SPOP_MOUSE
ID SPOP_MOUSE Reviewed; 374 AA.
AC Q6ZWS8; Q3TLC2; Q5ST07; Q76LV9;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Speckle-type POZ protein {ECO:0000305};
DE AltName: Full=HIB homolog 1;
DE AltName: Full=PDX-1 C-terminal-interacting factor 1;
GN Name=Spop {ECO:0000312|EMBL:AAT08952.1}; Synonyms=Pcif1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH PDX1/IPF1.
RC STRAIN=BALB/cJ; TISSUE=Pancreas;
RX PubMed=15121856; DOI=10.1128/mcb.24.10.4372-4383.2004;
RA Liu A., Desai B.M., Stoffers D.A.;
RT "Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4)
RT transcriptional activity.";
RL Mol. Cell. Biol. 24:4372-4383(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Colon;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-374.
RA Takahashi I., Hashimoto K.;
RT "mouse speckled type poz.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH MACROH2A1.
RX PubMed=12183056; DOI=10.1016/s0167-4889(02)00249-5;
RA Takahashi I., Kameoka Y., Hashimoto K.;
RT "MacroH2A1.2 binds the nuclear protein Spop.";
RL Biochim. Biophys. Acta 1591:63-68(2002).
RN [7]
RP IDENTIFICATION, AND FUNCTION.
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 [8]
RP FUNCTION, AND INTERACTION WITH GLI2 AND GLI3.
RX PubMed=20463034; DOI=10.1242/dev.052126;
RA Wang C., Pan Y., Wang B.;
RT "Suppressor of fused and Spop regulate the stability, processing and
RT function of Gli2 and Gli3 full-length activators but not their
RT repressors.";
RL Development 137:2001-2009(2010).
RN [9]
RP FUNCTION.
RX PubMed=20811152; DOI=10.1172/jci40440;
RA Claiborn K.C., Sachdeva M.M., Cannon C.E., Groff D.N., Singer J.D.,
RA Stoffers D.A.;
RT "Pcif1 modulates Pdx1 protein stability and pancreatic beta cell function
RT and survival in mice.";
RL J. Clin. Invest. 120:3713-3721(2010).
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 The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase
CC complex containing homodimeric SPOP has higher ubiquitin ligase
CC activity than the complex that contains the heterodimer formed by SPOP
CC and SPOPL (By similarity). In complex with CUL3, involved in
CC ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1,
CC GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of
CC MACROH2A1 and BMI1; this does not lead to their proteasomal
CC degradation. Inhibits transcriptional activation of PDX1/IPF1 targets,
CC such as insulin, by promoting PDX1/IPF1 degradation. Involved in the
CC regulation of bromodomain and extra-terminal motif (BET) proteins BRD2,
CC BRD3, BRD4 stability (By similarity). {ECO:0000250|UniProtKB:O43791,
CC ECO:0000269|PubMed:15121856, ECO:0000269|PubMed:16740475,
CC ECO:0000269|PubMed:20463034, ECO:0000269|PubMed:20811152}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer
CC interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-
CC CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and
CC homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a
CC target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX (By
CC similarity). Interacts with MACROH2A1, PDX1/IPF1, GLI2 and GLI3.
CC {ECO:0000250|UniProtKB:O43791, ECO:0000269|PubMed:12183056,
CC ECO:0000269|PubMed:15121856, ECO:0000269|PubMed:20463034}.
CC -!- INTERACTION:
CC Q6ZWS8; Q0VGT2: Gli2; NbExp=2; IntAct=EBI-7128920, EBI-9344284;
CC Q6ZWS8; P52946: Pdx1; NbExp=5; IntAct=EBI-7128920, EBI-7128945;
CC Q6ZWS8; P10071: GLI3; Xeno; NbExp=2; IntAct=EBI-7128920, EBI-308055;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15121856}. Nucleus
CC speckle {ECO:0000269|PubMed:15121856}.
CC -!- TISSUE SPECIFICITY: Widely expressed, mainly in pancreas and in
CC particular in adult pancreatic insulin-producing beta cells and in a
CC subset of exocrine acinar and duct cells.
CC -!- DOMAIN: The BTB (POZ) domain mediates dimerization and interaction with
CC CUL3. {ECO:0000250|UniProtKB:O43791}.
CC -!- DOMAIN: The MATH domain mediates interaction with protein-ubiquitin
CC ligase substrates, such as MACROH2A1 and BMI1.
CC -!- SIMILARITY: Belongs to the Tdpoz family. {ECO:0000305}.
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DR EMBL; AY538613; AAT08952.1; -; mRNA.
DR EMBL; AK028201; BAC25809.1; -; mRNA.
DR EMBL; AK030746; BAC27114.1; -; mRNA.
DR EMBL; AK159482; BAE35119.1; -; mRNA.
DR EMBL; AK166581; BAE38870.1; -; mRNA.
DR EMBL; AL662875; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043131; AAH43131.1; -; mRNA.
DR EMBL; BC045205; AAH45205.1; -; mRNA.
DR EMBL; AB071989; BAB68542.1; -; mRNA.
DR CCDS; CCDS36286.1; -.
DR RefSeq; NP_079563.2; NM_025287.2.
DR RefSeq; XP_006532755.1; XM_006532692.2.
DR AlphaFoldDB; Q6ZWS8; -.
DR SMR; Q6ZWS8; -.
DR BioGRID; 203465; 9.
DR DIP; DIP-43930N; -.
DR IntAct; Q6ZWS8; 4.
DR MINT; Q6ZWS8; -.
DR STRING; 10090.ENSMUSP00000103350; -.
DR iPTMnet; Q6ZWS8; -.
DR PhosphoSitePlus; Q6ZWS8; -.
DR MaxQB; Q6ZWS8; -.
DR PaxDb; Q6ZWS8; -.
DR PRIDE; Q6ZWS8; -.
DR ProteomicsDB; 261624; -.
DR DNASU; 20747; -.
DR Ensembl; ENSMUST00000107722; ENSMUSP00000103350; ENSMUSG00000057522.
DR Ensembl; ENSMUST00000107724; ENSMUSP00000103352; ENSMUSG00000057522.
DR GeneID; 20747; -.
DR KEGG; mmu:20747; -.
DR UCSC; uc007laj.1; mouse.
DR CTD; 8405; -.
DR MGI; MGI:1343085; Spop.
DR VEuPathDB; HostDB:ENSMUSG00000057522; -.
DR eggNOG; KOG1987; Eukaryota.
DR GeneTree; ENSGT00940000154376; -.
DR HOGENOM; CLU_004253_2_0_1; -.
DR InParanoid; Q6ZWS8; -.
DR OMA; IKFNYMW; -.
DR OrthoDB; 864323at2759; -.
DR PhylomeDB; Q6ZWS8; -.
DR TreeFam; TF313419; -.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 20747; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Spop; mouse.
DR PRO; PR:Q6ZWS8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q6ZWS8; protein.
DR Bgee; ENSMUSG00000057522; Expressed in temporalis muscle and 255 other tissues.
DR ExpressionAtlas; Q6ZWS8; baseline and differential.
DR Genevisible; Q6ZWS8; MM.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IGI:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IGI:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:2000676; P:positive regulation of type B pancreatic cell apoptotic process; IGI:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IGI:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:GO_Central.
DR GO; GO:0097050; P:type B pancreatic cell apoptotic process; IGI:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR CDD; cd18518; BACK_SPOP; 1.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
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 Disease variant; Nucleus; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..374
FT /note="Speckle-type POZ protein"
FT /id="PRO_0000191622"
FT DOMAIN 31..161
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 200..267
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 71..191
FT /note="Required for nuclear localization"
FT /evidence="ECO:0000250"
FT REGION 123..133
FT /note="Important for binding substrate proteins"
FT /evidence="ECO:0000250"
FT REGION 186..217
FT /note="Important for homodimerization"
FT /evidence="ECO:0000250"
FT REGION 297..355
FT /note="Important for homodimerization"
FT /evidence="ECO:0000250"
FT CONFLICT 54
FT /note="S -> G (in Ref. 2; BAE38870)"
FT /evidence="ECO:0000305"
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
