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Protein

Protein KIBRA

Gene

WWC1

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

Functioni

Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ. Plays a role in cognition and memory performance.7 Publications

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • protein-containing complex scaffold activity Source: BHF-UCL
  • transcription coactivator activity Source: UniProtKB

GO - Biological processi

  • cell migration Source: UniProtKB
  • establishment of cell polarity Source: BHF-UCL
  • hippo signaling Source: Reactome
  • negative regulation of hippo signaling Source: BHF-UCL
  • negative regulation of organ growth Source: BHF-UCL
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of transcription of Notch receptor target Source: Reactome
  • regulation of hippo signaling Source: UniProtKB
  • regulation of intracellular transport Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2028269 Signaling by Hippo
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription
SignaLinkiQ8IX03
SIGNORiQ8IX03

Names & Taxonomyi

Protein namesi
Recommended name:
Protein KIBRA
Alternative name(s):
HBeAg-binding protein 3
Kidney and brain protein
Short name:
KIBRA
WW domain-containing protein 1
Gene namesi
Name:WWC1
Synonyms:KIAA0869
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113645.13
HGNCiHGNC:29435 WWC1
MIMi610533 gene
neXtProtiNX_Q8IX03

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi23286
MalaCardsiWWC1
MIMi615602 phenotype
OpenTargetsiENSG00000113645
PharmGKBiPA143485670

Polymorphism and mutation databases

BioMutaiWWC1
DMDMi74714457

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002421531 – 1113Protein KIBRAAdd BLAST1113

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei141PhosphoserineBy similarity1
Modified residuei535PhosphoserineCombined sources1
Modified residuei542Phosphoserine; by CDK11 Publication1
Modified residuei899PhosphoserineCombined sources1
Modified residuei912PhosphothreonineCombined sources1
Modified residuei927PhosphoserineBy similarity1
Modified residuei929PhosphothreonineCombined sources1
Modified residuei931Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei947PhosphoserineCombined sources1
Modified residuei975Phosphoserine; by PKC/PRKCZ1 Publication1
Modified residuei978Phosphoserine; by PKC/PRKCZ1 Publication1

Post-translational modificationi

Phosphorylation at Ser-542 and Ser-931 by CDK1 in response to spindle damage stress regulates mitotic exit, these two sites are dephosphorylated by CDC14B.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8IX03
MaxQBiQ8IX03
PaxDbiQ8IX03
PeptideAtlasiQ8IX03
PRIDEiQ8IX03

PTM databases

CarbonylDBiQ8IX03
iPTMnetiQ8IX03
PhosphoSitePlusiQ8IX03

Expressioni

Tissue specificityi

Expressed in mammary epithelial cells and breast cancer cell lines. Found in the luminal epithelium surrounding the ducts in the normal breast. In the brain, expressed in somatodendritic compartment of neurons in the cortex and hippocampus and in the cerebellum it is found in the Purkinje cells and some granule cells (at protein level). Detected in brain, heart, colon and kidney. In the kidney, expressed in glomerular podocytes, in some tubules and in the collecting duct.4 Publications

Inductioni

Strongly up-regulated by progestin treatment.1 Publication

Gene expression databases

BgeeiENSG00000113645
CleanExiHS_WWC1
ExpressionAtlasiQ8IX03 baseline and differential
GenevisibleiQ8IX03 HS

Organism-specific databases

HPAiHPA038016
HPA038017

Interactioni

Subunit structurei

Homodimer. Interacts with DDN. Interacts with DYNLL1 and histone H3. The interaction with DYNLL1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin and the interaction with histone H3 ensures proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes with target chromatin. Interacts (via WW domains) with DDR1 (via PPxY motif) in a collagen-regulated manner. Interacts with PRKCZ (via the protein kinase domain). Forms a tripartite complex with DDR1 and PRKCZ, but predominantly in the absence of collagen. Interacts (via the ADDV motif) with PATJ (via PDZ domain 8). Interacts (via WW domains) with SYNPO (via PPxY motifs). Interacts with NF2 and SNX4.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Exoc4Q628243EBI-15812469,EBI-6959516From Rattus norvegicus.

GO - Molecular functioni

  • kinase binding Source: BHF-UCL
  • protein-containing complex scaffold activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi116884, 61 interactors
CORUMiQ8IX03
DIPiDIP-35287N
IntActiQ8IX03, 29 interactors
MINTiQ8IX03
STRINGi9606.ENSP00000427772

Structurei

Secondary structure

11113
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi660 – 669Combined sources10
Turni670 – 673Combined sources4
Beta strandi674 – 683Combined sources10
Helixi685 – 687Combined sources3
Beta strandi694 – 704Combined sources11
Helixi708 – 711Combined sources4
Beta strandi712 – 714Combined sources3
Beta strandi722 – 733Combined sources12
Helixi736 – 741Combined sources6
Beta strandi743 – 751Combined sources9
Beta strandi757 – 766Combined sources10
Beta strandi777 – 784Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z0UX-ray2.20A/B638-785[»]
ProteinModelPortaliQ8IX03
SMRiQ8IX03
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IX03

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 39WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini53 – 86WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini655 – 783C2Add BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni839 – 1113Interaction with histone H3Add BLAST275
Regioni953 – 996Interaction with PRKCZAdd BLAST44

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili107 – 193Sequence analysisAdd BLAST87
Coiled coili293 – 431Sequence analysisAdd BLAST139
Coiled coili1001 – 1032Sequence analysisAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1111 – 1113ADDV motif3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi261 – 265Poly-Ser5
Compositional biasi819 – 873Glu-richAdd BLAST55

Domaini

The C2-domain mediates homodimerization. It is a calcium-sensitive lipid-binding domain with preference for PI3P.1 Publication

Sequence similaritiesi

Belongs to the WWC family. KIBRA subfamily.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG3209 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00410000025556
HOGENOMiHOG000013211
HOVERGENiHBG058082
InParanoidiQ8IX03
KOiK16685
OMAiHHTHIPR
OrthoDBiEOG091G0UU4
PhylomeDBiQ8IX03
TreeFamiTF324040

Family and domain databases

CDDicd08680 C2_Kibra, 1 hit
cd00201 WW, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR035892 C2_domain_sf
IPR037771 C2_WWC
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00397 WW, 2 hits
SMARTiView protein in SMART
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 hits
PROSITEiView protein in PROSITE
PS01159 WW_DOMAIN_1, 1 hit
PS50020 WW_DOMAIN_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IX03-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRPELPLPE GWEEARDFDG KVYYIDHTNR TTSWIDPRDR YTKPLTFADC
60 70 80 90 100
ISDELPLGWE EAYDPQVGDY FIDHNTKTTQ IEDPRVQWRR EQEHMLKDYL
110 120 130 140 150
VVAQEALSAQ KEIYQVKQQR LELAQQEYQQ LHAVWEHKLG SQVSLVSGSS
160 170 180 190 200
SSSKYDPEIL KAEIATAKSR VNKLKREMVH LQHELQFKER GFQTLKKIDK
210 220 230 240 250
KMSDAQGSYK LDEAQAVLRE TKAIKKAITC GEKEKQDLIK SLAMLKDGFR
260 270 280 290 300
TDRGSHSDLW SSSSSLESSS FPLPKQYLDV SSQTDISGSF GINSNNQLAE
310 320 330 340 350
KVRLRLRYEE AKRRIANLKI QLAKLDSEAW PGVLDSERDR LILINEKEEL
360 370 380 390 400
LKEMRFISPR KWTQGEVEQL EMARKRLEKD LQAARDTQSK ALTERLKLNS
410 420 430 440 450
KRNQLVRELE EATRQVATLH SQLKSLSSSM QSLSSGSSPG SLTSSRGSLV
460 470 480 490 500
ASSLDSSTSA SFTDLYYDPF EQLDSELQSK VEFLLLEGAT GFRPSGCITT
510 520 530 540 550
IHEDEVAKTQ KAEGGGRLQA LRSLSGTPKS MTSLSPRSSL SSPSPPCSPL
560 570 580 590 600
MADPLLAGDA FLNSLEFEDP ELSATLCELS LGNSAQERYR LEEPGTEGKQ
610 620 630 640 650
LGQAVNTAQG CGLKVACVSA AVSDESVAGD SGVYEASVQR LGASEAAAFD
660 670 680 690 700
SDESEAVGAT RIQIALKYDE KNKQFAILII QLSNLSALLQ QQDQKVNIRV
710 720 730 740 750
AVLPCSESTT CLFRTRPLDA SDTLVFNEVF WVSMSYPALH QKTLRVDVCT
760 770 780 790 800
TDRSHLEECL GGAQISLAEV CRSGERSTRW YNLLSYKYLK KQSRELKPVG
810 820 830 840 850
VMAPASGPAS TDAVSALLEQ TAVELEKRQE GRSSTQTLED SWRYEETSEN
860 870 880 890 900
EAVAEEEEEE VEEEEGEEDV FTEKASPDMD GYPALKVDKE TNTETPAPSP
910 920 930 940 950
TVVRPKDRRV GTPSQGPFLR GSTIIRSKTF SPGPQSQYVC RLNRSDSDSS
960 970 980 990 1000
TLSKKPPFVR NSLERRSVRM KRPSSVKSLR SERLIRTSLD LELDLQATRT
1010 1020 1030 1040 1050
WHSQLTQEIS VLKELKEQLE QAKSHGEKEL PQWLREDERF RLLLRMLEKR
1060 1070 1080 1090 1100
QMDRAEHKGE LQTDKMMRAA AKDVHRLRGQ SCKEPPEVQS FREKMAFFTR
1110
PRMNIPALSA DDV
Length:1,113
Mass (Da):125,301
Last modified:March 1, 2003 - v1
Checksum:i9010B9C127129165
GO
Isoform 2 (identifier: Q8IX03-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     974-974: S → SPPPQPS

Show »
Length:1,119
Mass (Da):125,905
Checksum:i0AB48E74AB261693
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti561F → L in CAE45903 (PubMed:17974005).Curated1
Sequence conflicti759C → R in CAE45903 (PubMed:17974005).Curated1
Sequence conflicti811T → TVSWDQ in AAO73817 (Ref. 6) Curated1
Sequence conflicti834S → N in CAE45903 (PubMed:17974005).Curated1
Sequence conflicti865Missing in AAO73817 (Ref. 6) Curated1
Sequence conflicti1051Missing in CAE45903 (PubMed:17974005).Curated1
Sequence conflicti1051Missing in BAA74892 (PubMed:10048485).Curated1
Sequence conflicti1064 – 1065DK → AR in AAO73817 (Ref. 6) Curated2

Polymorphismi

Genetic variations in WWC1 define the memory quantitative trait locus (MEMRYQTL) [MIMi:615602].2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026844250R → C. Corresponds to variant dbSNP:rs17551608Ensembl.1
Natural variantiVAR_053449734M → I Polymorphism; associated with Ala-735; affects KIBRA lipid-binding specificity showing stronger interactions with PI(4)P and PI(5)P. 1 PublicationCorresponds to variant dbSNP:rs3822660Ensembl.1
Natural variantiVAR_053450735S → A Polymorphism; associated with Ile-734; affects KIBRA lipid-binding specificity showing stronger interactions with PI(4)P and PI(5)P. 1 PublicationCorresponds to variant dbSNP:rs3822659Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019448974S → SPPPQPS in isoform 2. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF506799 mRNA Translation: AAO15881.1
AK296323 mRNA Translation: BAG59017.1
AC020894 Genomic DNA No translation available.
AC026689 Genomic DNA No translation available.
BX640827 mRNA Translation: CAE45903.1
AB020676 mRNA Translation: BAA74892.1
AF530058 mRNA Translation: AAQ09942.1
AY189820 mRNA Translation: AAO73817.1
BC004394 mRNA Translation: AAH04394.1
BC017746 mRNA Translation: AAH17746.1
CCDSiCCDS4366.1 [Q8IX03-1]
CCDS54945.1 [Q8IX03-2]
RefSeqiNP_001155133.1, NM_001161661.1 [Q8IX03-2]
NP_001155134.1, NM_001161662.1
NP_056053.1, NM_015238.2 [Q8IX03-1]
UniGeneiHs.484047

Genome annotation databases

EnsembliENST00000265293; ENSP00000265293; ENSG00000113645 [Q8IX03-1]
ENST00000521089; ENSP00000427772; ENSG00000113645 [Q8IX03-2]
GeneIDi23286
KEGGihsa:23286
UCSCiuc003lzu.4 human [Q8IX03-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKIBRA_HUMAN
AccessioniPrimary (citable) accession number: Q8IX03
Secondary accession number(s): B4DK05
, O94946, Q6MZX4, Q6Y2F8, Q7Z4G8, Q8WVM4, Q9BT29
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: March 1, 2003
Last modified: May 23, 2018
This is version 126 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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