GPS2
entrez
2874
canonical
uniprot
Q13227
canonical
ensembl
ENSG00000132522
resolver
ensembl
ENSG00000288325
resolver
ensp
ENSP00000370104
resolver
genesymbol
GPS2
resolver
hgnc
HGNC:4550
resolver
uniprot
B4DXA1
resolver
uniprot
Q6FHM8
resolver
uniprot_entry
GPS2_HUMAN
resolver
uniprot_sec
B4DXA1
resolver
uniprot_sec
Q6FHM8
resolver
amino_acid_sequence
MPALLERPKLSNAMARALHRHIMMERERKRQEEEEVDKMMEQKMKEEQERRKKKEMEERMSLEETKEQILKLEEKLLALQEEKHQLFLQLKKVLHEEEKRRRKEQSDLTTLTSAAYQQSLTVHTGTHLLSMQGSPGGHNRPGTLMAADRAKQMFGPQVLTTRHYVGSAAAFAGTPEHGQFQGSPGGAYGTAQPPPHYGPTQPAYSPSQQLRAPSAFPAVQYLSQPQPQPYAVHGHFQPTQTGFLQPGGALSLQKQMEHANQQTGFSDSSSLRPMHPQALHPAPGLLASPQLPVQMQPAGKSGFAATSQPGPRLPFIQHSQNPRFYHK
uniprot
proteins
function
FUNCTION: Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:24943844). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation (By similarity). Promotes cholesterol efflux by acting as a transcription coactivator (PubMed:19481530). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways (By similarity). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (PubMed:20159957). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (By similarity). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF pathway; acts by repressing UBE2N/Ubc13 activity (By similarity). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (By similarity). Able to suppress G protein- and mitogen-activated protein kinase-mediated signal transduction (PubMed:8943324). Acts as a tumor-suppressor in liposarcoma (PubMed:27460081). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:19858209, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:27460081, ECO:0000269|PubMed:29499132, ECO:0000269|PubMed:8943324}.; FUNCTION: (Microbial infection) Required for efficient replication of hepatitis C virus (HCV) by promoting the interaction between VAPA and HCV virus protein NS5A. {ECO:0000269|PubMed:24223774}.
uniprot
proteins
mass_dalton
36689
uniprot
proteins
mutagenesis
MUTAGEN 19..22; /note="HRHI->AEHA: Abolishes interaction with TBL1X."; /evidence="ECO:0000269|PubMed:21240272"; MUTAGEN 45; /note="K->R: Abolishes sumoylation; when associated with R-71."; /evidence="ECO:0000269|PubMed:24943844"; MUTAGEN 61..94; /note="Missing: Abolishes interaction with sumoylated NR1H2 and NR5A2 proteins."; /evidence="ECO:0000269|PubMed:20159957"; MUTAGEN 69..70; /note="IL->AA: Weakly affects interaction with sumoylated NR1H2 and NR5A2 proteins."; /evidence="ECO:0000269|PubMed:20159957"; MUTAGEN 71; /note="K->R: Abolishes sumoylation; when associated with R-45."; /evidence="ECO:0000269|PubMed:24943844"; MUTAGEN 76..79; /note="LLAL->RRAR: Weakly affects interaction with sumoylated NR1H2 and NR5A2 proteins."; /evidence="ECO:0000269|PubMed:20159957"; MUTAGEN 86..90; /note="LFLQL->RFRQR: Weakly affects interaction with sumoylated NR1H2 and NR5A2 proteins."; /evidence="ECO:0000269|PubMed:20159957"; MUTAGEN 319; /note="S->A: Does not affect methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 320; /note="Q->A: Does not affect methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 321; /note="N->A: Strongly decreases methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 322; /note="P->A: Strongly decreases methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 324; /note="F->A: Abolishes methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 325; /note="Y->A: Abolishes methylation."; /evidence="ECO:0000269|PubMed:19917673"; MUTAGEN 327; /note="K->A: Decreases methylation."; /evidence="ECO:0000269|PubMed:19917673
uniprot
proteins
post_translational_modification
PTM: Sumoylation regulates its subcellular location (PubMed:24943844). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (PubMed:24943844). Sumoylation at Lys-71 is required for interaction with TBL1X (By similarity). Sumoylated at Lys-45 and Lys-71 in mitochondrion (By similarity). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (By similarity). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:24943844}.; PTM: Ubiquitinated at the C-terminus by SIAH2; leading to its degradation by the proteasome. Interaction with TBL1X and methylation at Arg-323 protect GPS2 against ubiquitination and degradation. {ECO:0000250|UniProtKB:Q921N8}.; PTM: Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323 protects from degradation by the proteasome. {ECO:0000250|UniProtKB:Q921N8}.
uniprot
proteins
pubmed
11931768
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19481530
uniprot
proteins
pubmed
19858209
uniprot
proteins
pubmed
19917673
uniprot
proteins
pubmed
20159957
uniprot
proteins
pubmed
21240272
uniprot
proteins
pubmed
22666460
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24223774
uniprot
proteins
pubmed
24943844
uniprot
proteins
pubmed
27270589
uniprot
proteins
pubmed
27460081
uniprot
proteins
pubmed
29499132
uniprot
proteins
pubmed
8943324
uniprot
proteins
sequence_length
327
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19858209, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:29499132}. Mitochondrion {ECO:0000269|PubMed:29499132}. Cytoplasm, cytosol {ECO:0000269|PubMed:24223774, ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:29499132}. Note=Sumoylation regulates the subcellular location (PubMed:24943844). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (By similarity). {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:24943844}.
uniprot
proteins