P63165

EV
Gene name
SUMO1 (SMT3C, SMT3H3, UBL1, OK/SW-cl.43)
Protein name
Small ubiquitin-related modifier 1
Names
SUMO-1, GAP-modifying protein 1, GMP1, SMT3 homolog 3, Sentrin, Ubiquitin-homology domain protein PIC1, Ubiquitin-like protein SMT3C, Smt3C, Ubiquitin-like protein UBL1
Species
Homo sapiens (Human)
KEGG Pathway
hsa:7341
EC number
Protein Class
SMALL UBIQUITIN-RELATED MODIFIER (PTHR10562)

Descriptions

The N-terminal region of SUMO1 functions as an autoinhibition domain by blocking its binding to the phosphorylated SIMs of PML and Daxx. This autoinhibition is relieved by zinc, which stabilizes the complex between SUMO1 and a phospho-mimetic form of the SIM of PML, suggesting a paralog specific function of SUMO1 in regulating SUMO1-SIM interactions required for PML-NB formation and function.

Autoinhibitory domains (AIDs)

17-97 (N-terminal region) EV

Target domain

20-97 (Ubiquitin-like domain)

Relief mechanism

Ligand binding

Assay

Deletion assay, Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

61 structures for P63165

Entry ID Method Resolution Chain Position Source
1A5R NMR - A 1-101 PDB
1TGZ X-ray 280 A B 18-97 PDB
1WYW X-ray 210 A B 1-97 PDB
1Y8R X-ray 275 A C/F 1-97 PDB
1Z5S X-ray 301 A B 18-97 PDB
2ASQ NMR - A 1-97 PDB
2BF8 X-ray 230 A B 21-97 PDB
2G4D X-ray 280 A B/D 20-97 PDB
2IO2 X-ray 290 A B 18-97 PDB
2IY0 X-ray 277 A B 20-101 PDB
2IY1 X-ray 246 A B/D 20-101 PDB
2KQS NMR - A 1-97 PDB
2LAS NMR - A 1-101 PDB
2MW5 NMR - A 1-97 PDB
2N1A NMR - A 1-101 PDB
2N1V NMR - A 1-97 PDB
2PE6 X-ray 240 A B 1-97 PDB
2UYZ X-ray 140 A B 20-97 PDB
2VRR X-ray 222 A B 20-97 PDB
3KYC X-ray 245 A D 1-97 PDB
3KYD X-ray 261 A D 1-94 PDB
3RZW X-ray 215 A C/D 1-97 PDB
3UIP X-ray 229 A B 18-97 PDB
4WJN X-ray 150 A A 17-97 PDB
4WJO X-ray 146 A A 17-97 PDB
4WJP X-ray 170 A A/C 17-97 PDB
4WJQ X-ray 135 A A/C 17-97 PDB
5AEK X-ray 300 A B/D/F/H/J/L/N/P/R/T/V/X 20-97 PDB
5B7A NMR - A 1-97 PDB
5ELJ X-ray 198 A B 18-97 PDB
5GHD NMR - A 1-97 PDB
6EOP X-ray 240 A D/E/F 61-68 PDB
6EOT X-ray 350 A C/E/F/H/J/L 61-68 PDB
6J4I NMR - A 1-97 PDB
6JXU NMR - A 1-101 PDB
6JXV NMR - A 1-101 PDB
6K5T NMR - A 21-97 PDB
6TRW X-ray 300 A D/E/F 61-75 PDB
6UYO X-ray 164 A A/C 17-97 PDB
6UYP X-ray 142 A A 17-97 PDB
6UYQ X-ray 150 A A 17-97 PDB
6UYR X-ray 130 A A 17-97 PDB
6UYS X-ray 159 A A/C 17-97 PDB
6UYT X-ray 166 A A 17-97 PDB
6UYU X-ray 166 A A/C 17-97 PDB
6UYV X-ray 140 A A 17-97 PDB
6UYX X-ray 170 A A/C 17-97 PDB
6UYY X-ray 160 A A 17-97 PDB
6UYZ X-ray 140 A A/C 17-97 PDB
6V7P X-ray 140 A A/C 17-97 PDB
6V7Q X-ray 135 A A/C 17-97 PDB
6V7R X-ray 155 A A/C 17-97 PDB
6V7S X-ray 147 A A/C 17-97 PDB
6WW3 X-ray 210 A A/B 2-7 PDB
6XOG X-ray 198 A C 1-101 PDB
6XOH X-ray 223 A C 1-101 PDB
6XOI X-ray 200 A C 1-101 PDB
8DJH X-ray 177 A A 2-97 PDB
8DJI X-ray 197 A A 2-97 PDB
8ODR X-ray 285 A B 18-97 PDB
AF-P63165-F1 Predicted AlphaFoldDB

46 variants for P63165

Variant ID(s) Position Change Description Diseaes Association Provenance
rs142025459 2 S>C No ESP
ExAC
TOPMed
gnomAD
rs1360385299 3 D>A No gnomAD
rs1183133930 3 D>E No TOPMed
rs1246545175 4 Q>H No TOPMed
TCGA novel 5 E>R Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs865944351 6 A>T No Ensembl
rs1466085744 6 A>V No gnomAD
TCGA novel 7 K>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs762396174 7 K>Q No ExAC
gnomAD
rs1258744066 8 P>L No gnomAD
COSM4833179 9 S>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
TCGA novel 15 D>I Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
COSM1134537 16 K>N Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs769332103 19 G>D No ExAC
gnomAD
rs769332103 19 G>V No ExAC
gnomAD
rs1279066314
COSM4583094
 20 E>D Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No gnomAD
NCI-TCGA Cosmic
rs952329386 23 K>T No TOPMed
TCGA novel 26 V>A Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs998380889 27 I>L No Ensembl
rs1286710471 28 G>R No gnomAD
COSM1134536 30 D>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs139098088 41 T>I No ESP
TOPMed
rs1235297281 45 K>E No gnomAD
TCGA novel 49 E>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
COSM1482659 50 S>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs759040827 55 Q>E No ExAC
gnomAD
COSM5917805 56 G>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1293611839 57 V>I No gnomAD
COSM3576399 58 P>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs757518063 59 M>L No ExAC
TOPMed
gnomAD
rs757518063 59 M>V No ExAC
TOPMed
gnomAD
rs751409542 62 L>F No ExAC
gnomAD
rs1559240018 62 L>P No Ensembl
TCGA novel 70 R>I Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs758112346 75 H>R No ExAC
gnomAD
COSM1591707 79 E>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
TCGA novel 81 G>E Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs753349557 82 M>V No ExAC
gnomAD
TCGA novel 84 E>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs1384477352 85 E>D No gnomAD
rs765931862 92 Q>P No ExAC
TOPMed
gnomAD
rs1320311472 95 T>M No gnomAD
rs1163101525 97 G>D No gnomAD
rs767056612 100 T>A No ExAC
gnomAD
rs1373778471 100 T>I No gnomAD
rs763400377 102 V>Q No ExAC
gnomAD

3 associated diseases with P63165

[MIM: 211600]: Cholestasis, progressive familial intrahepatic, 1 (PFIC1)

A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC1 inheritance is autosomal recessive. {ECO:0000269|PubMed:11093741, ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:20038848, ECO:0000269|PubMed:23197899, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:9500542}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 243300]: Cholestasis, benign recurrent intrahepatic, 1 (BRIC1)

A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. {ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:9500542, ECO:0000269|PubMed:9918928}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 147480]: Cholestasis of pregnancy, intrahepatic 1 (ICP1)

A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP1 causes fetal distress, spontaneous premature delivery and intrauterine death. ICP1 patients have spontaneous and progressive disappearance of cholestasis after delivery. {ECO:0000269|PubMed:15657619, ECO:0000269|PubMed:15888793, ECO:0000269|PubMed:19731236}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Without disease ID
  • A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC1 inheritance is autosomal recessive. {ECO:0000269|PubMed:11093741, ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:20038848, ECO:0000269|PubMed:23197899, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:9500542}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. {ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:9500542, ECO:0000269|PubMed:9918928}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP1 causes fetal distress, spontaneous premature delivery and intrauterine death. ICP1 patients have spontaneous and progressive disappearance of cholestasis after delivery. {ECO:0000269|PubMed:15657619, ECO:0000269|PubMed:15888793, ECO:0000269|PubMed:19731236}. Note=The disease may be caused by variants affecting the gene represented in this entry.

4 regional properties for P63165

Type Name Position InterPro Accession
ptm P-type ATPase, phosphorylation site 454 - 460 IPR018303
domain P-type ATPase, C-terminal 919 - 1173 IPR032630
domain P-type ATPase, N-terminal 66 - 145 IPR032631
domain P-type ATPase, haloacid dehalogenase domain 436 - 942 IPR044492

Functions

Description
EC Number
Subcellular Localization
  • Nucleus membrane
  • Nucleus speckle
  • Cytoplasm
  • Nucleus, PML body
  • Cell membrane
  • Nucleus
  • Recruited by BCL11A into the nuclear body (By similarity)
  • In the presence of ZFHX3, sequesterd to nuclear body (NB)-like dots in the nucleus some of which overlap or closely associate with PML body (PubMed:24651376)
PANTHER Family PTHR10562 SMALL UBIQUITIN-RELATED MODIFIER
PANTHER Subfamily PTHR10562:SF14 SMALL UBIQUITIN-RELATED MODIFIER 1
PANTHER Protein Class
PANTHER Pathway Category p53 pathway
Sumo-1 ligase

11 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nuclear body Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins.
nuclear membrane Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space.
nuclear pore A protein complex providing a discrete opening in the nuclear envelope of a eukaryotic cell, where the inner and outer nuclear membranes are joined.
nuclear speck A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
nuclear stress granule A dense aggregation in the nucleus composed of proteins and RNAs that appear when the cell is under stress.
nucleolus A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
PML body A class of nuclear body; they react against SP100 auto-antibodies (PML, promyelocytic leukemia); cells typically contain 10-30 PML bodies per nucleus; alterations in the localization of PML bodies occurs after viral infection.

9 GO annotations of molecular function

Name Definition
enzyme binding Binding to an enzyme, a protein with catalytic activity.
potassium channel regulator activity Binds to and modulates the activity of a potassium channel.
protein tag activity A molecular function exhibited by a protein that is covalently attached (AKA tagged or conjugated) to another protein where it acts as a marker, recognized by the cellular apparatus to target the tagged protein for some cellular process such as modification, sequestration, transport or degradation.
RNA binding Binding to an RNA molecule or a portion thereof.
small protein activating enzyme binding Binding to a small protein activating enzyme, such as ubiquitin-activating enzyme.
transcription factor binding Binding to a transcription factor, a protein required to initiate or regulate transcription.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
ubiquitin-like protein ligase binding Binding to a ubiquitin-like protein ligase, such as ubiquitin-ligase.
ubiquitin-specific protease binding Binding to a ubiquitin-specific protease.

16 GO annotations of biological process

Name Definition
cellular response to cadmium ion Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus.
cellular response to heat Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a heat stimulus, a temperature stimulus above the optimal temperature for that organism.
DNA repair The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
negative regulation of action potential Any process that stops, prevents, or reduces the frequency, rate or extent of action potential creation, propagation or termination. This typically occurs via modulation of the activity or expression of voltage-gated ion channels.
negative regulation of delayed rectifier potassium channel activity Any process that stops, prevents or reduces the frequency, rate or extent of delayed rectifier potassium channel activity.
negative regulation of DNA binding Any process that stops or reduces the frequency, rate or extent of DNA binding. DNA binding is any process in which a gene product interacts selectively with DNA (deoxyribonucleic acid).
negative regulation of DNA-binding transcription factor activity Any process that stops, prevents, or reduces the frequency, rate or extent of the activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
negative regulation of protein import into nucleus Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus.
negative regulation of transcription by transcription factor localization Any process that stops, prevents, or reduces the frequency, rate or extent of DNA-dependent transcription using a mechanism that involves the localization of a transcription factor.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of protein-containing complex assembly Any process that activates or increases the frequency, rate or extent of protein complex assembly.
protein stabilization Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
protein sumoylation The process in which a SUMO protein (small ubiquitin-related modifier) is conjugated to a target protein via an isopeptide bond between the carboxy-terminus of SUMO with an epsilon-amino group of a lysine residue of the target protein.
regulation of protein localization Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location.
roof of mouth development The biological process whose specific outcome is the progression of the roof of the mouth from an initial condition to its mature state. This process begins with the formation of the structure and ends with the mature structure. The roof of the mouth is the partition that separates the nasal and oral cavities.

34 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q12306 SMT3 Ubiquitin-like protein SMT3 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
Q17QV3 SUMO3 Small ubiquitin-related modifier 3 Bos taurus (Bovine) SS
Q5E9D1 SUMO1 Small ubiquitin-related modifier 1 Bos taurus (Bovine) SS
Q5ZHQ1 SUMO3 Small ubiquitin-related modifier 3 Gallus gallus (Chicken) SS
Q5ZJM9 SUMO2 Small ubiquitin-related modifier 2 Gallus gallus (Chicken) SS
Q8QGH2 SUMO1 Small ubiquitin-related modifier 1 Gallus gallus (Chicken) SS
Q9VCP1 CG4449 Uncharacterized protein CG4449 Drosophila melanogaster (Fruit fly) PR
P61956 SUMO2 Small ubiquitin-related modifier 2 Homo sapiens (Human) SS
Q6EEV6 SUMO4 Small ubiquitin-related modifier 4 Homo sapiens (Human) SS
P55854 SUMO3 Small ubiquitin-related modifier 3 Homo sapiens (Human) SS
G2XKQ0 SUMO1P1 Small ubiquitin-related modifier 5 Homo sapiens (Human) SS
P61957 Sumo2 Small ubiquitin-related modifier 2 Mus musculus (Mouse) SS
Q9Z172 Sumo3 Small ubiquitin-related modifier 3 Mus musculus (Mouse) SS
P63166 Sumo1 Small ubiquitin-related modifier 1 Mus musculus (Mouse) SS
P61958 SUMO2 Small ubiquitin-related modifier 2 Sus scrofa (Pig) SS
A7WLH8 SUMO1 Small ubiquitin-related modifier 1 Sus scrofa (Pig) SS
P61959 Sumo2 Small ubiquitin-related modifier 2 Rattus norvegicus (Rat) SS
Q5XIF4 Sumo3 Small ubiquitin-related modifier 3 Rattus norvegicus (Rat) SS
Q5I0H3 Sumo1 Small ubiquitin-related modifier 1 Rattus norvegicus (Rat) SS
P55857 SUMO1 Small ubiquitin-related modifier 1 Oryza sativa subsp. japonica (Rice) SS
P55853 smo-1 Small ubiquitin-related modifier Caenorhabditis elegans SS
Q9FKC5 SUMO4 Putative small ubiquitin-related modifier 4 Arabidopsis thaliana (Mouse-ear cress) SS
Q9FLP5 SUMO3 Small ubiquitin-related modifier 3 Arabidopsis thaliana (Mouse-ear cress) SS
P55852 SUMO1 Small ubiquitin-related modifier 1 Arabidopsis thaliana (Mouse-ear cress) SS
Q8VZI7 SUMO5 Small ubiquitin-related modifier 5 Arabidopsis thaliana (Mouse-ear cress) SS
B3H5R8 SUMO8 Putative small ubiquitin-related modifier 8 Arabidopsis thaliana (Mouse-ear cress) SS
Q3E8A8 SUMO7 Putative small ubiquitin-related modifier 7 Arabidopsis thaliana (Mouse-ear cress) SS
Q9FLP6 SUMO2 Small ubiquitin-related modifier 2 Arabidopsis thaliana (Mouse-ear cress) SS
Q28H04 sumo2 Small ubiquitin-related modifier 2 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q6DEP7 sumo1 Small ubiquitin-related modifier 1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q6DI05 sumo3 Small ubiquitin-related modifier 3 Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6DHL4 sumo2 Small ubiquitin-related modifier 2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6NV25 sumo3l Small ubiquitin-related modifier 3-like Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q7SZR5 sumo1 Small ubiquitin-related modifier 1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MSDQEAKPST EDLGDKKEGE YIKLKVIGQD SSEIHFKVKM TTHLKKLKES YCQRQGVPMN
70 80 90 100
SLRFLFEGQR IADNHTPKEL GMEEEDVIEV YQEQTGGHST V