ID   HAND1_SHEEP             Reviewed;         204 AA.
AC   Q28555;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   25-MAY-2022, entry version 99.
DE   RecName: Full=Heart- and neural crest derivatives-expressed protein 1;
DE   AltName: Full=Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1;
DE            Short=eHAND;
GN   Name=HAND1; Synonyms=EHAND, HXT;
OS   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Embryo;
RX   PubMed=7671815; DOI=10.1242/dev.121.8.2513;
RA   Cross J.C., Flannery M.L., Blanar M.A., Steingrimsson E., Jenkins N.A.,
RA   Copeland N.G., Rutter W.J., Werb Z.;
RT   "Hxt encodes a basic helix-loop-helix transcription factor that regulates
RT   trophoblast cell development.";
RL   Development 121:2513-2523(1995).
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 (By similarity). {ECO:0000250|UniProtKB:O96004,
CC       ECO:0000250|UniProtKB:Q64279}.
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|UniProtKB:Q64279}.
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   -!- 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; U43716; AAA86275.1; -; mRNA.
DR   RefSeq; NP_001009785.1; NM_001009785.1.
DR   AlphaFoldDB; Q28555; -.
DR   SMR; Q28555; -.
DR   STRING; 9940.ENSOARP00000010555; -.
DR   GeneID; 443353; -.
DR   KEGG; oas:443353; -.
DR   CTD; 9421; -.
DR   eggNOG; KOG4029; Eukaryota.
DR   OrthoDB; 1449816at2759; -.
DR   Proteomes; UP000002356; Unplaced.
DR   GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0060707; P:trophoblast giant cell differentiation; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Activator; Developmental protein; DNA-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Transcription; Transcription regulation.
FT   CHAIN           1..204
FT                   /note="Heart- and neural crest derivatives-expressed
FT                   protein 1"
FT                   /id="PRO_0000127188"
FT   DOMAIN          100..152
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          57..115
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          172..204
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        7..23
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        172..190
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         113
FT                   /note="Phosphothreonine; by PLK4"
FT                   /evidence="ECO:0000250|UniProtKB:Q64279"
FT   MOD_RES         115
FT                   /note="Phosphoserine; by PLK4"
FT                   /evidence="ECO:0000250|UniProtKB:Q64279"
SQ   SEQUENCE   204 AA;  22427 MW;  4FB3FAD6DF05B3A4 CRC64;
     MNLVGSYAHH HHHHHHHHHP HPAHPMLHEP FLFGPASRCH QERPYFQSWL LSPADAAPDF
     PAGGPPPTTA VRAAAASYGP DARPGQSPGR LEALGGRLGR RKGSGPKKER RRTESINSAF
     AELRECIPNV PADTKLSKIK TLRLATSYIA YLMDVLAKDA QAGDPEAFKA ELKKADGGRE
     SKRKRELQQH EGFPPALGPG EKRD