WT1_PIG
ID WT1_PIG Reviewed; 449 AA.
AC O62651;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Wilms tumor protein homolog;
GN Name=WT1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC STRAIN=Large white X Duroc; TISSUE=Kidney;
RX PubMed=9602131; DOI=10.1016/s0378-1119(98)00112-7;
RA Tsurutani N., Oda H., Nakatsuru Y., Imai Y., Zhang S., Ueno Y.,
RA Ishikawa T.;
RT "cDNA cloning and developmental expression of the porcine homologue of
RT WT1.";
RL Gene 211:215-220(1998).
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.
CC Interacts with RBM4 (By 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 Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=O62651-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O62651-2; Sequence=VSP_006870, VSP_006871;
CC Name=3;
CC IsoId=O62651-3; Sequence=VSP_006870;
CC Name=4;
CC IsoId=O62651-4; Sequence=VSP_006871;
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=281 {ECO:0000250}; Note=Partially
CC edited. {ECO:0000250};
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; AB010969; BAA28147.1; -; mRNA.
DR RefSeq; NP_001001264.1; NM_001001264.1. [O62651-1]
DR AlphaFoldDB; O62651; -.
DR BMRB; O62651; -.
DR SMR; O62651; -.
DR STRING; 9823.ENSSSCP00000019417; -.
DR PaxDb; O62651; -.
DR PeptideAtlas; O62651; -.
DR PRIDE; O62651; -.
DR GeneID; 397338; -.
DR KEGG; ssc:397338; -.
DR CTD; 7490; -.
DR eggNOG; KOG1721; Eukaryota.
DR InParanoid; O62651; -.
DR OrthoDB; 1318335at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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; ISS:UniProtKB.
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: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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
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:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; ISS:UniProtKB.
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: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:0030539; P:male genitalia development; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; ISS:UniProtKB.
DR GO; GO:0060231; P:mesenchymal to epithelial transition; ISS:UniProtKB.
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: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:0072302; P:negative regulation of metanephric glomerular mesangial cell proliferation; ISS:UniProtKB.
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:0072112; P:podocyte differentiation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
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:0045893; P:positive regulation of transcription, DNA-templated; ISS: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: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:0007530; P:sex determination; ISS:UniProtKB.
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; 2.
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..449
FT /note="Wilms tumor protein homolog"
FT /id="PRO_0000047133"
FT ZN_FING 323..347
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 353..377
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 383..405
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 414..438
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 48..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..381
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT REGION 393..401
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT MOTIF 236..244
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT MOTIF 408..410
FT /note="KTS motif"
FT /evidence="ECO:0000250"
FT COMPBIAS 53..72
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 424
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT SITE 430
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 177
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 444
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT VAR_SEQ 250..266
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:9602131"
FT /id="VSP_006870"
FT VAR_SEQ 408..410
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:9602131"
FT /id="VSP_006871"
FT VARIANT 281
FT /note="L -> P (in RNA edited version)"
SQ SEQUENCE 449 AA; 49166 MW; 9C3E557B96F5A7B3 CRC64;
MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAEWAPVLDF APPGASAYGS LGGPAPPPAP
PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYE PFGPPPPSQA
SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED
PMGQQGSLGE QQYSVPPPVY GCHTSTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ
MNLGATLKGV AAGTSSSMKW TEGQSNHGAG YESDSHATPI LCGAQYRIHT HGVFRGIQDV
RRVPGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC
ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT HTRTHTGKTS EKPFSCRWPS
CQKKFARSDE LVRHHNMHQR NMSKLQLAL
