WT1_SMIMA
ID WT1_SMIMA Reviewed; 239 AA.
AC P49953;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Wilms tumor protein homolog;
DE Flags: Fragment;
GN Name=WT1;
OS Sminthopsis macroura (Stripe-faced dunnart).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Dasyuromorphia; Dasyuridae; Sminthopsis.
OX NCBI_TaxID=9302;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
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).
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. {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 2]: Nucleus, nucleoplasm {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Nucleus speckle {ECO:0000250}. Note=Shuttles between nucleus and
CC cytoplasm. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49953-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49953-2; Sequence=VSP_006875;
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 -!- 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X85732; CAA59737.1; -; mRNA.
DR AlphaFoldDB; P49953; -.
DR SMR; P49953; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; 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: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: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: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: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: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; 1.
DR Pfam; PF00096; zf-C2H2; 3.
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; Repeat; RNA-binding; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN <1..239
FT /note="Wilms tumor protein homolog"
FT /id="PRO_0000047136"
FT ZN_FING 113..137
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 143..167
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 173..195
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 204..228
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 157..171
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT REGION 183..191
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT MOTIF 43..51
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT MOTIF 198..200
FT /note="KTS motif"
FT /evidence="ECO:0000250"
FT SITE 214
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT SITE 220
FT /note="Important for interaction with target DNA"
FT /evidence="ECO:0000250"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P19544"
FT VAR_SEQ 198..200
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7478606"
FT /id="VSP_006875"
FT NON_TER 1
SQ SEQUENCE 239 AA; 27793 MW; 6707678A7259A624 CRC64;
SVPPPVYGCH TPTDSCTGSQ ALLLRTPYNS DNLYQMTSQL ECMTWNQMNL GATLKGHTTG
YENDNHTTPI LCGAQYRIHT HGVFRGIQDV RRVPGVAPTI VRSATETNEK RPFMCAYPGC
NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR
KFSRSDHLKT HTRTHTGKTS EKPFSCRWPS CQKKFARSDE LVRHHNMHQR NMTKLQLTL
