WTIP_MOUSE
ID WTIP_MOUSE Reviewed; 398 AA.
AC Q7TQJ8; Q8CG89;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Wilms tumor protein 1-interacting protein;
DE Short=WT1-interacting protein;
GN Name=Wtip;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND INTERACTION WITH WT1 AND CD2AP.
RX PubMed=14736876; DOI=10.1074/jbc.m314155200;
RA Srichai M.B., Konieczkowski M., Padiyar A., Konieczkowski D.J.,
RA Mukherjee A., Hayden P.S., Kamat S., El-Meanawy M.A., Khan S., Mundel P.,
RA Lee S.B., Bruggeman L.A., Schelling J.R., Sedor J.R.;
RT "A WT1 co-regulator controls podocyte phenotype by shuttling between
RT adhesion structures and nucleus.";
RL J. Biol. Chem. 279:14398-14408(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15798086; DOI=10.1152/ajprenal.00389.2004;
RA Rico M., Mukherjee A., Konieczkowski M., Bruggeman L.A., Miller R.T.,
RA Khan S., Schelling J.R., Sedor J.R.;
RT "WT1-interacting protein and ZO-1 translocate into podocyte nuclei after
RT puromycin aminonucleoside treatment.";
RL Am. J. Physiol. 289:F431-F441(2005).
RN [5]
RP FUNCTION.
RX PubMed=17909014; DOI=10.1158/0008-5472.can-07-2987;
RA Ayyanathan K., Peng H., Hou Z., Fredericks W.J., Goyal R.K., Langer E.M.,
RA Longmore G.D., Rauscher F.J. III;
RT "The Ajuba LIM domain protein is a corepressor for SNAG domain mediated
RT repression and participates in nucleocytoplasmic Shuttling.";
RL Cancer Res. 67:9097-9106(2007).
RN [6]
RP INTERACTION WITH SNAI1; SNAI2/SLUG AND SCRT1.
RX PubMed=18331720; DOI=10.1016/j.devcel.2008.01.005;
RA Langer E.M., Feng Y., Zhaoyuan H., Rauscher F.J. III, Kroll K.L.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are snail/slug corepressors required for neural crest
RT development in Xenopus.";
RL Dev. Cell 14:424-436(2008).
RN [7]
RP INTERACTION WITH ROR2, HOMODIMERIZATION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=19785987; DOI=10.1016/j.bbrc.2009.09.086;
RA van Wijk N.V., Witte F., Feike A.C., Schambony A., Birchmeier W.,
RA Mundlos S., Stricker S.;
RT "The LIM domain protein Wtip interacts with the receptor tyrosine kinase
RT Ror2 and inhibits canonical Wnt signalling.";
RL Biochem. Biophys. Res. Commun. 390:211-216(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAPK8IP3 AND DYNEIN
RP INTERMEDIATE CHAIN, AND TISSUE SPECIFICITY.
RX PubMed=20086015; DOI=10.1074/jbc.m109.061671;
RA Kim J.H., Konieczkowski M., Mukherjee A., Schechtman S., Khan S.,
RA Schelling J.R., Ross M.D., Bruggeman L.A., Sedor J.R.;
RT "Podocyte injury induces nuclear translocation of WTIP via microtubule-
RT dependent transport.";
RL J. Biol. Chem. 285:9995-10004(2010).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=21900451; DOI=10.1152/ajprenal.00419.2011;
RA Kim J.H., Mukherjee A., Madhavan S.M., Konieczkowski M., Sedor J.R.;
RT "WT1-interacting protein (Wtip) regulates podocyte phenotype by cell-cell
RT and cell-matrix contact reorganization.";
RL Am. J. Physiol. 302:F103-F115(2012).
CC -!- FUNCTION: Adapter or scaffold protein which participates in the
CC assembly of numerous protein complexes and is involved in several
CC cellular processes such as cell fate determination, cytoskeletal
CC organization, repression of gene transcription, cell-cell adhesion,
CC cell differentiation, proliferation and migration. Positively regulates
CC microRNA (miRNA)-mediated gene silencing. Negatively regulates Hippo
CC signaling pathway and antagonizes phosphorylation of YAP1. Acts as a
CC transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent
CC repression of E-cadherin transcription. Acts as a hypoxic regulator by
CC bridging an association between the prolyl hydroxylases and VHL
CC enabling efficient degradation of HIF1A. In podocytes, may play a role
CC in the regulation of actin dynamics and/or foot process
CC cytoarchitecture. In the course of podocyte injury, shuttles into the
CC nucleus and acts as a transcription regulator that represses WT1-
CC dependent transcription regulation, thereby translating changes in slit
CC diaphragm structure into altered gene expression and a less
CC differentiated phenotype. Involved in the organization of the basal
CC body (By similarity). Involved in cilia growth and positioning (By
CC similarity). {ECO:0000250|UniProtKB:A9LS46,
CC ECO:0000269|PubMed:14736876, ECO:0000269|PubMed:15798086,
CC ECO:0000269|PubMed:17909014, ECO:0000269|PubMed:20086015}.
CC -!- SUBUNIT: Forms homodimers. Interacts with EIF4E, AGO1, AGO2, DCP2,
CC DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM
CC domains) with VHL (By similarity). Interacts with CD2AP and WT1.
CC Interacts (via LIM domains) with SNAI1 (via SNAG domain), SNAI2/SLUG
CC (via SNAG domain) and SCRT1 (via SNAG domain). Interacts with ROR2.
CC Following treatment with bacterial lipopolysaccharide (LPS), forms a
CC complex with MAPK8IP3 and dynein intermediate chain. Interacts with
CC PRICKLE3 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:A9LS46,
CC ECO:0000269|PubMed:14736876, ECO:0000269|PubMed:18331720,
CC ECO:0000269|PubMed:19785987, ECO:0000269|PubMed:20086015}.
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell junction,
CC adherens junction. Nucleus. Cytoplasm, cytosol. Cell membrane. Note=In
CC adherent but isolated podocytes, targets to focal adhesions and then
CC shifts to adherens junctions after cells make homotypic contacts.
CC Following podocyte injury, caused by treatment with LPS, puromycin
CC aminonucleoside, ultraviolet or hydrogen peroxide, translocates from
CC sites of cell-cell contacts into the cytosol and nucleus. Maximal
CC nuclear localization is achieved 6 hours after LPS treatment. Nuclear
CC translocation requires dynein motor activity and intact microtubule
CC network (By similarity). Returns to cell-cell contacts several hours
CC after LPS stimulation. In the presence of ROR2, localizes to the plasma
CC membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, lung, eye and ovary. In
CC kidney, restricted to podocytes. {ECO:0000269|PubMed:14736876,
CC ECO:0000269|PubMed:20086015}.
CC -!- DEVELOPMENTAL STAGE: From 9.5 to 11.5 dpc, expressed in the branchial
CC arches, otic vesicle, limb buds, somites, craniofacial mesenchyme and
CC tail buds. At 14.5 dpc, expressed in the developing tongue, nasal
CC cavity, palate, adrenal gland, in the forebrain, dorsal root ganglia
CC and in the somites. At 14.5 dpc, also detected in lung, rib cartilage,
CC kidney and intestine (at protein level). In the kidney, expression
CC peaks at 15 to 16 dpc and decreases thereafter, but persists in
CC adulthood. {ECO:0000269|PubMed:14736876, ECO:0000269|PubMed:19785987}.
CC -!- SIMILARITY: Belongs to the zyxin/ajuba family. {ECO:0000305}.
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DR EMBL; BX539331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042762; AAH42762.1; -; mRNA.
DR EMBL; BC054125; AAH54125.1; -; mRNA.
DR CCDS; CCDS21135.1; -.
DR RefSeq; NP_997095.1; NM_207212.2.
DR AlphaFoldDB; Q7TQJ8; -.
DR BioGRID; 221684; 1.
DR DIP; DIP-59507N; -.
DR IntAct; Q7TQJ8; 5.
DR MINT; Q7TQJ8; -.
DR STRING; 10090.ENSMUSP00000047623; -.
DR iPTMnet; Q7TQJ8; -.
DR PhosphoSitePlus; Q7TQJ8; -.
DR MaxQB; Q7TQJ8; -.
DR PaxDb; Q7TQJ8; -.
DR PeptideAtlas; Q7TQJ8; -.
DR PRIDE; Q7TQJ8; -.
DR ProteomicsDB; 299776; -.
DR Antibodypedia; 56892; 67 antibodies from 13 providers.
DR DNASU; 101543; -.
DR Ensembl; ENSMUST00000038537; ENSMUSP00000047623; ENSMUSG00000036459.
DR GeneID; 101543; -.
DR KEGG; mmu:101543; -.
DR UCSC; uc009gis.2; mouse.
DR CTD; 126374; -.
DR MGI; MGI:2141920; Wtip.
DR VEuPathDB; HostDB:ENSMUSG00000036459; -.
DR eggNOG; KOG1701; Eukaryota.
DR GeneTree; ENSGT00940000160924; -.
DR HOGENOM; CLU_001357_11_3_1; -.
DR InParanoid; Q7TQJ8; -.
DR OMA; QENEWHR; -.
DR OrthoDB; 326249at2759; -.
DR PhylomeDB; Q7TQJ8; -.
DR TreeFam; TF320310; -.
DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR BioGRID-ORCS; 101543; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Wtip; mouse.
DR PRO; PR:Q7TQJ8; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q7TQJ8; protein.
DR Bgee; ENSMUSG00000036459; Expressed in external carotid artery and 214 other tissues.
DR ExpressionAtlas; Q7TQJ8; baseline and differential.
DR Genevisible; Q7TQJ8; MM.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; ISO:MGI.
DR GO; GO:0035331; P:negative regulation of hippo signaling; ISS:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 3.
DR SMART; SM00132; LIM; 3.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 3.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cilium biogenesis/degradation; Cytoplasm;
KW LIM domain; Membrane; Metal-binding; Nucleus; Reference proteome; Repeat;
KW Repressor; RNA-mediated gene silencing; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..398
FT /note="Wilms tumor protein 1-interacting protein"
FT /id="PRO_0000328861"
FT DOMAIN 191..252
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 256..315
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 316..385
FT /note="LIM zinc-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT REGION 16..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..158
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 398 AA; 42254 MW; 6677EE0A882D1E40 CRC64;
MQRSRTAADD AALLLAGLGL RESEPTAGSP GRVRRGPRAV DEAAPASGRR GKGGCGGPEA
APDVPSRPER GPRASLAGSD GGSARSSGIS LGYDQRHGPG PGPPSGGSAR SSVSSLGSRG
SAGACADLLP PGVGPAPARS PEPAQFPFPL PSLPLPPGRE GGPSAAERRL EALTRELERA
LEARTARDYF GICIKCGLGI YGARQACQAM GSLYHTDCFI CDSCGRRLRG KAFYNVGEKV
YCQEDFLYSG FQQTADKCSV CGHLIMEMIL QALGKSYHPG CFRCSVCNEC LDGVPFTVDV
DNNIYCVRDY HTVFAPKCAS CARPILPAQG CETTIRVVSM DRDYHVECYH CEDCGLQLSG
EEGRRCYPLE GHLLCRRCHL RRLGQGPLPS PAVHVTEL
