The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
Functional site class:
SPOP SBC docking motif
Functional site description:
SPOP is part of a multiprotein E3 ligase assembled with the cullin cul3. SPOP has two globular domains. Cullin E3 ligase binds to the BTB domain while the MATH domain directly recruits the substrates of the E3 ligase complex for ubiquitination. Substrate have a degron termed the SPOP-binding consensus (SCB) that binds to the MATH domain. The SCB degron is an unusual ST-rich peptide motif and is known in several substrate proteins including MacroH2A, the transcriptional regulators Ci/GLI3, the phosphatase Puc and DAXX. The SPOP/Cul3 E3 ligase complex is an important regulator of the cell cycle. Due to the high conformational flexibility of the SPOP complex substrates with several SCB configurations can be polyubiquinated.
ELM Description:
The degron targeted by SPOP is known as the SPOP-binding consensus (SBC). It binds to the MATH domain of the Speckle-type POZ protein (SPOP) that is part of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. This mediates the ubiquitination of target proteins, leading to their proteasomal degradation. The peptide motif is unusually S/T rich while there is a hydrophobic amino acid located at the start of the peptide sequence. Therefore, SPOPMATH-SBC interactions are anchored with both hydrophobic and polar interactions. In complex with Cul3, the binding of SPOP to the motif leads to the proteasomal degradation of DAXX, PUC, Ci, GLI2 and GLI3 as well as of MacroH2A. While in the case of MacroH2A the motif was found only once in the protein sequence, it can be found two or three times in most of the other SPOP substrates. Since a dimeric SPOP BTB domain can assemble with two molecules of Cul3 it generates a dimeric ubiquitin ligase containing two substrate-binding sites (Zhuang,2009). As with other short motifs (SBC spans only 5 amino acids) database searches are likely to return numerous false positive hits. All experimentally verified motifs found in the SPOP substrates were located in natively disordered regions of the substrate proteins. In case of MacroH2A, alignments showed that the motif was highly conserved between many species. This and conservation in other substrates allowed the motif positions to be defined.
Pattern: [AVP].[ST][ST][ST]
Pattern Probability: 0.0009380
Present in taxon: Eukaryota
Interaction Domain:
MATH (PF00917) MATH domain (Stochiometry: 1 : 1)
o See 8 Instances for DEG_SPOP_SBC_1
o Abstract
Ubiquitin-mediated proteolysis has diverse regulatory functions in eukaryotic cells (Hershko,1998). An E1-E2-E3 enzyme cascade attaches ubiquitin covalently to substrates. The ubiquitination of a specific protein is performed by an ubiquitin-protein ligase (E3) under the influence of ATP hydroxylation (18282298). An ubiquitin-activating enzyme (E1) transfers the bound ubiquitin to an ubiquitin-conjugating enzyme (E2), which binds to the E3 ligase that specifically recognizes the target protein (Kamura,2003). The largest E3 class is the RING-type E3s or Cullin-RING Ligases (Havens,2011). The Cullin3 Ligase is a CRL and assembles with different BTB domain proteins that perform as adaptors for specific substrates (15340381; 13679921). The MATH-BTB protein, called SPOP (or HIP/SPOP) has been, in complex with Cul3, linked to ubiquitination of substrates that bind to the SPOP-binding consensus (SCB) on the MATH domain (15093836). The SPOP Cullin E3 ligase recognizes an unusual ST-rich degron motif in substrate proteins including MacroH2A, the phosphatase Puc, DAXX and the transcription factor Ci/GLI 2&3 (Zhuang,2009, Zhang,2009).
o 3 selected references:

o 6 GO-Terms:

o 8 Instances for DEG_SPOP_SBC_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q9UER7 DAXX
DAXX_HUMAN
680 684 LASLAPVADSSTRVDSPSHG TP 3 Homo sapiens (Human)
1 
Q9UER7 DAXX
DAXX_HUMAN
608 612 LENGAGMVSSTSFNGGVSPH TP 3 Homo sapiens (Human)
1 
Q9VHV8 puc
Q9VHV8_DROME
381 385 SVSELDSPSSTSSSSGICSL TP 4 Drosophila melanogaster (Fruit fly)
1 
Q9VHV8 puc
Q9VHV8_DROME
289 293 HLNSPSNPSSSSVGLSTQSS TP 4 Drosophila melanogaster (Fruit fly)
1 
Q9VHV8 puc
Q9VHV8_DROME
98 102 ENLACDEVTSTTSSSTAMNG TP 4 Drosophila melanogaster (Fruit fly)
1 
P19538 ci
CI_DROME
1362 1366 NNTLFPDVSSSTHPYHGTNM TP 5 Drosophila melanogaster (Fruit fly)
1 
P19538 ci
CI_DROME
371 375 KDVVPEQPSSTSGGVAQVEA TP 5 Drosophila melanogaster (Fruit fly)
1 
O75367 H2AFY
H2AY_HUMAN
171 175 EVSKAASADSTTEGTPADGF TP 4 Homo sapiens (Human)
1 
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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