KLHL2_MOUSE
ID KLHL2_MOUSE Reviewed; 593 AA.
AC Q8JZP3; Q8CCU0; Q8R3U4;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Kelch-like protein 2;
GN Name=Klhl2 {ECO:0000312|MGI:MGI:1924363};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:AAH31142.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II {ECO:0000312|EMBL:AAH24572.1}, and
RC FVB/N {ECO:0000312|EMBL:AAH31142.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH31142.1}, and
RC Lung {ECO:0000312|EMBL:AAH24572.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-593.
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NPTXR AND CUL3.
RX PubMed=21549840; DOI=10.1016/j.mcn.2011.04.005;
RA Tseng L.A., Bixby J.L.;
RT "Interaction of an intracellular pentraxin with a BTB-Kelch protein is
RT associated with ubiquitylation, aggregation and neuronal apoptosis.";
RL Mol. Cell. Neurosci. 47:254-264(2011).
CC -!- FUNCTION: Promotes growth of cell projections in oligodendrocyte
CC precursors. Responsible for degradative ubiquitination of the WNK
CC kinases WNK1, WNK3 and WNK4 (By similarity). Component of a cullin-
CC RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that
CC mediates the ubiquitination of target proteins, such as NPTXR, leading
CC most often to their proteasomal degradation. Plays a role in the
CC reorganization of the actin cytoskeleton. {ECO:0000250,
CC ECO:0000269|PubMed:21549840}.
CC -!- SUBUNIT: Binds actin. Interacts with KLHL12. Interacts (via N-terminus)
CC with FYN (via SH3 domain) (By similarity). Component of a cullin-RING-
CC based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex.
CC Interacts with NPTXR and CUL3. {ECO:0000250,
CC ECO:0000269|PubMed:21549840}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:21549840}. Cell projection, ruffle
CC {ECO:0000269|PubMed:21549840}. Cell projection {ECO:0000250}. Cell
CC projection, lamellipodium {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:21549840}. Note=A proportion colocalizes with the
CC actin cytoskeleton (By similarity). When over-expressed, colocalizes
CC with NPTXR in perinuclear aggresomes. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC27712.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC024572; AAH24572.1; -; mRNA.
DR EMBL; BC031142; AAH31142.1; -; mRNA.
DR EMBL; BC031144; AAH31144.1; -; mRNA.
DR EMBL; AK032116; BAC27712.1; ALT_INIT; mRNA.
DR CCDS; CCDS85544.1; -.
DR RefSeq; NP_848748.2; NM_178633.3.
DR AlphaFoldDB; Q8JZP3; -.
DR SMR; Q8JZP3; -.
DR BioGRID; 218522; 4.
DR STRING; 10090.ENSMUSP00000034017; -.
DR PhosphoSitePlus; Q8JZP3; -.
DR EPD; Q8JZP3; -.
DR MaxQB; Q8JZP3; -.
DR PaxDb; Q8JZP3; -.
DR PRIDE; Q8JZP3; -.
DR ProteomicsDB; 263658; -.
DR Antibodypedia; 28300; 306 antibodies from 23 providers.
DR DNASU; 77113; -.
DR Ensembl; ENSMUST00000034017; ENSMUSP00000034017; ENSMUSG00000031605.
DR GeneID; 77113; -.
DR KEGG; mmu:77113; -.
DR UCSC; uc057alr.1; mouse.
DR CTD; 11275; -.
DR MGI; MGI:1924363; Klhl2.
DR VEuPathDB; HostDB:ENSMUSG00000031605; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000156434; -.
DR HOGENOM; CLU_004253_14_2_1; -.
DR InParanoid; Q8JZP3; -.
DR OMA; PSCMSTG; -.
DR OrthoDB; 635140at2759; -.
DR PhylomeDB; Q8JZP3; -.
DR TreeFam; TF329218; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 77113; 2 hits in 20 CRISPR screens.
DR ChiTaRS; Klhl2; mouse.
DR PRO; PR:Q8JZP3; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8JZP3; protein.
DR Bgee; ENSMUSG00000031605; Expressed in caudate-putamen and 236 other tissues.
DR ExpressionAtlas; Q8JZP3; baseline and differential.
DR Genevisible; Q8JZP3; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0001725; C:stress fiber; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR CDD; cd18338; BTB_POZ_KLHL2_Mayven; 1.
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; IPR044072; KLHL2_BTB/POZ.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
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 1: Evidence at protein level;
KW Actin-binding; Cell projection; Cytoplasm; Cytoskeleton; Kelch repeat;
KW Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..593
FT /note="Kelch-like protein 2"
FT /id="PRO_0000119102"
FT DOMAIN 56..123
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 308..353
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 354..400
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 402..447
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 449..496
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 497..543
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REPEAT 545..591
FT /note="Kelch 6"
FT /evidence="ECO:0000255"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 593 AA; 65983 MW; 15B3ADEB5DDD0144 CRC64;
METPPLPPAC TKQGHQKPLD SKDENPEKHC PLTVNPWHMK KAFKVMNELR SQNLLCDVTI
VAEDMEIPAH RVVLAACSPY FHAMFTGEMS ESRAKRVRIK EVDGWTLRML VDYVYTAEIQ
VTEENVQVLL PAAGLLQLQD VKKTCCEFLE SQLHPVNCLG IRAFADMHAC TDLLNKANTY
AEQHFADVVL SEEFLNLGIE QVCSLISSDK LTISSEEKVF EAVIAWVNHD KDVRQEFMAR
LMEHVRLPLL PREYLVQRVE EEALVKNSSA CKDYLIEAMK YHLLPTEQRM LMKSVRTRLR
TPMNLPKLMV VVGGQAPKAI RSVECYDFKE ERWHQVAELP SRRCRAGMVY MAGLVFAVGG
FNGSLRVRTV DSYDPVKDQW TSVANMRDRR STLGAAVLNG LLYAVGGFDG STGLSSVEAY
NIKSNEWFHV APMNTRRSSV GVGVVGGLLY AVGGYDGASR QCLSTVECYN ATANEWTYIA
EMSTRRSGAG VGVLNNLLYA VGGHDGPLVR KSVEVYDPTT NAWRQVADMN MCRRNAGVCA
VNGLLYVVGG DDGSCNLASV EYYNPTTDKW TVVSSCMSTG RSYAGVTVID KPL
