KLH12_HUMAN
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 03-AUG-2022, entry version 157.
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=12; 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; 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=7; IntAct=EBI-740929, EBI-740929;
CC Q53G59; O95198: KLHL2; NbExp=5; IntAct=EBI-740929, EBI-746999;
CC Q53G59; Q6TFL4: KLHL24; NbExp=3; 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=8; 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}.
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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; 104.
DR CORUM; Q53G59; -.
DR IntAct; Q53G59; 87.
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; Q53G59; -.
DR PeptideAtlas; Q53G59; -.
DR PRIDE; Q53G59; -.
DR ProteomicsDB; 62474; -. [Q53G59-1]
DR ProteomicsDB; 62475; -. [Q53G59-2]
DR Antibodypedia; 34533; 340 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 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; 709680at2759; -.
DR PhylomeDB; Q53G59; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q53G59; -.
DR Reactome; R-HSA-4641258; Degradation of DVL.
DR SignaLink; Q53G59; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 59349; 21 hits in 1113 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 186 other tissues.
DR ExpressionAtlas; Q53G59; baseline and differential.
DR Genevisible; Q53G59; HS.
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 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 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
