SQ SEQUENCE 215 AA; 23627 MW; 7ED98EA081A8D6BA CRC64;
MNLVGSYAHH HHHHHPHPAH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPAGG
PPPAAAAAAT AYGPDARPGQ SPGRLEALGG RLGRRKGSGP KKERRRTESI NSAFAELREC
IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQSGDPE AFKAELKKAD GGRESKRKRE
LQQHEGFPPA LGPVEKRIKG RTGWPQQVWA LELNQ
