SPP2A_HUMAN
ID SPP2A_HUMAN Reviewed; 520 AA.
AC Q8TCT8; B2RDS0; Q8TAW1; Q96SZ8;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Signal peptide peptidase-like 2A {ECO:0000303|PubMed:15385547, ECO:0000312|HGNC:HGNC:30227};
DE Short=SPP-like 2A {ECO:0000303|PubMed:15385547};
DE Short=SPPL2a {ECO:0000303|PubMed:15385547};
DE EC=3.4.23.-;
DE AltName: Full=Intramembrane protease 3 {ECO:0000303|PubMed:12139484};
DE Short=IMP-3 {ECO:0000303|PubMed:12139484};
DE AltName: Full=Presenilin-like protein 2;
DE Flags: Precursor;
GN Name=SPPL2A {ECO:0000303|PubMed:15385547, ECO:0000312|HGNC:HGNC:30227};
GN Synonyms=IMP3 {ECO:0000303|PubMed:12139484}, PSL2; ORFNames=PSEC0147;
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].
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].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 91-520.
RC TISSUE=Cervix carcinoma;
RX PubMed=12077416; DOI=10.1126/science.1070925;
RA Weihofen A., Binns K., Lemberg M.K., Ashman K., Martoglio B.;
RT "Identification of signal peptide peptidase, a presenilin-type aspartic
RT protease.";
RL Science 296:2215-2218(2002).
RN [8]
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 [9]
RP FUNCTION IN CLEAVAGE OF TNF, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-412.
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 [10]
RP FUNCTION IN CLEAVAGE OF TNF.
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 [11]
RP FUNCTION IN CLEAVAGE OF FASLG, AND MUTAGENESIS OF ASP-412.
RX PubMed=17557115; DOI=10.1038/sj.cdd.4402175;
RA Kirkin V., Cahuzac N., Guardiola-Serrano F., Huault S., Luckerath K.,
RA Friedmann E., Novac N., Wels W.S., Martoglio B., Hueber A.O., Zornig M.;
RT "The Fas ligand intracellular domain is released by ADAM10 and SPPL2a
RT cleavage in T-cells.";
RL Cell Death Differ. 14:1678-1687(2007).
RN [12]
RP FUNCTION IN CLEAVAGE OF ITM2B, INTERACTION WITH ITM2B, AND MUTAGENESIS OF
RP ASP-412.
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 [13]
RP GLYCOSYLATION AT ASN-155.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF ASP-412.
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).
RN [15]
RP INVOLVEMENT IN IMD86.
RX PubMed=30127434; DOI=10.1038/s41590-018-0178-z;
RA Kong X.F., Martinez-Barricarte R., Kennedy J., Mele F., Lazarov T.,
RA Deenick E.K., Ma C.S., Breton G., Lucero K.B., Langlais D., Bousfiha A.,
RA Aytekin C., Markle J., Trouillet C., Jabot-Hanin F., Arlehamn C.S.L.,
RA Rao G., Picard C., Lasseau T., Latorre D., Hambleton S., Deswarte C.,
RA Itan Y., Abarca K., Moraes-Vasconcelos D., Ailal F., Ikinciogullari A.,
RA Dogu F., Benhsaien I., Sette A., Abel L., Boisson-Dupuis S., Schroeder B.,
RA Nussenzweig M.C., Liu K., Geissmann F., Tangye S.G., Gros P., Sallusto F.,
RA Bustamante J., Casanova J.L.;
RT "Disruption of an antimycobacterial circuit between dendritic and helper T
RT cells in human SPPL2a deficiency.";
RL Nat. Immunol. 19:973-985(2018).
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 FASLG, ITM2B and TNF processing
CC (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014).
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). Also responsible
CC for the intramembrane cleavage of Fas antigen ligand FASLG, which
CC promotes the release of the intracellular FasL domain (FasL ICD)
CC (PubMed:17557115). Essential for degradation of the invariant chain
CC CD74 that plays a central role in the function of antigen-presenting
CC cells in the immune system (By similarity). Plays a role in the
CC regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes
CC the intramembrane cleavage of the simian foamy virus envelope
CC glycoprotein gp130 independently of prior ectodomain shedding by furin
CC or furin-like proprotein convertase (PC)-mediated cleavage proteolysis
CC (PubMed:23132852). {ECO:0000250|UniProtKB:Q9JJF9,
CC ECO:0000269|PubMed:16829951, ECO:0000269|PubMed:16829952,
CC ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:17965014,
CC ECO:0000269|PubMed:23132852}.
CC -!- SUBUNIT: Interacts with ITM2B (PubMed:17965014).
CC {ECO:0000269|PubMed:17965014}.
CC -!- INTERACTION:
CC Q8TCT8; O43765: SGTA; NbExp=7; IntAct=EBI-750784, EBI-347996;
CC Q8TCT8; O76024: WFS1; NbExp=3; IntAct=EBI-750784, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:16829952}; Multi-pass membrane protein
CC {ECO:0000305}. Lysosome membrane {ECO:0000250|UniProtKB:Q9JJF9}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q9JJF9}. Membrane
CC {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein
CC {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}.
CC Note=Colocalizes with palmitoylated and myristoylated proteins at the
CC plasma membrane.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {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. The C-terminal tail is necessary for lysosomal
CC transport. {ECO:0000250|UniProtKB:P49768,
CC ECO:0000250|UniProtKB:Q9JJF9}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:15385547,
CC ECO:0000269|PubMed:19139490}.
CC -!- DISEASE: Immunodeficiency 86 (IMD86) [MIM:619549]: An autosomal
CC recessive disorder characterized by susceptibility to mycobacterial
CC disease after exposure to BCG vaccine. Affected individuals usually
CC develop localized mycobacterial lymphadenopathy.
CC {ECO:0000269|PubMed:30127434}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55117.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD13133.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ345028; CAC87789.1; -; mRNA.
DR EMBL; AY169314; AAO12539.1; -; mRNA.
DR EMBL; AK027446; BAB55117.1; ALT_INIT; mRNA.
DR EMBL; AK315651; BAG38017.1; -; mRNA.
DR EMBL; AK075454; BAC11630.1; -; mRNA.
DR EMBL; CH471082; EAW77410.1; -; Genomic_DNA.
DR EMBL; BC025740; AAH25740.1; -; mRNA.
DR EMBL; AJ420896; CAD13133.1; ALT_INIT; mRNA.
DR CCDS; CCDS10138.1; -.
DR RefSeq; NP_116191.2; NM_032802.3.
DR AlphaFoldDB; Q8TCT8; -.
DR BioGRID; 124328; 8.
DR IntAct; Q8TCT8; 6.
DR MINT; Q8TCT8; -.
DR STRING; 9606.ENSP00000261854; -.
DR BindingDB; Q8TCT8; -.
DR ChEMBL; CHEMBL4105833; -.
DR MEROPS; A22.007; -.
DR TCDB; 1.A.54.3.2; the presenilin er ca(2+) leak channel (presenilin) family.
DR GlyConnect; 1746; 4 N-Linked glycans (1 site).
DR GlyGen; Q8TCT8; 7 sites, 4 N-linked glycans (1 site).
DR iPTMnet; Q8TCT8; -.
DR PhosphoSitePlus; Q8TCT8; -.
DR SwissPalm; Q8TCT8; -.
DR BioMuta; SPPL2A; -.
DR DMDM; 25008981; -.
DR EPD; Q8TCT8; -.
DR jPOST; Q8TCT8; -.
DR MassIVE; Q8TCT8; -.
DR MaxQB; Q8TCT8; -.
DR PaxDb; Q8TCT8; -.
DR PeptideAtlas; Q8TCT8; -.
DR PRIDE; Q8TCT8; -.
DR ProteomicsDB; 74164; -.
DR Antibodypedia; 24774; 119 antibodies from 24 providers.
DR DNASU; 84888; -.
DR Ensembl; ENST00000261854.10; ENSP00000261854.5; ENSG00000138600.10.
DR GeneID; 84888; -.
DR KEGG; hsa:84888; -.
DR MANE-Select; ENST00000261854.10; ENSP00000261854.5; NM_032802.4; NP_116191.2.
DR UCSC; uc001zyv.4; human.
DR CTD; 84888; -.
DR DisGeNET; 84888; -.
DR GeneCards; SPPL2A; -.
DR HGNC; HGNC:30227; SPPL2A.
DR HPA; ENSG00000138600; Low tissue specificity.
DR MIM; 608238; gene.
DR MIM; 619549; phenotype.
DR neXtProt; NX_Q8TCT8; -.
DR OpenTargets; ENSG00000138600; -.
DR VEuPathDB; HostDB:ENSG00000138600; -.
DR eggNOG; KOG2442; Eukaryota.
DR GeneTree; ENSGT00940000157722; -.
DR HOGENOM; CLU_023799_2_1_1; -.
DR InParanoid; Q8TCT8; -.
DR OMA; LSKDYCM; -.
DR OrthoDB; 535101at2759; -.
DR PhylomeDB; Q8TCT8; -.
DR TreeFam; TF319186; -.
DR BRENDA; 3.4.23.B24; 2681.
DR PathwayCommons; Q8TCT8; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR SignaLink; Q8TCT8; -.
DR BioGRID-ORCS; 84888; 11 hits in 1041 CRISPR screens.
DR ChiTaRS; SPPL2A; human.
DR GeneWiki; SPPL2A; -.
DR GenomeRNAi; 84888; -.
DR Pharos; Q8TCT8; Tchem.
DR PRO; PR:Q8TCT8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8TCT8; protein.
DR Bgee; ENSG00000138600; Expressed in ileal mucosa and 188 other tissues.
DR ExpressionAtlas; Q8TCT8; baseline and differential.
DR Genevisible; Q8TCT8; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
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 InterPro; IPR003137; PA_domain.
DR InterPro; IPR007369; Peptidase_A22B_SPP.
DR InterPro; IPR006639; Preselin/SPP.
DR PANTHER; PTHR12174; PTHR12174; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04258; Peptidase_A22B; 1.
DR SMART; SM00730; PSN; 1.
PE 1: Evidence at protein level;
KW Endosome; Glycoprotein; Hydrolase; Lysosome; Membrane; Protease;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15385547"
FT CHAIN 26..520
FT /note="Signal peptide peptidase-like 2A"
FT /id="PRO_0000073910"
FT TOPO_DOM 26..172
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15385547"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..241
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 242..247
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..285
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..311
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..399
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15385547"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 421..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..460
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 482..520
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15385547"
FT DOMAIN 63..151
FT /note="PA"
FT MOTIF 463..465
FT /note="PAL"
FT MOTIF 495..498
FT /note="YXXo lysosomal targeting motif"
FT ACT_SITE 351
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT ACT_SITE 412
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 126
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490"
FT VARIANT 90
FT /note="V -> I (in dbSNP:rs8034443)"
FT /id="VAR_051790"
FT MUTAGEN 412
FT /note="D->A: Loss of intramembrane-cleaving activity toward
FT FASLG, ITM2B, TNF and the simian foamy virus envelope
FT glycoprotein gp130."
FT /evidence="ECO:0000269|PubMed:16829952,
FT ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:17965014,
FT ECO:0000269|PubMed:23132852"
FT CONFLICT 126
FT /note="N -> D (in Ref. 3; BAB55117)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="I -> T (in Ref. 4; BAC11630)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="S -> L (in Ref. 4; BAC11630)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="I -> F (in Ref. 4; BAC11630)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="V -> E (in Ref. 3; BAB55117)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 58143 MW; A7A933A6504507DC CRC64;
MGPQRRLSPA GAALLWGFLL QLTAAQEAIL HASGNGTTKD YCMLYNPYWT ALPSTLENAT
SISLMNLTST PLCNLSDIPP VGIKSKAVVV PWGSCHFLEK ARIAQKGGAE AMLVVNNSVL
FPPSGNRSEF PDVKILIAFI SYKDFRDMNQ TLGDNITVKM YSPSWPNFDY TMVVIFVIAV
FTVALGGYWS GLVELENLKA VTTEDREMRK KKEEYLTFSP LTVVIFVVIC CVMMVLLYFF
YKWLVYVMIA IFCIASAMSL YNCLAALIHK IPYGQCTIAC RGKNMEVRLI FLSGLCIAVA
VVWAVFRNED RWAWILQDIL GIAFCLNLIK TLKLPNFKSC VILLGLLLLY DVFFVFITPF
ITKNGESIMV ELAAGPFGNN EKLPVVIRVP KLIYFSVMSV CLMPVSILGF GDIIVPGLLI
AYCRRFDVQT GSSYIYYVSS TVAYAIGMIL TFVVLVLMKK GQPALLYLVP CTLITASVVA
WRRKEMKKFW KGNSYQMMDH LDCATNEENP VISGEQIVQQ
