WT1_RAT
ID WT1_RAT Reviewed; 448 AA.
AC P49952;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Wilms tumor protein homolog;
GN Name=Wt1; Synonyms=Wt-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=1330293;
RA Sharma P.M., Yang X., Bowman M., Roberts V., Sukumar S.;
RT "Molecular cloning of rat Wilms' tumor complementary DNA and a study of
RT messenger RNA expression in the urogenital system and the brain.";
RL Cancer Res. 52:6407-6412(1992).
RN [2]
RP RNA EDITING OF POSITION 280.
RX PubMed=7926762; DOI=10.1101/gad.8.6.720;
RA Sharma P.M., Bowman M., Madden S.L., Rauscher F.J. III, Sukumar S.;
RT "RNA editing in the Wilms' tumor susceptibility gene, WT1.";
RL Genes Dev. 8:720-731(1994).
CC -!- FUNCTION: Transcription factor that plays an important role in cellular
CC development and cell survival. Recognizes and binds to the DNA sequence
CC 5'-GCG(T/G)GGGCG-3'. Regulates the expression of numerous target genes,
CC including EPO. Plays an essential role for development of the
CC urogenital system. It has a tumor suppressor as well as an oncogenic
CC role in tumor formation. Function may be isoform-specific: isoforms
CC lacking the KTS motif may act as transcription factors. Isoforms
CC containing the KTS motif may bind mRNA and play a role in mRNA
CC metabolism or splicing. Isoform 1 has lower affinity for DNA, and can
CC bind RNA. {ECO:0000250|UniProtKB:P19544}.
CC -!- SUBUNIT: Interacts with ZNF224 via the zinc-finger region. Interacts
CC with WTAP, AMER1 and SRY. Homodimer. Interacts with WTIP. Interacts
CC with actively translating polysomes. Detected in nuclear
CC ribonucleoprotein (mRNP) particles. Interacts with U2AF2. Interacts
CC with HNRNPU via the zinc-finger region. Interacts with CITED2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus speckle {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus, nucleoplasm {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleolus
CC {ECO:0000250}. Cytoplasm {ECO:0000250}. Nucleus speckle {ECO:0000250}.
CC Note=Shuttles between nucleus and cytoplasm. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P49952-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49952-2; Sequence=VSP_006872, VSP_006873;
CC Name=3;
CC IsoId=P49952-3; Sequence=VSP_006872;
CC Name=4;
CC IsoId=P49952-4; Sequence=VSP_006873;
CC -!- TISSUE SPECIFICITY: Kidney.
CC -!- DEVELOPMENTAL STAGE: Expressed during kidney development.
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 -!- RNA EDITING: Modified_positions=280 {ECO:0000269|PubMed:7926762};
CC Note=Partially edited.;
CC -!- MISCELLANEOUS: Presence of the KTS motif hinders interactions between
CC DNA and zinc-finger 4. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; X69716; CAA49373.1; -; mRNA.
DR PIR; S33926; S33926.
DR RefSeq; NP_113722.2; NM_031534.2.
DR AlphaFoldDB; P49952; -.
DR BMRB; P49952; -.
DR SMR; P49952; -.
DR BioGRID; 246993; 1.
DR STRING; 10116.ENSRNOP00000060038; -.
DR PaxDb; P49952; -.
DR GeneID; 24883; -.
DR KEGG; rno:24883; -.
DR UCSC; RGD:3974; rat. [P49952-1]
DR CTD; 7490; -.
DR RGD; 3974; Wt1.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; P49952; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; P49952; -.
DR PRO; PR:P49952; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0070742; F:C2H2 zinc finger domain binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0035802; P:adrenal cortex formation; ISS:UniProtKB.
DR GO; GO:0030325; P:adrenal gland development; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; ISS:UniProtKB.
DR GO; GO:0060923; P:cardiac muscle cell fate commitment; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; ISS:UniProtKB.
DR GO; GO:0060539; P:diaphragm development; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; ISO:RGD.
DR GO; GO:0007281; P:germ cell development; ISS:UniProtKB.
DR GO; GO:0032836; P:glomerular basement membrane development; ISS:UniProtKB.
DR GO; GO:0032835; P:glomerulus development; ISS:UniProtKB.
DR GO; GO:0008406; P:gonad development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0030539; P:male genitalia development; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
DR GO; GO:0060231; P:mesenchymal to epithelial transition; ISS:UniProtKB.
DR GO; GO:0001823; P:mesonephros development; ISO:RGD.
DR GO; GO:0072278; P:metanephric comma-shaped body morphogenesis; ISO:RGD.
DR GO; GO:0072207; P:metanephric epithelium development; ISO:RGD.
DR GO; GO:0072075; P:metanephric mesenchyme development; ISS:UniProtKB.
DR GO; GO:0072284; P:metanephric S-shaped body morphogenesis; ISS:UniProtKB.
DR GO; GO:0001656; P:metanephros development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000195; P:negative regulation of female gonad development; ISS:UniProtKB.
DR GO; GO:1900212; P:negative regulation of mesenchymal cell apoptotic process involved in metanephros development; ISO:RGD.
DR GO; GO:0072302; P:negative regulation of metanephric glomerular mesangial cell proliferation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0072015; P:podocyte development; ISO:RGD.
DR GO; GO:0072112; P:podocyte differentiation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1905643; P:positive regulation of DNA methylation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0060421; P:positive regulation of heart growth; ISS:UniProtKB.
DR GO; GO:2000020; P:positive regulation of male gonad development; ISS:UniProtKB.
DR GO; GO:2001076; P:positive regulation of metanephric ureteric bud development; ISS:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0072166; P:posterior mesonephric tubule development; ISS:UniProtKB.
DR GO; GO:0003156; P:regulation of animal organ formation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; ISS:UniProtKB.
DR GO; GO:0072520; P:seminiferous tubule development; ISO:RGD.
DR GO; GO:0060009; P:Sertoli cell development; ISO:RGD.
DR GO; GO:0007530; P:sex determination; ISS:UniProtKB.
DR GO; GO:0007338; P:single fertilization; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0007356; P:thorax and anterior abdomen determination; ISS:UniProtKB.
DR GO; GO:0009888; P:tissue development; ISS:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; ISS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR GO; GO:0061032; P:visceral serous pericardium development; ISS:UniProtKB.
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; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Reference proteome; Repeat; RNA editing;
KW RNA-binding; Transcription; Transcription regulation; Tumor suppressor;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..448
FT /note="Wilms tumor protein homolog"
FT /id="PRO_0000047134"
FT ZN_FING 322..346
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 352..376
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 382..404
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 413..437
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 48..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 166..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..380
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT REGION 392..400
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT MOTIF 235..243
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT MOTIF 407..409
FT /note="KTS motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 53..71
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 423
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT SITE 429
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT CROSSLNK 72
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 176
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT VAR_SEQ 249..265
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1330293"
FT /id="VSP_006872"
FT VAR_SEQ 407..409
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:1330293"
FT /id="VSP_006873"
FT VARIANT 280
FT /note="L -> P (in RNA edited version)"
SQ SEQUENCE 448 AA; 49193 MW; 329AC9AC1FF73F76 CRC64;
MGSDVRDLNA LLPAVSSLGG GGGCGLPVSG ARQWAPVLDF APPGASAYGS LGGPAPPPAP
PPPPPPPHSF IKQEPSWGGA EPHEEQCLSA FTLHFSGQFT GTAGACRYGP FGPPPPSQAS
SGQARMFPNA PYLPSCLESQ PSIRNQGYST VTFDGAPSYG HTPSHHAAQF PNHSFKHEDP
MGQQGSLGEQ QYSVPPPVYG CHTPTDSCTG SQALLLRTPY SSDNLYQMTS QLECMTWNQM
NLGATLKGMA AGSSSSVKWT EGQSNHGTGY ESENHTTPIL CGAQYRIHTH GVFRGIQDVR
RVSGVAPTLV RSASETSEKR PFMCAYPGCN KRYFKLSHLQ MHSRKHTGEK PYQCDFKDCE
RRFSRSDQLK RHQRRHTGVK PFQCKTCQRK FSRSDHLKTH TRTHTGKTSE KPFSCRWHSC
QKKFARSDEL VRHHNMHQRN MTKLHVAL
