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Wilms tumor protein homolog A (XWT1a) (xWT1)

 WT1A_XENLA              Reviewed;         414 AA.
B7ZSG3; Q788P8; Q91657;
09-FEB-2010, integrated into UniProtKB/Swiss-Prot.
03-MAR-2009, sequence version 1.
10-MAY-2017, entry version 40.
RecName: Full=Wilms tumor protein homolog A;
Short=XWT1a {ECO:0000303|PubMed:16818449};
Short=xWT1 {ECO:0000303|PubMed:8725280};
Name=wt1-a; Synonyms=wt1;
Xenopus laevis (African clawed frog).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus;
Xenopus.
NCBI_TaxID=8355;
[1] {ECO:0000305, ECO:0000312|EMBL:AAB53152.1}
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND
DEVELOPMENTAL STAGE.
TISSUE=Mesonephros {ECO:0000269|PubMed:8725280};
PubMed=8725280;
DOI=10.1002/(SICI)1097-0177(199606)206:2<131::AID-AJA2>3.3.CO;2-I;
Carroll T.J., Vize P.D.;
"Wilms' tumor suppressor gene is involved in the development of
disparate kidney forms: evidence from expression in the Xenopus
pronephros.";
Dev. Dyn. 206:131-138(1996).
[2] {ECO:0000305, ECO:0000312|EMBL:AAI70513.1}
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
NIH - Xenopus Gene Collection (XGC) project;
Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
[3] {ECO:0000305, ECO:0000312|EMBL:CAA59738.1}
NUCLEOTIDE SEQUENCE [MRNA] OF 291-372 (ISOFORM 1/2), AND TISSUE
SPECIFICITY.
TISSUE=Mesonephros {ECO:0000312|EMBL:CAA59738.1};
PubMed=7478606;
Kent J., Coriat A.M., Sharpe P.T., Hastie N.D., van Heyningen V.;
"The evolution of WT1 sequence and expression pattern in the
vertebrates.";
Oncogene 11:1781-1792(1995).
[4] {ECO:0000305}
FUNCTION.
PubMed=9758706; DOI=10.1006/dbio.1998.8989;
Wallingford J.B., Carroll T.J., Vize P.D.;
"Precocious expression of the Wilms' tumor gene xWT1 inhibits
embryonic kidney development in Xenopus laevis.";
Dev. Biol. 202:103-112(1998).
[5] {ECO:0000305}
TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
PubMed=10572058;
Brennan H.C., Nijjar S., Jones E.A.;
"The specification and growth factor inducibility of the pronephric
glomus in Xenopus laevis.";
Development 126:5847-5856(1999).
[6] {ECO:0000305}
TISSUE SPECIFICITY.
PubMed=10322628;
DOI=10.1002/(SICI)1520-6408(1999)24:3/4<199::AID-DVG3>3.0.CO;2-D;
Carroll T.J., Wallingford J.B., Vize P.D.;
"Dynamic patterns of gene expression in the developing pronephros of
Xenopus laevis.";
Dev. Genet. 24:199-207(1999).
[7] {ECO:0000305}
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=16818449; DOI=10.1242/dev.02458;
Taelman V., Van Campenhout C., Soelter M., Pieler T., Bellefroid E.J.;
"The Notch-effector HRT1 gene plays a role in glomerular development
and patterning of the Xenopus pronephros anlagen.";
Development 133:2961-2971(2006).
[8] {ECO:0000305}
FUNCTION.
PubMed=16574097; DOI=10.1016/j.ydbio.2006.02.040;
Van Campenhout C., Nichane M., Antoniou A., Pendeville H.,
Bronchain O.J., Marine J.C., Mazabraud A., Voz M.L., Bellefroid E.J.;
"Evi1 is specifically expressed in the distal tubule and duct of the
Xenopus pronephros and plays a role in its formation.";
Dev. Biol. 294:203-219(2006).
[9] {ECO:0000305}
TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
PubMed=18687324; DOI=10.1016/j.ydbio.2008.07.012;
Haldin C.E., Masse K.L., Bhamra S., Simrick S., Kyuno J., Jones E.A.;
"The lmx1b gene is pivotal in glomus development in Xenopus laevis.";
Dev. Biol. 322:74-85(2008).
[10] {ECO:0000305}
FUNCTION.
PubMed=19549856; DOI=10.1073/pnas.0901591106;
Kim M.K., McGarry T.J., O'Broin P., Flatow J.M., Golden A.A.,
Licht J.D.;
"An integrated genome screen identifies the Wnt signaling pathway as a
major target of WT1.";
Proc. Natl. Acad. Sci. U.S.A. 106:11154-11159(2009).
-!- FUNCTION: Transcription factor required for development of the
vascular component of the pronephric kidney, the glomus; may
repress tubule-specific gene expression in the portion of the
pronephros fated to form the glomus. Recognizes and binds to the
DNA sequence 5'-GCG(T/G)GGGCG-3' (By similarity). Inhibits Wnt-
signaling during embryonic development. Function may be isoform-
specific: the isoform containing the KTS motif is less effective
in inhibiting wnt signaling. {ECO:0000250|UniProtKB:P19544,
ECO:0000269|PubMed:16574097, ECO:0000269|PubMed:16818449,
ECO:0000269|PubMed:19549856, ECO:0000269|PubMed:9758706}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P22561}.
Cytoplasm {ECO:0000250|UniProtKB:P22561}. Nucleus speckle
{ECO:0000250|UniProtKB:P22561}. Note=Shuttles between nucleus and
cytoplasm. {ECO:0000250|UniProtKB:P22561}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=B7ZSG3-1; Sequence=Displayed;
Note=No experimental confirmation available. {ECO:0000305};
Name=2 {ECO:0000269|PubMed:8725280};
IsoId=B7ZSG3-2; Sequence=VSP_038721;
-!- TISSUE SPECIFICITY: Expressed around the pronephric anlage and in
the pronephros; expression is restricted to the splanchnic
mesoderm (the site where the glomus forms) from tailbud stages,
and the glomus of early tadpoles. Not expressed in the pronephric
tubules or pronephric duct. In tadpoles (stage 38-39), additional
expression begins in the heart. Also expressed in the adult kidney
(mesonephros). {ECO:0000269|PubMed:10322628,
ECO:0000269|PubMed:10572058, ECO:0000269|PubMed:16818449,
ECO:0000269|PubMed:18687324, ECO:0000269|PubMed:7478606,
ECO:0000269|PubMed:8725280}.
-!- DEVELOPMENTAL STAGE: Expression begins around stage 18 (late
neurula). {ECO:0000269|PubMed:10572058,
ECO:0000269|PubMed:18687324, ECO:0000269|PubMed:8725280}.
-!- INDUCTION: By retinoic acid in combination with fgf. By lmx1b in
combination with lhx1/lim1. {ECO:0000269|PubMed:10572058,
ECO:0000269|PubMed:18687324}.
-!- DOMAIN: Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3'
via its C2H2-type zinc fingers. Starting from the N-terminus, the
second zinc finger binds to the 3'-GCG motif, the middle zinc
finger interacts with the central TGG motif, and the C-terminal
zinc finger binds to the 5'-GCG motif. Binds double-stranded
target DNA, irrespective of the cytosine methylation status. Has
reduced affinity for target DNA where the cytosines have been
oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-
carboxylcytosine. {ECO:0000250|UniProtKB:P19544}.
-!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein
family. {ECO:0000255}.
-!- SEQUENCE CAUTION:
Sequence=AAB53152.1; Type=Frameshift; Positions=41, 53; Evidence={ECO:0000305};
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EMBL; U42011; AAB53152.1; ALT_FRAME; mRNA.
EMBL; BC170513; AAI70513.1; -; mRNA.
EMBL; X85733; CAA59738.1; -; mRNA.
RefSeq; NP_001079057.1; NM_001085588.1.
UniGene; Xl.172; -.
SMR; B7ZSG3; -.
GeneID; 373588; -.
KEGG; xla:373588; -.
CTD; 373588; -.
Xenbase; XB-GENE-864792; wt1.
HOVERGEN; HBG006960; -.
KO; K09234; -.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
GO; GO:0010385; F:double-stranded methylated DNA binding; ISS:UniProtKB.
GO; GO:0044729; F:hemi-methylated DNA-binding; ISS:UniProtKB.
GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
GO; GO:0072013; P:glomus development; IMP:UniProtKB.
GO; GO:0061440; P:kidney vasculature development; TAS:AgBase.
GO; GO:1900207; P:negative regulation of pronephric nephron tubule development; IMP:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:UniProtKB.
GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
GO; GO:0039004; P:specification of pronephric proximal tubule identity; IMP:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
InterPro; IPR017987; Wilms_tumour.
InterPro; IPR000976; Wilms_tumour_N.
InterPro; IPR013087; Znf_C2H2_type.
Pfam; PF02165; WT1; 1.
PRINTS; PR00049; WILMSTUMOUR.
SMART; SM00355; ZnF_C2H2; 4.
SUPFAM; SSF57667; SSF57667; 2.
PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4.
PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
2: Evidence at transcript level;
Alternative splicing; Cytoplasm; Developmental protein; DNA-binding;
Isopeptide bond; Metal-binding; Nucleus; Repeat; RNA editing;
RNA-binding; Transcription; Transcription regulation;
Tumor suppressor; Ubl conjugation; Wnt signaling pathway; Zinc;
Zinc-finger.
CHAIN 1 414 Wilms tumor protein homolog A.
/FTId=PRO_0000391387.
ZN_FING 288 312 C2H2-type 1. {ECO:0000255|PROSITE-
ProRule:PRU00042}.
ZN_FING 318 342 C2H2-type 2. {ECO:0000255|PROSITE-
ProRule:PRU00042}.
ZN_FING 348 370 C2H2-type 3. {ECO:0000255|PROSITE-
ProRule:PRU00042}.
ZN_FING 379 403 C2H2-type 4. {ECO:0000255|PROSITE-
ProRule:PRU00042}.
REGION 332 346 Important for interaction with target
DNA. {ECO:0000250|UniProtKB:P19544}.
REGION 358 366 Important for interaction with target
DNA. {ECO:0000250|UniProtKB:P19544}.
MOTIF 373 375 KTS motif. {ECO:0000255}.
SITE 389 389 Important for interaction with target
DNA. {ECO:0000250|UniProtKB:P19544}.
SITE 395 395 Important for interaction with target
DNA. {ECO:0000250|UniProtKB:P19544}.
CROSSLNK 55 55 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
{ECO:0000250|UniProtKB:P19544}.
CROSSLNK 158 158 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
{ECO:0000250|UniProtKB:P19544}.
VAR_SEQ 373 375 Missing (in isoform 2).
{ECO:0000303|PubMed:8725280}.
/FTId=VSP_038721.
CONFLICT 147 147 Missing (in Ref. 1; AAB53152).
{ECO:0000305}.
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


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