WT1A_XENLA
ID WT1A_XENLA Reviewed; 414 AA.
AC B7ZSG3; Q788P8; Q91657;
DT 09-FEB-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Wilms tumor protein homolog A;
DE Short=XWT1a {ECO:0000303|PubMed:16818449};
DE Short=xWT1 {ECO:0000303|PubMed:8725280};
GN Name=wt1-a; Synonyms=wt1;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB53152.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Mesonephros {ECO:0000269|PubMed:8725280};
RX PubMed=8725280;
RX DOI=10.1002/(sici)1097-0177(199606)206:2<131::aid-aja2>3.0.co;2-j;
RA Carroll T.J., Vize P.D.;
RT "Wilms' tumor suppressor gene is involved in the development of disparate
RT kidney forms: evidence from expression in the Xenopus pronephros.";
RL Dev. Dyn. 206:131-138(1996).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAI70513.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAA59738.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 291-372 (ISOFORM 1/2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Mesonephros {ECO:0000312|EMBL:CAA59738.1};
RX PubMed=7478606;
RA Kent J., Coriat A.M., Sharpe P.T., Hastie N.D., van Heyningen V.;
RT "The evolution of WT1 sequence and expression pattern in the vertebrates.";
RL Oncogene 11:1781-1792(1995).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=9758706; DOI=10.1006/dbio.1998.8989;
RA Wallingford J.B., Carroll T.J., Vize P.D.;
RT "Precocious expression of the Wilms' tumor gene xWT1 inhibits embryonic
RT kidney development in Xenopus laevis.";
RL Dev. Biol. 202:103-112(1998).
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=10572058; DOI=10.1242/dev.126.24.5847;
RA Brennan H.C., Nijjar S., Jones E.A.;
RT "The specification and growth factor inducibility of the pronephric glomus
RT in Xenopus laevis.";
RL Development 126:5847-5856(1999).
RN [6] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=10322628;
RX DOI=10.1002/(sici)1520-6408(1999)24:3/4<199::aid-dvg3>3.0.co;2-d;
RA Carroll T.J., Wallingford J.B., Vize P.D.;
RT "Dynamic patterns of gene expression in the developing pronephros of
RT Xenopus laevis.";
RL Dev. Genet. 24:199-207(1999).
RN [7] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16818449; DOI=10.1242/dev.02458;
RA Taelman V., Van Campenhout C., Soelter M., Pieler T., Bellefroid E.J.;
RT "The Notch-effector HRT1 gene plays a role in glomerular development and
RT patterning of the Xenopus pronephros anlagen.";
RL Development 133:2961-2971(2006).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=16574097; DOI=10.1016/j.ydbio.2006.02.040;
RA Van Campenhout C., Nichane M., Antoniou A., Pendeville H., Bronchain O.J.,
RA Marine J.C., Mazabraud A., Voz M.L., Bellefroid E.J.;
RT "Evi1 is specifically expressed in the distal tubule and duct of the
RT Xenopus pronephros and plays a role in its formation.";
RL Dev. Biol. 294:203-219(2006).
RN [9] {ECO:0000305}
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=18687324; DOI=10.1016/j.ydbio.2008.07.012;
RA Haldin C.E., Masse K.L., Bhamra S., Simrick S., Kyuno J., Jones E.A.;
RT "The lmx1b gene is pivotal in glomus development in Xenopus laevis.";
RL Dev. Biol. 322:74-85(2008).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=19549856; DOI=10.1073/pnas.0901591106;
RA Kim M.K., McGarry T.J., O'Broin P., Flatow J.M., Golden A.A., Licht J.D.;
RT "An integrated genome screen identifies the Wnt signaling pathway as a
RT major target of WT1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11154-11159(2009).
CC -!- FUNCTION: Transcription factor required for development of the vascular
CC component of the pronephric kidney, the glomus; may repress tubule-
CC specific gene expression in the portion of the pronephros fated to form
CC the glomus. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-
CC 3' (By similarity). Inhibits Wnt-signaling during embryonic
CC development. Function may be isoform-specific: the isoform containing
CC the KTS motif is less effective in inhibiting wnt signaling.
CC {ECO:0000250|UniProtKB:P19544, ECO:0000269|PubMed:16574097,
CC ECO:0000269|PubMed:16818449, ECO:0000269|PubMed:19549856,
CC ECO:0000269|PubMed:9758706}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P22561}. Cytoplasm
CC {ECO:0000250|UniProtKB:P22561}. Nucleus speckle
CC {ECO:0000250|UniProtKB:P22561}. Note=Shuttles between nucleus and
CC cytoplasm. {ECO:0000250|UniProtKB:P22561}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=B7ZSG3-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:8725280};
CC IsoId=B7ZSG3-2; Sequence=VSP_038721;
CC -!- TISSUE SPECIFICITY: Expressed around the pronephric anlage and in the
CC pronephros; expression is restricted to the splanchnic mesoderm (the
CC site where the glomus forms) from tailbud stages, and the glomus of
CC early tadpoles. Not expressed in the pronephric tubules or pronephric
CC duct. In tadpoles (stage 38-39), additional expression begins in the
CC heart. Also expressed in the adult kidney (mesonephros).
CC {ECO:0000269|PubMed:10322628, ECO:0000269|PubMed:10572058,
CC ECO:0000269|PubMed:16818449, ECO:0000269|PubMed:18687324,
CC ECO:0000269|PubMed:7478606, ECO:0000269|PubMed:8725280}.
CC -!- DEVELOPMENTAL STAGE: Expression begins around stage 18 (late neurula).
CC {ECO:0000269|PubMed:10572058, ECO:0000269|PubMed:18687324,
CC ECO:0000269|PubMed:8725280}.
CC -!- INDUCTION: By retinoic acid in combination with fgf. By lmx1b in
CC combination with lhx1/lim1. {ECO:0000269|PubMed:10572058,
CC ECO:0000269|PubMed:18687324}.
CC -!- DOMAIN: Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via
CC its C2H2-type zinc fingers. Starting from the N-terminus, the second
CC zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts
CC with the central TGG motif, and the C-terminal zinc finger binds to the
CC 5'-GCG motif. Binds double-stranded target DNA, irrespective of the
CC cytosine methylation status. Has reduced affinity for target DNA where
CC the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-
CC formylcytosine or 5-carboxylcytosine. {ECO:0000250|UniProtKB:P19544}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P19544}.
CC -!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB53152.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U42011; AAB53152.1; ALT_FRAME; mRNA.
DR EMBL; BC170513; AAI70513.1; -; mRNA.
DR EMBL; X85733; CAA59738.1; -; mRNA.
DR RefSeq; NP_001079057.1; NM_001085588.1.
DR AlphaFoldDB; B7ZSG3; -.
DR BMRB; B7ZSG3; -.
DR SMR; B7ZSG3; -.
DR GeneID; 373588; -.
DR KEGG; xla:373588; -.
DR CTD; 373588; -.
DR Xenbase; XB-GENE-864792; wt1.S.
DR OMA; LDADPHC; -.
DR OrthoDB; 1318335at2759; -.
DR Proteomes; UP000186698; Chromosome 4S.
DR Bgee; 373588; Expressed in spleen and 11 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; ISS:UniProtKB.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0072013; P:glomus development; IMP:UniProtKB.
DR GO; GO:0061440; P:kidney vasculature development; TAS:AgBase.
DR GO; GO:1900207; P:negative regulation of pronephric nephron tubule development; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0039004; P:specification of pronephric proximal tubule identity; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR017987; Wilms_tumour.
DR InterPro; IPR000976; Wilms_tumour_N.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR23235:SF49; PTHR23235:SF49; 1.
DR Pfam; PF02165; WT1; 1.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Developmental protein; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Reference proteome; Repeat;
KW RNA editing; RNA-binding; Transcription; Transcription regulation;
KW Tumor suppressor; Ubl conjugation; Wnt signaling pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..414
FT /note="Wilms tumor protein homolog A"
FT /id="PRO_0000391387"
FT ZN_FING 288..312
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 318..342
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 348..370
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 379..403
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 332..346
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT REGION 358..366
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT MOTIF 217..225
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT MOTIF 373..375
FT /note="KTS motif"
FT /evidence="ECO:0000255"
FT SITE 389
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT SITE 395
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT CROSSLNK 55
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT CROSSLNK 158
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT VAR_SEQ 373..375
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8725280"
FT /id="VSP_038721"
FT CONFLICT 147
FT /note="Missing (in Ref. 1; AAB53152)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 414 AA; 46660 MW; E9B3A657961F7BE1 CRC64;
MGSDVRDMNL LPPVSSLSGN SSCNMPVSSS AQWAPVLDFP PGAPYSSLTP HSFIKQEPTW
NPDPHEDQCL SAFTVHFSGQ FTGTAGACRY GPFGAPTPSQ ATTGQARMFS NAPYLSNCLD
NQQGMRNQGY SAVAFDGTPS YGHTPSHHTS QFTNHSFKHE DPLSQQTSLG EQQYSVPPPV
YGCHTPTDTC TGSQALLLRT PYNSDNLYPM TSQLDCMTWN QMNLGSSLKS HGTSYENDSH
SSPMLYNCGG QYRIHTHGVF RGIQDVRRVP GVTPAIVRST EANEKRPFMC AYPGCNKRYF
KLSHLQMHSR KHTGEKPYQC DFKDCERRFS RSDQLKRHQR RHTGIKPFQC KTCQRKFSRS
DHLKTHTRTH TGKTSEKPFS CRWPSCQKKF ARSDELVRHH NMHQRNMTKL QLAL
