KLH25_MOUSE
ID KLH25_MOUSE Reviewed; 589 AA.
AC Q8R2P1;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Kelch-like protein 25;
DE AltName: Full=Ectoderm-neural cortex protein 2;
DE Short=ENC-2;
GN Name=Klhl25; Synonyms=Enc2;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP FUNCTION.
RX PubMed=22578813; DOI=10.1016/j.molcel.2012.04.004;
RA Yanagiya A., Suyama E., Adachi H., Svitkin Y.V., Aza-Blanc P., Imataka H.,
RA Mikami S., Martineau Y., Ronai Z.A., Sonenberg N.;
RT "Translational homeostasis via the mRNA cap-binding protein, eIF4E.";
RL Mol. Cell 46:847-858(2012).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex required for translational homeostasis. The
CC BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination
CC of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent
CC degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as
CC a homeostatic mechanism to maintain translation and prevent eIF4E
CC inhibition when eIF4E levels are low. The BCR(KLHL25) complex does not
CC target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated
CC with eIF4E. {ECO:0000269|PubMed:22578813}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at
CC least composed of CUL3, KLHL25 and RBX1. Interacts with EIF4EBP1 (when
CC hypophosphorylated) (By similarity). {ECO:0000250}.
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DR EMBL; AK143086; BAE25266.1; -; mRNA.
DR EMBL; BC027373; AAH27373.1; -; mRNA.
DR CCDS; CCDS21369.1; -.
DR RefSeq; NP_001116252.1; NM_001122780.1.
DR RefSeq; NP_083928.1; NM_029652.1.
DR RefSeq; NP_877583.1; NM_182782.2.
DR RefSeq; XP_011249134.1; XM_011250832.2.
DR AlphaFoldDB; Q8R2P1; -.
DR SMR; Q8R2P1; -.
DR STRING; 10090.ENSMUSP00000089707; -.
DR iPTMnet; Q8R2P1; -.
DR PhosphoSitePlus; Q8R2P1; -.
DR EPD; Q8R2P1; -.
DR MaxQB; Q8R2P1; -.
DR PaxDb; Q8R2P1; -.
DR PeptideAtlas; Q8R2P1; -.
DR PRIDE; Q8R2P1; -.
DR ProteomicsDB; 265001; -.
DR Antibodypedia; 15613; 241 antibodies from 29 providers.
DR DNASU; 207952; -.
DR Ensembl; ENSMUST00000092073; ENSMUSP00000089707; ENSMUSG00000055652.
DR Ensembl; ENSMUST00000171155; ENSMUSP00000133175; ENSMUSG00000055652.
DR Ensembl; ENSMUST00000206019; ENSMUSP00000146102; ENSMUSG00000055652.
DR GeneID; 207952; -.
DR KEGG; mmu:207952; -.
DR UCSC; uc009hwy.2; mouse.
DR CTD; 64410; -.
DR MGI; MGI:2668031; Klhl25.
DR VEuPathDB; HostDB:ENSMUSG00000055652; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00950000182983; -.
DR HOGENOM; CLU_004253_14_6_1; -.
DR InParanoid; Q8R2P1; -.
DR OMA; KIYQVDQ; -.
DR OrthoDB; 709680at2759; -.
DR PhylomeDB; Q8R2P1; -.
DR TreeFam; TF329218; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 207952; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Klhl25; mouse.
DR PRO; PR:Q8R2P1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8R2P1; protein.
DR Bgee; ENSMUSG00000055652; Expressed in cortical plate and 186 other tissues.
DR ExpressionAtlas; Q8R2P1; baseline and differential.
DR Genevisible; Q8R2P1; MM.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0006446; P:regulation of translational initiation; 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; IPR030565; KLHL25.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24410:SF10; PTHR24410:SF10; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 4.
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 Kelch repeat; Reference proteome; Repeat; Translation regulation;
KW Ubl conjugation pathway.
FT CHAIN 1..589
FT /note="Kelch-like protein 25"
FT /id="PRO_0000272309"
FT DOMAIN 46..114
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 149..250
FT /note="BACK"
FT REPEAT 296..340
FT /note="Kelch 1"
FT REPEAT 341..388
FT /note="Kelch 2"
FT REPEAT 389..444
FT /note="Kelch 3"
FT REPEAT 446..492
FT /note="Kelch 4"
FT REPEAT 493..538
FT /note="Kelch 5"
FT REPEAT 539..585
FT /note="Kelch 6"
SQ SEQUENCE 589 AA; 65826 MW; 5B8C746A80287C20 CRC64;
MSVSVHETRK SRSSTGSMNI SVFHKASHPD CVLAHLNTLR KHCMFTDVTL WAGDRAFPCH
RAVLAASSRY FEAMFSHGLR ESRDDTVNFQ DNLHPEVLEL LLDFAYSSRI VINEENAESL
LEAGDMLQFH DVRDAAAEFL EKNLSPSNCL GMMVLSDAHQ CRRLYEFSCR MSLVHFETVR
QSEDFNSLSR DTLLDLISRD ELETEDERVV FEAILQWVKH DLEQRKAHLP LLLRNVRLAL
LPSDCLKNAV SGEALLMADE CTKLILDEAF RCKTKILLND GVVTSPFARP RKAGHTLLIL
GGQTFMCDKI YQVDHKAKEI IPKADLPSPR KEFSASAIGC KVYVTGGRGS ENGVSKDVWV
YDTVHEEWSK AAPMLIARFG HGSAELENCL YVVGGHTSLA GIFPASPSVS LKQVEKYDPG
DNKWTMVAPM RDGVSNAAVV SAKLKLFVFG GTSIHRDMVS KVQCFDPSEN RWTIKAECPQ
PWRYTAAAVL GSQIFIMGGD TEYTAASAYR FDCETNQWTR IGDMTAKRMS CHAVASGNKL
YVVGGYFGTQ RCKTLDCYDP TSDTWNCITT VPYSLIPTAF VSTWKHLPA
