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Protein

Wilms tumor protein 1-interacting protein

Gene

WTIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates Hippo signaling pathway and antagonizes phosphorylation of YAP1. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. In podocytes, may play a role in the regulation of actin dynamics and/or foot process cytoarchitecture (By similarity). In the course of podocyte injury, shuttles into the nucleus and acts as a transcription regulator that represses WT1-dependent transcription regulation, thereby translating changes in slit diaphragm structure into altered gene expression and a less differentiated phenotype.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

  • cytoskeleton organization Source: UniProtKB
  • gene silencing by miRNA Source: MGI
  • negative regulation of hippo signaling Source: UniProtKB
  • positive regulation of gene silencing by miRNA Source: UniProtKB
  • regulation of cell morphogenesis Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to hypoxia Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

RNA-mediated gene silencing, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Wilms tumor protein 1-interacting protein
Short name:
WT1-interacting protein
Gene namesi
Name:WTIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:20964. WTIP.

Subcellular locationi

  • Cell junctionadherens junction
  • Nucleus By similarity
  • CytoplasmP-body

  • Note: Following podocyte injury, caused by treatment with LPS, puromycin aminonucleoside, ultraviolet or hydrogen peroxide, translocates from sites of cell-cell contacts into the cytosol and nucleus. The shift from cell contacts to intracellular plaques starts as early as 1 hour after LPS stimulation and intranuclear localization begins 3 hours after LPS treatment. Maximal nuclear localization is achieved 6 hours after LPS treatment. Nuclear translocation requires dynein motor activity and intact microtubule network (By similarity). Returns to cell-cell contacts 24 hours after LPS stimulation. In the presence of ROR2, localizes to the plasma membrane (By similarity).By similarity

GO - Cellular componenti

  • adherens junction Source: UniProtKB-SubCell
  • cytoplasmic mRNA processing body Source: MGI
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus

Pathology & Biotechi

Polymorphism and mutation databases

BioMutaiWTIP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 430430Wilms tumor protein 1-interacting proteinPRO_0000328860Add
BLAST

Proteomic databases

PaxDbiA6NIX2.
PRIDEiA6NIX2.

PTM databases

iPTMnetiA6NIX2.

Expressioni

Gene expression databases

BgeeiA6NIX2.
CleanExiHS_WTIP.
ExpressionAtlasiA6NIX2. baseline and differential.
GenevisibleiA6NIX2. HS.

Interactioni

Subunit structurei

Forms homodimers (By similarity). Interacts with CD2AP and WT1. Interacts (via LIM domains) with SNAI1 (via SNAG domain), SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain) (By similarity). Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains) with isoform 1 and isoform 3 of VHL. Interacts with ROR2 (By similarity). Following treatment with bacterial lipopolysaccharide (LPS), forms a complex with MAPK8IP3 and dynein intermediate chain (By similarity).By similarity

Protein-protein interaction databases

BioGridi125985. 9 interactions.
STRINGi9606.ENSP00000270288.

Structurei

3D structure databases

ProteinModelPortaliA6NIX2.
SMRiA6NIX2. Positions 225-411.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini223 – 28462LIM zinc-binding 1PROSITE-ProRule annotationAdd
BLAST
Domaini288 – 34861LIM zinc-binding 2PROSITE-ProRule annotationAdd
BLAST
Domaini349 – 41769LIM zinc-binding 3PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi26 – 154129Gly-richAdd
BLAST
Compositional biasi161 – 18929Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the zyxin/ajuba family.Curated
Contains 3 LIM zinc-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiKOG1701. Eukaryota.
ENOG410Y3GP. LUCA.
GeneTreeiENSGT00760000119039.
HOGENOMiHOG000007533.
HOVERGENiHBG108679.
InParanoidiA6NIX2.
KOiK16682.
OMAiLADSEGC.
OrthoDBiEOG793B7F.
TreeFamiTF320310.

Family and domain databases

Gene3Di2.10.110.10. 3 hits.
InterProiIPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 3 hits.
[Graphical view]
SMARTiSM00132. LIM. 3 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A6NIX2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRSRAGADE AALLLAGLAL RELEPGCGSP GRGRRGPRPG PGDEAAPALG
60 70 80 90 100
RRGKGSGGPE AGADGLSRGE RGPRRAAVPE LSAQPAGSPR ASLAGSDGGG
110 120 130 140 150
GGGSARSSGI SLGYDQRHGS PRSGRSDPRP GPGPPSVGSA RSSVSSLGSR
160 170 180 190 200
GSAGAYADFL PPGACPAPAR SPEPAGPAPF PLPALPLPPG REGGPSAAER
210 220 230 240 250
RLEALTRELE RALEARTARD YFGICIKCGL GIYGAQQACQ AMGSLYHTDC
260 270 280 290 300
FTCDSCGRRL RGKAFYNVGE KVYCQEDFLY SGFQQTADKC SVCGHLIMEM
310 320 330 340 350
ILQALGKSYH PGCFRCSVCN ECLDGVPFTV DVENNIYCVR DYHTVFAPKC
360 370 380 390 400
ASCARPILPA QGCETTIRVV SMDRDYHVAC YHCEDCGLQL SGEEGRRCYP
410 420 430
LAGHLLCRRC HLRRLQPGPL PSPTVHVTEL
Length:430
Mass (Da):45,124
Last modified:April 18, 2012 - v3
Checksum:iB95E162B3009B886
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC008747 Genomic DNA. No translation available.
CCDSiCCDS59375.1.
RefSeqiNP_001073905.1. NM_001080436.1.
UniGeneiHs.585010.

Genome annotation databases

EnsembliENST00000590071; ENSP00000466953; ENSG00000142279.
GeneIDi126374.
KEGGihsa:126374.
UCSCiuc002nvm.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC008747 Genomic DNA. No translation available.
CCDSiCCDS59375.1.
RefSeqiNP_001073905.1. NM_001080436.1.
UniGeneiHs.585010.

3D structure databases

ProteinModelPortaliA6NIX2.
SMRiA6NIX2. Positions 225-411.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125985. 9 interactions.
STRINGi9606.ENSP00000270288.

PTM databases

iPTMnetiA6NIX2.

Polymorphism and mutation databases

BioMutaiWTIP.

Proteomic databases

PaxDbiA6NIX2.
PRIDEiA6NIX2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000590071; ENSP00000466953; ENSG00000142279.
GeneIDi126374.
KEGGihsa:126374.
UCSCiuc002nvm.4. human.

Organism-specific databases

CTDi126374.
GeneCardsiWTIP.
HGNCiHGNC:20964. WTIP.
MIMi614790. gene.
neXtProtiNX_A6NIX2.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1701. Eukaryota.
ENOG410Y3GP. LUCA.
GeneTreeiENSGT00760000119039.
HOGENOMiHOG000007533.
HOVERGENiHBG108679.
InParanoidiA6NIX2.
KOiK16682.
OMAiLADSEGC.
OrthoDBiEOG793B7F.
TreeFamiTF320310.

Miscellaneous databases

ChiTaRSiWTIP. human.
GenomeRNAii126374.
PROiA6NIX2.
SOURCEiSearch...

Gene expression databases

BgeeiA6NIX2.
CleanExiHS_WTIP.
ExpressionAtlasiA6NIX2. baseline and differential.
GenevisibleiA6NIX2. HS.

Family and domain databases

Gene3Di2.10.110.10. 3 hits.
InterProiIPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 3 hits.
[Graphical view]
SMARTiSM00132. LIM. 3 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "Ajuba LIM proteins are negative regulators of the Hippo signaling pathway."
    Das Thakur M., Feng Y., Jagannathan R., Seppa M.J., Skeath J.B., Longmore G.D.
    Curr. Biol. 20:657-662(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH LATS1; LATS2 AND SAV1.
  3. "Podocyte injury induces nuclear translocation of WTIP via microtubule-dependent transport."
    Kim J.H., Konieczkowski M., Mukherjee A., Schechtman S., Khan S., Schelling J.R., Ross M.D., Bruggeman L.A., Sedor J.R.
    J. Biol. Chem. 285:9995-10004(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  4. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF4E; AGO1; AGO2; DCP2 AND DDX6.
  5. "Identification and characterization of a set of conserved and new regulators of cytoskeletal organisation, cell morphology and migration."
    Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V., Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.
    BMC Biol. 9:54-54(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: FUNCTION, INTERACTION WITH EGLN2/PHD1; EGLN3/PHD3 AND VHL.

Entry informationi

Entry nameiWTIP_HUMAN
AccessioniPrimary (citable) accession number: A6NIX2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 18, 2012
Last modified: June 8, 2016
This is version 74 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.