SPOP_HUMAN
ID SPOP_HUMAN Reviewed; 374 AA.
AC O43791; B2R6S3; D3DTW7; Q53HJ1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Speckle-type POZ protein {ECO:0000305};
DE AltName: Full=HIB homolog 1;
DE AltName: Full=Roadkill homolog 1;
GN Name=SPOP {ECO:0000312|HGNC:HGNC:11254};
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9414087; DOI=10.1016/s0014-5793(97)01340-9;
RA Nagai Y., Kojima T., Muro Y., Hachiya T., Nishizawa Y., Wakabayashi T.,
RA Hagiwara M.;
RT "Identification of a novel nuclear speckle-type protein, SPOP.";
RL FEBS Lett. 418:23-26(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
RC TISSUE=Coronary artery;
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Placenta;
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 FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, AND INTERACTION WITH CUL3.
RX PubMed=14528312; DOI=10.1038/ncb1056;
RA Furukawa M., He Y.J., Borchers C., Xiong Y.;
RT "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin
RT ligases.";
RL Nat. Cell Biol. 5:1001-1007(2003).
RN [7]
RP INTERACTION WITH DAXX, AND HOMODIMERIZATION.
RX PubMed=15240113; DOI=10.1016/j.bbrc.2004.06.022;
RA La M., Kim K., Park J., Won J., Lee J.-H., Fu Y.M., Meadows G.G., Joe C.O.;
RT "Daxx-mediated transcriptional repression of MMP1 gene is reversed by
RT SPOP.";
RL Biochem. Biophys. Res. Commun. 320:760-765(2004).
RN [8]
RP INTERACTION WITH BMI1, IDENTIFICATION IN A COMPLEX WITH CUL3 AND BMI1,
RP IDENTIFICATION IN A COMPLEX WITH CUL3 AND MACROH2A1, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=15897469; DOI=10.1073/pnas.0408918102;
RA Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I.,
RA Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M.;
RT "Stable X chromosome inactivation involves the PRC1 Polycomb complex and
RT requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005).
RN [9]
RP IDENTIFICATION.
RX PubMed=16651542; DOI=10.1242/dev.02370;
RA Kent D., Bush E.W., Hooper J.E.;
RT "Roadkill attenuates Hedgehog responses through degradation of Cubitus
RT interruptus.";
RL Development 133:2001-2010(2006).
RN [10]
RP IDENTIFICATION.
RX PubMed=16740475; DOI=10.1016/j.devcel.2006.05.004;
RA Zhang Q., Zhang L., Wang B., Ou C.-Y., Chien C.-T., Jiang J.;
RT "A hedgehog-induced BTB protein modulates hedgehog signaling by degrading
RT Ci/Gli transcription factor.";
RL Dev. Cell 10:719-729(2006).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH CUL3 AND DAXX, AND FUNCTION.
RX PubMed=16524876; DOI=10.1074/jbc.m600204200;
RA Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H.,
RA Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H.;
RT "BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor
RT of Daxx for ubiquitination by Cul3-based ubiquitin ligase.";
RL J. Biol. Chem. 281:12664-12672(2006).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BRMS1, AND IDENTIFICATION
RP IN A COMPLEX WITH CUL3 AND BRMS1.
RX PubMed=22085717; DOI=10.1016/j.bbrc.2011.10.154;
RA Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H.,
RA Yoon J.B., Baek S.H., Kim J.H.;
RT "Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-
RT SPOP E3 ubiquitin ligase complex.";
RL Biochem. Biophys. Res. Commun. 415:720-726(2011).
RN [13]
RP STRUCTURE BY NMR OF 28-173.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of N-terminal domain of speckle-type POZ protein.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 28-166 IN COMPLEXES WITH
RP MACROH2A1 AND SUBSTRATE PEPTIDES, INTERACTION WITH CUL3; MACROH2A1 AND
RP DAXX, SUBUNIT, FUNCTION, DOMAIN, MUTAGENESIS OF TYR-87; TYR-123; ASP-130;
RP TRP-131; PHE-133; LEU-186; LEU-190; LEU-193 AND ILE-217, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RX PubMed=19818708; DOI=10.1016/j.molcel.2009.09.022;
RA Zhuang M., Calabrese M.F., Liu J., Waddell M.B., Nourse A., Hammel M.,
RA Miller D.J., Walden H., Duda D.M., Seyedin S.N., Hoggard T., Harper J.W.,
RA White K.P., Schulman B.A.;
RT "Structures of SPOP-substrate complexes: insights into molecular
RT architectures of BTB-Cul3 ubiquitin ligases.";
RL Mol. Cell 36:39-50(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 177-319 IN COMPLEX WITH CUL3,
RP FUNCTION, INTERACTION WITH CUL3 AND MACROH2A1, AND SUBUNIT.
RX PubMed=22632832; DOI=10.1016/j.str.2012.04.009;
RA Errington W.J., Khan M.Q., Bueler S.A., Rubinstein J.L., Chakrabartty A.,
RA Prive G.G.;
RT "Adaptor protein self-assembly drives the control of a cullin-RING
RT ubiquitin ligase.";
RL Structure 20:1141-1153(2012).
RN [16]
RP VARIANTS NSDVS2 ALA-25; CYS-83; VAL-132 AND CYS-138, CHARACTERIZATION OF
RP VARIANTS NSDVS2 ALA-25; CYS-83; VAL-132 AND CYS-138, VARIANTS NSDVS1
RP GLN-121 AND ASN-144, CHARACTERIZATION OF VARIANTS NSDVS1 GLN-121 AND
RP ASN-144, AND FUNCTION.
RX PubMed=32109420; DOI=10.1016/j.ajhg.2020.02.001;
RA Nabais Sa M.J., El Tekle G., de Brouwer A.P.M., Sawyer S.L., Del Gaudio D.,
RA Parker M.J., Kanani F., van den Boogaard M.H., van Gassen K.,
RA Van Allen M.I., Wierenga K., Purcarin G., Elias E.R., Begtrup A.,
RA Keller-Ramey J., Bernasocchi T., van de Wiel L., Gilissen C., Venselaar H.,
RA Pfundt R., Vissers L.E.L.M., Theurillat J.P., de Vries B.B.A.;
RT "De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental
RT Disorders.";
RL Am. J. Hum. Genet. 106:405-411(2020).
CC -!- FUNCTION: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complex that mediates the ubiquitination of
CC target proteins, leading most often to their proteasomal degradation.
CC In complex with CUL3, involved in ubiquitination and proteasomal
CC degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with
CC CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not
CC lead to their proteasomal degradation. Inhibits transcriptional
CC activation of PDX1/IPF1 targets, such as insulin, by promoting
CC PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complex containing homodimeric SPOP has higher
CC ubiquitin ligase activity than the complex that contains the
CC heterodimer formed by SPOP and SPOPL. Involved in the regulation of
CC bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4
CC stability (PubMed:32109420). {ECO:0000269|PubMed:14528312,
CC ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876,
CC ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717,
CC ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:32109420}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15897469,
CC ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708,
CC ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832,
CC ECO:0000269|PubMed:32109420}.
CC -!- SUBUNIT: Interacts with GLI2 and GLI3 (By similarity). Homodimer and
CC homooligomer. Heterodimer with SPOPL. Each dimer interacts with two
CC CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complexes that contain CUL3 and homodimeric
CC SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target
CC protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX.
CC {ECO:0000250, ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15240113,
CC ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876,
CC ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717,
CC ECO:0000269|PubMed:22632832}.
CC -!- INTERACTION:
CC O43791; Q13618: CUL3; NbExp=2; IntAct=EBI-743549, EBI-456129;
CC O43791; Q9UER7: DAXX; NbExp=5; IntAct=EBI-743549, EBI-77321;
CC O43791; Q16829: DUSP7; NbExp=5; IntAct=EBI-743549, EBI-1265847;
CC O43791; Q99836: MYD88; NbExp=7; IntAct=EBI-743549, EBI-447677;
CC O43791; Q9Y6Q9: NCOA3; NbExp=6; IntAct=EBI-743549, EBI-81196;
CC O43791; P60484: PTEN; NbExp=4; IntAct=EBI-743549, EBI-696162;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22085717}. Nucleus
CC speckle {ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9414087}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9414087}.
CC -!- DOMAIN: The BTB (POZ) domain mediates dimerization and interaction with
CC CUL3. {ECO:0000269|PubMed:19818708}.
CC -!- DOMAIN: The MATH domain mediates interaction with protein-ubiquitin
CC ligase substrates, such as MACROH2A1 and BMI1.
CC {ECO:0000269|PubMed:19818708}.
CC -!- DISEASE: Nabais Sa-de Vries syndrome 1 (NSDVS1) [MIM:618828]: An
CC autosomal dominant disorder characterized by global developmental
CC delay, impaired intellectual development, speech delay, and variable
CC behavioral abnormalities. Affected individuals show congenital
CC microcephaly and dysmorphic facial features, including round face,
CC small palpebral fissures, highly arched eyebrows, and short nose.
CC {ECO:0000269|PubMed:32109420}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Nabais Sa-de Vries syndrome 2 (NSDVS2) [MIM:618829]: An
CC autosomal dominant disorder characterized by global developmental delay
CC apparent from birth, impaired intellectual development, speech delay,
CC dysmorphic facial features, and additional anomalies including
CC congenital heart defects, sleep disturbances, hypotonia, and variable
CC endocrine abnormalities. {ECO:0000269|PubMed:32109420}. Note=The
CC disease is caused by variants affecting distinct genetic loci,
CC including the gene represented in this entry.
CC -!- MISCELLANEOUS: Antigen recognized by serum from scleroderma patient.
CC -!- SIMILARITY: Belongs to the Tdpoz family. {ECO:0000305}.
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DR EMBL; AJ000644; CAA04199.1; -; mRNA.
DR EMBL; AK222589; BAD96309.1; -; mRNA.
DR EMBL; AK312691; BAG35570.1; -; mRNA.
DR EMBL; CH471109; EAW94671.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94672.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94673.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94674.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94675.1; -; Genomic_DNA.
DR EMBL; BC001269; AAH01269.1; -; mRNA.
DR EMBL; BC003385; AAH03385.1; -; mRNA.
DR CCDS; CCDS11551.1; -.
DR RefSeq; NP_001007227.1; NM_001007226.1.
DR RefSeq; NP_001007228.1; NM_001007227.1.
DR RefSeq; NP_001007229.1; NM_001007228.1.
DR RefSeq; NP_001007230.1; NM_001007229.1.
DR RefSeq; NP_001007231.1; NM_001007230.1.
DR RefSeq; NP_003554.1; NM_003563.3.
DR RefSeq; XP_005257780.1; XM_005257723.4.
DR RefSeq; XP_005257781.1; XM_005257724.4.
DR RefSeq; XP_016880693.1; XM_017025204.1.
DR PDB; 2CR2; NMR; -; A=28-173.
DR PDB; 3HQH; X-ray; 2.30 A; A=28-166.
DR PDB; 3HQI; X-ray; 2.62 A; A/B=28-329.
DR PDB; 3HQL; X-ray; 1.66 A; A/B=28-166.
DR PDB; 3HQM; X-ray; 1.74 A; A/B=28-166.
DR PDB; 3HSV; X-ray; 1.43 A; A/B=28-166.
DR PDB; 3HTM; X-ray; 2.50 A; A/B/C/D=172-329.
DR PDB; 3HU6; X-ray; 2.70 A; A/B=28-329.
DR PDB; 3IVB; X-ray; 1.75 A; A=28-166.
DR PDB; 3IVQ; X-ray; 2.10 A; A/B=28-166.
DR PDB; 3IVV; X-ray; 1.25 A; A=28-166.
DR PDB; 4EOZ; X-ray; 2.40 A; A/C=177-319.
DR PDB; 4HS2; X-ray; 1.53 A; A=270-374.
DR PDB; 4J8Z; X-ray; 2.42 A; A/B=169-374.
DR PDB; 4O1V; X-ray; 2.00 A; A=28-166.
DR PDB; 6F8F; X-ray; 2.00 A; D=28-166.
DR PDB; 6F8G; X-ray; 2.03 A; A/B/C/D=28-166.
DR PDB; 6I41; X-ray; 1.90 A; A=28-166.
DR PDB; 6I5P; X-ray; 1.81 A; A/C/E/G=28-166.
DR PDB; 6I68; X-ray; 1.85 A; A/C/E/G=28-166.
DR PDB; 6I7A; X-ray; 2.20 A; A/C/E/G=28-166.
DR PDB; 7D3D; X-ray; 1.45 A; A/B=28-166.
DR PDB; 7KLZ; X-ray; 3.40 A; A/B=29-166.
DR PDB; 7LIN; X-ray; 1.44 A; A=29-166.
DR PDB; 7LIO; X-ray; 3.01 A; A/B=29-166.
DR PDB; 7LIP; X-ray; 1.48 A; A=29-166.
DR PDB; 7LIQ; X-ray; 1.98 A; A=29-166.
DR PDBsum; 2CR2; -.
DR PDBsum; 3HQH; -.
DR PDBsum; 3HQI; -.
DR PDBsum; 3HQL; -.
DR PDBsum; 3HQM; -.
DR PDBsum; 3HSV; -.
DR PDBsum; 3HTM; -.
DR PDBsum; 3HU6; -.
DR PDBsum; 3IVB; -.
DR PDBsum; 3IVQ; -.
DR PDBsum; 3IVV; -.
DR PDBsum; 4EOZ; -.
DR PDBsum; 4HS2; -.
DR PDBsum; 4J8Z; -.
DR PDBsum; 4O1V; -.
DR PDBsum; 6F8F; -.
DR PDBsum; 6F8G; -.
DR PDBsum; 6I41; -.
DR PDBsum; 6I5P; -.
DR PDBsum; 6I68; -.
DR PDBsum; 6I7A; -.
DR PDBsum; 7D3D; -.
DR PDBsum; 7KLZ; -.
DR PDBsum; 7LIN; -.
DR PDBsum; 7LIO; -.
DR PDBsum; 7LIP; -.
DR PDBsum; 7LIQ; -.
DR AlphaFoldDB; O43791; -.
DR SMR; O43791; -.
DR BioGRID; 113993; 262.
DR CORUM; O43791; -.
DR DIP; DIP-50517N; -.
DR ELM; O43791; -.
DR IntAct; O43791; 40.
DR MINT; O43791; -.
DR STRING; 9606.ENSP00000377001; -.
DR BindingDB; O43791; -.
DR ChEMBL; CHEMBL4523140; -.
DR iPTMnet; O43791; -.
DR PhosphoSitePlus; O43791; -.
DR BioMuta; SPOP; -.
DR EPD; O43791; -.
DR jPOST; O43791; -.
DR MassIVE; O43791; -.
DR MaxQB; O43791; -.
DR PaxDb; O43791; -.
DR PeptideAtlas; O43791; -.
DR PRIDE; O43791; -.
DR ProteomicsDB; 49171; -.
DR Antibodypedia; 30402; 204 antibodies from 26 providers.
DR DNASU; 8405; -.
DR Ensembl; ENST00000347630.6; ENSP00000240327.2; ENSG00000121067.19.
DR Ensembl; ENST00000393328.6; ENSP00000377001.2; ENSG00000121067.19.
DR Ensembl; ENST00000503676.5; ENSP00000420908.1; ENSG00000121067.19.
DR Ensembl; ENST00000504102.6; ENSP00000425905.1; ENSG00000121067.19.
DR Ensembl; ENST00000509079.6; ENSP00000426986.2; ENSG00000121067.19.
DR Ensembl; ENST00000514121.6; ENSP00000424119.2; ENSG00000121067.19.
DR Ensembl; ENST00000665825.1; ENSP00000499562.1; ENSG00000121067.19.
DR GeneID; 8405; -.
DR KEGG; hsa:8405; -.
DR MANE-Select; ENST00000504102.6; ENSP00000425905.1; NM_001007228.2; NP_001007229.1.
DR UCSC; uc002ipd.4; human.
DR CTD; 8405; -.
DR DisGeNET; 8405; -.
DR GeneCards; SPOP; -.
DR HGNC; HGNC:11254; SPOP.
DR HPA; ENSG00000121067; Low tissue specificity.
DR MalaCards; SPOP; -.
DR MIM; 602650; gene.
DR MIM; 618828; phenotype.
DR MIM; 618829; phenotype.
DR neXtProt; NX_O43791; -.
DR OpenTargets; ENSG00000121067; -.
DR PharmGKB; PA36084; -.
DR VEuPathDB; HostDB:ENSG00000121067; -.
DR eggNOG; KOG1987; Eukaryota.
DR GeneTree; ENSGT00940000154376; -.
DR HOGENOM; CLU_004253_2_0_1; -.
DR InParanoid; O43791; -.
DR OMA; IKFNYMW; -.
DR OrthoDB; 864323at2759; -.
DR PhylomeDB; O43791; -.
DR TreeFam; TF313419; -.
DR PathwayCommons; O43791; -.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR SignaLink; O43791; -.
DR SIGNOR; O43791; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8405; 68 hits in 1130 CRISPR screens.
DR ChiTaRS; SPOP; human.
DR EvolutionaryTrace; O43791; -.
DR GeneWiki; SPOP; -.
DR GenomeRNAi; 8405; -.
DR Pharos; O43791; Tbio.
DR PRO; PR:O43791; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O43791; protein.
DR Bgee; ENSG00000121067; Expressed in blood vessel layer and 217 other tissues.
DR ExpressionAtlas; O43791; baseline and differential.
DR Genevisible; O43791; HS.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:GO_Central.
DR CDD; cd18518; BACK_SPOP; 1.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR IDEAL; IID00529; -.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR034089; SPOP_C.
DR InterPro; IPR008974; TRAF-like.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00917; MATH; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00061; MATH; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS50144; MATH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Intellectual disability; Nucleus; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..374
FT /note="Speckle-type POZ protein"
FT /id="PRO_0000191621"
FT DOMAIN 31..161
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 173..297
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 71..191
FT /note="Required for nuclear localization"
FT REGION 123..133
FT /note="Important for binding substrate proteins"
FT REGION 186..217
FT /note="Important for homodimerization"
FT REGION 297..355
FT /note="Important for homodimerization"
FT VARIANT 25
FT /note="T -> A (in NSDVS2; dominant-negative, increased BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083851"
FT VARIANT 83
FT /note="Y -> C (in NSDVS2; dominant-negative, increased BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083852"
FT VARIANT 121
FT /note="R -> Q (in NSDVS1; gain-of-function, reduced BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083853"
FT VARIANT 132
FT /note="G -> V (in NSDVS2; dominant-negative, increased BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083854"
FT VARIANT 138
FT /note="R -> C (in NSDVS2; dominant-negative, increased BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083855"
FT VARIANT 144
FT /note="D -> N (in NSDVS1; gain-of-function, reduced BET
FT proteins stability)"
FT /evidence="ECO:0000269|PubMed:32109420"
FT /id="VAR_083856"
FT MUTAGEN 87
FT /note="Y->A: Strongly reduced affinity for substrate
FT proteins."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 123
FT /note="Y->A: Strongly reduced affinity for substrate
FT proteins."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 130
FT /note="D->A: Strongly reduced affinity for substrate
FT proteins."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 131
FT /note="W->A: Strongly reduced affinity for substrate
FT proteins."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 133
FT /note="F->A: Strongly reduced affinity for substrate
FT proteins."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 186
FT /note="L->D: Strongly reduced homodimerization. Reduces the
FT activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3
FT ubiquitin-protein ligase complex."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 190
FT /note="L->D: Strongly reduced homodimerization. Reduces the
FT activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3
FT ubiquitin-protein ligase complex."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 193
FT /note="L->D: Strongly reduced homodimerization. Reduces the
FT activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3
FT ubiquitin-protein ligase complex."
FT /evidence="ECO:0000269|PubMed:19818708"
FT MUTAGEN 217
FT /note="I->K: Strongly reduced homodimerization. Reduces the
FT activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3
FT ubiquitin-protein ligase complex."
FT /evidence="ECO:0000269|PubMed:19818708"
FT CONFLICT 239
FT /note="N -> S (in Ref. 3; BAD96309)"
FT /evidence="ECO:0000305"
FT STRAND 31..40
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:3IVB"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:6F8F"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 83..92
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 94..107
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 130..138
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:7LIN"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3IVV"
FT STRAND 155..163
FT /evidence="ECO:0007829|PDB:3IVV"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:4EOZ"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:4EOZ"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 215..221
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 223..230
FT /evidence="ECO:0007829|PDB:4EOZ"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 234..238
FT /evidence="ECO:0007829|PDB:4EOZ"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 248..260
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 270..279
FT /evidence="ECO:0007829|PDB:4EOZ"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:4EOZ"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:4HS2"
FT HELIX 302..311
FT /evidence="ECO:0007829|PDB:4HS2"
FT HELIX 315..327
FT /evidence="ECO:0007829|PDB:4HS2"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:4HS2"
FT HELIX 336..344
FT /evidence="ECO:0007829|PDB:4HS2"
FT HELIX 346..357
FT /evidence="ECO:0007829|PDB:4HS2"
SQ SEQUENCE 374 AA; 42132 MW; EE5F4C5CF6FD09DC CRC64;
MSRVPSPPPP AEMSSGPVAE SWCYTQIKVV KFSYMWTINN FSFCREEMGE VIKSSTFSSG
ANDKLKWCLR VNPKGLDEES KDYLSLYLLL VSCPKSEVRA KFKFSILNAK GEETKAMESQ
RAYRFVQGKD WGFKKFIRRD FLLDEANGLL PDDKLTLFCE VSVVQDSVNI SGQNTMNMVK
VPECRLADEL GGLWENSRFT DCCLCVAGQE FQAHKAILAA RSPVFSAMFE HEMEESKKNR
VEINDVEPEV FKEMMCFIYT GKAPNLDKMA DDLLAAADKY ALERLKVMCE DALCSNLSVE
NAAEILILAD LHSADQLKTQ AVDFINYHAS DVLETSGWKS MVVSHPHLVA EAYRSLASAQ
CPFLGPPRKR LKQS
