PITX2_DANRE
ID PITX2_DANRE Reviewed; 314 AA.
AC Q9W5Z2; Q568C4; Q9W5Z1;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Pituitary homeobox 2;
DE AltName: Full=Homeobox protein PITX2;
DE AltName: Full=Paired-like homeodomain transcription factor 2;
GN Name=pitx2; Synonyms=pitx2a, pitx2b; ORFNames=zgc:110508;
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 [MRNA] (ISOFORMS A AND C).
RX PubMed=10521397; DOI=10.1101/gad.13.19.2527;
RA Yan Y.-T., Gritsman K., Ding J., Burdine R.D., Corrales J.D., Price S.M.,
RA Talbot W.S., Schier A.F., Shen M.M.;
RT "Conserved requirement for EGF-CFC genes in vertebrate left-right axis
RT formation.";
RL Genes Dev. 13:2527-2537(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Embryo;
RX PubMed=10500184; DOI=10.1073/pnas.96.20.11376;
RA Tsukui T., Capdevila J., Tamura K., Ruiz-Lozano P., Rodriguez-Esteban C.,
RA Yonei-Tamura S., Magallon J., Chandraratna R.A.S., Chien K., Blumberg B.,
RA Evans R.M., Izpisua-Belmonte J.-C.;
RT "Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a
RT convergence of the Shh and retinoic acid pathways in the control of Lefty-
RT 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11376-11381(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), FUNCTION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC TISSUE=Embryo;
RX PubMed=10662647; DOI=10.1242/dev.127.5.1081;
RA Essner J.J., Branford W.W., Zhang J., Yost H.J.;
RT "Mesendoderm and left-right brain, heart and gut development are
RT differentially regulated by pitx2 isoforms.";
RL Development 127:1081-1093(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Isoform a and isoform c differentially regulate mesendoderm
CC formation and asymmetric organ development. Both isoforms regulate
CC left-right development, but isoform a has a stronger effect on heart
CC laterality. {ECO:0000269|PubMed:10662647}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=c; Synonyms=Pitx2c;
CC IsoId=Q9W5Z2-1; Sequence=Displayed;
CC Name=a; Synonyms=Pitx2a;
CC IsoId=Q9W5Z2-2; Sequence=VSP_002268, VSP_002269;
CC -!- TISSUE SPECIFICITY: Isoform a and isoform c have distinct expression
CC patterns during early mesendoderm development; isoform c is expressed
CC symmetrically in presumptive mesendoderm during late blastula stages,
CC and in both the anterior (polster) and posterior prechordal plate
CC during late gastrulation. In contrast, isoform a expression begins at
CC bud stage, in the anterior prechordal plate (polster). At 4- to 6-
CC somite stages, isoform a and isoform c are both expressed in the
CC polster, and weak isoform c expression remains in the posterior
CC prechordal plate. Isoform a is also expressed in lateral head
CC mesendoderm. Isoform a and isoform c are also expressed in different
CC asymmetric domains during development of the diencephalon, gut and
CC heart; isoform c is restricted to the dorsal diencephalon and left hand
CC side of the developing gut, whereas isoform a shows left-sided
CC asymmetric expression in the developing heart, with strongest
CC expression in ther anterior regions. {ECO:0000269|PubMed:10662647}.
CC -!- DEVELOPMENTAL STAGE: Isoform c is expressed during dome stage, while
CC isoform a is not expressed until bud stage, following gastrulation.
CC Isoform a shows strong expression during heart looping stages (30-36
CC hpf) and at 48 hpf. {ECO:0000269|PubMed:10662647}.
CC -!- INDUCTION: Isoform c is regulated by tgf-beta signaling in the early
CC mesendoderm. {ECO:0000269|PubMed:10662647}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
CC {ECO:0000305}.
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DR EMBL; AF156905; AAD40179.1; -; mRNA.
DR EMBL; AF156906; AAD40180.1; -; mRNA.
DR EMBL; AF181681; AAF00486.2; -; mRNA.
DR EMBL; AF132446; AAD34390.1; -; mRNA.
DR EMBL; AF132447; AAD34391.1; -; mRNA.
DR EMBL; BC092922; AAH92922.1; -; mRNA.
DR RefSeq; NP_571050.1; NM_130975.2. [Q9W5Z2-1]
DR RefSeq; XP_005157364.1; XM_005157307.3. [Q9W5Z2-2]
DR AlphaFoldDB; Q9W5Z2; -.
DR SMR; Q9W5Z2; -.
DR STRING; 7955.ENSDARP00000052568; -.
DR PaxDb; Q9W5Z2; -.
DR Ensembl; ENSDART00000052569; ENSDARP00000052568; ENSDARG00000036194. [Q9W5Z2-1]
DR Ensembl; ENSDART00000148319; ENSDARP00000120155; ENSDARG00000036194. [Q9W5Z2-2]
DR Ensembl; ENSDART00000181864; ENSDARP00000156780; ENSDARG00000036194. [Q9W5Z2-2]
DR Ensembl; ENSDART00000186872; ENSDARP00000149868; ENSDARG00000036194. [Q9W5Z2-2]
DR GeneID; 30164; -.
DR KEGG; dre:30164; -.
DR CTD; 5308; -.
DR ZFIN; ZDB-GENE-990714-27; pitx2.
DR eggNOG; KOG0486; Eukaryota.
DR GeneTree; ENSGT00940000154518; -.
DR HOGENOM; CLU_030301_0_0_1; -.
DR InParanoid; Q9W5Z2; -.
DR OMA; NSMRNPL; -.
DR OrthoDB; 1432356at2759; -.
DR PhylomeDB; Q9W5Z2; -.
DR TreeFam; TF351940; -.
DR PRO; PR:Q9W5Z2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000036194; Expressed in pharyngeal epithelium and 71 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0043010; P:camera-type eye development; IMP:ZFIN.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IMP:ZFIN.
DR GO; GO:0061386; P:closure of optic fissure; IMP:ZFIN.
DR GO; GO:0061303; P:cornea development in camera-type eye; IMP:ZFIN.
DR GO; GO:0071907; P:determination of digestive tract left/right asymmetry; IDA:ZFIN.
DR GO; GO:0035462; P:determination of left/right asymmetry in diencephalon; IMP:ZFIN.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IMP:ZFIN.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:ZFIN.
DR GO; GO:0060971; P:embryonic heart tube left/right pattern formation; IDA:ZFIN.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IMP:ZFIN.
DR GO; GO:0021538; P:epithalamus development; IMP:ZFIN.
DR GO; GO:0060325; P:face morphogenesis; IMP:ZFIN.
DR GO; GO:0021986; P:habenula development; IMP:ZFIN.
DR GO; GO:0061072; P:iris morphogenesis; IMP:ZFIN.
DR GO; GO:0048382; P:mesendoderm development; IDA:ZFIN.
DR GO; GO:0042476; P:odontogenesis; IMP:ZFIN.
DR GO; GO:0021501; P:prechordal plate formation; IGI:ZFIN.
DR GO; GO:1904103; P:regulation of convergent extension involved in gastrulation; IMP:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043114; P:regulation of vascular permeability; IGI:ZFIN.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IMP:ZFIN.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR016233; Homeobox_Pitx/unc30.
DR InterPro; IPR003654; OAR_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF03826; OAR; 1.
DR PIRSF; PIRSF000563; Homeobox_protein_Pitx/Unc30; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS50803; OAR; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Reference proteome.
FT CHAIN 1..314
FT /note="Pituitary homeobox 2"
FT /id="PRO_0000049227"
FT DNA_BIND 82..141
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..289
FT /note="OAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
FT MOTIF 282..286
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 25..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000303|PubMed:10500184,
FT ECO:0000303|PubMed:10521397, ECO:0000303|PubMed:10662647"
FT /id="VSP_002268"
FT VAR_SEQ 46..60
FT /note="LDVHTVSDTSSPESV -> MDSHCRKLASTCAQL (in isoform a)"
FT /evidence="ECO:0000303|PubMed:10500184,
FT ECO:0000303|PubMed:10521397, ECO:0000303|PubMed:10662647"
FT /id="VSP_002269"
FT CONFLICT 25
FT /note="A -> T (in Ref. 4; AAH92922)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 35187 MW; 52D0F7855664A6B5 CRC64;
MTSMKDPLSL DHHHHNHHVT GSKHAPLSMA SSLQPLQRSV DSKHRLDVHT VSDTSSPESV
EKEKGQSKNE DSNDDPSKKK RQRRQRTHFT SQQLQELEAT FQRNRYPDMS TREEIAVWTN
LTEARVRVWF KNRRAKWRKR ERNQQAELCK NGFGPQFNGL MQPYDDMYPS YTYNNWAAKG
LTSASLSTKS FPFFNSMNVN PLSSQTMFSP PNSISSMSMS SSMVPSAVTG VPGSSLNSLN
NLNNLSNPSL NSGVPTPACP YAPPTPPYVY RDTCNSSLAS LRLKAKQHSS FGYASVQNPA
SNLSACQYAV DRPV
