ID KLH12_HUMAN Reviewed; 568 AA. AC Q53G59; A6NEN8; B7Z7B8; Q9HBX5; DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2006, sequence version 2. DT 27-MAR-2024, entry version 166. DE RecName: Full=Kelch-like protein 12; DE AltName: Full=CUL3-interacting protein 1 {ECO:0000303|Ref.1}; DE AltName: Full=DKIR homolog {ECO:0000303|PubMed:15383316}; DE Short=hDKIR {ECO:0000303|PubMed:15383316}; GN Name=KLHL12; Synonyms=C3IP1 {ECO:0000303|Ref.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Du M., Zu Z., Liou J.-Y., Chu K.-Y., Sansores Garcia L., Yeh E., Wu K.K.; RT "Sequence of a novel kelch-like protein, C3IP1."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Teratocarcinoma, Testis, and Thyroid; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney adenocarcinoma; 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 [6] RP TISSUE SPECIFICITY, AND INTERACTION WITH KLHL2. RX PubMed=15383316; DOI=10.1016/j.yexcr.2004.06.023; RA Mai A., Jung S.K., Yonehara S.; RT "hDKIR, a human homologue of the Drosophila kelch protein, involved in a RT ring-like structure."; RL Exp. Cell Res. 300:72-83(2004). RN [7] RP TISSUE SPECIFICITY. RX PubMed=16108817; DOI=10.1111/j.1365-2567.2005.02197.x; RA Uchida K., Akita Y., Matsuo K., Fujiwara S., Nakagawa A., Kazaoka Y., RA Hachiya H., Naganawa Y., Oh-Iwa I., Ohura K., Saga S., Kawai T., RA Matsumoto Y., Shimozato K., Kozaki K.; RT "Identification of specific autoantigens in Sjoegren's syndrome by SEREX."; RL Immunology 116:53-63(2005). RN [8] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH CUL3 RP AND DVL3. 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). RN [9] RP FUNCTION, AND INTERACTION WITH DRD4. RX PubMed=18303015; DOI=10.1074/jbc.m708473200; RA Rondou P., Haegeman G., Vanhoenacker P., Van Craenenbroeck K.; RT "BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by RT a Cul3-based E3 ligase."; RL J. Biol. Chem. 283:11083-11096(2008). RN [10] RP FUNCTION. RX PubMed=20100572; DOI=10.1016/j.cellsig.2010.01.014; RA Rondou P., Skieterska K., Packeu A., Lintermans B., Vanhoenacker P., RA Vauquelin G., Haegeman G., Van Craenenbroeck K.; RT "KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target RT the receptor for degradation."; RL Cell. Signal. 22:900-913(2010). RN [11] RP IDENTIFICATION IN THE BCR(KLHL12) COMPLEX, FUNCTION, SUBCELLULAR LOCATION, RP INTERACTION WITH SEC31A, AND MUTAGENESIS OF 289-PHE-GLY-290. RX PubMed=22358839; DOI=10.1038/nature10822; RA Jin L., Pahuja K.B., Wickliffe K.E., Gorur A., Baumgartel C., Schekman R., RA Rape M.; RT "Ubiquitin-dependent regulation of COPII coat size and function."; RL Nature 482:495-500(2012). RN [12] RP FUNCTION. RX PubMed=27565346; DOI=10.1016/j.cell.2016.07.027; RA Scott D.C., Rhee D.Y., Duda D.M., Kelsall I.R., Olszewski J.L., Paulo J.A., RA de Jong A., Ovaa H., Alpi A.F., Harper J.W., Schulman B.A.; RT "Two distinct types of E3 ligases work in unison to regulate substrate RT ubiquitylation."; RL Cell 166:1198-1214(2016). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PEF1 AND PDCD6, AND RP MUTAGENESIS OF. RX PubMed=27716508; DOI=10.1016/j.cell.2016.09.026; RA McGourty C.A., Akopian D., Walsh C., Gorur A., Werner A., Schekman R., RA Bautista D., Rape M.; RT "Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co- RT adaptor."; RL Cell 167:525-538(2016). RN [14] RP UBIQUITINATION, AND MUTAGENESIS OF HIS-15; ASP-34; VAL-50 AND ALA-60. RX PubMed=30190310; DOI=10.1126/science.aap8236; RA Mena E.L., Kjolby R.A.S., Saxton R.A., Werner A., Lew B.G., Boyle J.M., RA Harland R., Rape M.; RT "Dimerization quality control ensures neuronal development and survival."; RL Science 362:eaap8236-eaap8236(2018). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 268-567. RX PubMed=23349464; DOI=10.1074/jbc.m112.437996; RA Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A., RA Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O., RA Knapp S., von Delft F., Bullock A.N.; RT "Structural basis for Cul3 assembly with the BTB-Kelch family of E3 RT ubiquitin ligases."; RL J. Biol. Chem. 288:7803-7814(2013). 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 (PubMed:22358839, CC PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi CC transport by regulating the size of COPII coats, thereby playing a key CC role in collagen export, which is required for embryonic stem (ES) CC cells division: BCR(KLHL12) acts by mediating monoubiquitination of CC SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The CC BCR(KLHL12) complex is also involved in neural crest specification: in CC response to cytosolic calcium increase, interacts with the heterodimer CC formed with PEF1 and PDCD6/ALG-2, leading to bridge together the CC BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting CC monoubiquitination of SEC31 and subsequent collagen export CC (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a CC negative regulator of the Wnt signaling pathway by mediating CC ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). CC The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and CC PEF1, without leading to degradation of these proteins CC (PubMed:18303015, PubMed:20100572, PubMed:27716508). CC {ECO:0000269|PubMed:16547521, ECO:0000269|PubMed:18303015, CC ECO:0000269|PubMed:20100572, ECO:0000269|PubMed:22358839, CC ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508}. 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 (PubMed:22358839). This CC complex interacts with DVL3 upon activation of the Wnt signaling CC pathway by WNT3A (PubMed:16547521). Interacts with DRD4, KLHL2 and CC SEC31A (PubMed:15383316, PubMed:18303015, PubMed:22358839). Interacts CC with PEF1 and PDCD6/ALG-2; interaction takes place in response to CC cytosolic calcium increase and leads to bridge together the BCR(KLHL12) CC complex and SEC31 (SEC31A or SEC31B) (PubMed:27716508). CC {ECO:0000269|PubMed:15383316, ECO:0000269|PubMed:16547521, CC ECO:0000269|PubMed:18303015, ECO:0000269|PubMed:22358839, CC ECO:0000269|PubMed:27716508}. CC -!- INTERACTION: CC Q53G59; Q8N5I2: ARRDC1; NbExp=3; IntAct=EBI-740929, EBI-2339564; CC Q53G59; P54253: ATXN1; NbExp=8; IntAct=EBI-740929, EBI-930964; CC Q53G59; P46379: BAG6; NbExp=4; IntAct=EBI-740929, EBI-347552; CC Q53G59; P46379-2: BAG6; NbExp=3; IntAct=EBI-740929, EBI-10988864; CC Q53G59; P41182: BCL6; NbExp=3; IntAct=EBI-740929, EBI-765407; CC Q53G59; Q9BXJ5: C1QTNF2; NbExp=6; IntAct=EBI-740929, EBI-2817707; CC Q53G59; Q17RA1: CARD10; NbExp=3; IntAct=EBI-740929, EBI-10238571; CC Q53G59; Q6UXH8: CCBE1; NbExp=3; IntAct=EBI-740929, EBI-3923278; CC Q53G59; Q6UXH8-3: CCBE1; NbExp=3; IntAct=EBI-740929, EBI-12013534; CC Q53G59; P02461-2: COL3A1; NbExp=3; IntAct=EBI-740929, EBI-12214501; CC Q53G59; Q13618: CUL3; NbExp=24; IntAct=EBI-740929, EBI-456129; CC Q53G59; Q86TH3: DVL1; NbExp=3; IntAct=EBI-740929, EBI-10185025; CC Q53G59; Q92997: DVL3; NbExp=4; IntAct=EBI-740929, EBI-739789; CC Q53G59; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-740929, EBI-6658203; CC Q53G59; Q9UF56: FBXL17; NbExp=11; IntAct=EBI-740929, EBI-8835653; CC Q53G59; Q7Z6J4: FGD2; NbExp=3; IntAct=EBI-740929, EBI-1057190; CC Q53G59; P21333-2: FLNA; NbExp=6; IntAct=EBI-740929, EBI-9641086; CC Q53G59; Q8IVS8: GLYCTK; NbExp=3; IntAct=EBI-740929, EBI-748515; CC Q53G59; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-740929, EBI-14103818; CC Q53G59; P42858: HTT; NbExp=3; IntAct=EBI-740929, EBI-466029; CC Q53G59; O95050: INMT; NbExp=6; IntAct=EBI-740929, EBI-10191038; CC Q53G59; Q53G59: KLHL12; NbExp=8; IntAct=EBI-740929, EBI-740929; CC Q53G59; O95198: KLHL2; NbExp=8; IntAct=EBI-740929, EBI-746999; CC Q53G59; Q6TFL4: KLHL24; NbExp=6; IntAct=EBI-740929, EBI-2510117; CC Q53G59; Q8N4I8: KLHL3; NbExp=3; IntAct=EBI-740929, EBI-10230467; CC Q53G59; Q9UH77: KLHL3; NbExp=3; IntAct=EBI-740929, EBI-8524663; CC Q53G59; Q9C0E8-2: LNPK; NbExp=6; IntAct=EBI-740929, EBI-11024283; CC Q53G59; Q8TBB1: LNX1; NbExp=4; IntAct=EBI-740929, EBI-739832; CC Q53G59; Q15691: MAPRE1; NbExp=3; IntAct=EBI-740929, EBI-1004115; CC Q53G59; Q71SY5: MED25; NbExp=3; IntAct=EBI-740929, EBI-394558; CC Q53G59; Q00013: MPP1; NbExp=6; IntAct=EBI-740929, EBI-711788; CC Q53G59; Q7Z7H8: MRPL10; NbExp=3; IntAct=EBI-740929, EBI-723524; CC Q53G59; Q96HA8: NTAQ1; NbExp=8; IntAct=EBI-740929, EBI-741158; CC Q53G59; P09619: PDGFRB; NbExp=6; IntAct=EBI-740929, EBI-641237; CC Q53G59; Q9UBV8: PEF1; NbExp=10; IntAct=EBI-740929, EBI-724639; CC Q53G59; Q9H4M7-2: PLEKHA4; NbExp=3; IntAct=EBI-740929, EBI-12394782; CC Q53G59; Q96T60: PNKP; NbExp=3; IntAct=EBI-740929, EBI-1045072; CC Q53G59; P28340: POLD1; NbExp=3; IntAct=EBI-740929, EBI-716569; CC Q53G59; Q9NZ81: PRR13; NbExp=7; IntAct=EBI-740929, EBI-740924; CC Q53G59; Q3MIN7: RGL3; NbExp=3; IntAct=EBI-740929, EBI-2856274; CC Q53G59; Q13671: RIN1; NbExp=3; IntAct=EBI-740929, EBI-366017; CC Q53G59; P78317: RNF4; NbExp=3; IntAct=EBI-740929, EBI-2340927; CC Q53G59; Q8N5L8: RPP25L; NbExp=6; IntAct=EBI-740929, EBI-10189722; CC Q53G59; O00560: SDCBP; NbExp=8; IntAct=EBI-740929, EBI-727004; CC Q53G59; Q7Z614: SNX20; NbExp=4; IntAct=EBI-740929, EBI-744896; CC Q53G59; Q7Z614-3: SNX20; NbExp=3; IntAct=EBI-740929, EBI-12336127; CC Q53G59; Q8N205: SYNE4; NbExp=3; IntAct=EBI-740929, EBI-7131783; CC Q53G59; Q8IV04: TBC1D10C; NbExp=6; IntAct=EBI-740929, EBI-10261452; CC Q53G59; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-740929, EBI-11955057; CC Q53G59; Q6IQ55: TTBK2; NbExp=6; IntAct=EBI-740929, EBI-1050303; CC Q53G59; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-740929, EBI-10180829; CC Q53G59; P49765: VEGFB; NbExp=3; IntAct=EBI-740929, EBI-2799898; CC Q53G59; Q7LAP4: VEGFB; NbExp=3; IntAct=EBI-740929, EBI-10256629; CC Q53G59; P40337-2: VHL; NbExp=3; IntAct=EBI-740929, EBI-12157263; CC Q53G59; A2RRL9: ZBP1; NbExp=3; IntAct=EBI-740929, EBI-10173066; CC Q53G59; Q9P1Z0: ZBTB4; NbExp=3; IntAct=EBI-740929, EBI-2564133; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, COPII-coated vesicle CC {ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:27716508}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q53G59-1; Sequence=Displayed; CC Name=2; CC IsoId=Q53G59-2; Sequence=VSP_042975; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highly expressed in testis CC and at lower levels in the submandibular salivary gland. CC {ECO:0000269|PubMed:15383316, ECO:0000269|PubMed:16108817}. CC -!- DOMAIN: The BTB domain is required for interaction with CUL3. 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:0000269|PubMed:30190310}. 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; AF190900; AAG17175.1; -; mRNA. DR EMBL; AK027656; BAB55271.1; -; mRNA. DR EMBL; AK301791; BAH13554.1; -; mRNA. DR EMBL; AK223072; BAD96792.1; -; mRNA. DR EMBL; AC096632; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003183; AAH03183.1; -; mRNA. DR EMBL; BC004175; AAH04175.1; -; mRNA. DR CCDS; CCDS1429.1; -. [Q53G59-1] DR RefSeq; NP_001289980.1; NM_001303051.1. [Q53G59-2] DR RefSeq; NP_001290038.1; NM_001303109.1. DR RefSeq; NP_067646.1; NM_021633.3. [Q53G59-1] DR PDB; 2VPJ; X-ray; 1.85 A; A=268-567. DR PDB; 6TTK; X-ray; 2.38 A; A/B/C/D=268-567. DR PDB; 6V7O; X-ray; 2.90 A; A/B=268-567. DR PDBsum; 2VPJ; -. DR PDBsum; 6TTK; -. DR PDBsum; 6V7O; -. DR AlphaFoldDB; Q53G59; -. DR SMR; Q53G59; -. DR BioGRID; 121890; 114. DR ComplexPortal; CPX-8089; CRL3 E3 ubiquitin ligase complex, KLHL12 variant. DR CORUM; Q53G59; -. DR IntAct; Q53G59; 108. DR MINT; Q53G59; -. DR STRING; 9606.ENSP00000356230; -. DR iPTMnet; Q53G59; -. DR MetOSite; Q53G59; -. DR PhosphoSitePlus; Q53G59; -. DR BioMuta; KLHL12; -. DR DMDM; 97054498; -. DR EPD; Q53G59; -. DR jPOST; Q53G59; -. DR MassIVE; Q53G59; -. DR MaxQB; Q53G59; -. DR PaxDb; 9606-ENSP00000356230; -. DR PeptideAtlas; Q53G59; -. DR ProteomicsDB; 62474; -. [Q53G59-1] DR ProteomicsDB; 62475; -. [Q53G59-2] DR Pumba; Q53G59; -. DR Antibodypedia; 34533; 389 antibodies from 30 providers. DR DNASU; 59349; -. DR Ensembl; ENST00000367261.8; ENSP00000356230.3; ENSG00000117153.16. [Q53G59-1] DR GeneID; 59349; -. DR KEGG; hsa:59349; -. DR MANE-Select; ENST00000367261.8; ENSP00000356230.3; NM_021633.4; NP_067646.1. DR UCSC; uc001gyo.2; human. [Q53G59-1] DR AGR; HGNC:19360; -. DR CTD; 59349; -. DR DisGeNET; 59349; -. DR GeneCards; KLHL12; -. DR HGNC; HGNC:19360; KLHL12. DR HPA; ENSG00000117153; Low tissue specificity. DR MIM; 614522; gene. DR neXtProt; NX_Q53G59; -. DR OpenTargets; ENSG00000117153; -. DR PharmGKB; PA134952416; -. DR VEuPathDB; HostDB:ENSG00000117153; -. DR eggNOG; KOG4441; Eukaryota. DR GeneTree; ENSGT00940000155199; -. DR HOGENOM; CLU_004253_14_2_1; -. DR InParanoid; Q53G59; -. DR OMA; SLGTQRC; -. DR OrthoDB; 5472491at2759; -. DR PhylomeDB; Q53G59; -. DR TreeFam; TF329218; -. DR PathwayCommons; Q53G59; -. DR Reactome; R-HSA-4641258; Degradation of DVL. DR SignaLink; Q53G59; -. DR SIGNOR; Q53G59; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 59349; 22 hits in 1192 CRISPR screens. DR ChiTaRS; KLHL12; human. DR EvolutionaryTrace; Q53G59; -. DR GeneWiki; KLHL12; -. DR GenomeRNAi; 59349; -. DR Pharos; Q53G59; Tbio. DR PRO; PR:Q53G59; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q53G59; Protein. DR Bgee; ENSG00000117153; Expressed in oocyte and 188 other cell types or tissues. DR ExpressionAtlas; Q53G59; baseline and differential. DR GO; GO:0034451; C:centriolar satellite; IDA:HPA. DR GO; GO:0030127; C:COPII vesicle coat; IDA:UniProtKB. DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IDA:UniProtKB. DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0048208; P:COPII vesicle coating; IMP:UniProtKB. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IDA:UniProtKB. DR GO; GO:0014032; P:neural crest cell development; IMP:UniProtKB. DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB. DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IMP:UniProtKB. DR CDD; cd18452; BACK_KLHL12; 1. DR CDD; cd18242; BTB_POZ_KLHL12_C3IP1_DKIR; 1. DR Gene3D; 1.25.40.420; -; 1. DR Gene3D; 2.120.10.80; Kelch-type beta propeller; 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 PANTHER; PTHR24412:SF35; ACTIN-BINDING PROTEIN IPP; 1. DR PANTHER; PTHR24412; KELCH PROTEIN; 1. 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 PRINTS; PR00501; KELCHREPEAT. DR SMART; SM00875; BACK; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00612; Kelch; 6. DR SUPFAM; SSF117281; Kelch motif; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR PROSITE; PS50097; BTB; 1. DR Genevisible; Q53G59; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasmic vesicle; KW ER-Golgi transport; Kelch repeat; Reference proteome; Repeat; Transport; KW Ubl conjugation; Ubl conjugation pathway; Wnt signaling pathway. FT CHAIN 1..568 FT /note="Kelch-like protein 12" FT /id="PRO_0000234349" 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:0000269|PubMed:16547521" FT VAR_SEQ 1 FT /note="M -> MDVNKFEASVGFLDVKKFLSTWKLQNPRTHFVLSPHCFM (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042975" FT VARIANT 72 FT /note="P -> L (in dbSNP:rs12569087)" FT /id="VAR_050049" FT MUTAGEN 15 FT /note="H->A: Abolished ubiquitination by the SCF(FBXL17) FT complex." FT /evidence="ECO:0000269|PubMed:30190310" FT MUTAGEN 34 FT /note="D->A: Abolished ubiquitination by the SCF(FBXL17) FT complex." FT /evidence="ECO:0000269|PubMed:30190310" FT MUTAGEN 50 FT /note="V->A: Increased recognition and ubiquitination by FT the SCF(FBXL17) complex." FT /evidence="ECO:0000269|PubMed:30190310" FT MUTAGEN 60 FT /note="A->E,K: Abolished ubiquitination by the SCF(FBXL17) FT complex." FT /evidence="ECO:0000269|PubMed:30190310" FT MUTAGEN 289..290 FT /note="FG->AA: Abolishes interaction with SEC31A and FT subsequent monoubiquitination of SEC31A. Abolishes FT ubiquitination of PEF1." FT /evidence="ECO:0000269|PubMed:22358839, ECO:0000269|Ref.3" FT CONFLICT 122 FT /note="C -> R (in Ref. 3; BAD96792)" FT /evidence="ECO:0000305" FT CONFLICT 197..198 FT /note="FE -> LG (in Ref. 3; BAD96792)" FT /evidence="ECO:0000305" FT CONFLICT 394 FT /note="T -> A (in Ref. 3; BAD96792)" FT /evidence="ECO:0000305" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 291..293 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 299..303 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 304..307 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 308..311 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 323..327 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 330..334 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 346..350 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 373..377 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 380..384 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 395..400 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 401..404 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 405..411 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 420..424 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 427..431 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 436..439 FT /evidence="ECO:0007829|PDB:6V7O" FT STRAND 443..446 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 448..450 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 453..456 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 467..471 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 474..478 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 483..486 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 490..494 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 495..498 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 499..503 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 514..518 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 521..525 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 530..541 FT /evidence="ECO:0007829|PDB:2VPJ" FT TURN 542..545 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 546..559 FT /evidence="ECO:0007829|PDB:2VPJ" FT STRAND 561..566 FT /evidence="ECO:0007829|PDB:2VPJ" SQ SEQUENCE 568 AA; 63277 MW; 4EB1BC33B6351B5D CRC64; MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE KLIKCDEIQV DSEEPVFEAV INWVKHAKKE REESLPNLLQ YVRMPLLTPR YITDVIDAEP FIRCSLQCRD LVDEAKKFHL RPELRSQMQG PRTRARLGAN EVLLVVGGFG SQQSPIDVVE KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG LVVASGVIYC LGGYDGLNIL NSVEKYDPHT GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY DPIIDSWEVV TSMGTQRCDA GVCVLREK //