UniProt:O43462 MBTPS2

chain
  • chain:1-519
checksum 247D69E0FD7747BD
comment
  • FUNCTION Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:10805775, PubMed:11163209). Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached (PubMed:10805775, PubMed:27380894, PubMed:9659902). Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription (PubMed:10805775, PubMed:27380894, PubMed:9659902). Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:11163209). Involved in intramembrane proteolysis during bone formation (PubMed:27380894). In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the second step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression (PubMed:16417584).CATALYTIC ACTIVITY Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The residues Asn-Pro, 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.COFACTOR Binds 1 zinc ion per subunit.SUBCELLULAR LOCATION Expressed in heart, brain, placenta, lung, liver, muscle, kidney and pancreas.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the peptidase M50A family.
crossReference
databaseName UniProt
dbId 59577
description
  • recommendedName: fullName evidence="15"Membrane-bound transcription factor site-2 protease ecNumber evidence="4 5"3.4.24.85 alternativeName: fullName evidence="14"Endopeptidase S2P alternativeName: fullName evidence="14"Sterol regulatory element-binding proteins intramembrane protease shortName evidence="14"SREBPs intramembrane protease
displayName UniProt:O43462 MBTPS2
geneName
  • MBTPS2
  • S2P
identifier O43462
isSequenceChanged false
keyword
  • Cholesterol metabolism
  • Cytoplasm
  • Disease variant
  • Glycoprotein
  • Golgi apparatus
  • Hydrolase
  • Ichthyosis
  • Lipid metabolism
  • Membrane
  • Metal-binding
  • Metalloprotease
  • Osteogenesis imperfecta
  • Palmoplantar keratoderma
  • Protease
  • Proteomics identification
  • Reference proteome
  • Steroid metabolism
  • Sterol metabolism
  • Transmembrane
  • Transmembrane helix
  • Zinc
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • MBTPS2
otherIdentifier
  • 11723207_at
  • 11723208_a_at
  • 11737447_at
  • 1554604_PM_at
  • 1554604_at
  • 17102017
  • 17102032
  • 206473_PM_at
  • 206473_at
  • 216531_PM_at
  • 216531_at
  • 226760_PM_at
  • 226760_at
  • 31416_at
  • 3971330
  • 3971331
  • 3971332
  • 3971333
  • 3971335
  • 3971336
  • 3971338
  • 3971339
  • 3971342
  • 3971343
  • 3971344
  • 3971345
  • 3971347
  • 3971348
  • 3971349
  • 3971350
  • 3971351
  • 3971352
  • 3971353
  • 3971354
  • 3971355
  • 3971356
  • 3971357
  • 3971359
  • 3971360
  • 3971361
  • 3971368
  • 3971369
  • 3971370
  • 3971371
  • 3971372
  • 3971373
  • 3971374
  • 3971375
  • 44012_at
  • 51360
  • 62564_at
  • 8166382
  • 8166398
  • 91300_at
  • A_14_P110364
  • A_14_P202437
  • A_23_P114095
  • A_24_P213856
  • A_33_P3283237
  • GE54155
  • GE88614
  • GO:0000139
  • GO:0004222
  • GO:0005515
  • GO:0005737
  • GO:0005794
  • GO:0006355
  • GO:0006508
  • GO:0006607
  • GO:0006629
  • GO:0006886
  • GO:0006913
  • GO:0007095
  • GO:0008202
  • GO:0008203
  • GO:0008233
  • GO:0008237
  • GO:0012505
  • GO:0016020
  • GO:0016787
  • GO:0030968
  • GO:0031293
  • GO:0034976
  • GO:0036500
  • GO:0045540
  • GO:0045542
  • GO:0045944
  • GO:0046872
  • GO:0051604
  • GO:0070977
  • GO:0140537
  • GO:1905897
  • HMNXSV003011431
  • HMNXSV003054083
  • Hs.297007.1.A1_3p_at
  • Hs.297007.1.A1_3p_x_at
  • Hs.302065.0.S1_3p_at
  • Hs2.350970.2.S1_3p_at
  • ILMN_1798311
  • ILMN_1814994
  • ILMN_1860288
  • PH_hs_0024887
  • PH_hs_0036200
  • PH_hs_0039207
  • TC0X000098.hg
  • TC0X001618.hg
  • g7706692_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • MBTP2_HUMAN
  • Q9UM70
  • Q9UMD3
sequenceLength 519
species [Species:48887] Homo sapiens
stId uniprot:O43462
url http://purl.uniprot.org/uniprot/O43462
Cite Us!