NPS4L_DANRE
ID NPS4L_DANRE Reviewed; 647 AA.
AC P0DOC7; A0A1B0ZA14; A0A1B0ZA19;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Neuronal PAS domain-containing protein 4-like {ECO:0000303|PubMed:27411634};
DE AltName: Full=Protein cloche {ECO:0000303|PubMed:27411634, ECO:0000303|PubMed:7588049};
GN Name=npas4l {ECO:0000303|PubMed:27411634};
GN Synonyms=clo {ECO:0000303|PubMed:27411634, ECO:0000303|PubMed:7588049};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DISRUPTION PHENOTYPE,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=27411634; DOI=10.1038/nature18614;
RA Reischauer S., Stone O.A., Villasenor A., Chi N., Jin S.W., Martin M.,
RA Lee M.T., Fukuda N., Marass M., Witty A., Fiddes I., Kuo T., Chung W.S.,
RA Salek S., Lerrigo R., Alsioe J., Luo S., Tworus D., Augustine S.M.,
RA Mucenieks S., Nystedt B., Giraldez A.J., Schroth G.P., Andersson O.,
RA Stainier D.Y.;
RT "Cloche is a bHLH-PAS transcription factor that drives haemato-vascular
RT specification.";
RL Nature 535:294-298(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=7588049; DOI=10.1242/dev.121.10.3141;
RA Stainier D.Y., Weinstein B.M., Detrich H.W. III, Zon L.I., Fishman M.C.;
RT "Cloche, an early acting zebrafish gene, is required by both the
RT endothelial and hematopoietic lineages.";
RL Development 121:3141-3150(1995).
CC -!- FUNCTION: Transcription factor specifically expressed in endothelial
CC and hematopoietic precursor cells that acts as a key regulator of the
CC endothelial differentiation cascade. Acts as an early-response
CC transcription factor that regulates the expression of early regulators
CC of endothelial and haematopoietic differentiation, such as etv2 and
CC tal1. {ECO:0000269|PubMed:27411634}.
CC -!- SUBUNIT: Heterodimer; efficient DNA binding requires dimerization with
CC another bHLH protein. {ECO:0000250|UniProtKB:Q8BGD7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in endothelial and
CC hematopoietic precursor cells (PubMed:27411634).
CC {ECO:0000269|PubMed:27411634}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks before the end of gastrulation
CC and drops down by 24 hours post-fertilization, when the heart starts
CC beating (PubMed:27411634). Expression precedes that of the earliest
CC endothelial and haematopoietic markers etv2 and tal1 (PubMed:27411634).
CC {ECO:0000269|PubMed:27411634}.
CC -!- DISRUPTION PHENOTYPE: Loss of most endothelial and haematopoietic cells
CC and a significant increase in cardiomyocyte numbers (PubMed:27411634,
CC PubMed:7588049). Embryos show defects in the endothelial and
CC hematopoietic lineages at a very early embryonic stage, characterized
CC by the absence of the endocardium (PubMed:27411634). Early cardiac
CC morphogenesis proceeds normally even in the absence of the endocardium
CC (PubMed:27411634). The myocardial cells form a tube that is demarcated
CC into chambers, beats rhythmically, but exhibits a reduced contractility
CC (PubMed:27411634). Mutant embryos survive for one week of development
CC (PubMed:27411634). {ECO:0000269|PubMed:27411634,
CC ECO:0000269|PubMed:7588049}.
CC -!- MISCELLANEOUS: Was named 'cloche', which means 'bell' in French,
CC because of the bell-shaped heart in mutant embryos.
CC {ECO:0000303|PubMed:7588049}.
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DR EMBL; KX066018; ANP24256.1; -; Genomic_DNA.
DR EMBL; KX066019; ANP24257.1; -; mRNA.
DR EMBL; CABZ01080135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001316841.1; NM_001329912.1.
DR AlphaFoldDB; P0DOC7; -.
DR SMR; P0DOC7; -.
DR GeneID; 108449885; -.
DR KEGG; dre:108449885; -.
DR CTD; 108449885; -.
DR ZFIN; ZDB-GENE-070117-2515; npas4l.
DR OrthoDB; 219290at2759; -.
DR PRO; PR:P0DOC7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IMP:ZFIN.
DR GO; GO:0060216; P:definitive hemopoiesis; IMP:ZFIN.
DR GO; GO:0003157; P:endocardium development; IMP:ZFIN.
DR GO; GO:0001885; P:endothelial cell development; IMP:ZFIN.
DR GO; GO:0045446; P:endothelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:ZFIN.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:ZFIN.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:ZFIN.
DR GO; GO:0051892; P:negative regulation of cardioblast differentiation; IMP:ZFIN.
DR GO; GO:0060215; P:primitive hemopoiesis; IMP:UniProtKB.
DR GO; GO:0045601; P:regulation of endothelial cell differentiation; IMP:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:ZFIN.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:ZFIN.
DR CDD; cd00130; PAS; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF08447; PAS_3; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Activator; Differentiation; DNA-binding; Nucleus; Reference proteome;
KW Repeat; Transcription; Transcription regulation.
FT CHAIN 1..647
FT /note="Neuronal PAS domain-containing protein 4-like"
FT /id="PRO_0000438134"
FT DOMAIN 16..67
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 117..181
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 238..274
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 16..29
FT /note="Basic motif; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 30..67
FT /note="Helix-loop-helix motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT CONFLICT 349
FT /note="S -> T (in Ref. 1; ANP24257)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 69525 MW; 9EE9E8D269F75A54 CRC64;
MSCGDSGIRR ILRASKRFRS TKGASKARRD QMNSEIRNLR ALLPISPEHR LSYLHSMSIT
CTYIRKSVEL RGVCEESTVF SAVNGCVPQD CALQDCALQE CVLQECVLQE CVLQECVLQA
LPGFIVAFTT DGKLLYVSEN VHEYLGLSMV DVLQSDSFFD MLDRSDVEAV RSVLADASPS
GERWVVCRML VSKAMRLRSS CCPLLVRIRL RDGVCVSLCR PTADRLPARN ADFHTHHSAD
MRLASASSSV LFHLGFSADE LIGRSWYELL HPDDLRHAAD RHAAILAAAT ADAEMLIRVQ
CKDLSWVWMY THASATAERD AISCSNYMIS EAEAVYLQQR LSSSSSSSSS SSSSSASPQC
SSVSDSSDAH SAHTLFCTPP YSPTSSQCSD FLSEGYGSLE ALVDSAFCSP PYPPLFPNPC
CTPTVCPPDT ALDPARLCPP DSALVPAALC PPDAALDPTQ LCPPGAALDP TLLCPPGAAL
DPTQLCLPDG ALVPAVFCPP NGALVPARLC PSDAALVPAA LGRPDAALVP VCRPLQVCEC
PLDGAVPLED LSMFPLPQGG GSRLMPPEAS PTTHTHFSYD AAQQAGIGTL AMQIHTLICS
FDAYSAARHT HSHHTSCWAP EPLLDEGIID SILRELDSTH TDAHTLI
