ID   KLHL3_PONAB             Reviewed;         587 AA.
AC   Q5REP9;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   25-MAY-2022, entry version 81.
DE   RecName: Full=Kelch-like protein 3;
GN   Name=KLHL3;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC       ubiquitin ligase complex that acts as a regulator of ion transport in
CC       the distal nephron. The BCR(KLHL3) complex acts by mediating
CC       ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1,
CC       leading to WNK4 degradation (By similarity). The BCR(KLHL3) complex
CC       also mediates ubiquitination and degradation of CLDN8, a tight-junction
CC       protein required for paracellular chloride transport in the kidney (By
CC       similarity). {ECO:0000250|UniProtKB:E0CZ16,
CC       ECO:0000250|UniProtKB:Q9UH77}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:Q9UH77}.
CC   -!- SUBUNIT: Homodimer. Component of the BCR(KLHL3) E3 ubiquitin ligase
CC       complex, at least composed of CUL3 and KLHL3 and RBX1 (By similarity).
CC       Interacts with SLC12A3 (By similarity). Interacts with WNK1 and WNK4
CC       (By similarity). Interacts with CLDN8 (By similarity).
CC       {ECO:0000250|UniProtKB:E0CZ16, ECO:0000250|UniProtKB:Q9UH77}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC       {ECO:0000250|UniProtKB:Q9UH77}. Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:Q9UH77}.
CC   -!- PTM: Phosphorylation at Ser-433 by PKA decreases the interaction with
CC       WNK4, Leading to inhibit WNK4 degradation by the BCR(KLHL3) complex.
CC       Phosphorylation at Ser-433 is increased by insulin.
CC       {ECO:0000250|UniProtKB:Q9UH77}.
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DR   EMBL; CR857470; CAH89758.1; -; mRNA.
DR   RefSeq; NP_001127192.1; NM_001133720.1.
DR   AlphaFoldDB; Q5REP9; -.
DR   SMR; Q5REP9; -.
DR   STRING; 9601.ENSPPYP00000017680; -.
DR   GeneID; 100174246; -.
DR   KEGG; pon:100174246; -.
DR   CTD; 26249; -.
DR   eggNOG; KOG4441; Eukaryota.
DR   InParanoid; Q5REP9; -.
DR   OrthoDB; 635140at2759; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR   GO; GO:0072156; P:distal tubule morphogenesis; ISS:UniProtKB.
DR   GO; GO:0050801; P:ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR   GO; GO:0070294; P:renal sodium ion absorption; ISS:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   Gene3D; 2.120.10.80; -; 1.
DR   Gene3D; 3.30.710.10; -; 1.
DR   InterPro; IPR011705; BACK.
DR   InterPro; IPR017096; BTB-kelch_protein.
DR   InterPro; IPR000210; BTB/POZ_dom.
DR   InterPro; IPR015915; Kelch-typ_b-propeller.
DR   InterPro; IPR006652; Kelch_1.
DR   InterPro; IPR030578; KLHL3.
DR   InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR   PANTHER; PTHR24412:SF179; PTHR24412:SF179; 1.
DR   Pfam; PF07707; BACK; 1.
DR   Pfam; PF00651; BTB; 1.
DR   Pfam; PF01344; Kelch_1; 6.
DR   PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR   SMART; SM00875; BACK; 1.
DR   SMART; SM00225; BTB; 1.
DR   SMART; SM00612; Kelch; 6.
DR   SUPFAM; SSF117281; SSF117281; 1.
DR   SUPFAM; SSF54695; SSF54695; 1.
DR   PROSITE; PS50097; BTB; 1.
PE   2: Evidence at transcript level;
KW   Actin-binding; Cytoplasm; Cytoskeleton; Kelch repeat; Phosphoprotein;
KW   Reference proteome; Repeat; Ubl conjugation pathway.
FT   CHAIN           1..587
FT                   /note="Kelch-like protein 3"
FT                   /id="PRO_0000286395"
FT   DOMAIN          50..117
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT   DOMAIN          152..254
FT                   /note="BACK"
FT   REPEAT          302..347
FT                   /note="Kelch 1"
FT   REPEAT          348..394
FT                   /note="Kelch 2"
FT   REPEAT          396..441
FT                   /note="Kelch 3"
FT   REPEAT          442..490
FT                   /note="Kelch 4"
FT   REPEAT          491..537
FT                   /note="Kelch 5"
FT   REPEAT          539..585
FT                   /note="Kelch 6"
FT   MOD_RES         10
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UH77"
FT   MOD_RES         295
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UH77"
FT   MOD_RES         375
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UH77"
FT   MOD_RES         376
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UH77"
FT   MOD_RES         433
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UH77"
SQ   SEQUENCE   587 AA;  64884 MW;  A5BE855715BD8DFC CRC64;
     MEGESVKLSS QTLIQAGDDE KNQRTITVNP AHMGKAFKVM NELRSKQLLC DVMIVAEDVE
     IEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT LSKLIDYVYT AEIEVTEENV
     QVLLPAASLL QLMDVRQNCC DFLQSQLHPT NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP
     EVMLGEEFLS LSLDQVCSLI SSDKLTVSSE EKVFEAVISW INYEKGTRLE HMAKLMEHVR
     LPLLPRDYLV QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
     KVMIVVGGQA PKAIRSVECY DFEEDRWDQI AELPSRRCRA GVVFMAGHVY AVGGFNGSLR
     VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG GFDGSTGLAS VEAYSYKTNE
     WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD GASRQCLSTV EQYNPATNEW IYVADMSTRR
     SGAGVGVLSG QLYATGGHDG PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY
     VVGGDDGSCN LASVEYYNPV TDKWTLLPTN MSTGRSYAGV AVIHKSL