Detail Information for IndEnz0002001767
IED ID IndEnz0002001767
Enzyme Type ID protease001767
Protein Name Signal peptide peptidase-like 2B
SPP-like 2B
SPPL2b
EC 3.4.23.-
Intramembrane protease 4
IMP-4
Presenilin homologous protein 4
PSH4
Presenilin-like protein 1
Gene Name SPPL2B IMP4 KIAA1532 PSL1
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MAAAVAAALARLLAAFLLLAAQVACEYGMVHVVSQAGGPEGKDYCILYNPQWAHLPHDLSKASFLQLRNWTASLLCSAADLPARGFSNQIPLVARGNCTFYEKVRLAQGSGARGLLIVSRERLVPPGGNKTQYDEIGIPVALLSYKDMLDIFTRFGRTVRAALYAPKEPVLDYNMVIIFIMAVGTVAIGGYWAGSRDVKKRYMKHKRDDGPEKQEDEAVDVTPVMTCVFVVMCCSMLVLLYYFYDLLVYVVIGIFCLASATGLYSCLAPCVRRLPFGKCRIPNNSLPYFHKRPQARMLLLALFCVAVSVVWGVFRNEDQWAWVLQDALGIAFCLYMLKTIRLPTFKACTLLLLVLFLYDIFFVFITPFLTKSGSSIMVEVATGPSDSATREKLPMVLKVPRLNSSPLALCDRPFSLLGFGDILVPGLLVAYCHRFDIQVQSSRVYFVACTIAYGVGLLVTFVALALMQRGQPALLYLVPCTLVTSCAVALWRRELGVFWTGSGFAKVLPPSPWAPAPADGPQPPKDSATPLSPQPPSEEPATSPWPAEQSPKSRTSEEMGAGAPMREPGSPAESEGRDQAQPSPVTQPGASA
Enzyme Length 592
Uniprot Accession Number Q8TCT7
Absorption
Active Site ACT_SITE 359; /evidence=ECO:0000250|UniProtKB:P49810; ACT_SITE 421; /evidence=ECO:0000250|UniProtKB:P49810
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number 3.4.23.-
Enzyme Function FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17965014, PubMed:19114711, PubMed:22194595). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952, PubMed:16829951). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus processed leader peptide gp18 of the envelope glycoprotein gp130 dependently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). {ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:22194595, ECO:0000269|PubMed:23132852}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (2); Alternative sequence (3); Chain (1); Compositional bias (2); Domain (1); Erroneous gene model prediction (1); Erroneous initiation (2); Erroneous translation (1); Glycosylation (2); Motif (1); Mutagenesis (1); Natural variant (1); Region (1); Sequence caution (1); Signal peptide (1); Topological domain (10); Transmembrane (9)
Keywords Alternative splicing;Cell membrane;Endosome;Glycoprotein;Golgi apparatus;Hydrolase;Lysosome;Membrane;Protease;Reference proteome;Signal;Transmembrane;Transmembrane helix
Interact With Q8WUW1; Q01658; P29692-2; Q06787-7; Q00403; Q9Y5Q9; P04792; O60333-2; O60260-5; P60891; Q9Y3C5; P37840
Induction
Subcellular Location SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16829952}; Multi-pass membrane protein {ECO:0000305}. Golgi apparatus membrane {ECO:0000269|PubMed:17965014}; Multi-pass membrane protein {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein {ECO:0000305}. Endosome membrane {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}. Note=targeted through the entire secretory pathway to endosomes/lysosomes (PubMed:15998642). {ECO:0000269|PubMed:15998642}.
Modified Residue
Post Translational Modification PTM: Glycosylated (PubMed:15385547, PubMed:15998642). {ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:15998642}.
Signal Peptide SIGNAL 1..25; /evidence=ECO:0000269|PubMed:15385547
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 18768471; 20711500; 23384347; 30819724;
Motif MOTIF 472..474; /note=PAL
Gene Encoded By
Mass 64,644
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda