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 27-MAR-2024, entry version 208. 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 FUNCTION. RX PubMed=36791496; DOI=10.1016/j.bbrc.2023.02.012; RA Sanada S., Maekawa M., Tate S., Nakaoka H., Fujisawa Y., Sayama K., RA Higashiyama S.; RT "SPOP is essential for DNA replication licensing through maintaining RT translation of CDT1 and CDC6 in HaCaT cells."; RL Biochem. Biophys. Res. Commun. 651:30-38(2023). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IRF1. RX PubMed=37622993; DOI=10.7554/elife.89951; RA Schwartz I., Vunjak M., Budroni V., Cantoran Garcia A., Mastrovito M., RA Soderholm A., Hinterndorfer M., de Almeida M., Hacker K., Wang J., RA Froussios K., Jude J., Decker T., Zuber J., Versteeg G.A.; RT "SPOP targets the immune transcription factor IRF1 for proteasomal RT degradation."; RL Elife 12:0-0(2023). RN [15] RP FUNCTION, AND INTERACTION WITH ENTEROVIRUS EV71 PROTEASE 2A (MICROBIAL RP INFECTION). RX PubMed=37796126; DOI=10.1128/jvi.00786-23; RA Zang L., Yang X., Chen Y., Huang F., Yuan Y., Chen X., Zuo Y., Miao Y., RA Gu J., Guo H., Xia W., Peng Y., Tang M., Huang Z., Wang Y., Ma J., RA Jiang J., Zhou W., Zheng H., Shi W.; RT "Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71- RT encoded 2A protease."; RL J. Virol. 97:e0078623-e0078623(2023). RN [16] RP FUNCTION, INTERACTION WITH HNF1A, AND SUBCELLULAR LOCATION. RX PubMed=38018242; DOI=10.1002/jmv.29254; RA Pi Y., Li Y., Yan Q., Luo H., Zhou P., Chang W., Gong D., Hu Y., Wang K., RA Tang N., Huang A., Chen Y.; RT "SPOP inhibits HBV transcription and replication by ubiquitination and RT degradation of HNF1alpha."; RL J. Med. Virol. 95:e29254-e29254(2023). RN [17] 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 [18] 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 [19] 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 [20] 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). Plays an essential role for proper CC translation, but not for their degradation, of critical DNA replication CC licensing factors CDT1 and CDC6, thereby participating in DNA synthesis CC and cell proliferation (PubMed:36791496). Regulates interferon CC regulatory factor 1/IRF1 proteasomal turnover by targeting S/T-rich CC degrons in IRF1 (PubMed:37622993). Facilitates the lysosome-dependent CC degradation of enterovirus EV71 protease 2A by inducing its 'Lys-48'- CC linked polyubiquitination, which ultimately restricts EV71 replication CC (PubMed:37796126). Acts as an antiviral factor also against hepatitis B CC virus/HBV by promoting ubiquitination and subsequent degradation of CC HNF1A (PubMed:38018242). In turn, inhibits HBV transcription and CC replication by preventing HNF1A stimulating activity of HBV preS1 CC promoter and enhancer II (PubMed:38018242). 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, ECO:0000269|PubMed:37622993, CC ECO:0000269|PubMed:37796126, ECO:0000269|PubMed:38018242}. 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. Interacts CC with IRF1; this interaction mediates IRF1 proteasomal degradation CC (PubMed:37622993). Interacts with HNF1A (PubMed:38018242). 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, ECO:0000269|PubMed:37622993, CC ECO:0000269|PubMed:38018242}. 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, CC ECO:0000269|PubMed:37622993, ECO:0000269|PubMed:38018242}. Nucleus CC speckle {ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9414087}. CC Cytoplasm {ECO:0000269|PubMed:38018242}. 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}. 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; 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 PDB; 8DWS; EM; 3.73 A; A/B/D/E/F/G/H=1-374. DR PDB; 8DWT; EM; 6.20 A; A/B/C/D/E/F/G/H/I/J/K/L=2-374. DR PDB; 8DWU; EM; 3.40 A; A/B/C/D/E/F/H/I/J=1-374. DR PDB; 8DWV; EM; 3.60 A; A/B/E/F/G/H=1-373. 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 PDBsum; 8DWS; -. DR PDBsum; 8DWT; -. DR PDBsum; 8DWU; -. DR PDBsum; 8DWV; -. DR AlphaFoldDB; O43791; -. DR EMDB; EMD-27758; -. DR EMDB; EMD-27759; -. DR EMDB; EMD-27760; -. DR EMDB; EMD-27761; -. DR EMDB; EMD-3317; -. DR SMR; O43791; -. DR BioGRID; 113993; 495. DR CORUM; O43791; -. DR DIP; DIP-50517N; -. DR ELM; O43791; -. DR IntAct; O43791; 41. DR MINT; O43791; -. DR STRING; 9606.ENSP00000377001; -. DR BindingDB; O43791; -. DR ChEMBL; CHEMBL4523140; -. DR GlyGen; O43791; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43791; -. DR PhosphoSitePlus; O43791; -. DR BioMuta; SPOP; -. DR EPD; O43791; -. DR jPOST; O43791; -. DR MassIVE; O43791; -. DR MaxQB; O43791; -. DR PaxDb; 9606-ENSP00000377001; -. DR PeptideAtlas; O43791; -. DR ProteomicsDB; 49171; -. DR Pumba; O43791; -. DR Antibodypedia; 30402; 236 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 AGR; HGNC:11254; -. 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; VEDNAAY; -. DR OrthoDB; 5473088at2759; -. 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; 75 hits in 1216 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 219 other cell types or tissues. DR ExpressionAtlas; O43791; baseline and differential. 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:0140678; F:molecular function inhibitor activity; EXP:DisProt. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0051179; P:localization; IDA:DisProt. 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 CDD; cd18279; BTB_POZ_SPOP-like; 1. DR CDD; cd03774; MATH_SPOP; 1. DR Gene3D; 6.10.250.3030; -; 1. DR Gene3D; 6.20.250.50; -; 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 PANTHER; PTHR24413; SPECKLE-TYPE POZ PROTEIN; 1. DR PANTHER; PTHR24413:SF97; SPECKLE-TYPE POZ PROTEIN; 1. DR Pfam; PF00651; BTB; 1. DR Pfam; PF00917; MATH; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00061; MATH; 1. DR SUPFAM; SSF54695; POZ domain; 1. DR SUPFAM; SSF49599; TRAF domain-like; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS50144; MATH; 1. DR Genevisible; O43791; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Host-virus interaction; Intellectual disability; KW Nucleus; Reference proteome; 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 109..111 FT /evidence="ECO:0007829|PDB:8DWU" 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 //