KLHL3_RAT
ID KLHL3_RAT Reviewed; 587 AA.
AC F1LZ52;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 3.
DT 25-MAY-2022, entry version 48.
DE RecName: Full=Kelch-like protein 3;
GN Name=Klhl3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-20.
RG Amgen EST program;
RT "Amgen rat EST program.";
RL Submitted (APR-2003) 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; CB614643; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; F1LZ52; -.
DR SMR; F1LZ52; -.
DR STRING; 10116.ENSRNOP00000037981; -.
DR PaxDb; F1LZ52; -.
DR RGD; 1565218; Klhl3.
DR eggNOG; KOG4441; Eukaryota.
DR InParanoid; F1LZ52; -.
DR Reactome; R-RNO-8951664; Neddylation.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:F1LZ52; -.
DR Proteomes; UP000002494; 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:0097602; F:cullin family protein binding; ISO:RGD.
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_0000417532"
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 REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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; 64845 MW; F5329887333DE266 CRC64;
MEGESVKPSP QPTEQAGDGE KNRRMITVNP AHMGKAFKVM NELRSKRLLC DVMIVAEDVE
VEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT LSKLIDYIYT AEIEVTEENV
QVLLPAASLL QLMDVRQNCC DFLQSQLHPT NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP
EVMLGEEFLS LSLDQVCSLI SSDKLTVSSE EKVFEAVISW INYEKETRLD HMAKLMEHVR
LPLLPRDYLV QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
KVMIVVGGQA PKAIRSVECY DFEEGRWDQI AELPSRRCRA GVVFMAGHVY AVGGFNGSLR
VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG GFDGSTGLAS VEAYSYKTNE
WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD GASRQCLSTV EQYNPATNEW IYVADMSTRR
SGAGVGVLSG QLYATGGHDG PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY
VVGGDDGSCN LASVEYYNPV TDKWTLLPTN MSTGRSYAGQ WVSASGA
