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Protein

Kelch-like protein 3

Gene

Klhl3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2445185 Klhl3

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

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Disruption phenotypei

Mice display pseudohypoaldosteronism type II (PHA2)-like phenotype, such as salt-sensitive hypertension (PubMed:28052936). In kidney, increased level of Wnk1 and Wnk4 kinases is observed, while Wnk1 and Wnk4 levels are unchanged in other tissues (PubMed:28052936).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004175311 – 587Kelch-like protein 3Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei295PhosphothreonineBy similarity1
Modified residuei375PhosphothreonineBy similarity1
Modified residuei376PhosphoserineBy similarity1
Modified residuei433PhosphoserineBy similarity1

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

Phosphoprotein

Proteomic databases

PaxDbiE0CZ16
PRIDEiE0CZ16

PTM databases

iPTMnetiE0CZ16
PhosphoSitePlusiE0CZ16

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

BgeeiENSMUSG00000014164 Expressed in 18 organ(s), highest expression level in Ammon's horn

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 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiE0CZ16, 1 interactor
STRINGi10090.ENSMUSP00000089173

Structurei

3D structure databases

ProteinModelPortaliE0CZ16
SMRiE0CZ16
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini50 – 117BTBPROSITE-ProRule annotationAdd BLAST68
Domaini152 – 254BACKAdd BLAST103
Repeati302 – 347Kelch 1Add BLAST46
Repeati348 – 394Kelch 2Add BLAST47
Repeati396 – 441Kelch 3Add BLAST46
Repeati442 – 490Kelch 4Add BLAST49
Repeati491 – 537Kelch 5Add BLAST47
Repeati539 – 585Kelch 6Add BLAST47

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
InParanoidiE0CZ16
OMAiKVFEAMI
OrthoDBiEOG091G04QJ
TreeFamiTF329218

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF50952 SSF50952, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: E0CZ16-1) [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
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
Length:587
Mass (Da):64,922
Last modified:May 16, 2012 - v2
Checksum:i96A7B7D0B80E11E9
GO
Isoform 2 (identifier: E0CZ16-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MEGE → MAYYIMIPCQVGKRGHRLWTWTRVAARINVALCFVGGESAWFLLVSRLTSASGGKGL

Show »
Length:640
Mass (Da):70,758
Checksum:i34C93EC129469538
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0532971 – 4MEGE → MAYYIMIPCQVGKRGHRLWT WTRVAARINVALCFVGGESA WFLLVSRLTSASGGKGL in isoform 2. Curated4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC142258 Genomic DNA No translation available.
AC165251 Genomic DNA No translation available.
RefSeqiNP_001182004.1, NM_001195075.1
UniGeneiMm.379256
Mm.491612

Genome annotation databases

EnsembliENSMUST00000091583; ENSMUSP00000089173; ENSMUSG00000014164 [E0CZ16-2]
ENSMUST00000160860; ENSMUSP00000123701; ENSMUSG00000014164 [E0CZ16-1]
GeneIDi100503085
UCSCiuc011zal.1 mouse [E0CZ16-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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.
RefSeqiNP_001182004.1, NM_001195075.1
UniGeneiMm.379256
Mm.491612

3D structure databases

ProteinModelPortaliE0CZ16
SMRiE0CZ16
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiE0CZ16, 1 interactor
STRINGi10090.ENSMUSP00000089173

PTM databases

iPTMnetiE0CZ16
PhosphoSitePlusiE0CZ16

Proteomic databases

PaxDbiE0CZ16
PRIDEiE0CZ16

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000091583; ENSMUSP00000089173; ENSMUSG00000014164 [E0CZ16-2]
ENSMUST00000160860; ENSMUSP00000123701; ENSMUSG00000014164 [E0CZ16-1]
GeneIDi100503085
UCSCiuc011zal.1 mouse [E0CZ16-2]

Organism-specific databases

CTDi26249
MGIiMGI:2445185 Klhl3

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
GeneTreeiENSGT00760000118931
InParanoidiE0CZ16
OMAiKVFEAMI
OrthoDBiEOG091G04QJ
TreeFamiTF329218

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

PROiPR:E0CZ16
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014164 Expressed in 18 organ(s), highest expression level in Ammon's horn

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF50952 SSF50952, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKLHL3_MOUSE
AccessioniPrimary (citable) accession number: E0CZ16
Secondary accession number(s): F7A5U9, I6L891
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2012
Last sequence update: May 16, 2012
Last modified: November 7, 2018
This is version 58 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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