KLH12_RAT
ID KLH12_RAT Reviewed; 568 AA.
AC Q8R2H4; F8WG02;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 2.
DT 25-MAY-2022, entry version 122.
DE RecName: Full=Kelch-like protein 12;
DE AltName: Full=CUL3-interacting protein 1;
GN Name=Klhl12; Synonyms=C3ip1;
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 [MRNA].
RC TISSUE=Brain;
RA Horikawa H.P.M., Betz H.;
RT "Kelch-like protein.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex that acts as a negative regulator of Wnt
CC signaling pathway and ER-Golgi transport. The BCR(KLHL12) complex is
CC involved in ER-Golgi transport by regulating the size of COPII coats,
CC thereby playing a key role in collagen export, which is required for
CC embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating
CC monoubiquitination of SEC31 (SEC31A or SEC31B). The BCR(KLHL12) complex
CC is also involved in neural crest specification: in response to
CC cytosolic calcium increase, interacts with the heterodimer formed with
CC PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12)
CC complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of
CC SEC31 and subsequent collagen export. As part of the BCR(KLHL12)
CC complex, also acts as a negative regulator of the Wnt signaling pathway
CC by mediating ubiquitination and subsequent proteolysis of DVL3. The
CC BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1,
CC without leading to degradation of these proteins.
CC {ECO:0000250|UniProtKB:Q53G59}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at
CC least composed of CUL3 and KLHL12 and RBX1. This complex interacts with
CC DVL3 upon activation of the Wnt signaling pathway by WNT3A. Interacts
CC with DRD4, KLHL2 and SEC31A. Interacts with PEF1 and PDCD6/ALG-2;
CC interaction takes place in response to cytosolic calcium increase and
CC leads to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or
CC SEC31B). {ECO:0000250|UniProtKB:Q53G59}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, COPII-coated vesicle
CC {ECO:0000250|UniProtKB:Q53G59}.
CC -!- DOMAIN: The BTB domain is required for interaction with CUL3.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the SCF(FBXL17) complex, leading to its
CC degradation by the proteasome: ubiquitination by the SCF(FBXL17)
CC complex takes place when aberrant BTB domain dimers are formed.
CC {ECO:0000250|UniProtKB:Q53G59}.
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DR EMBL; AJ133126; CAC79640.1; -; mRNA.
DR EMBL; BC086983; AAH86983.1; -; mRNA.
DR RefSeq; NP_714952.1; NM_153730.2.
DR RefSeq; XP_006249907.1; XM_006249845.1.
DR RefSeq; XP_017454168.1; XM_017598679.1.
DR AlphaFoldDB; Q8R2H4; -.
DR SMR; Q8R2H4; -.
DR STRING; 10116.ENSRNOP00000005832; -.
DR PaxDb; Q8R2H4; -.
DR GeneID; 266772; -.
DR KEGG; rno:266772; -.
DR UCSC; RGD:628717; rat.
DR CTD; 59349; -.
DR RGD; 628717; Klhl12.
DR eggNOG; KOG4441; Eukaryota.
DR InParanoid; Q8R2H4; -.
DR OrthoDB; 709680at2759; -.
DR TreeFam; TF329218; -.
DR Reactome; R-RNO-4641258; Degradation of DVL.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q8R2H4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030127; C:COPII vesicle coat; ISS:UniProtKB.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; ISS:UniProtKB.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0048208; P:COPII vesicle coating; ISS:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR GO; GO:0014032; P:neural crest cell development; ISS:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; 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; 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 2: Evidence at transcript level;
KW Cytoplasmic vesicle; ER-Golgi transport; Kelch repeat; Reference proteome;
KW Repeat; Transport; Ubl conjugation; Ubl conjugation pathway;
KW Wnt signaling pathway.
FT CHAIN 1..568
FT /note="Kelch-like protein 12"
FT /id="PRO_0000234351"
FT DOMAIN 33..100
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 135..236
FT /note="BACK"
FT REPEAT 282..329
FT /note="Kelch 1"
FT REPEAT 331..379
FT /note="Kelch 2"
FT REPEAT 380..426
FT /note="Kelch 3"
FT REPEAT 427..473
FT /note="Kelch 4"
FT REPEAT 475..520
FT /note="Kelch 5"
FT REPEAT 522..567
FT /note="Kelch 6"
FT REGION 405..568
FT /note="Interaction with DVL3"
FT /evidence="ECO:0000250"
FT CONFLICT 279
FT /note="D -> A (in Ref. 1; CAC79640 and 3; AAH86983)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 568 AA; 63306 MW; 0405EBB80FEADA94 CRC64;
MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA
MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ
ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE
KLIKCDEIQV DSEEPVFEAV INWVKHAKKE REESLPDLLQ YVRMPLLTPR YITDVIDAEP
FIRCSLQCRD LVDEAKKFHL RPELRSQMQG PRTRARLGDN EVLLVVGGFG SQQSPIDVVE
KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY
SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG
LVVASGIIYC LGGYDGLNIL NSVEKYDPHT GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG
FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY
DPIIDSWEVV ASMGTQRCDA GVCVLREK
