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Protein

Protein KIBRA

Gene

WWC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 complex scaffold 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 from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of MAPK cascade Source: UniProtKB
  • regulation of hippo signaling Source: UniProtKB
  • regulation of intracellular transport Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2028269. Signaling by Hippo.
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

HGNCiHGNC:29435. WWC1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: BHF-UCL
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • protein complex Source: Ensembl
  • ruffle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi23286.
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

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

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi116884. 39 interactors.
DIPiDIP-35287N.
IntActiQ8IX03. 26 interactors.
MINTiMINT-1405937.
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
Contains 1 C2 domain.Curated
Contains 2 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
PROSITEiPS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]

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 rs17551608dbSNPEnsembl.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 rs3822660dbSNPEnsembl.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 rs3822659dbSNPEnsembl.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

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi116884. 39 interactors.
DIPiDIP-35287N.
IntActiQ8IX03. 26 interactors.
MINTiMINT-1405937.
STRINGi9606.ENSP00000427772.

PTM databases

iPTMnetiQ8IX03.
PhosphoSitePlusiQ8IX03.

Polymorphism and mutation databases

BioMutaiWWC1.
DMDMi74714457.

Proteomic databases

EPDiQ8IX03.
MaxQBiQ8IX03.
PaxDbiQ8IX03.
PeptideAtlasiQ8IX03.
PRIDEiQ8IX03.

Protocols and materials databases

DNASUi23286.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23286.
DisGeNETi23286.
GeneCardsiWWC1.
HGNCiHGNC:29435. WWC1.
HPAiHPA038016.
HPA038017.
MIMi610533. gene.
615602. phenotype.
neXtProtiNX_Q8IX03.
OpenTargetsiENSG00000113645.
PharmGKBiPA143485670.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-2028269. Signaling by Hippo.
SignaLinkiQ8IX03.
SIGNORiQ8IX03.

Miscellaneous databases

ChiTaRSiWWC1. human.
EvolutionaryTraceiQ8IX03.
GeneWikiiWWC1.
GenomeRNAii23286.
PROiQ8IX03.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113645.
CleanExiHS_WWC1.
ExpressionAtlasiQ8IX03. baseline and differential.
GenevisibleiQ8IX03. HS.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00397. WW. 2 hits.
[Graphical view]
SMARTiSM00456. WW. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 2 hits.
PROSITEiPS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKIBRA_HUMAN
AccessioniPrimary (citable) accession number: Q8IX03
Secondary accession number(s): B4DK05
, O94946, Q6MZX4, Q6Y2F8, Q7Z4G8, Q8WVM4, Q9BT29
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 115 of the entry and version 1 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

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

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.