SPPL3
entrez
121665
canonical
uniprot
Q8TCT6
canonical
ensembl
ENSG00000157837
resolver
ensp
ENSP00000288680
resolver
genesymbol
SPPL3
resolver
genesymbol_syn
IMP2
resolver
genesymbol_syn
PSL4
resolver
hgnc
HGNC:30424
resolver
uniprot
Q3MJ04
resolver
uniprot
Q8TAU4
resolver
uniprot
Q96DD9
resolver
uniprot_entry
SPPL3_HUMAN
resolver
uniprot_sec
Q3MJ04
resolver
uniprot_sec
Q8TAU4
resolver
uniprot_sec
Q96DD9
resolver
activity_regulation
ACTIVITY REGULATION: Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575 (PubMed:16873890). However, is not inhibited by ZLL and LY411,575 for activity on simian foamy virus envelope glycoprotein gp130 (PubMed:23132852). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852}.
uniprot
proteins
amino_acid_sequence
MAEQTYSWAYSLVDSSQVSTFLISILLIVYGSFRSLNMDFENQDKEKDSNSSSGSFNGNSTNNSIQTIDSTQALFLPIGASVSLLVMFFFFDSVQVVFTICTAVLATIAFAFLLLPMCQYLTRPCSPQNKISFGCCGRFTAAELLSFSLSVMLVLIWVLTGHWLLMDALAMGLCVAMIAFVRLPSLKVSCLLLSGLLIYDVFWVFFSAYIFNSNVMVKVATQPADNPLDVLSRKLHLGPNVGRDVPRLSLPGKLVFPSSTGSHFSMLGIGDIVMPGLLLCFVLRYDNYKKQASGDSCGAPGPANISGRMQKVSYFHCTLIGYFVGLLTATVASRIHRAAQPALLYLVPFTLLPLLTMAYLKGDLRRMWSEPFHSKSSSSRFLEV
uniprot
proteins
ec_number
3.4.23.-
uniprot
proteins
function
FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries (PubMed:16873890, PubMed:25354954, PubMed:25827571). Acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, PubMed:25827571). Catalyzes the intramembrane cleavage of the envelope glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy virus independent of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852). May also have the ability to serve as a shedding protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B of the envelope glycoprotein gp130 (PubMed:23132852). Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner (PubMed:25384971). {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954, ECO:0000269|PubMed:25384971, ECO:0000269|PubMed:25827571}.
uniprot
proteins
mass_dalton
42261
uniprot
proteins
mutagenesis
MUTAGEN 200; /note="D->A: Does not affect complex glycosylation pattern of cellular glycoproteins; when associated with A-271."; /evidence="ECO:0000269|PubMed:25354954"; MUTAGEN 271; /note="D->A: Loss of intramembrane-cleaving activity toward the simian foamy virus envelope glycoprotein gp130. Does not affect complex glycosylation pattern of cellular glycoproteins; when associated with A-200."; /evidence="ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954
uniprot
proteins
post_translational_modification
PTM: Not glycosylated (PubMed:15385547, PubMed:15998642). {ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:15998642}.
uniprot
proteins
protein_family
Peptidase A22B family
uniprot
proteins
pubmed
11978763
uniprot
proteins
pubmed
12077416
uniprot
proteins
pubmed
12139484
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15385547
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15998642
uniprot
proteins
pubmed
16829952
uniprot
proteins
pubmed
16873890
uniprot
proteins
pubmed
23132852
uniprot
proteins
pubmed
25354954
uniprot
proteins
pubmed
25384971
uniprot
proteins
pubmed
25827571
uniprot
proteins
sequence_length
384
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein {ECO:0000305}. Golgi apparatus {ECO:0000269|PubMed:16829952}. Membrane {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}.
uniprot
proteins
transmembrane_region
TRANSMEM 9..29; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 75..95; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 98..118; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 137..159; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 165..185; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 191..211; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 263..283; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 312..332; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 340..360; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins