O43791 (SPOP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Speckle-type POZ protein

Alternative name(s):
HIB homolog 1
Roadkill homolog 1

Gene names

Name:

SPOP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.12. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from direct assay Ref.12. Source: UniProtKB nucleus Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CUL3	Q13618	2	EBI-743549,EBI-456129
DAXX	Q9UER7	5	EBI-743549,EBI-77321
MYD88	Q99836	6	EBI-743549,EBI-447677
NCOA3	Q9Y6Q9	6	EBI-743549,EBI-81196

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 374

374

Speckle-type POZ protein

PRO_0000191621

Regions

Domain

31 – 161

131

MATH

Domain

173 – 297

125

BTB

Region

71 – 191

121

Required for nuclear localization

Region

123 – 133

11

Important for binding substrate proteins

Region

186 – 217

32

Important for homodimerization

Region

297 – 355

59

Important for homodimerization

Experimental info

Mutagenesis

87

1

Y → A: Strongly reduced affinity for substrate proteins. Ref.14

Mutagenesis

123

1

Y → A: Strongly reduced affinity for substrate proteins. Ref.14

Mutagenesis

130

1

D → A: Strongly reduced affinity for substrate proteins. Ref.14

Mutagenesis

131

1

W → A: Strongly reduced affinity for substrate proteins. Ref.14

Mutagenesis

133

1

F → A: Strongly reduced affinity for substrate proteins. Ref.14

Mutagenesis

186

1

L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14

Mutagenesis

190

1

L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14

Mutagenesis

193

1

L → D: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14

Mutagenesis

217

1

I → K: Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Ref.14

Sequence conflict

239

1

N → S in BAD96309. Ref.3

Secondary structure

1

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374

Helix Strand Turn

Details...

Beta strand

31 – 40

10

Helix

41 – 43

3

Helix

45 – 48

4

Beta strand

57 – 60

4

Helix

61 – 63

3

Beta strand

65 – 72

8

Helix

78 – 80

3

Beta strand

83 – 92

10

Beta strand

94 – 107

14

Beta strand

113 – 118

6

Beta strand

123 – 126

4

Beta strand

130 – 138

9

Helix

139 – 143

5

Helix

145 – 147

3

Beta strand

148 – 150

3

Helix

151 – 153

3

Beta strand

155 – 163

9

Helix

186 – 196

11

Beta strand

202 – 206

5

Beta strand

209 – 213

5

Helix

215 – 221

7

Helix

223 – 230

8

Beta strand

231 – 233

3

Helix

234 – 238

5

Beta strand

240 – 243

4

Helix

248 – 260

13

Helix

266 – 268

3

Helix

270 – 279

10

Helix

283 – 290

8

Turn

299 – 301

3

Helix

302 – 311

10

Helix

315 – 327

13

Sequences

	Sequence		Length	Mass (Da)
	O43791 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: EE5F4C5CF6FD09DC	FASTA	374	42,132
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00013978.

RefSeq

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.

UniGene

Hs.463382.
Hs.740407.

3D structure databases

PDBe
RCSB PDB
PDBj

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	28-337	[»]
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	172-337	[»]
3HU6	X-ray	2.70	A/B	28-337	[»]
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	[»]

ProteinModelPortal

O43791.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43791. 14 interactions.

MINT

MINT-1438409.

STRING

9606.ENSP00000240327.

PTM databases

PhosphoSite

O43791.

Proteomic databases

PaxDb

O43791.

PRIDE

O43791.

Protocols and materials databases

DNASU

8405.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000347630; ENSP00000240327; ENSG00000121067.
ENST00000393328; ENSP00000377001; ENSG00000121067.
ENST00000393331; ENSP00000377004; ENSG00000121067.
ENST00000503676; ENSP00000420908; ENSG00000121067.
ENST00000504102; ENSP00000425905; ENSG00000121067.

GeneID

8405.

KEGG

hsa:8405.

UCSC

uc002ipb.3. human.

Organism-specific databases

CTD

8405.

GeneCards

GC17M047676.

HGNC

HGNC:11254. SPOP.

HPA

HPA046820.

MIM

602650. gene.

neXtProt

NX_O43791.

PharmGKB

PA36084.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG273048.

HOGENOM

HOG000231621.

HOVERGEN

HBG001393.

InParanoid

O43791.

KO

K10523.

OMA

LLLVQCN.

OrthoDB

EOG42BX8K.

PhylomeDB

O43791.

Enzyme and pathway databases

Pathway_Interaction_DB

hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

O43791.

Bgee

O43791.

CleanEx

HS_SPOP.

Genevestigator

O43791.

GermOnline

ENSG00000121067. Homo sapiens.

Family and domain databases

Gene3D

3.30.710.10. 1 hit.

InterPro

IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR002083. MATH.
IPR008974. TRAF-like.
[Graphical view]

Pfam

PF00651. BTB. 1 hit.
PF00917. MATH. 1 hit.
[Graphical view]

SMART

SM00225. BTB. 1 hit.
SM00061. MATH. 1 hit.
[Graphical view]

SUPFAM

SSF54695. BTB/POZ_fold. 1 hit.
SSF49599. Traf_like. 1 hit.

PROSITE

PS50097. BTB. 1 hit.
PS50144. MATH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SPOP. human.

EvolutionaryTrace

O43791.

GenomeRNAi

8405.

NextBio

31454.

SOURCE

Search...

Entry information

Entry name

SPOP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.