KLH12_BOVIN
ID KLH12_BOVIN Reviewed; 568 AA.
AC E1B932;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 2.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Kelch-like protein 12;
GN Name=KLHL12;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DAAA02043311; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E1B932; -.
DR SMR; E1B932; -.
DR STRING; 9913.ENSBTAP00000040061; -.
DR PaxDb; E1B932; -.
DR PRIDE; E1B932; -.
DR eggNOG; KOG4441; Eukaryota.
DR HOGENOM; CLU_004253_14_2_1; -.
DR InParanoid; E1B932; -.
DR TreeFam; TF329218; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; 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: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; IPR011043; Gal_Oxase/kelch_b-propeller.
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; SSF50965; SSF50965; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 3: Inferred from homology;
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_0000416892"
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 474..520
FT /note="Kelch 5"
FT REPEAT 522..567
FT /note="Kelch 6"
SQ SEQUENCE 568 AA; 63237 MW; 93063C3AAA6F2F2B CRC64;
MRGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA
MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ
ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE
KLIKCDEIQV DSEEPVFEAV ISWVKHAKKE REGSLPDLLQ YVRMPLLTPR YITDVIDTEP
FIRCSLQCRD LVDEAKKFHL RPELRTQMQG PRTRAHIRAN EVLLVVGGFG SQQSPIDVVE
KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY
SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG
LVVASGVIYC LGGYDGLNIL NSVEKYDPHT GHWANVTPMA TKRSGAGVAL LNDHIYVVGG
FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSSLSSIECY
DPIIDSYGLV TSMGTQRCDA GVCALREK
