WTIP_HUMAN
ID WTIP_HUMAN Reviewed; 430 AA.
AC A6NIX2;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Wilms tumor protein 1-interacting protein;
DE Short=WT1-interacting protein;
GN Name=WTIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP FUNCTION, AND INTERACTION WITH LATS1; LATS2 AND SAV1.
RX PubMed=20303269; DOI=10.1016/j.cub.2010.02.035;
RA Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B.,
RA Longmore G.D.;
RT "Ajuba LIM proteins are negative regulators of the Hippo signaling
RT pathway.";
RL Curr. Biol. 20:657-662(2010).
RN [3]
RP SUBCELLULAR LOCATION.
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4E; AGO1; AGO2;
RP DCP2 AND DDX6.
RX PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA Longmore G.D., Bushell M., Sharp T.V.;
RT "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-
RT mediated gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN [5]
RP FUNCTION.
RX PubMed=21834987; DOI=10.1186/1741-7007-9-54;
RA Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V.,
RA Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.;
RT "Identification and characterization of a set of conserved and new
RT regulators of cytoskeletal organisation, cell morphology and migration.";
RL BMC Biol. 9:54-54(2011).
RN [6]
RP FUNCTION, AND INTERACTION WITH EGLN2/PHD1; EGLN3/PHD3 AND VHL.
RX PubMed=22286099; DOI=10.1038/ncb2424;
RA Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y.,
RA Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S.,
RA Ratcliffe P.J., Longmore G.D., Sharp T.V.;
RT "The LIMD1 protein bridges an association between the prolyl hydroxylases
RT and VHL to repress HIF-1 activity.";
RL Nat. Cell Biol. 14:201-208(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 (By similarity). In the course of podocyte injury,
CC shuttles into the nucleus and acts as a transcription regulator that
CC represses WT1-dependent transcription regulation, thereby translating
CC changes in slit diaphragm structure into altered gene expression and a
CC less differentiated phenotype. Involved in the organization of the
CC basal body (By similarity). Involved in cilia growth and positioning
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:A9LS46,
CC ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046,
CC ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}.
CC -!- SUBUNIT: Forms homodimers (By similarity). Interacts with CD2AP and
CC WT1. Interacts (via LIM domains) with SNAI1 (via SNAG domain),
CC SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain) (By
CC similarity). Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1,
CC LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains)
CC with isoform 1 and isoform 3 of VHL. Interacts with ROR2 (By
CC similarity). Following treatment with bacterial lipopolysaccharide
CC (LPS), forms a complex with MAPK8IP3 and dynein intermediate chain (By
CC similarity). Interacts with PRICKLE3 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:A9LS46}.
CC -!- INTERACTION:
CC A6NIX2; Q9H9G7: AGO3; NbExp=3; IntAct=EBI-20730502, EBI-2267883;
CC A6NIX2; Q14160: SCRIB; NbExp=2; IntAct=EBI-20730502, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction. Nucleus
CC {ECO:0000250}. Cytoplasm, P-body. Note=Following podocyte injury,
CC caused by treatment with LPS, puromycin aminonucleoside, ultraviolet or
CC hydrogen peroxide, translocates from sites of cell-cell contacts into
CC the cytosol and nucleus. The shift from cell contacts to intracellular
CC plaques starts as early as 1 hour after LPS stimulation and
CC intranuclear localization begins 3 hours after LPS treatment. 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 24 hours after
CC LPS stimulation. In the presence of ROR2, localizes to the plasma
CC membrane (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the zyxin/ajuba family. {ECO:0000305}.
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DR EMBL; AC008747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS59375.1; -.
DR RefSeq; NP_001073905.1; NM_001080436.1.
DR AlphaFoldDB; A6NIX2; -.
DR BioGRID; 125985; 13.
DR IntAct; A6NIX2; 8.
DR STRING; 9606.ENSP00000466953; -.
DR iPTMnet; A6NIX2; -.
DR PhosphoSitePlus; A6NIX2; -.
DR BioMuta; WTIP; -.
DR EPD; A6NIX2; -.
DR jPOST; A6NIX2; -.
DR MassIVE; A6NIX2; -.
DR MaxQB; A6NIX2; -.
DR PaxDb; A6NIX2; -.
DR PeptideAtlas; A6NIX2; -.
DR PRIDE; A6NIX2; -.
DR ProteomicsDB; 1294; -.
DR Antibodypedia; 56892; 67 antibodies from 13 providers.
DR DNASU; 126374; -.
DR Ensembl; ENST00000590071.7; ENSP00000466953.2; ENSG00000142279.13.
DR GeneID; 126374; -.
DR KEGG; hsa:126374; -.
DR MANE-Select; ENST00000590071.7; ENSP00000466953.2; NM_001080436.2; NP_001073905.1.
DR UCSC; uc002nvm.4; human.
DR CTD; 126374; -.
DR DisGeNET; 126374; -.
DR GeneCards; WTIP; -.
DR HGNC; HGNC:20964; WTIP.
DR HPA; ENSG00000142279; Low tissue specificity.
DR MIM; 614790; gene.
DR neXtProt; NX_A6NIX2; -.
DR OpenTargets; ENSG00000142279; -.
DR VEuPathDB; HostDB:ENSG00000142279; -.
DR eggNOG; KOG1701; Eukaryota.
DR GeneTree; ENSGT00940000160924; -.
DR HOGENOM; CLU_001357_11_3_1; -.
DR InParanoid; A6NIX2; -.
DR OMA; QENEWHR; -.
DR OrthoDB; 326249at2759; -.
DR TreeFam; TF320310; -.
DR PathwayCommons; A6NIX2; -.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR SignaLink; A6NIX2; -.
DR BioGRID-ORCS; 126374; 15 hits in 1075 CRISPR screens.
DR ChiTaRS; WTIP; human.
DR GenomeRNAi; 126374; -.
DR Pharos; A6NIX2; Tbio.
DR PRO; PR:A6NIX2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; A6NIX2; protein.
DR Bgee; ENSG00000142279; Expressed in popliteal artery and 139 other tissues.
DR ExpressionAtlas; A6NIX2; baseline and differential.
DR Genevisible; A6NIX2; HS.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; IDA:MGI.
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; IBA:GO_Central.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; IMP:MGI.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IDA:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IMP:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
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; Cilium biogenesis/degradation; Cytoplasm; LIM domain;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Repressor;
KW RNA-mediated gene silencing; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..430
FT /note="Wilms tumor protein 1-interacting protein"
FT /id="PRO_0000328860"
FT DOMAIN 223..284
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 288..348
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 349..417
FT /note="LIM zinc-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT REGION 22..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..190
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 430 AA; 45124 MW; B95E162B3009B886 CRC64;
MQRSRAGADE AALLLAGLAL RELEPGCGSP GRGRRGPRPG PGDEAAPALG RRGKGSGGPE
AGADGLSRGE RGPRRAAVPE LSAQPAGSPR ASLAGSDGGG GGGSARSSGI SLGYDQRHGS
PRSGRSDPRP GPGPPSVGSA RSSVSSLGSR GSAGAYADFL PPGACPAPAR SPEPAGPAPF
PLPALPLPPG REGGPSAAER RLEALTRELE RALEARTARD YFGICIKCGL GIYGAQQACQ
AMGSLYHTDC FTCDSCGRRL RGKAFYNVGE KVYCQEDFLY SGFQQTADKC SVCGHLIMEM
ILQALGKSYH PGCFRCSVCN ECLDGVPFTV DVENNIYCVR DYHTVFAPKC ASCARPILPA
QGCETTIRVV SMDRDYHVAC YHCEDCGLQL SGEEGRRCYP LAGHLLCRRC HLRRLQPGPL
PSPTVHVTEL
