HAND2_HUMAN
ID HAND2_HUMAN Reviewed; 217 AA.
AC P61296; B6ECG9; O95300; O95301; P97833; Q494T1;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Heart- and neural crest derivatives-expressed protein 2;
DE AltName: Full=Class A basic helix-loop-helix protein 26;
DE Short=bHLHa26;
DE AltName: Full=Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2;
DE Short=dHAND;
GN Name=HAND2; Synonyms=BHLHA26, DHAND;
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] (ISOFORM 1).
RC TISSUE=Embryonic heart;
RX PubMed=9878849; DOI=10.1016/s0167-4781(98)00237-1;
RA Russell M.W., Kemp P., Wang L., Brody L.C., Izumo S.;
RT "Molecular cloning of the human HAND2 gene.";
RL Biochim. Biophys. Acta 1443:393-399(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Neuroblastoma;
RX PubMed=19348682; DOI=10.1186/1471-2199-10-28;
RA Voth H., Oberthuer A., Simon T., Kahlert Y., Berthold F., Fischer M.;
RT "Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with
RT asymmetrical activity in neuroblastoma.";
RL BMC Mol. Biol. 10:28-28(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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: Essential for cardiac morphogenesis, particularly for the
CC formation of the right ventricle and of the aortic arch arteries.
CC Required for vascular development and regulation of angiogenesis,
CC possibly through a VEGF signaling pathway. Also plays an important role
CC in limb development, particularly in the establishment of anterior-
CC posterior polarization, acting as an upstream regulator of sonic
CC hedgehog (SHH) induction in the limb bud. Is involved in the
CC development of branchial arches, which give rise to unique structures
CC in the head and neck. Binds DNA on E-box consensus sequence 5'-CANNTG-
CC 3' (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms homodimers and heterodimers with TCF3 gene products E12
CC and E47, HAND1 and HEY1, HEY2 and HEYL (hairy-related transcription
CC factors) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P61296; P15884: TCF4; NbExp=3; IntAct=EBI-10218584, EBI-533224;
CC P61296-2; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-13086076, EBI-6658203;
CC P61296-2; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-13086076, EBI-2556193;
CC P61296-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-13086076, EBI-748974;
CC P61296-2; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-13086076, EBI-10226430;
CC P61296-2; Q5MJ09: SPANXN3; NbExp=3; IntAct=EBI-13086076, EBI-12037215;
CC P61296-2; Q99081-3: TCF12; NbExp=3; IntAct=EBI-13086076, EBI-11952764;
CC P61296-2; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-13086076, EBI-14096082;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61296-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61296-2; Sequence=VSP_056880, VSP_056881;
CC -!- TISSUE SPECIFICITY: Heart.
CC -!- DEVELOPMENTAL STAGE: Expressed in the fetal heart.
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DR EMBL; AF087940; AAD13185.1; -; mRNA.
DR EMBL; AF087941; AAD13186.1; -; Genomic_DNA.
DR EMBL; FJ226608; ACI42790.1; -; mRNA.
DR EMBL; CH471056; EAX04749.1; -; Genomic_DNA.
DR EMBL; BC101406; AAI01407.1; -; mRNA.
DR CCDS; CCDS3819.1; -. [P61296-1]
DR RefSeq; NP_068808.1; NM_021973.2. [P61296-1]
DR AlphaFoldDB; P61296; -.
DR SMR; P61296; -.
DR BioGRID; 114850; 29.
DR IntAct; P61296; 9.
DR STRING; 9606.ENSP00000352565; -.
DR iPTMnet; P61296; -.
DR PhosphoSitePlus; P61296; -.
DR BioMuta; HAND2; -.
DR DMDM; 47117699; -.
DR jPOST; P61296; -.
DR MassIVE; P61296; -.
DR PaxDb; P61296; -.
DR PeptideAtlas; P61296; -.
DR PRIDE; P61296; -.
DR ProteomicsDB; 57292; -. [P61296-1]
DR Antibodypedia; 28534; 296 antibodies from 30 providers.
DR DNASU; 9464; -.
DR Ensembl; ENST00000359562.4; ENSP00000352565.4; ENSG00000164107.9. [P61296-1]
DR GeneID; 9464; -.
DR KEGG; hsa:9464; -.
DR MANE-Select; ENST00000359562.4; ENSP00000352565.4; NM_021973.3; NP_068808.1.
DR UCSC; uc003ith.2; human. [P61296-1]
DR CTD; 9464; -.
DR DisGeNET; 9464; -.
DR GeneCards; HAND2; -.
DR HGNC; HGNC:4808; HAND2.
DR HPA; ENSG00000164107; Tissue enhanced (heart muscle, intestine).
DR MalaCards; HAND2; -.
DR MIM; 602407; gene.
DR neXtProt; NX_P61296; -.
DR OpenTargets; ENSG00000164107; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR PharmGKB; PA29184; -.
DR VEuPathDB; HostDB:ENSG00000164107; -.
DR eggNOG; KOG4029; Eukaryota.
DR GeneTree; ENSGT00940000160772; -.
DR InParanoid; P61296; -.
DR OMA; CHEDSGA; -.
DR OrthoDB; 1449816at2759; -.
DR PhylomeDB; P61296; -.
DR TreeFam; TF315153; -.
DR PathwayCommons; P61296; -.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR SignaLink; P61296; -.
DR SIGNOR; P61296; -.
DR BioGRID-ORCS; 9464; 14 hits in 1096 CRISPR screens.
DR ChiTaRS; HAND2; human.
DR GeneWiki; HAND2; -.
DR GenomeRNAi; 9464; -.
DR Pharos; P61296; Tbio.
DR PRO; PR:P61296; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P61296; protein.
DR Bgee; ENSG00000164107; Expressed in muscle layer of sigmoid colon and 96 other tissues.
DR ExpressionAtlas; P61296; baseline and differential.
DR Genevisible; P61296; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0003680; F:minor groove of adenine-thymine-rich DNA binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; ISS:BHF-UCL.
DR GO; GO:0007512; P:adult heart development; IEP:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; IEA:Ensembl.
DR GO; GO:0061309; P:cardiac neural crest cell development involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0003219; P:cardiac right ventricle formation; IEA:Ensembl.
DR GO; GO:0060536; P:cartilage morphogenesis; IEA:Ensembl.
DR GO; GO:0061325; P:cell proliferation involved in outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0060982; P:coronary artery morphogenesis; IEA:Ensembl.
DR GO; GO:0032502; P:developmental process; IBA:GO_Central.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0003357; P:noradrenergic neuron differentiation; NAS:BHF-UCL.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0048935; P:peripheral nervous system neuron development; IEA:Ensembl.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:BHF-UCL.
DR GO; GO:2000764; P:positive regulation of semaphorin-plexin signaling pathway involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000763; P:positive regulation of transcription from RNA polymerase II promoter involved in norepinephrine biosynthetic process; ISS:BHF-UCL.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:BHF-UCL.
DR GO; GO:1903929; P:primary palate development; IEA:Ensembl.
DR GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; ISS:BHF-UCL.
DR GO; GO:0034103; P:regulation of tissue remodeling; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
DR GO; GO:0048485; P:sympathetic nervous system development; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; ISS:BHF-UCL.
DR GO; GO:0043586; P:tongue development; IEA:Ensembl.
DR GO; GO:0061032; P:visceral serous pericardium development; IEA:Ensembl.
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 Alternative splicing; Angiogenesis; Developmental protein; Differentiation;
KW DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..217
FT /note="Heart- and neural crest derivatives-expressed
FT protein 2"
FT /id="PRO_0000127191"
FT DOMAIN 99..151
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 76..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 21..26
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056880"
FT VAR_SEQ 71..101
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056881"
SQ SEQUENCE 217 AA; 23666 MW; 528F541BB2173F1E CRC64;
MSLVGGFPHH PVVHHEGYPF AAAAAAAAAA AASRCSHEEN PYFHGWLIGH PEMSPPDYSM
ALSYSPEYAS GAAGLDHSHY GGVPPGAGPP GLGGPRPVKR RGTANRKERR RTQSINSAFA
ELRECIPNVP ADTKLSKIKT LRLATSYIAY LMDLLAKDDQ NGEAEAFKAE IKKTDVKEEK
RKKELNEILK STVSSNDKKT KGRTGWPQHV WALELKQ
