SPP2B_HUMAN
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 03-AUG-2022, entry version 171.
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, 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};
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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; 245.
DR IntAct; Q8TCT7; 113.
DR MINT; Q8TCT7; -.
DR STRING; 9606.ENSP00000478298; -.
DR BindingDB; Q8TCT7; -.
DR ChEMBL; CHEMBL4105912; -.
DR MEROPS; A22.004; -.
DR GlyGen; Q8TCT7; 2 sites.
DR iPTMnet; Q8TCT7; -.
DR PhosphoSitePlus; Q8TCT7; -.
DR BioMuta; SPPL2B; -.
DR DMDM; 97537015; -.
DR EPD; Q8TCT7; -.
DR jPOST; Q8TCT7; -.
DR MassIVE; Q8TCT7; -.
DR MaxQB; Q8TCT7; -.
DR PeptideAtlas; Q8TCT7; -.
DR PRIDE; 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; 73 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 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; 535101at2759; -.
DR PhylomeDB; Q8TCT7; -.
DR PathwayCommons; Q8TCT7; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR SignaLink; Q8TCT7; -.
DR BioGRID-ORCS; 56928; 11 hits in 196 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 145 other tissues.
DR ExpressionAtlas; Q8TCT7; baseline and differential.
DR Genevisible; Q8TCT7; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
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:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0071556; C:integral component of 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:UniProtKB.
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 InterPro; IPR003137; PA_domain.
DR InterPro; IPR007369; Peptidase_A22B_SPP.
DR InterPro; IPR006639; Preselin/SPP.
DR InterPro; IPR033149; SPPL2B.
DR PANTHER; PTHR12174; PTHR12174; 1.
DR PANTHER; PTHR12174:SF39; PTHR12174:SF39; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04258; Peptidase_A22B; 1.
DR SMART; SM00730; PSN; 1.
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
