ID SPP2B_HUMAN Reviewed; 592 AA. AC Q8TCT7; D6W609; O60365; Q567S3; Q8IUH9; Q9BUY6; Q9H3M4; Q9NPN2; Q9P1Z6; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2006, sequence version 2. DT 24-JAN-2024, entry version 179. DE RecName: Full=Signal peptide peptidase-like 2B {ECO:0000303|PubMed:15385547, ECO:0000312|HGNC:HGNC:30627}; DE Short=SPP-like 2B {ECO:0000303|PubMed:15385547}; DE Short=SPPL2b {ECO:0000303|PubMed:15385547}; DE EC=3.4.23.-; DE AltName: Full=Intramembrane protease 4 {ECO:0000303|PubMed:12139484}; DE Short=IMP-4 {ECO:0000303|PubMed:12139484}; DE AltName: Full=Presenilin homologous protein 4; DE Short=PSH4; DE AltName: Full=Presenilin-like protein 1; DE Flags: Precursor; GN Name=SPPL2B {ECO:0000303|PubMed:15385547, GN ECO:0000312|HGNC:HGNC:30627}; GN Synonyms=IMP4 {ECO:0000303|PubMed:12139484}, KIAA1532, PSL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Irmler M., Tomiuk S., Korner M.R., Hofmann K., Conradt M.; RT "Characterization of a new protein family with homology to presenilins."; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Martoglio B.; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Blood; RX PubMed=12139484; DOI=10.1023/a:1016365227942; RA Grigorenko A.P., Moliaka Y.K., Korovaitseva G.I., Rogaev E.I.; RT "Novel class of polytopic proteins with domains associated with putative RT protease activity."; RL Biochemistry (Mosc.) 67:826-834(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4). RC TISSUE=Brain, Eye, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 201-279 (ISOFORM 1). RG The European IMAGE consortium; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [9] RP GLYCOSYLATION, TOPOLOGY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15385547; DOI=10.1074/jbc.m407898200; RA Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., RA Martoglio B.; RT "Consensus analysis of signal peptide peptidase and homologous human RT aspartic proteases reveals opposite topology of catalytic domains compared RT with presenilins."; RL J. Biol. Chem. 279:50790-50798(2004). RN [10] RP SUBUNIT, GLYCOSYLATION, AND SUBCELLULAR LOCATION. RX PubMed=15998642; DOI=10.1074/jbc.m501645200; RA Krawitz P., Haffner C., Fluhrer R., Steiner H., Schmid B., Haass C.; RT "Differential localization and identification of a critical aspartate RT suggest non-redundant proteolytic functions of the presenilin homologues RT SPPL2b and SPPL3."; RL J. Biol. Chem. 280:39515-39523(2005). RN [11] RP SUBUNIT. RX PubMed=16873890; DOI=10.1096/fj.06-5762com; RA Nyborg A.C., Ladd T.B., Jansen K., Kukar T., Golde T.E.; RT "Intramembrane proteolytic cleavage by human signal peptide peptidase like RT 3 and malaria signal peptide peptidase."; RL FASEB J. 20:1671-1679(2006). RN [12] RP FUNCTION IN CLEAVAGE OF TNF, AND SUBCELLULAR LOCATION. RX PubMed=16829952; DOI=10.1038/ncb1440; RA Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S., RA Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B.; RT "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in RT activated dendritic cells to trigger IL-12 production."; RL Nat. Cell Biol. 8:843-848(2006). RN [13] RP FUNCTION IN CLEAVAGE OF TNF, INTERACTION WITH TNF, AND MUTAGENESIS OF RP ASP-421. RX PubMed=16829951; DOI=10.1038/ncb1450; RA Fluhrer R., Grammer G., Israel L., Condron M.M., Haffner C., Friedmann E., RA Bohland C., Imhof A., Martoglio B., Teplow D.B., Haass C.; RT "A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD RT aspartyl protease SPPL2b."; RL Nat. Cell Biol. 8:894-896(2006). RN [14] RP FUNCTION IN CLEAVAGE OF ITM2B, SUBCELLULAR LOCATION, INTERACTION WITH RP ITM2B, AND MUTAGENESIS OF ASP-421. RX PubMed=17965014; DOI=10.1074/jbc.m706661200; RA Martin L., Fluhrer R., Reiss K., Kremmer E., Saftig P., Haass C.; RT "Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and RT SPPL2a/SPPL2b."; RL J. Biol. Chem. 283:1644-1652(2008). RN [15] RP FUNCTION IN CLEAVAGE OF ITM2B, AND MUTAGENESIS OF ASP-421. RX PubMed=19114711; DOI=10.1074/jbc.m807485200; RA Martin L., Fluhrer R., Haass C.; RT "Substrate requirements for SPPL2b-dependent regulated intramembrane RT proteolysis."; RL J. Biol. Chem. 284:5662-5670(2009). RN [16] RP FUNCTION IN CLEAVAGE OF ITM2B, AND MUTAGENESIS OF ASP-421. RX PubMed=22194595; DOI=10.1074/jbc.m111.328104; RA Fluhrer R., Martin L., Klier B., Haug-Kroper M., Grammer G., Nuscher B., RA Haass C.; RT "The alpha-helical content of the transmembrane domain of the British RT dementia protein-2 (Bri2) determines its processing by signal peptide RT peptidase-like 2b (SPPL2b)."; RL J. Biol. Chem. 287:5156-5163(2012). RN [17] RP FUNCTION, INTERACTION WITH SIMIAN FOAMY VIRUS ENVELOPE GLYCOPROTEIN GP130, RP AND MUTAGENESIS OF ASP-421. RX PubMed=23132852; DOI=10.1074/jbc.m112.371369; RA Voss M., Fukumori A., Kuhn P.H., Kunzel U., Klier B., Grammer G., RA Haug-Kroper M., Kremmer E., Lichtenthaler S.F., Steiner H., Schroder B., RA Haass C., Fluhrer R.; RT "Foamy virus envelope protein is a substrate for signal peptide peptidase- RT like 3 (SPPL3)."; RL J. Biol. Chem. 287:43401-43409(2012). CC -!- FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that CC cleaves type II membrane signal peptides in the hydrophobic plane of CC the membrane. Functions in ITM2B and TNF processing (PubMed:16829952, CC PubMed:16829951, PubMed:17965014, PubMed:19114711, PubMed:22194595). CC Catalyzes the intramembrane cleavage of the anchored fragment of shed CC TNF-alpha (TNF), which promotes the release of the intracellular domain CC (ICD) for signaling to the nucleus (PubMed:16829952, PubMed:16829951). CC May play a role in the regulation of innate and adaptive immunity CC (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian CC foamy virus processed leader peptide gp18 of the envelope glycoprotein CC gp130 dependently of prior ectodomain shedding by furin or furin-like CC proprotein convertase (PC)-mediated cleavage proteolysis CC (PubMed:23132852). {ECO:0000269|PubMed:16829951, CC ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:17965014, CC ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:22194595, CC ECO:0000269|PubMed:23132852}. CC -!- SUBUNIT: Monomer (PubMed:15998642, PubMed:16873890). Homodimer CC (PubMed:15998642, PubMed:16873890). Interacts with ITM2B CC (PubMed:17965014). Interacts with TNF (PubMed:16829951). Interacts with CC the simian foamy virus envelope glycoprotein gp130 and its processed CC leader peptide gp18LP; preferentially interacts with the leader peptide CC gp18LP (PubMed:23132852). {ECO:0000269|PubMed:15998642, CC ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16873890, CC ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:23132852}. CC -!- INTERACTION: CC Q8TCT7-2; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-8345366, EBI-2837444; CC Q8TCT7-2; Q01658: DR1; NbExp=3; IntAct=EBI-8345366, EBI-750300; CC Q8TCT7-2; P29692-2: EEF1D; NbExp=3; IntAct=EBI-8345366, EBI-5280572; CC Q8TCT7-2; Q06787-7: FMR1; NbExp=3; IntAct=EBI-8345366, EBI-25856644; CC Q8TCT7-2; Q00403: GTF2B; NbExp=3; IntAct=EBI-8345366, EBI-389564; CC Q8TCT7-2; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-8345366, EBI-1054873; CC Q8TCT7-2; P04792: HSPB1; NbExp=3; IntAct=EBI-8345366, EBI-352682; CC Q8TCT7-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-8345366, EBI-10975473; CC Q8TCT7-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-8345366, EBI-21251460; CC Q8TCT7-2; P60891: PRPS1; NbExp=3; IntAct=EBI-8345366, EBI-749195; CC Q8TCT7-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-8345366, EBI-396669; CC Q8TCT7-2; P37840: SNCA; NbExp=3; IntAct=EBI-8345366, EBI-985879; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16829952}; CC Multi-pass membrane protein {ECO:0000305}. Golgi apparatus membrane CC {ECO:0000269|PubMed:17965014}; Multi-pass membrane protein CC {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:15998642}; Multi- CC pass membrane protein {ECO:0000305}. Endosome membrane CC {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein CC {ECO:0000305}. Membrane {ECO:0000269|PubMed:15385547}; Multi-pass CC membrane protein {ECO:0000305}; Lumenal side CC {ECO:0000269|PubMed:15385547}. Note=targeted through the entire CC secretory pathway to endosomes/lysosomes (PubMed:15998642). CC {ECO:0000269|PubMed:15998642}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Experimental confirmation may be lacking for some isoforms.; CC Name=1; CC IsoId=Q8TCT7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TCT7-2; Sequence=VSP_005204; CC Name=4; CC IsoId=Q8TCT7-4; Sequence=VSP_009221, VSP_009222; CC -!- TISSUE SPECIFICITY: Expressed predominantly in adrenal cortex and CC mammary gland. {ECO:0000269|PubMed:15385547}. CC -!- DOMAIN: The PAL motif is required for normal active site conformation. CC The catalytic domains embedded in the membrane are in the opposite CC orientation to that of the presenilin protein family; therefore, it is CC predicted to cleave type II-oriented substrate peptides like the CC prototypic protease SPP. {ECO:0000250|UniProtKB:P49768}. CC -!- PTM: Glycosylated (PubMed:15385547, PubMed:15998642). CC {ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:15998642}. CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC05601.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=AAG45441.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA96056.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAB96951.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; CC Sequence=CAB96951.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ345027; CAC87788.1; -; mRNA. DR EMBL; AJ420897; CAD13134.1; -; mRNA. DR EMBL; AY169315; AAO12540.1; -; mRNA. DR EMBL; AB040965; BAA96056.1; ALT_INIT; mRNA. DR EMBL; AC004410; AAC05601.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC005258; AAG45441.1; ALT_INIT; Genomic_DNA. DR EMBL; CH471139; EAW69383.1; -; Genomic_DNA. DR EMBL; CH471139; EAW69388.1; -; Genomic_DNA. DR EMBL; BC001788; AAH01788.2; -; mRNA. DR EMBL; BC028391; AAH28391.2; -; mRNA. DR EMBL; BC093046; AAH93046.1; -; mRNA. DR EMBL; AL365405; CAB96951.1; ALT_SEQ; mRNA. DR CCDS; CCDS74252.1; -. [Q8TCT7-1] DR CCDS; CCDS74253.1; -. [Q8TCT7-4] DR RefSeq; NP_001070706.1; NM_001077238.1. [Q8TCT7-4] DR RefSeq; NP_694533.1; NM_152988.2. [Q8TCT7-1] DR AlphaFoldDB; Q8TCT7; -. DR BioGRID; 121255; 247. DR IntAct; Q8TCT7; 113. DR MINT; Q8TCT7; -. DR STRING; 9606.ENSP00000478298; -. DR BindingDB; Q8TCT7; -. DR ChEMBL; CHEMBL4105912; -. DR MEROPS; A22.004; -. DR GlyCosmos; Q8TCT7; 2 sites, No reported glycans. DR GlyGen; Q8TCT7; 4 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8TCT7; -. DR PhosphoSitePlus; Q8TCT7; -. DR SwissPalm; Q8TCT7; -. DR BioMuta; SPPL2B; -. DR DMDM; 97537015; -. DR EPD; Q8TCT7; -. DR jPOST; Q8TCT7; -. DR MassIVE; Q8TCT7; -. DR MaxQB; Q8TCT7; -. DR PaxDb; 9606-ENSP00000478298; -. DR PeptideAtlas; Q8TCT7; -. DR ProteomicsDB; 74160; -. [Q8TCT7-1] DR ProteomicsDB; 74161; -. [Q8TCT7-2] DR ProteomicsDB; 74163; -. [Q8TCT7-4] DR TopDownProteomics; Q8TCT7-4; -. [Q8TCT7-4] DR Antibodypedia; 3352; 91 antibodies from 15 providers. DR DNASU; 56928; -. DR Ensembl; ENST00000610743.4; ENSP00000478510.1; ENSG00000005206.17. [Q8TCT7-4] DR Ensembl; ENST00000613503.5; ENSP00000478298.1; ENSG00000005206.17. [Q8TCT7-1] DR Ensembl; ENST00000618220.4; ENSP00000480813.1; ENSG00000005206.17. [Q8TCT7-2] DR GeneID; 56928; -. DR KEGG; hsa:56928; -. DR MANE-Select; ENST00000613503.5; ENSP00000478298.1; NM_152988.3; NP_694533.1. DR UCSC; uc032hjm.2; human. [Q8TCT7-1] DR AGR; HGNC:30627; -. DR CTD; 56928; -. DR DisGeNET; 56928; -. DR GeneCards; SPPL2B; -. DR HGNC; HGNC:30627; SPPL2B. DR HPA; ENSG00000005206; Low tissue specificity. DR MIM; 608239; gene. DR neXtProt; NX_Q8TCT7; -. DR OpenTargets; ENSG00000005206; -. DR VEuPathDB; HostDB:ENSG00000005206; -. DR eggNOG; KOG2442; Eukaryota. DR GeneTree; ENSGT00940000158753; -. DR HOGENOM; CLU_023799_2_1_1; -. DR InParanoid; Q8TCT7; -. DR OMA; VIAPVNC; -. DR OrthoDB; 907832at2759; -. DR PhylomeDB; Q8TCT7; -. DR PathwayCommons; Q8TCT7; -. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR SignaLink; Q8TCT7; -. DR BioGRID-ORCS; 56928; 12 hits in 254 CRISPR screens. DR ChiTaRS; SPPL2B; human. DR GeneWiki; SPPL2B; -. DR GenomeRNAi; 56928; -. DR Pharos; Q8TCT7; Tchem. DR PRO; PR:Q8TCT7; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q8TCT7; Protein. DR Bgee; ENSG00000005206; Expressed in right uterine tube and 147 other cell types or tissues. DR ExpressionAtlas; Q8TCT7; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:UniProtKB. DR GO; GO:0098553; C:lumenal side of endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:UniProtKB. DR GO; GO:0033619; P:membrane protein proteolysis; IDA:UniProtKB. DR GO; GO:0050776; P:regulation of immune response; IMP:UniProtKB. DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; TAS:Reactome. DR CDD; cd02129; PA_hSPPL_like; 1. DR Gene3D; 3.50.30.30; -; 1. DR InterPro; IPR046450; PA_dom_sf. DR InterPro; IPR003137; PA_domain. DR InterPro; IPR007369; Peptidase_A22B_SPP. DR InterPro; IPR006639; Preselin/SPP. DR PANTHER; PTHR12174; SIGNAL PEPTIDE PEPTIDASE; 1. DR PANTHER; PTHR12174:SF39; SIGNAL PEPTIDE PEPTIDASE-LIKE 2B; 1. DR Pfam; PF02225; PA; 1. DR Pfam; PF04258; Peptidase_A22B; 1. DR SMART; SM00730; PSN; 1. DR SUPFAM; SSF52025; PA domain; 1. DR Genevisible; Q8TCT7; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Endosome; Glycoprotein; KW Golgi apparatus; Hydrolase; Lysosome; Membrane; Protease; KW Reference proteome; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..25 FT /evidence="ECO:0000269|PubMed:15385547" FT CHAIN 26..592 FT /note="Signal peptide peptidase-like 2B" FT /id="PRO_0000073909" FT TOPO_DOM 26..174 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:15385547" FT TRANSMEM 175..195 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 196..221 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 222..244 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 245..248 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 249..271 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 272..293 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 294..314 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 315..319 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 320..340 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 341..348 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 349..369 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 370..412 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:15385547" FT TRANSMEM 413..433 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 434..445 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 446..466 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 467..470 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 471..491 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 492..592 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:15385547" FT DOMAIN 71..149 FT /note="PA" FT REGION 512..592 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 472..474 FT /note="PAL" FT COMPBIAS 512..542 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 576..592 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 359 FT /evidence="ECO:0000250|UniProtKB:P49810" FT ACT_SITE 421 FT /evidence="ECO:0000250|UniProtKB:P49810" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 129 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 320..592 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_005204" FT VAR_SEQ 506..511 FT /note="KVLPPS -> VNTSLL (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_009221" FT VAR_SEQ 512..592 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_009222" FT VARIANT 574 FT /note="S -> P (in dbSNP:rs10402284)" FT /id="VAR_059780" FT MUTAGEN 421 FT /note="D->A: Loss of intramembrane-cleaving activity toward FT ITM2B, TNF and the simian foamy virus envelope glycoprotein FT gp130." FT /evidence="ECO:0000269|PubMed:16829951, FT ECO:0000269|PubMed:17965014, ECO:0000269|PubMed:19114711, FT ECO:0000269|PubMed:22194595" SQ SEQUENCE 592 AA; 64644 MW; 0F49370F16D36AA0 CRC64; MAAAVAAALA RLLAAFLLLA AQVACEYGMV HVVSQAGGPE GKDYCILYNP QWAHLPHDLS KASFLQLRNW TASLLCSAAD LPARGFSNQI PLVARGNCTF YEKVRLAQGS GARGLLIVSR ERLVPPGGNK TQYDEIGIPV ALLSYKDMLD IFTRFGRTVR AALYAPKEPV LDYNMVIIFI MAVGTVAIGG YWAGSRDVKK RYMKHKRDDG PEKQEDEAVD VTPVMTCVFV VMCCSMLVLL YYFYDLLVYV VIGIFCLASA TGLYSCLAPC VRRLPFGKCR IPNNSLPYFH KRPQARMLLL ALFCVAVSVV WGVFRNEDQW AWVLQDALGI AFCLYMLKTI RLPTFKACTL LLLVLFLYDI FFVFITPFLT KSGSSIMVEV ATGPSDSATR EKLPMVLKVP RLNSSPLALC DRPFSLLGFG DILVPGLLVA YCHRFDIQVQ SSRVYFVACT IAYGVGLLVT FVALALMQRG QPALLYLVPC TLVTSCAVAL WRRELGVFWT GSGFAKVLPP SPWAPAPADG PQPPKDSATP LSPQPPSEEP ATSPWPAEQS PKSRTSEEMG AGAPMREPGS PAESEGRDQA QPSPVTQPGA SA //