ID   KLH12_DANRE             Reviewed;         564 AA.
AC   Q5U374; B0S5Y1;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   18-APR-2012, sequence version 2.
DT   03-AUG-2022, entry version 111.
DE   RecName: Full=Kelch-like protein 12;
GN   Name=klhl12; ORFNames=si:dkeyp-53e12.5, zgc:92570;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=AB;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=16547521; DOI=10.1038/ncb1381;
RA   Angers S., Thorpe C.J., Biechele T.L., Goldenberg S.J., Zheng N.,
RA   Maccoss M.J., Moon R.T.;
RT   "The KLHL12-cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-
RT   catenin pathway by targeting Dishevelled for degradation.";
RL   Nat. Cell Biol. 8:348-357(2006).
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 (By similarity). Negatively
CC       regulates the Wnt signaling pathway, possibly via the targeted
CC       ubiquitination and subsequent proteolysis of dvl2 and dvl3
CC       (PubMed:16547521). Regulates convergent-extension movements during
CC       early embryonic development (PubMed:16547521).
CC       {ECO:0000250|UniProtKB:Q53G59, ECO:0000269|PubMed:16547521}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Component of the BCR(KLHL12) E3 ubiquitin ligase complex.
CC       {ECO:0000250|UniProtKB:Q53G59}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, COPII-coated vesicle
CC       {ECO:0000250|UniProtKB:Q53G59}.
CC   -!- DEVELOPMENTAL STAGE: Expressed ubiquitously throughout development.
CC       {ECO:0000269|PubMed:16547521}.
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DR   EMBL; CABZ01042196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CABZ01087210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX322655; CAQ14259.1; -; Genomic_DNA.
DR   EMBL; BC085673; AAH85673.1; -; mRNA.
DR   RefSeq; NP_001007329.1; NM_001007328.1.
DR   RefSeq; XP_017212974.1; XM_017357485.1.
DR   AlphaFoldDB; Q5U374; -.
DR   SMR; Q5U374; -.
DR   BioGRID; 93389; 2.
DR   STRING; 7955.ENSDARP00000043814; -.
DR   PaxDb; Q5U374; -.
DR   GeneID; 108178999; -.
DR   GeneID; 492362; -.
DR   KEGG; dre:108178999; -.
DR   KEGG; dre:492362; -.
DR   CTD; 59349; -.
DR   ZFIN; ZDB-GENE-041114-205; klhl12.
DR   eggNOG; KOG4441; Eukaryota.
DR   InParanoid; Q5U374; -.
DR   OrthoDB; 709680at2759; -.
DR   TreeFam; TF329218; -.
DR   Reactome; R-DRE-4641258; Degradation of DVL.
DR   SignaLink; Q5U374; -.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:Q5U374; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; 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:0009952; P:anterior/posterior pattern specification; IGI:ZFIN.
DR   GO; GO:0060028; P:convergent extension involved in axis elongation; IGI:ZFIN.
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; IMP:ZFIN.
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; Developmental protein; ER-Golgi transport;
KW   Kelch repeat; Reference proteome; Repeat; Transport;
KW   Ubl conjugation pathway; Wnt signaling pathway.
FT   CHAIN           1..564
FT                   /note="Kelch-like protein 12"
FT                   /id="PRO_0000234352"
FT   DOMAIN          29..96
FT                   /note="BTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT   DOMAIN          131..232
FT                   /note="BACK"
FT   REPEAT          278..325
FT                   /note="Kelch 1"
FT   REPEAT          327..375
FT                   /note="Kelch 2"
FT   REPEAT          376..422
FT                   /note="Kelch 3"
FT   REPEAT          423..469
FT                   /note="Kelch 4"
FT   REPEAT          471..516
FT                   /note="Kelch 5"
FT   REPEAT          518..563
FT                   /note="Kelch 6"
FT   CONFLICT        183
FT                   /note="E -> V (in Ref. 2; AAH85673)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   564 AA;  62963 MW;  75304D6507266B4D CRC64;
     MAPKDIMTNS HAKSILNAMN ALRKSNTLCD ITLRVEGTDF PAHRIVLAAC SDYFCAMFTS
     ELAEKGKSFV DIQGLTASTM EILLDFVYTE TVLVTVENVQ ELLPAACLLQ LKGVKRACCD
     FLNSQLDPSN CLGIRDFAET HNCLDLMQAA ELFSQKHFAE VVQQEEFMLL SQSEVEKLIK
     CDEIQVDSEE PVFEAVLNWV KHNRKEREPY LPDLLEYVRM PLLTPRYITD VIDAEPLIRC
     SLPCRDLVDE AKKFHLRPEL RSEMQSPRTQ ARLGAKEVLL VIGGFGSQQS PIDIVEKYDP
     KTREWSFLPN IARKRRYVAT VALNDRVYVI GGYDGRSRLS SVECLDYTAD EDGVWYSVAT
     MNVRRGLAGA TTLGDMIYVA GGFDGSRRHT SMERYDPNID QWSMLGDMQT AREGAGLVVA
     SGLIYCLGGY DGLNILNSVE RYDPHTGHWT SVTPMANKRS GAGVALLNDH IYVVGGFDGT
     AHLSSVEVYN IRTDYWTTVA NMTTPRCYVG ATVLRGRLYA IAGYDGNSLL SSIECYDPVI
     DSWEVVTSMA TQRCDAGVCV LREK