UniProtKB - E0CZ16 (KLHL3_MOUSE)
Protein
Kelch-like protein 3
Gene
Klhl3
Organism
Mus musculus (Mouse)
Status
Functioni
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:25831548, PubMed:28052936). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (By similarity). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (PubMed:25831548).By similarity2 Publications
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarityView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
- catalytic activity Source: InterPro
- cullin family protein binding Source: MGI
GO - Biological processi
- distal tubule morphogenesis Source: UniProtKB
- ion homeostasis Source: UniProtKB
- protein K48-linked ubiquitination Source: UniProtKB
- protein ubiquitination Source: UniProtKB
- renal sodium ion absorption Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: UniProtKB
Keywordsi
Molecular function | Actin-binding |
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
Reactomei | R-MMU-8951664, Neddylation R-MMU-983168, Antigen processing: Ubiquitination & Proteasome degradation |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Kelch-like protein 3 |
Gene namesi | Name:Klhl3 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2445185, Klhl3 |
Subcellular locationi
Cytoskeleton
- cytoskeleton By similarity
Cytosol
- cytosol By similarity
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Cytosol
- cytosol Source: UniProtKB
Other locations
- Cul3-RING ubiquitin ligase complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, CytoskeletonPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000417531 | 1 – 587 | Kelch-like protein 3Add BLAST | 587 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 295 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 375 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 376 | PhosphoserineBy similarity | 1 | |
Modified residuei | 433 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylation at Ser-433 by PKA decreases the interaction with WNK4, Leading to inhibit WNK4 degradation by the BCR(KLHL3) complex. Phosphorylation at Ser-433 is increased by insulin.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | E0CZ16 |
PRIDEi | E0CZ16 |
PTM databases
iPTMneti | E0CZ16 |
PhosphoSitePlusi | E0CZ16 |
Expressioni
Tissue specificityi
Present at high level in brain and kidney (at protein level) (PubMed:28052936). Weakly expressed in other tissues (PubMed:28052936). In kidney, predominantly localizes to the distal convoluted tubule (DCT) and collecting duct, with apical localization in the DCT (at protein level) (PubMed:22266938, PubMed:22406640).3 Publications
Gene expression databases
Bgeei | ENSMUSG00000014164, Expressed in dentate gyrus of hippocampal formation granule cell and 49 other tissues |
Interactioni
Subunit structurei
Homodimer.
Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (By similarity).
Interacts with SLC12A3 (By similarity).
Interacts with WNK1 and WNK4 (By similarity).
Interacts with CLDN8 (PubMed:25831548).
By similarity1 PublicationGO - Molecular functioni
- actin binding Source: UniProtKB-KW
- cullin family protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 437092, 8 interactors |
IntActi | E0CZ16, 1 interactor |
STRINGi | 10090.ENSMUSP00000089173 |
Miscellaneous databases
RNActi | E0CZ16, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 50 – 117 | BTBPROSITE-ProRule annotationAdd BLAST | 68 | |
Domaini | 152 – 254 | BACKAdd BLAST | 103 | |
Repeati | 302 – 347 | Kelch 1Add BLAST | 46 | |
Repeati | 348 – 394 | Kelch 2Add BLAST | 47 | |
Repeati | 396 – 441 | Kelch 3Add BLAST | 46 | |
Repeati | 442 – 490 | Kelch 4Add BLAST | 49 | |
Repeati | 491 – 537 | Kelch 5Add BLAST | 47 | |
Repeati | 539 – 585 | Kelch 6Add BLAST | 47 |
Keywords - Domaini
Kelch repeat, RepeatPhylogenomic databases
eggNOGi | KOG4441, Eukaryota |
GeneTreei | ENSGT00940000157891 |
InParanoidi | E0CZ16 |
OMAi | EERWDQI |
OrthoDBi | 635140at2759 |
TreeFami | TF329218 |
Family and domain databases
Gene3Di | 2.120.10.80, 1 hit |
InterProi | View protein in InterPro IPR011705, BACK IPR017096, BTB-kelch_protein IPR000210, BTB/POZ_dom IPR015915, Kelch-typ_b-propeller IPR006652, Kelch_1 IPR011041, Quinoprot_gluc/sorb_DH IPR011333, SKP1/BTB/POZ_sf |
Pfami | View protein in Pfam PF07707, BACK, 1 hit PF00651, BTB, 1 hit PF01344, Kelch_1, 6 hits |
PIRSFi | PIRSF037037, Kelch-like_protein_gigaxonin, 1 hit |
SMARTi | View protein in SMART SM00875, BACK, 1 hit SM00225, BTB, 1 hit SM00612, Kelch, 6 hits |
SUPFAMi | SSF117281, SSF117281, 1 hit SSF50952, SSF50952, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: E0CZ16-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEGESVKPSP QPTAQAEDEE KNRRTVTVNA AHMGKAFKVM NELRSKRLLC
60 70 80 90 100
DVMIVAEDVE VEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT
110 120 130 140 150
LSKLIDYIYT AEIEVTEENV QVLLPAASLL QLMDVRQNCC DFLQSQLHPT
160 170 180 190 200
NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP EVMLGEEFLS LSLDQVCSLI
210 220 230 240 250
SSDKLTVSSE EKVFEAVISW INYEKETRLD HMAKLMEHVR LPLLPRDYLV
260 270 280 290 300
QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
310 320 330 340 350
KVMIVVGGQA PKAIRSVECY DFEEGRWDQI AELPSRRCRA GVVFMAGHVY
360 370 380 390 400
AVGGFNGSLR VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG
410 420 430 440 450
GFDGSTGLAS VEAYSYKTNE WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD
460 470 480 490 500
GASRQCLSTV EQYNPATNEW IYVADMSTRR SGAGVGVLSG QLYATGGHDG
510 520 530 540 550
PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY VVGGDDGSCN
560 570 580
LASVEYYNPV TDKWTLLPTN MSTGRSYAGV AVIHKSL
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053297 | 1 – 4 | MEGE → MAYYIMIPCQVGKRGHRLWT WTRVAARINVALCFVGGESA WFLLVSRLTSASGGKGL in isoform 2. Curated | 4 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC142258 Genomic DNA No translation available. AC165251 Genomic DNA No translation available. |
CCDSi | CCDS88463.1 [E0CZ16-1] |
RefSeqi | NP_001182004.1, NM_001195075.1 |
Genome annotation databases
Ensembli | ENSMUST00000160860; ENSMUSP00000123701; ENSMUSG00000014164 [E0CZ16-1] |
UCSCi | uc011zal.1, mouse [E0CZ16-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC142258 Genomic DNA No translation available. AC165251 Genomic DNA No translation available. |
CCDSi | CCDS88463.1 [E0CZ16-1] |
RefSeqi | NP_001182004.1, NM_001195075.1 |
3D structure databases
SMRi | E0CZ16 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 437092, 8 interactors |
IntActi | E0CZ16, 1 interactor |
STRINGi | 10090.ENSMUSP00000089173 |
PTM databases
iPTMneti | E0CZ16 |
PhosphoSitePlusi | E0CZ16 |
Proteomic databases
PaxDbi | E0CZ16 |
PRIDEi | E0CZ16 |
Protocols and materials databases
Antibodypediai | 14776, 248 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000160860; ENSMUSP00000123701; ENSMUSG00000014164 [E0CZ16-1] |
UCSCi | uc011zal.1, mouse [E0CZ16-2] |
Organism-specific databases
MGIi | MGI:2445185, Klhl3 |
Phylogenomic databases
eggNOGi | KOG4441, Eukaryota |
GeneTreei | ENSGT00940000157891 |
InParanoidi | E0CZ16 |
OMAi | EERWDQI |
OrthoDBi | 635140at2759 |
TreeFami | TF329218 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Reactomei | R-MMU-8951664, Neddylation R-MMU-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
BioGRID-ORCSi | 100503085, 2 hits in 17 CRISPR screens |
PROi | PR:E0CZ16 |
RNActi | E0CZ16, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000014164, Expressed in dentate gyrus of hippocampal formation granule cell and 49 other tissues |
Family and domain databases
Gene3Di | 2.120.10.80, 1 hit |
InterProi | View protein in InterPro IPR011705, BACK IPR017096, BTB-kelch_protein IPR000210, BTB/POZ_dom IPR015915, Kelch-typ_b-propeller IPR006652, Kelch_1 IPR011041, Quinoprot_gluc/sorb_DH IPR011333, SKP1/BTB/POZ_sf |
Pfami | View protein in Pfam PF07707, BACK, 1 hit PF00651, BTB, 1 hit PF01344, Kelch_1, 6 hits |
PIRSFi | PIRSF037037, Kelch-like_protein_gigaxonin, 1 hit |
SMARTi | View protein in SMART SM00875, BACK, 1 hit SM00225, BTB, 1 hit SM00612, Kelch, 6 hits |
SUPFAMi | SSF117281, SSF117281, 1 hit SSF50952, SSF50952, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KLHL3_MOUSE | |
Accessioni | E0CZ16Primary (citable) accession number: E0CZ16 Secondary accession number(s): F7A5U9, I6L891 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 16, 2012 |
Last sequence update: | May 16, 2012 | |
Last modified: | December 2, 2020 | |
This is version 71 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways