UniProtKB - O43791 (SPOP_HUMAN)
Protein
Speckle-type POZ protein
Gene
SPOP
Organism
Homo sapiens (Human)
Status
Functioni
Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420).7 Publications
Miscellaneous
Antigen recognized by serum from scleroderma patient.
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.7 PublicationsView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
GO - Molecular functioni
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
- protein polyubiquitination Source: UniProtKB
- regulation of proteolysis Source: GO_Central
- ubiquitin-dependent protein catabolic process Source: GO_Central
Keywordsi
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
BRENDAi | 6.3.2.19, 2681 |
PathwayCommonsi | O43791 |
Reactomei | R-HSA-5632684, Hedgehog 'on' state |
SignaLinki | O43791 |
SIGNORi | O43791 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Speckle-type POZ proteinCuratedAlternative name(s): HIB homolog 1 Roadkill homolog 1 |
Gene namesi | Name:SPOPImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000121067.17 |
HGNCi | HGNC:11254, SPOP |
MIMi | 602650, gene |
neXtProti | NX_O43791 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
- Nucleus speckle 2 Publications
Nucleus
- nuclear speck Source: UniProtKB-SubCell
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- Cul3-RING ubiquitin ligase complex Source: UniProtKB
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Nabais Sa-de Vries syndrome 1 (NSDVS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show congenital microcephaly and dysmorphic facial features, including round face, small palpebral fissures, highly arched eyebrows, and short nose.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083853 | 121 | R → Q in NSDVS1; gain-of-function, reduced BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083856 | 144 | D → N in NSDVS1; gain-of-function, reduced BET proteins stability. 1 Publication | 1 |
Nabais Sa-de Vries syndrome 2 (NSDVS2)1 Publication
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by global developmental delay apparent from birth, impaired intellectual development, speech delay, dysmorphic facial features, and additional anomalies including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083851 | 25 | T → A in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083852 | 83 | Y → C in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083854 | 132 | G → V in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083855 | 138 | R → C in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 87 | Y → A: Strongly reduced affinity for substrate proteins. 1 Publication | 1 | |
Mutagenesisi | 123 | Y → A: Strongly reduced affinity for substrate proteins. 1 Publication | 1 | |
Mutagenesisi | 130 | D → A: Strongly reduced affinity for substrate proteins. 1 Publication | 1 | |
Mutagenesisi | 131 | W → A: Strongly reduced affinity for substrate proteins. 1 Publication | 1 | |
Mutagenesisi | 133 | F → A: Strongly reduced affinity for substrate proteins. 1 Publication | 1 | |
Mutagenesisi | 186 | L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. 1 Publication | 1 | |
Mutagenesisi | 190 | L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. 1 Publication | 1 | |
Mutagenesisi | 193 | L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. 1 Publication | 1 | |
Mutagenesisi | 217 | I → K: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. 1 Publication | 1 |
Keywords - Diseasei
Mental retardationOrganism-specific databases
DisGeNETi | 8405 |
MalaCardsi | SPOP |
MIMi | 618828, phenotype 618829, phenotype |
OpenTargetsi | ENSG00000121067 |
PharmGKBi | PA36084 |
Miscellaneous databases
Pharosi | O43791, Tbio |
Polymorphism and mutation databases
BioMutai | SPOP |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000191621 | 1 – 374 | Speckle-type POZ proteinAdd BLAST | 374 |
Proteomic databases
EPDi | O43791 |
jPOSTi | O43791 |
MassIVEi | O43791 |
MaxQBi | O43791 |
PaxDbi | O43791 |
PeptideAtlasi | O43791 |
PRIDEi | O43791 |
ProteomicsDBi | 49171 |
PTM databases
iPTMneti | O43791 |
PhosphoSitePlusi | O43791 |
Expressioni
Tissue specificityi
Widely expressed.1 Publication
Gene expression databases
Bgeei | ENSG00000121067, Expressed in vagina and 253 other tissues |
ExpressionAtlasi | O43791, baseline and differential |
Genevisiblei | O43791, HS |
Organism-specific databases
HPAi | ENSG00000121067, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with GLI2 and GLI3 (By similarity). Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX.
By similarity7 PublicationsBinary interactionsi
Hide detailsO43791
GO - Molecular functioni
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 113993, 108 interactors |
CORUMi | O43791 |
DIPi | DIP-50517N |
ELMi | O43791 |
IntActi | O43791, 37 interactors |
MINTi | O43791 |
STRINGi | 9606.ENSP00000377001 |
Miscellaneous databases
RNActi | O43791, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O43791 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O43791 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 31 – 161 | MATHPROSITE-ProRule annotationAdd BLAST | 131 | |
Domaini | 173 – 297 | BTBPROSITE-ProRule annotationAdd BLAST | 125 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 71 – 191 | Required for nuclear localizationAdd BLAST | 121 | |
Regioni | 123 – 133 | Important for binding substrate proteinsAdd BLAST | 11 | |
Regioni | 186 – 217 | Important for homodimerizationAdd BLAST | 32 | |
Regioni | 297 – 355 | Important for homodimerizationAdd BLAST | 59 |
Domaini
The BTB (POZ) domain mediates dimerization and interaction with CUL3.1 Publication
The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1.1 Publication
Sequence similaritiesi
Belongs to the Tdpoz family.Curated
Phylogenomic databases
eggNOGi | KOG1987, Eukaryota |
GeneTreei | ENSGT00940000154376 |
HOGENOMi | CLU_004253_2_0_1 |
InParanoidi | O43791 |
OMAi | MCEQALC |
OrthoDBi | 864323at2759 |
PhylomeDBi | O43791 |
TreeFami | TF313419 |
Family and domain databases
Gene3Di | 2.60.210.10, 1 hit |
IDEALi | IID00529 |
InterProi | View protein in InterPro IPR000210, BTB/POZ_dom IPR002083, MATH/TRAF_dom IPR011333, SKP1/BTB/POZ_sf IPR008974, TRAF-like |
Pfami | View protein in Pfam PF00651, BTB, 1 hit PF00917, MATH, 1 hit |
SMARTi | View protein in SMART SM00225, BTB, 1 hit SM00061, MATH, 1 hit |
SUPFAMi | SSF49599, SSF49599, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit PS50144, MATH, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 9 potential isoforms that are computationally mapped.Show allAlign All
O43791-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSRVPSPPPP AEMSSGPVAE SWCYTQIKVV KFSYMWTINN FSFCREEMGE
60 70 80 90 100
VIKSSTFSSG ANDKLKWCLR VNPKGLDEES KDYLSLYLLL VSCPKSEVRA
110 120 130 140 150
KFKFSILNAK GEETKAMESQ RAYRFVQGKD WGFKKFIRRD FLLDEANGLL
160 170 180 190 200
PDDKLTLFCE VSVVQDSVNI SGQNTMNMVK VPECRLADEL GGLWENSRFT
210 220 230 240 250
DCCLCVAGQE FQAHKAILAA RSPVFSAMFE HEMEESKKNR VEINDVEPEV
260 270 280 290 300
FKEMMCFIYT GKAPNLDKMA DDLLAAADKY ALERLKVMCE DALCSNLSVE
310 320 330 340 350
NAAEILILAD LHSADQLKTQ AVDFINYHAS DVLETSGWKS MVVSHPHLVA
360 370
EAYRSLASAQ CPFLGPPRKR LKQS
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RDG8 | D6RDG8_HUMAN | Speckle-type POZ protein | SPOP | 238 | Annotation score: | ||
D6RGZ4 | D6RGZ4_HUMAN | Speckle-type POZ protein | SPOP | 185 | Annotation score: | ||
H0Y977 | H0Y977_HUMAN | Speckle-type POZ protein | SPOP | 72 | Annotation score: | ||
D6RFL7 | D6RFL7_HUMAN | Speckle-type POZ protein | SPOP | 117 | Annotation score: | ||
D6RD94 | D6RD94_HUMAN | Speckle-type POZ protein | SPOP | 66 | Annotation score: | ||
D6RIS7 | D6RIS7_HUMAN | Speckle-type POZ protein | SPOP | 40 | Annotation score: | ||
D6RA79 | D6RA79_HUMAN | Speckle-type POZ protein | SPOP | 32 | Annotation score: | ||
D6RBR3 | D6RBR3_HUMAN | Speckle-type POZ protein | SPOP | 44 | Annotation score: | ||
A0A590UJA7 | A0A590UJA7_HUMAN | Speckle-type POZ protein | SPOP | 165 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 239 | N → S in BAD96309 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083851 | 25 | T → A in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083852 | 83 | Y → C in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083853 | 121 | R → Q in NSDVS1; gain-of-function, reduced BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083854 | 132 | G → V in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083855 | 138 | R → C in NSDVS2; dominant-negative, increased BET proteins stability. 1 Publication | 1 | |
Natural variantiVAR_083856 | 144 | D → N in NSDVS1; gain-of-function, reduced BET proteins stability. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ000644 mRNA Translation: CAA04199.1 AK222589 mRNA Translation: BAD96309.1 AK312691 mRNA Translation: BAG35570.1 CH471109 Genomic DNA Translation: EAW94671.1 CH471109 Genomic DNA Translation: EAW94672.1 CH471109 Genomic DNA Translation: EAW94673.1 CH471109 Genomic DNA Translation: EAW94674.1 CH471109 Genomic DNA Translation: EAW94675.1 BC001269 mRNA Translation: AAH01269.1 BC003385 mRNA Translation: AAH03385.1 |
CCDSi | CCDS11551.1 |
RefSeqi | NP_001007227.1, NM_001007226.1 NP_001007228.1, NM_001007227.1 NP_001007229.1, NM_001007228.1 NP_001007230.1, NM_001007229.1 NP_001007231.1, NM_001007230.1 NP_003554.1, NM_003563.3 XP_005257780.1, XM_005257723.4 XP_005257781.1, XM_005257724.4 XP_016880693.1, XM_017025204.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ000644 mRNA Translation: CAA04199.1 AK222589 mRNA Translation: BAD96309.1 AK312691 mRNA Translation: BAG35570.1 CH471109 Genomic DNA Translation: EAW94671.1 CH471109 Genomic DNA Translation: EAW94672.1 CH471109 Genomic DNA Translation: EAW94673.1 CH471109 Genomic DNA Translation: EAW94674.1 CH471109 Genomic DNA Translation: EAW94675.1 BC001269 mRNA Translation: AAH01269.1 BC003385 mRNA Translation: AAH03385.1 |
CCDSi | CCDS11551.1 |
RefSeqi | NP_001007227.1, NM_001007226.1 NP_001007228.1, NM_001007227.1 NP_001007229.1, NM_001007228.1 NP_001007230.1, NM_001007229.1 NP_001007231.1, NM_001007230.1 NP_003554.1, NM_003563.3 XP_005257780.1, XM_005257723.4 XP_005257781.1, XM_005257724.4 XP_016880693.1, XM_017025204.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2CR2 | NMR | - | A | 28-173 | [»] | |
3HQH | X-ray | 2.30 | A | 28-166 | [»] | |
3HQI | X-ray | 2.62 | A/B | 28-329 | [»] | |
3HQL | X-ray | 1.66 | A/B | 28-166 | [»] | |
3HQM | X-ray | 1.74 | A/B | 28-166 | [»] | |
3HSV | X-ray | 1.43 | A/B | 28-166 | [»] | |
3HTM | X-ray | 2.50 | A/B/C/D | 172-329 | [»] | |
3HU6 | X-ray | 2.70 | A/B | 28-329 | [»] | |
3IVB | X-ray | 1.75 | A | 28-166 | [»] | |
3IVQ | X-ray | 2.10 | A/B | 28-166 | [»] | |
3IVV | X-ray | 1.25 | A | 28-166 | [»] | |
4EOZ | X-ray | 2.40 | A/C | 177-319 | [»] | |
4HS2 | X-ray | 1.53 | A | 270-374 | [»] | |
4J8Z | X-ray | 2.42 | A/B | 169-374 | [»] | |
4O1V | X-ray | 2.00 | A | 28-166 | [»] | |
6F8F | X-ray | 2.00 | D | 28-166 | [»] | |
6F8G | X-ray | 2.03 | A/B/C/D | 28-166 | [»] | |
6I41 | X-ray | 1.90 | A | 28-166 | [»] | |
6I5P | X-ray | 1.81 | A/C/E/G | 28-166 | [»] | |
6I68 | X-ray | 1.85 | A/C/E/G | 28-166 | [»] | |
6I7A | X-ray | 2.20 | A/C/E/G | 28-166 | [»] | |
SMRi | O43791 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113993, 108 interactors |
CORUMi | O43791 |
DIPi | DIP-50517N |
ELMi | O43791 |
IntActi | O43791, 37 interactors |
MINTi | O43791 |
STRINGi | 9606.ENSP00000377001 |
PTM databases
iPTMneti | O43791 |
PhosphoSitePlusi | O43791 |
Polymorphism and mutation databases
BioMutai | SPOP |
Proteomic databases
EPDi | O43791 |
jPOSTi | O43791 |
MassIVEi | O43791 |
MaxQBi | O43791 |
PaxDbi | O43791 |
PeptideAtlasi | O43791 |
PRIDEi | O43791 |
ProteomicsDBi | 49171 |
Protocols and materials databases
Antibodypediai | 30402, 192 antibodies |
DNASUi | 8405 |
Genome annotation databases
Organism-specific databases
CTDi | 8405 |
DisGeNETi | 8405 |
EuPathDBi | HostDB:ENSG00000121067.17 |
GeneCardsi | SPOP |
HGNCi | HGNC:11254, SPOP |
HPAi | ENSG00000121067, Low tissue specificity |
MalaCardsi | SPOP |
MIMi | 602650, gene 618828, phenotype 618829, phenotype |
neXtProti | NX_O43791 |
OpenTargetsi | ENSG00000121067 |
PharmGKBi | PA36084 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1987, Eukaryota |
GeneTreei | ENSGT00940000154376 |
HOGENOMi | CLU_004253_2_0_1 |
InParanoidi | O43791 |
OMAi | MCEQALC |
OrthoDBi | 864323at2759 |
PhylomeDBi | O43791 |
TreeFami | TF313419 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
BRENDAi | 6.3.2.19, 2681 |
PathwayCommonsi | O43791 |
Reactomei | R-HSA-5632684, Hedgehog 'on' state |
SignaLinki | O43791 |
SIGNORi | O43791 |
Miscellaneous databases
BioGRID-ORCSi | 8405, 41 hits in 851 CRISPR screens |
ChiTaRSi | SPOP, human |
EvolutionaryTracei | O43791 |
GeneWikii | SPOP |
GenomeRNAii | 8405 |
Pharosi | O43791, Tbio |
PROi | PR:O43791 |
RNActi | O43791, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000121067, Expressed in vagina and 253 other tissues |
ExpressionAtlasi | O43791, baseline and differential |
Genevisiblei | O43791, HS |
Family and domain databases
Gene3Di | 2.60.210.10, 1 hit |
IDEALi | IID00529 |
InterProi | View protein in InterPro IPR000210, BTB/POZ_dom IPR002083, MATH/TRAF_dom IPR011333, SKP1/BTB/POZ_sf IPR008974, TRAF-like |
Pfami | View protein in Pfam PF00651, BTB, 1 hit PF00917, MATH, 1 hit |
SMARTi | View protein in SMART SM00225, BTB, 1 hit SM00061, MATH, 1 hit |
SUPFAMi | SSF49599, SSF49599, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit PS50144, MATH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SPOP_HUMAN | |
Accessioni | O43791Primary (citable) accession number: O43791 Secondary accession number(s): B2R6S3, D3DTW7, Q53HJ1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | June 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 192 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations