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O43791 (SPOP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Speckle-type POZ protein
Alternative name(s):
HIB homolog 1
Roadkill homolog 1
Gene names
Name:SPOP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length374 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 H2AFY 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. Ref.6 Ref.8 Ref.11 Ref.12 Ref.14 Ref.15

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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 H2AFY, PDX1/IPF1, BMI1, BRMS1 and DAXX. Ref.6 Ref.7 Ref.8 Ref.11 Ref.12 Ref.14 Ref.15

Subcellular location

Nucleus. Nucleus speckle Ref.1 Ref.8 Ref.12.

Tissue specificity

Widely expressed. Ref.1

Domain

The BTB (POZ) domain mediates dimerization and interaction with CUL3. Ref.14

The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as H2AFY and BMI1. Ref.14

Miscellaneous

Antigen recognized by serum from scleroderma patient.

Sequence similarities

Belongs to the Tdpoz family.

Contains 1 BTB (POZ) domain.

Contains 1 MATH domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 374374Speckle-type POZ protein
PRO_0000191621

Regions

Domain31 – 161131MATH
Domain173 – 297125BTB
Region71 – 191121Required for nuclear localization
Region123 – 13311Important for binding substrate proteins
Region186 – 21732Important for homodimerization
Region297 – 35559Important for homodimerization

Experimental info

Mutagenesis871Y → A: Strongly reduced affinity for substrate proteins. Ref.14
Mutagenesis1231Y → A: Strongly reduced affinity for substrate proteins. Ref.14
Mutagenesis1301D → A: Strongly reduced affinity for substrate proteins. Ref.14
Mutagenesis1311W → A: Strongly reduced affinity for substrate proteins. Ref.14
Mutagenesis1331F → A: Strongly reduced affinity for substrate proteins. Ref.14
Mutagenesis1861L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14
Mutagenesis1901L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14
Mutagenesis1931L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14
Mutagenesis2171I → K: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14
Sequence conflict2391N → S in BAD96309. Ref.3

Secondary structure

............................................................... 374
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43791 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: EE5F4C5CF6FD09DC

FASTA37442,132
        10         20         30         40         50         60 
MSRVPSPPPP AEMSSGPVAE SWCYTQIKVV KFSYMWTINN FSFCREEMGE VIKSSTFSSG 

        70         80         90        100        110        120 
ANDKLKWCLR VNPKGLDEES KDYLSLYLLL VSCPKSEVRA KFKFSILNAK GEETKAMESQ 

       130        140        150        160        170        180 
RAYRFVQGKD WGFKKFIRRD FLLDEANGLL PDDKLTLFCE VSVVQDSVNI SGQNTMNMVK 

       190        200        210        220        230        240 
VPECRLADEL GGLWENSRFT DCCLCVAGQE FQAHKAILAA RSPVFSAMFE HEMEESKKNR 

       250        260        270        280        290        300 
VEINDVEPEV FKEMMCFIYT GKAPNLDKMA DDLLAAADKY ALERLKVMCE DALCSNLSVE 

       310        320        330        340        350        360 
NAAEILILAD LHSADQLKTQ AVDFINYHAS DVLETSGWKS MVVSHPHLVA EAYRSLASAQ 

       370 
CPFLGPPRKR LKQS 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a novel nuclear speckle-type protein, SPOP."
Nagai Y., Kojima T., Muro Y., Hachiya T., Nishizawa Y., Wakabayashi T., Hagiwara M.
FEBS Lett. 418:23-26(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Coronary artery.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cervix and Placenta.
[6]"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Furukawa M., He Y.J., Borchers C., Xiong Y.
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3.
[7]"Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP."
La M., Kim K., Park J., Won J., Lee J.-H., Fu Y.M., Meadows G.G., Joe C.O.
Biochem. Biophys. Res. Commun. 320:760-765(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAXX, HOMODIMERIZATION.
[8]"Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase."
Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I., Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M.
Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BMI1, IDENTIFICATION IN A COMPLEX WITH CUL3 AND BMI1, IDENTIFICATION IN A COMPLEX WITH CUL3 AND H2AFY, SUBCELLULAR LOCATION, FUNCTION.
[9]"Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus."
Kent D., Bush E.W., Hooper J.E.
Development 133:2001-2010(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[10]"A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor."
Zhang Q., Zhang L., Wang B., Ou C.-Y., Chien C.-T., Jiang J.
Dev. Cell 10:719-729(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[11]"BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase."
Kwon J.E., La M., Oh K.H., Oh Y.M., Kim G.R., Seol J.H., Baek S.H., Chiba T., Tanaka K., Bang O.S., Joe C.O., Chung C.H.
J. Biol. Chem. 281:12664-12672(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH CUL3 AND DAXX, FUNCTION.
[12]"Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex."
Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H., Yoon J.B., Baek S.H., Kim J.H.
Biochem. Biophys. Res. Commun. 415:720-726(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BRMS1, IDENTIFICATION IN A COMPLEX WITH CUL3 AND BRMS1.
[13]"Solution structure of N-terminal domain of speckle-type POZ protein."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 28-173.
[14]"Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases."
Zhuang M., Calabrese M.F., Liu J., Waddell M.B., Nourse A., Hammel M., Miller D.J., Walden H., Duda D.M., Seyedin S.N., Hoggard T., Harper J.W., White K.P., Schulman B.A.
Mol. Cell 36:39-50(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 28-166 IN COMPLEXES WITH H2AFY AND SUBSTRATE PEPTIDES, INTERACTION WITH CUL3; H2AFY AND DAXX, SUBUNIT, FUNCTION, DOMAIN, MUTAGENESIS OF TYR-87; TYR-123; ASP-130; TRP-131; PHE-133; LEU-186; LEU-190; LEU-193 AND ILE-217, MASS SPECTROMETRY.
[15]"Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase."
Errington W.J., Khan M.Q., Bueler S.A., Rubinstein J.L., Chakrabartty A., Prive G.G.
Structure 20:1141-1153(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 177-319 IN COMPLEX WITH CUL3, FUNCTION, INTERACTION WITH CUL3 AND H2AFY, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_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_005257779.1. XM_005257722.1.
XP_005257780.1. XM_005257723.1.
XP_005257781.1. XM_005257724.1.
UniGeneHs.463382.
Hs.740407.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CR2NMR-A28-173[»]
3HQHX-ray2.30A28-166[»]
3HQIX-ray2.62A/B28-337[»]
3HQLX-ray1.66A/B28-166[»]
3HQMX-ray1.74A/B28-166[»]
3HSVX-ray1.43A/B28-166[»]
3HTMX-ray2.50A/B/C/D172-337[»]
3HU6X-ray2.70A/B28-337[»]
3IVBX-ray1.75A28-166[»]
3IVQX-ray2.10A/B28-166[»]
3IVVX-ray1.25A28-166[»]
4EOZX-ray2.40A/C177-319[»]
4HS2X-ray1.53A270-374[»]
4J8ZX-ray2.42A/B169-374[»]
ProteinModelPortalO43791.
SMRO43791. Positions 28-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113993. 28 interactions.
IntActO43791. 15 interactions.
MINTMINT-1438409.
STRING9606.ENSP00000240327.

PTM databases

PhosphoSiteO43791.

Proteomic databases

PaxDbO43791.
PRIDEO43791.

Protocols and materials databases

DNASU8405.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000347630; ENSP00000240327; ENSG00000121067.
ENST00000393328; ENSP00000377001; ENSG00000121067.
ENST00000393331; ENSP00000377004; ENSG00000121067.
ENST00000503676; ENSP00000420908; ENSG00000121067.
ENST00000504102; ENSP00000425905; ENSG00000121067.
GeneID8405.
KEGGhsa:8405.
UCSCuc002ipb.3. human.

Organism-specific databases

CTD8405.
GeneCardsGC17M047676.
HGNCHGNC:11254. SPOP.
HPAHPA046820.
MIM602650. gene.
neXtProtNX_O43791.
PharmGKBPA36084.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG273048.
HOGENOMHOG000231621.
HOVERGENHBG001393.
InParanoidO43791.
KOK10523.
OMAKVIKFSY.
OrthoDBEOG73NG3G.
PhylomeDBO43791.
TreeFamTF313419.

Enzyme and pathway databases

SignaLinkO43791.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO43791.
BgeeO43791.
CleanExHS_SPOP.
GenevestigatorO43791.

Family and domain databases

Gene3D3.30.710.10. 1 hit.
InterProIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR002083. MATH.
IPR008974. TRAF-like.
[Graphical view]
PfamPF00651. BTB. 1 hit.
PF00917. MATH. 1 hit.
[Graphical view]
SMARTSM00225. BTB. 1 hit.
SM00061. MATH. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
SSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
PS50144. MATH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSPOP. human.
EvolutionaryTraceO43791.
GeneWikiSPOP.
GenomeRNAi8405.
NextBio31454.
PROO43791.
SOURCESearch...

Entry information

Entry nameSPOP_HUMAN
AccessionPrimary (citable) accession number: O43791
Secondary accession number(s): B2R6S3, D3DTW7, Q53HJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: March 19, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM