ID   HAND1_RABIT             Reviewed;         215 AA.
AC   P57100;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 1.
DT   25-MAY-2022, entry version 88.
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;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Heart;
RA   Sayeed R.A., Grace A.A., Vandenberg J.I.;
RT   "Immediate-early gene response to acute pressure-overload in the rabbit
RT   heart.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
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,
CC       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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB94841.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AJ291309; CAB94841.1; ALT_INIT; mRNA.
DR   AlphaFoldDB; P57100; -.
DR   SMR; P57100; -.
DR   STRING; 9986.ENSOCUP00000009548; -.
DR   eggNOG; KOG4029; Eukaryota.
DR   InParanoid; P57100; -.
DR   Proteomes; UP000001811; 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..215
FT                   /note="Heart- and neural crest derivatives-expressed
FT                   protein 1"
FT                   /id="PRO_0000127186"
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          169..202
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        169..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;  23687 MW;  134B30BE946267A0 CRC64;
     MNLVGSYAHH HHHHHPHPAH PMLHEPFLFG PASRCHQERP YFQSWLLSPA DAAPDFPTGG
     PPPTAAAAAA TYGPDTRPGQ SPGRLEALGG RLGRRKGSGP KKERRRTESI NSAFAELREC
     IPNVPADTKL SKIKTLRLAT SYIAYLMDVL AKDAQAGDPE AFKAELKKVD GGRESKRKRE
     LQQHEGFPPA LGPGEKRIKG RTGWPQQVWA LELNQ