SPOP | ENSG00000121067 | NCBI 8405

Details for: SPOP

Gene ID: 8405

Gene Type: Protein-coding - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SPOP

Ensembl ID: ENSG00000121067

Description: speckle type BTB/POZ protein

Cell Significance Landscape

Display Count:

Associated with

Hedgehog 'on' state
(R-HSA-5632684)
Signaling by hedgehog
(R-HSA-5358351)
Signal transduction
(R-HSA-162582)
Cul3-ring ubiquitin ligase complex
(GO:0031463)
Cytoplasm
(GO:0005737)
Identical protein binding
(GO:0042802)
Molecular function inhibitor activity
(GO:0140678)
Nuclear speck
(GO:0016607)
Nucleoplasm
(GO:0005654)
Nucleus
(GO:0005634)
Proteasome-mediated ubiquitin-dependent protein catabolic process
(GO:0043161)
Protein binding
(GO:0005515)
Protein polyubiquitination
(GO:0000209)
Regulation of proteolysis
(GO:0030162)
Ubiquitin protein ligase binding
(GO:0031625)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

T follicular helper cell CL0002038

CSI 17.17

rCSI 12.85%

PRS 41.02
L6b glutamatergic cortical neuron CL4023038

CSI 16.26

rCSI 50.8%

PRS 17.58
bronchus fibroblast of lung CL2000093

CSI 14.73

rCSI 11.97%

PRS 28.33
near-projecting glutamatergic cortical neuron CL4023012

CSI 13.23

rCSI 50.01%

PRS 17.45
transit amplifying cell CL0009010

CSI 12.34

rCSI 18.87%

PRS 42.47
corticothalamic-projecting glutamatergic cortical neuron CL4023013

CSI 9.12

rCSI 53.72%

PRS 17.62
pulmonary ionocyte CL0017000

CSI 9.11

rCSI 11.1%

PRS 33.63
kidney connecting tubule epithelial cell CL1000768

CSI 9.1

rCSI 23.07%

PRS 20.99
L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040

CSI 8.02

rCSI 19.49%

PRS 16.38
myoepithelial cell CL0000185

CSI 7.84

rCSI 19.83%

PRS 33.46
microcirculation associated smooth muscle cell CL0008035

CSI 7.61

rCSI 22.03%

PRS 30.31
podocyte CL0000653

CSI 7.59

rCSI 33.73%

PRS 26.42
Bergmann glial cell CL0000644

CSI 7.44

rCSI 10.17%

PRS 26.61
mucus secreting cell CL0000319

CSI 7.4

rCSI 11.76%

PRS 34.89
megakaryocyte-erythroid progenitor cell CL0000050

CSI 7.08

rCSI 6.39%

PRS 24.87
effector CD4-positive, alpha-beta T cell CL0001044

CSI 6.74

rCSI 19.32%

PRS 40.26
L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041

CSI 6.73

rCSI 24.22%

PRS 15.9
ciliated cell CL0000064

CSI 6.42

rCSI 10.4%

PRS 27.13
helper T cell CL0000912

CSI 6.19

rCSI 8.75%

PRS 36.96
pvalb GABAergic cortical interneuron CL4023018

CSI 5.84

rCSI 7.26%

PRS 15.74
CD14-positive monocyte CL0001054

CSI 5.83

rCSI 7.26%

PRS 36.96
blood vessel smooth muscle cell CL0019018

CSI 5.79

rCSI 47.11%

PRS 25.62
perivascular cell CL4033054

CSI 5.41

rCSI 7.4%

PRS 30.73
effector memory CD4-positive, alpha-beta T cell CL0000905

CSI 5.25

rCSI 7.15%

PRS 55.95
enteroendocrine cell CL0000164

CSI 5.2

rCSI 7.11%

PRS 30
tissue-resident macrophage CL0000864

CSI 4.87

rCSI 22.79%

PRS 48.46
activated CD4-positive, alpha-beta T cell CL0000896

CSI 4.84

rCSI 4.47%

PRS 46.41
hematopoietic multipotent progenitor cell CL0000837

CSI 4.28

rCSI 10.31%

PRS 41.94
periportal region hepatocyte CL0019026

CSI 4.26

rCSI 16.57%

PRS 36.41
class switched memory B cell CL0000972

CSI 4.24

rCSI 3.17%

PRS 43.8
neuroendocrine cell CL0000165

CSI 4.24

rCSI 16.39%

PRS 47.74
sst GABAergic cortical interneuron CL4023017

CSI 4.08

rCSI 5.27%

PRS 17.36
type B pancreatic cell CL0000169

CSI 3.89

rCSI 8.61%

PRS 25.18
alveolar type 1 fibroblast cell CL4028004

CSI 3.85

rCSI 4.22%

PRS 30.44
intestine goblet cell CL0019031

CSI 3.8

rCSI 3.38%

PRS 27.34
multi-ciliated epithelial cell CL0005012

CSI 3.63

rCSI 3.62%

PRS 23.37
lung pericyte CL0009089

CSI 3.45

rCSI 9.11%

PRS 32.45
CD4-positive, alpha-beta thymocyte CL0000810

CSI 3.43

rCSI 2.75%

PRS 46.26
alveolar macrophage CL0000583

CSI 3.36

rCSI 5.53%

PRS 31.8
double negative thymocyte CL0002489

CSI 3.33

rCSI 2.31%

PRS 32.91
pro-B cell CL0000826

CSI 3.1

rCSI 2.57%

PRS 27.67
colon macrophage CL0009038

CSI 3.09

rCSI 14.27%

PRS 50.68
myeloid leukocyte CL0000766

CSI 3.06

rCSI 2.83%

PRS 28.34
direct pathway medium spiny neuron CL4023026

CSI 2.98

rCSI 71.24%

PRS 15.71
effector CD8-positive, alpha-beta T cell CL0001050

CSI 2.96

rCSI 2.25%

PRS 35.77
erythrocyte CL0000232

CSI 2.91

rCSI 6.61%

PRS 34.33
ionocyte CL0005006

CSI 2.88

rCSI 3.08%

PRS 25.22
indirect pathway medium spiny neuron CL4023029

CSI 2.86

rCSI 69.02%

PRS 16.56
unswitched memory B cell CL0000970

CSI 2.86

rCSI 2.4%

PRS 41.67
mature T cell CL0002419

CSI 2.84

rCSI 2.21%

PRS 39.65
skin fibroblast CL0002620

CSI 2.77

rCSI 2.39%

PRS 38.64
secretory cell CL0000151

CSI 2.73

rCSI 2.85%

PRS 28.02
mesenchymal stem cell CL0000134

CSI 2.7

rCSI 29.53%

PRS 45.21
CD4-positive, alpha-beta memory T cell CL0000897

CSI 2.67

rCSI 1.92%

PRS 37.05
colon epithelial cell CL0011108

CSI 2.65

rCSI 2.78%

PRS 25.48
erythroid progenitor cell CL0000038

CSI 2.65

rCSI 15.18%

PRS 38.34
kidney loop of Henle thin descending limb epithelial cell CL1001111

CSI 2.64

rCSI 3.75%

PRS 25.38
melanocyte CL0000148

CSI 2.63

rCSI 1.95%

PRS 23.45
elicited macrophage CL0000861

CSI 2.61

rCSI 2.4%

PRS 32.43
pulmonary capillary endothelial cell CL4028001

CSI 2.61

rCSI 4.98%

PRS 42.03
neural crest cell CL0011012

CSI 2.61

rCSI 2.07%

PRS 18.9
hepatocyte CL0000182

CSI 2.61

rCSI 4.66%

PRS 25.49
common myeloid progenitor CL0000049

CSI 2.57

rCSI 2.08%

PRS 27.43
goblet cell CL0000160

CSI 2.45

rCSI 2.31%

PRS 28.49
double-positive, alpha-beta thymocyte CL0000809

CSI 2.24

rCSI 2.29%

PRS 38.09
glioblast CL0000030

CSI 2.23

rCSI 3.56%

PRS 23.31
Mueller cell CL0000636

CSI 2.18

rCSI 4.97%

PRS 23.46
cardiac endothelial cell CL0010008

CSI 2.16

rCSI 8.72%

PRS 25.7
cerebral cortex neuron CL0010012

CSI 2.16

rCSI 8.81%

PRS 27.73
IgA plasma cell CL0000987

CSI 2.15

rCSI 2.21%

PRS 46.27
naive T cell CL0000898

CSI 2.14

rCSI 1.49%

PRS 37.63
cerebral cortex GABAergic interneuron CL0010011

CSI 2.14

rCSI 6.31%

PRS 31.65
pulmonary alveolar type 1 cell CL0002062

CSI 2.13

rCSI 12.26%

PRS 32.52
epithelial cell of lower respiratory tract CL0002632

CSI 2.12

rCSI 1.65%

PRS 26.64
renal alpha-intercalated cell CL0005011

CSI 2.11

rCSI 2.82%

PRS 34.35
alveolar adventitial fibroblast CL4028006

CSI 2.11

rCSI 3.33%

PRS 27.55
granulocyte CL0000094

CSI 2.09

rCSI 3.2%

PRS 34.84
midzonal region hepatocyte CL0019028

CSI 2.09

rCSI 4.91%

PRS 37.53
myofibroblast cell CL0000186

CSI 2.08

rCSI 2.88%

PRS 35.28
retinal rod cell CL0000604

CSI 2.02

rCSI 3.57%

PRS 26.61
neuroblast (sensu Vertebrata) CL0000031

CSI 2.01

rCSI 2.57%

PRS 26.06
fallopian tube secretory epithelial cell CL4030006

CSI 1.99

rCSI 1.92%

PRS 28.17
effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062

CSI 1.99

rCSI 9.98%

PRS 35.7
medium spiny neuron CL1001474

CSI 1.97

rCSI 16.96%

PRS 16.61
adipocyte CL0000136

CSI 1.94

rCSI 2.48%

PRS 26.14
cardiac neuron CL0010022

CSI 1.93

rCSI 6.18%

PRS 23.7
cerebellar granule cell CL0001031

CSI 1.91

rCSI 2.81%

PRS 25.33
hematopoietic precursor cell CL0008001

CSI 1.9

rCSI 1.95%

PRS 42.37
epithelial cell of lung CL0000082

CSI 1.89

rCSI 1.56%

PRS 25.98
cardiac muscle cell CL0000746

CSI 1.83

rCSI 2.63%

PRS 21.51
small intestine goblet cell CL1000495

CSI 1.76

rCSI 3.86%

PRS 35.84
precursor B cell CL0000817

CSI 1.75

rCSI 1.54%

PRS 35.43
CD8-positive, alpha-beta thymocyte CL0000811

CSI 1.75

rCSI 2.73%

PRS 54.93
chondrocyte CL0000138

CSI 1.75

rCSI 2.78%

PRS 23
interstitial cell of Cajal CL0002088

CSI 1.74

rCSI 2.22%

PRS 31.28
plasmacytoid dendritic cell, human CL0001058

CSI 1.74

rCSI 1.21%

PRS 28.82
vascular associated smooth muscle cell CL0000359

CSI 1.72

rCSI 5.57%

PRS 31.78
interneuron CL0000099

CSI 1.69

rCSI 3.4%

PRS 20.37
epithelial cell of proximal tubule CL0002306

CSI 1.68

rCSI 4.11%

PRS 26.14
promonocyte CL0000559

CSI 1.68

rCSI 2.88%

PRS 35.9

cytotoxic T cell CL0000910

CSI 0.1

rCSI 0.4%

PRS 38.9%
vein endothelial cell of respiratory system CL4033008

CSI 0.1

rCSI 1.0%

PRS 48.5%
Cajal-Retzius cell CL0000695

CSI 0.2

rCSI 1.4%

PRS 47.5%
acinar cell of salivary gland CL0002623

CSI 0.2

rCSI 5.4%

PRS 48.4%
bronchiolar smooth muscle cell CL4033017

CSI 0.3

rCSI 3.8%

PRS 60.1%
flat midget bipolar cell CL4033033

CSI 0.3

rCSI 1.9%

PRS 27.1%
eye photoreceptor cell CL0000287

CSI 0.3

rCSI 3.1%

PRS 56.9%
myeloid lineage restricted progenitor cell CL0000839

CSI 0.3

rCSI 1.5%

PRS 49.7%
regular atrial cardiac myocyte CL0002129

CSI 0.3

rCSI 1.0%

PRS 28.2%
stromal cell of ovary CL0002132

CSI 0.3

rCSI 0.8%

PRS 42.8%
Hofbauer cell CL3000001

CSI 0.3

rCSI 0.6%

PRS 34.5%
paneth cell CL0000510

CSI 0.3

rCSI 0.5%

PRS 41.6%
P/D1 enteroendocrine cell CL0002268

CSI 0.3

rCSI 1.8%

PRS 54.3%
GABAergic interneuron CL0011005

CSI 0.4

rCSI 5.6%

PRS 27.8%
regular ventricular cardiac myocyte CL0002131

CSI 0.4

rCSI 2.3%

PRS 22.0%
eosinophil CL0000771

CSI 0.4

rCSI 2.5%

PRS 60.1%
L5/6 near-projecting glutamatergic neuron CL4030067

CSI 0.4

rCSI 1.3%

PRS 19.4%
duct epithelial cell CL0000068

CSI 0.4

rCSI 0.6%

PRS 29.0%
diffuse bipolar 3a cell CL4033029

CSI 0.4

rCSI 2.8%

PRS 27.8%
pancreatic PP cell CL0002275

CSI 0.4

rCSI 1.7%

PRS 43.5%
ON parasol ganglion cell CL4033052

CSI 0.4

rCSI 6.1%

PRS 22.4%
colon goblet cell CL0009039

CSI 0.4

rCSI 1.0%

PRS 39.0%
megakaryocyte CL0000556

CSI 0.4

rCSI 1.9%

PRS 43.7%
germinal center B cell CL0000844

CSI 0.5

rCSI 1.4%

PRS 53.4%
parietal epithelial cell CL1000452

CSI 0.5

rCSI 1.2%

PRS 22.9%
diffuse bipolar 2 cell CL4033028

CSI 0.5

rCSI 3.6%

PRS 28.6%
H2 horizontal cell CL0004218

CSI 0.5

rCSI 2.3%

PRS 29.0%
primitive red blood cell CL0002355

CSI 0.5

rCSI 2.5%

PRS 42.7%
myeloid dendritic cell, human CL0001057

CSI 0.5

rCSI 2.9%

PRS 65.1%
endothelial cell of placenta CL0009092

CSI 0.5

rCSI 2.6%

PRS 36.4%
OFF midget ganglion cell CL4033047

CSI 0.5

rCSI 11.0%

PRS 24.2%
ON midget ganglion cell CL4033046

CSI 0.5

rCSI 11.0%

PRS 22.9%
amacrine cell CL0000561

CSI 0.6

rCSI 1.6%

PRS 21.6%
diffuse bipolar 3b cell CL4033030

CSI 0.6

rCSI 3.8%

PRS 28.3%
lung ciliated cell CL1000271

CSI 0.6

rCSI 0.7%

PRS 20.3%
CD14-positive, CD16-positive monocyte CL0002397

CSI 0.6

rCSI 0.8%

PRS 38.1%
fibroblast of breast CL4006000

CSI 0.6

rCSI 2.5%

PRS 56.0%
thymocyte CL0000893

CSI 0.6

rCSI 2.1%

PRS 67.2%
mesodermal cell CL0000222

CSI 0.6

rCSI 0.7%

PRS 26.4%
pancreatic stellate cell CL0002410

CSI 0.6

rCSI 3.5%

PRS 38.7%
kidney epithelial cell CL0002518

CSI 0.6

rCSI 1.2%

PRS 51.9%
dopaminergic neuron CL0000700

CSI 0.6

rCSI 3.4%

PRS 17.2%
fraction A pre-pro B cell CL0002045

CSI 0.6

rCSI 0.7%

PRS 50.1%
T-helper 17 cell CL0000899

CSI 0.6

rCSI 0.5%

PRS 46.4%
S cone cell CL0003050

CSI 0.6

rCSI 2.8%

PRS 25.9%
bronchial goblet cell CL1000312

CSI 0.6

rCSI 2.5%

PRS 51.2%
mesenchymal cell CL0008019

CSI 0.6

rCSI 1.6%

PRS 26.5%
chandelier pvalb GABAergic cortical interneuron CL4023036

CSI 0.7

rCSI 2.1%

PRS 19.1%
tracheobronchial smooth muscle cell CL0019019

CSI 0.7

rCSI 1.2%

PRS 34.7%
erythroblast CL0000765

CSI 0.7

rCSI 1.8%

PRS 40.0%
lung secretory cell CL1000272

CSI 0.7

rCSI 1.7%

PRS 25.5%
renal interstitial pericyte CL1001318

CSI 0.7

rCSI 1.9%

PRS 25.6%
H1 horizontal cell CL0004217

CSI 0.7

rCSI 2.7%

PRS 33.8%
endothelial cell of pericentral hepatic sinusoid CL0019022

CSI 0.7

rCSI 2.2%

PRS 39.0%
large pre-B-II cell CL0000957

CSI 0.7

rCSI 2.0%

PRS 42.5%
progenitor cell CL0011026

CSI 0.7

rCSI 1.5%

PRS 36.9%
L2/3 intratelencephalic projecting glutamatergic neuron CL4030059

CSI 0.7

rCSI 1.6%

PRS 20.7%
neural progenitor cell CL0011020

CSI 0.8

rCSI 3.3%

PRS 24.4%
glycinergic amacrine cell CL4030028

CSI 0.8

rCSI 2.0%

PRS 27.5%
central nervous system neuron CL2000029

CSI 0.8

rCSI 5.9%

PRS 17.9%
intermediate monocyte CL0002393

CSI 0.8

rCSI 1.2%

PRS 28.0%
rod bipolar cell CL0000751

CSI 0.8

rCSI 1.5%

PRS 22.8%
basal-myoepithelial cell of mammary gland CL0002324

CSI 0.8

rCSI 1.5%

PRS 52.4%
serotonergic neuron CL0000850

CSI 0.8

rCSI 3.6%

PRS 19.1%
mature B cell CL0000785

CSI 0.8

rCSI 0.7%

PRS 33.9%
innate lymphoid cell CL0001065

CSI 0.8

rCSI 1.7%

PRS 37.6%
contractile cell CL0000183

CSI 0.9

rCSI 2.5%

PRS 26.4%
keratinocyte CL0000312

CSI 0.9

rCSI 0.7%

PRS 31.9%
retinal cone cell CL0000573

CSI 0.9

rCSI 1.4%

PRS 21.1%
central memory CD8-positive, alpha-beta T cell CL0000907

CSI 0.9

rCSI 0.6%

PRS 33.9%
respiratory suprabasal cell CL4033048

CSI 0.9

rCSI 1.2%

PRS 31.3%
dendritic cell, human CL0001056

CSI 0.9

rCSI 1.4%

PRS 32.4%
retinal ganglion cell CL0000740

CSI 0.9

rCSI 2.0%

PRS 19.7%
group 3 innate lymphoid cell CL0001071

CSI 0.9

rCSI 0.7%

PRS 29.2%
enteroendocrine cell of small intestine CL0009006

CSI 0.9

rCSI 2.1%

PRS 40.1%
granulocyte monocyte progenitor cell CL0000557

CSI 1.0

rCSI 0.8%

PRS 30.4%
glutamatergic neuron CL0000679

CSI 1.0

rCSI 2.0%

PRS 25.9%
lung neuroendocrine cell CL1000223

CSI 1.0

rCSI 1.4%

PRS 31.0%
L4 intratelencephalic projecting glutamatergic neuron CL4030063

CSI 1.0

rCSI 2.3%

PRS 19.5%
kidney loop of Henle thin ascending limb epithelial cell CL1001107

CSI 1.0

rCSI 2.5%

PRS 25.1%
pancreatic A cell CL0000171

CSI 1.0

rCSI 1.0%

PRS 29.0%
glial cell CL0000125

CSI 1.0

rCSI 3.9%

PRS 25.2%
intrahepatic cholangiocyte CL0002538

CSI 1.0

rCSI 2.4%

PRS 44.8%
CD14-low, CD16-positive monocyte CL0002396

CSI 1.0

rCSI 0.8%

PRS 25.7%
GABAergic amacrine cell CL4030027

CSI 1.0

rCSI 3.6%

PRS 23.4%
forebrain radial glial cell CL0013000

CSI 1.1

rCSI 3.4%

PRS 36.3%
pancreatic ductal cell CL0002079

CSI 1.1

rCSI 2.1%

PRS 28.2%
retinal pigment epithelial cell CL0002586

CSI 1.1

rCSI 2.2%

PRS 28.3%
lymphoid lineage restricted progenitor cell CL0000838

CSI 1.1

rCSI 4.2%

PRS 43.8%
Langerhans cell CL0000453

CSI 1.1

rCSI 1.7%

PRS 44.9%
acinar cell CL0000622

CSI 1.1

rCSI 1.6%

PRS 35.5%
pancreatic D cell CL0000173

CSI 1.1

rCSI 1.1%

PRS 29.2%
mononuclear phagocyte CL0000113

CSI 1.1

rCSI 2.5%

PRS 30.9%
GABAergic neuron CL0000617

CSI 1.1

rCSI 3.8%

PRS 20.0%
inflammatory macrophage CL0000863

CSI 1.1

rCSI 1.9%

PRS 51.7%
renal beta-intercalated cell CL0002201

CSI 1.1

rCSI 2.7%

PRS 30.3%
mature alpha-beta T cell CL0000791

CSI 1.2

rCSI 4.2%

PRS 44.2%
choroid plexus epithelial cell CL0000706

CSI 1.2

rCSI 1.9%

PRS 21.2%
keratocyte CL0002363

CSI 1.2

rCSI 2.8%

PRS 38.4%
conjunctival epithelial cell CL1000432

CSI 1.2

rCSI 1.8%

PRS 27.5%

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Interaction Source:

Pathway Categories (for ONTOLOGY source):

Baseline Cell Type:

Baseline Cell Context(s): Comma-separated if multiple.

Target Cell Type:

Target Cell Context(s): Comma-separated if multiple.

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Query Gene
Node Color (Target Cell CSI, relative to current network):
- Very High
- High
- Medium
- Low
- Very Low
- CSI N/A
Node Size: Proportional to Target Cell CSI magnitude
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description
Proteins

## Summary [SPOP](/details-gene/8405) (Speckle Type BTB/POZ Protein) is a protein-coding gene located on chromosome 17q21.33. It functions as a substrate-recognition adaptor for a CUL3-RING E3 ubiquitin ligase complex. This complex targets specific proteins for polyubiquitination and subsequent degradation by the proteasome. [SPOP](/details-gene/8405) is localized to nuclear speckles and is implicated in diverse cellular processes, including signal transduction, transcriptional regulation, and DNA replication licensing ([Link](https://doi.org/10.1016/s0014-5793(97)01340-9), [Link](https://doi.org/10.1016/j.bbrc.2023.02.012)). Expression data indicates its significance across a wide range of functionally distinct cell types, including high relevance in immune cells such as [T follicular helper cells](/details-cell/CL0002038), various neuronal subtypes, and fibroblasts, suggesting a fundamental role in protein turnover and cellular homeostasis. Somatic mutations in [SPOP](/details-gene/8405) are associated with several cancers, highlighting its clinical relevance ([153245](https://omim.org/entry/602650)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [SPOP](/details-gene/8405) indicates it is a broadly important but selectively utilized component of the ubiquitin-proteasome system. Its significance is not restricted to a single lineage, but is instead prominent in a diverse set of highly specialized cells, suggesting its regulatory activity is tailored to specific cellular contexts. The highest significance score is observed in [T follicular helper cells](/details-cell/CL0002038) (CSI: 17.17), which is consistent with recent findings that [SPOP](/details-gene/8405) targets the immune transcription factor IRF1 for degradation ([Link](https://doi.org/10.7554/elife.89951)). This suggests a critical role in regulating adaptive immune responses. A similarly high significance is noted in multiple glutamatergic neuron subtypes, including [L6b glutamatergic cortical neurons](/details-cell/CL4023038) (CSI: 16.26) and [near-projecting glutamatergic cortical neurons](/details-cell/CL4023012) (CSI: 13.23), which may relate to its involvement in Hedgehog signaling, a key pathway in neurodevelopment ([Link](https://doi.org/10.1016/j.devcel.2006.05.004)). Furthermore, [SPOP](/details-gene/8405) shows significant expression in structural and progenitor cells, such as [bronchus fibroblasts of lung](/details-cell/CL2000093) (CSI: 14.73) and [transit amplifying cells](/details-cell/CL0009010) (CSI: 12.34). This widespread but potent expression pattern across immune, nervous, and stromal compartments underscores its role as a master regulator of protein stability, essential for the function of disparate cell types. ## Pathways and Molecular Function Functionally, [SPOP](/details-gene/8405) serves as a critical adaptor protein within the [Cul3-ring ubiquitin ligase complex](/details-cell/GO:0031463) ([Link](https://doi.org/10.1038/ncb1056)). Its primary molecular function is to bind specific substrate proteins, facilitating their [protein polyubiquitination](/details-cell/GO:0000209) and targeting them for the [proteasome-mediated ubiquitin-dependent protein catabolic process](/details-cell/GO:0043161). The gene's involvement in major signaling pathways is well-documented. It is a key negative regulator in the [Signaling by hedgehog](/details-cell/R-HSA-5358351) pathway, where it mediates the degradation of the transcription factors Ci/Gli, thereby attenuating the pathway's output ([Link](https://doi.org/10.1242/dev.02370)). This activity is central to its role in development and tissue homeostasis. More recent studies have expanded the repertoire of [SPOP](/details-gene/8405) substrates to include key regulators of immunity and cancer, such as the transcription factor IRF1, the metastasis suppressor BRMS1, and the transcriptional co-repressor Daxx, positioning [SPOP](/details-gene/8405) as a pivotal node in controlling cell fate and function ([Link](https://doi.org/10.7554/elife.89951), [Link](https://doi.org/10.1016/j.bbrc.2011.10.154), [Link](https://doi.org/10.1074/jbc.m600204200)). ## Research Directions The diverse expression profile and expanding list of substrates for [SPOP](/details-gene/8405) present several avenues for future investigation. Its role as a regulator of key transcription factors in disparate cell types suggests it is a critical homeostatic checkpoint. **Proposed Hypotheses:** 1. Given the high CSI of [SPOP](/details-gene/8405) in [T follicular helper cells](/details-cell/CL0002038) and its demonstrated ability to degrade the interferon regulatory factor 1 (IRF1), [SPOP](/details-gene/8405) may act as a crucial negative regulator of Tfh differentiation and function. By controlling IRF1 levels, [SPOP](/details-gene/8405) could fine-tune the transcriptional programs that govern the germinal center reaction. 2. The high significance of [SPOP](/details-gene/8405) in multiple cortical neuron subtypes suggests that its role extends beyond developmental Hedgehog signaling. [SPOP](/details-gene/8405) may be essential for mature neuronal function by mediating the activity-dependent turnover of proteins involved in synaptic plasticity or neurotransmission. **Experimental Approach:** To test the hypothesis regarding the role of [SPOP](/details-gene/8405) in Tfh cells, a conditional knockout mouse model could be generated (e.g., *SPOP*^fl/fl x Cd4-Cre). Following immunization to induce a T-dependent antibody response, Tfh cell differentiation, germinal center formation, and antibody production could be compared between knockout and wild-type mice. In vitro, CD4+ T cells from these mice could be differentiated under Tfh-polarizing conditions, followed by RNA-sequencing and proteomic analysis to identify changes in the Tfh transcriptional network and quantify the stabilization of SPOP substrates like IRF1. **Therapeutic Potential:** [SPOP](/details-gene/8405) is a compelling but challenging therapeutic target. As loss-of-function mutations are common in prostate and endometrial cancers, leading to the accumulation of oncoproteins, a therapeutic strategy would likely involve restoring or enhancing its activity rather than inhibition. The development of molecular glues or specific protein degraders (PROTACs) that leverage the endogenous SPOP-CUL3 E3 ligase machinery to target novel oncoproteins could be a viable strategy. Conversely, in contexts where [SPOP](/details-gene/8405) may degrade tumor suppressors, targeted inhibition could be beneficial, though this would require a deep understanding of its substrate specificity in a given cancer type.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

HIB homolog 1

Genular Protein ID: 2502911978

Symbol: SPOP_HUMAN

Name: HIB homolog 1

UniProtKB Accession Codes:

O43791 B2R6S3 D3DTW7 Q53HJ1

Database IDs:

Citations:

PubMed ID: 9414087

Title: Identification of a novel nuclear speckle-type protein, SPOP.

PubMed ID: 9414087

DOI: 10.1016/s0014-5793(97)01340-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14528312

Title: Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.

PubMed ID: 14528312

DOI: 10.1038/ncb1056

PubMed ID: 15240113

Title: Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP.

PubMed ID: 15240113

DOI: 10.1016/j.bbrc.2004.06.022

PubMed ID: 15897469

Title: Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase.

PubMed ID: 15897469

DOI: 10.1073/pnas.0408918102

PubMed ID: 16651542

Title: Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus.

PubMed ID: 16651542

DOI: 10.1242/dev.02370

PubMed ID: 16740475

Title: A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor.

PubMed ID: 16740475

DOI: 10.1016/j.devcel.2006.05.004

PubMed ID: 16524876

Title: BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase.

PubMed ID: 16524876

DOI: 10.1074/jbc.m600204200

PubMed ID: 22085717

Title: Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex.

PubMed ID: 22085717

DOI: 10.1016/j.bbrc.2011.10.154

PubMed ID: 36791496

Title: SPOP is essential for DNA replication licensing through maintaining translation of CDT1 and CDC6 in HaCaT cells.

PubMed ID: 36791496

DOI: 10.1016/j.bbrc.2023.02.012

PubMed ID: 37622993

Title: SPOP targets the immune transcription factor IRF1 for proteasomal degradation.

PubMed ID: 37622993

DOI: 10.7554/elife.89951

PubMed ID: 37796126

Title: Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease.

PubMed ID: 37796126

DOI: 10.1128/jvi.00786-23

PubMed ID: 38018242

Title: SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1alpha.

PubMed ID: 38018242

DOI: 10.1002/jmv.29254

PubMed ID: 19818708

Title: Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.

PubMed ID: 19818708

DOI: 10.1016/j.molcel.2009.09.022

PubMed ID: 22632832

Title: Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase.

PubMed ID: 22632832

DOI: 10.1016/j.str.2012.04.009

PubMed ID: 32109420

Title: De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders.

PubMed ID: 32109420

DOI: 10.1016/j.ajhg.2020.02.001

Sequence Information:

Length: 374
Mass: 42132
Checksum: EE5F4C5CF6FD09DC
Sequence:

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

Details for: SPOP

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Identification of a novel nuclear speckle-type protein, SPOP. PubMed ID: 9414087

Complete sequencing and characterization of 21,243 full-length human cDNAs. PubMed ID: 14702039

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. PubMed ID: 14528312

Daxx-mediated transcriptional repression of MMP1 gene is reversed by SPOP. PubMed ID: 15240113

Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase. PubMed ID: 15897469

Roadkill attenuates Hedgehog responses through degradation of Cubitus interruptus. PubMed ID: 16651542

A hedgehog-induced BTB protein modulates hedgehog signaling by degrading Ci/Gli transcription factor. PubMed ID: 16740475

BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase. PubMed ID: 16524876

Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex. PubMed ID: 22085717

SPOP is essential for DNA replication licensing through maintaining translation of CDT1 and CDC6 in HaCaT cells. PubMed ID: 36791496

SPOP targets the immune transcription factor IRF1 for proteasomal degradation. PubMed ID: 37622993

Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease. PubMed ID: 37796126

SPOP inhibits HBV transcription and replication by ubiquitination and degradation of HNF1alpha. PubMed ID: 38018242

Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. PubMed ID: 19818708

Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase. PubMed ID: 22632832

De Novo Variants in SPOP Cause Two Clinically Distinct Neurodevelopmental Disorders. PubMed ID: 32109420