Entry euk:SPPL3_HUMAN

ID   SPPL3_HUMAN             Reviewed;         385 AA.
AC   Q8TCT6; Q3MJ04; Q8TAU4; Q96DD9;
DT   08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   12-APR-2017, entry version 132.
DE   RecName: Full=Signal peptide peptidase-like 3 {ECO:0000303|PubMed:12077416, ECO:0000312|HGNC:HGNC:30424};
DE            Short=SPP-like 3 {ECO:0000303|PubMed:12077416};
DE            EC=3.4.23.-;
DE   AltName: Full=Intramembrane protease 2 {ECO:0000303|PubMed:12139484};
DE            Short=IMP-2 {ECO:0000303|PubMed:12139484};
DE   AltName: Full=Presenilin homologous protein 1 {ECO:0000303|PubMed:11978763};
DE            Short=PSH1 {ECO:0000303|PubMed:11978763};
DE   AltName: Full=Presenilin-like protein 4 {ECO:0000303|Ref.1};
GN   Name=SPPL3 {ECO:0000303|PubMed:12077416, ECO:0000312|HGNC:HGNC:30424};
GN   Synonyms=IMP2 {ECO:0000303|PubMed:12139484}, PSL4 {ECO:0000303|Ref.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   presenilins.";
RL   Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
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
RT   aspartic protease.";
RL   Science 296:2215-2218(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
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
RT   putative protease activity.";
RL   Biochemistry (Mosc.) 67:826-834(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Fetal brain;
RA   Kondo K., Heike T., Yorifuji T., Nishikomori R., Kawai M., Ma F.,
RA   Ma L., Adachi S., Nakahata T.;
RT   "Proteolytic processing, N-glycosylation, and proteasomal degradation
RT   of human signal peptide peptidase-like protein 3: the YD and PAL
RT   motifs, but not the GXGD motif, are critical for protein stability.";
RL   Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Liver, Pancreas, 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-385 (ISOFORM 2).
RC   TISSUE=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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=11978763; DOI=10.1093/hmg/11.9.1037;
RA   Ponting C.P., Hutton M., Nyborg A., Baker M., Jansen K., Golde T.E.;
RT   "Identification of a novel family of presenilin homologues.";
RL   Hum. Mol. Genet. 11:1037-1044(2002).
RN   [9]
RP   SUBUNIT, TOPOLOGY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND LACK
RP   OF GLYCOSYLATION.
RX   PubMed=15385547; DOI=10.1074/jbc.M407898200;
RA   Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U.,
RA   Rovelli G., Martoglio B.;
RT   "Consensus analysis of signal peptide peptidase and homologous human
RT   aspartic proteases reveals opposite topology of catalytic domains
RT   compared with presenilins.";
RL   J. Biol. Chem. 279:50790-50798(2004).
RN   [10]
RP   SUBUNIT, SUBCELLULAR LOCATION, AND LACK OF GLYCOSYLATION.
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
RT   homologues SPPL2b and SPPL3.";
RL   J. Biol. Chem. 280:39515-39523(2005).
RN   [11]
RP   FUNCTION, ENZYME REGULATION, AND 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
RT   like 3 and malaria signal peptide peptidase.";
RL   FASEB J. 20:1671-1679(2006).
RN   [12]
RP   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, LACK OF ENZYME REGULATION, INTERACTION WITH ENV, AND
RP   MUTAGENESIS OF ASP-272.
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.,
RA   Schroder B., Haass C., Fluhrer R.;
RT   "Foamy virus envelope protein is a substrate for signal peptide
RT   peptidase-like 3 (SPPL3).";
RL   J. Biol. Chem. 287:43401-43409(2012).
RN   [14]
RP   FUNCTION, AND MUTAGENESIS OF ASP-201 AND ASP-272.
RX   PubMed=25354954; DOI=10.15252/embj.201488375;
RA   Voss M., Kunzel U., Higel F., Kuhn P.H., Colombo A., Fukumori A.,
RA   Haug-Kroper M., Klier B., Grammer G., Seidl A., Schroder B., Obst R.,
RA   Steiner H., Lichtenthaler S.F., Haass C., Fluhrer R.;
RT   "Shedding of glycan-modifying enzymes by signal peptide peptidase-like
RT   3 (SPPL3) regulates cellular N-glycosylation.";
RL   EMBO J. 33:2890-2905(2014).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH STIM1.
RX   PubMed=25384971; DOI=10.1128/MCB.01124-14;
RA   Makowski S.L., Wang Z., Pomerantz J.L.;
RT   "A protease-independent function for SPPL3 in NFAT activation.";
RL   Mol. Cell. Biol. 35:451-467(2015).
RN   [16]
RP   FUNCTION.
RX   PubMed=25827571; DOI=10.1074/mcp.M115.048298;
RA   Kuhn P.H., Voss M., Haug-Kroper M., Schroder B., Schepers U.,
RA   Brase S., Haass C., Lichtenthaler S.F., Fluhrer R.;
RT   "Secretome analysis identifies novel signal peptide peptidase-like 3
RT   (SPPL3) substrates and reveals a role of SPPL3 in multiple Golgi
RT   glycosylation pathways.";
RL   Mol. Cell. Proteomics 14:1584-1598(2015).
CC   -!- FUNCTION: Intramembrane-cleaving aspartic protease (I-CLiP) that
CC       cleaves type II membrane protein substrates in or close to their
CC       luminal transmembrane domain boundaries (PubMed:16873890,
CC       PubMed:25354954, PubMed:25827571). Acts like a sheddase by
CC       mediating the proteolytic release and secretion of active site-
CC       containing ectodomains of glycan-modifiying glycosidase and
CC       glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1
CC       (PubMed:25354954, PubMed:25827571). Catalyzes the intramembrane
CC       cleavage of the envelope glycoprotein gp130 and/or the leader
CC       peptide gp18LP of the simian foamy virus independent of prior
CC       ectodomain shedding by furin or furin-like proprotein convertase
CC       (PC)-mediated cleavage proteolysis (PubMed:23132852). May also
CC       have the ability to serve as a shedding protease for subsequent
CC       intramembrane proteolysis by SPPL2A and SPPL2B of the envelope
CC       glycoprotein gp130 (PubMed:23132852). Plays a role in the
CC       regulation of cellular glycosylation processes (PubMed:25354954).
CC       Required to link T-cell antigen receptor (TCR) and calcineurin-
CC       NFAT signaling cascades in lymphocytes by promoting the
CC       association of STIM1 and ORAI1 during store-operated calcium entry
CC       (SOCE) in a protease-independent manner (PubMed:25384971).
CC       {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852,
CC       ECO:0000269|PubMed:25354954, ECO:0000269|PubMed:25384971,
CC       ECO:0000269|PubMed:25827571}.
CC   -!- ENZYME REGULATION: Its proteolytic activity is blocked by a signal
CC       peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-
CC       secretase inhibitor, LY411,575 (PubMed:16873890). However, is not
CC       inhibited by ZLL and LY411,575 for activity on simian foamy virus
CC       envelope glycoprotein gp130 (PubMed:23132852).
CC       {ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852}.
CC   -!- SUBUNIT: Monomer (PubMed:15385547, PubMed:15998642,
CC       PubMed:16873890). Homodimer (PubMed:15385547, PubMed:15998642,
CC       PubMed:16873890). Interacts with STIM1 (via the transmembrane
CC       region and the SOAR/CAD domain); the interaction promotes the
CC       binding of STIM1 to ORAI1 (PubMed:25384971). Interacts with the
CC       simian foamy virus envelope glycoprotein gp130 and its processed
CC       leader peptide gp18LP; preferentially interacts with the envelope
CC       glycoprotein gp130 (PubMed:23132852).
CC       {ECO:0000250|UniProtKB:Q9CUS9, ECO:0000269|PubMed:15385547,
CC       ECO:0000269|PubMed:15998642, ECO:0000269|PubMed:16873890,
CC       ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25384971}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:15998642}; Multi-pass membrane protein
CC       {ECO:0000305}. Golgi apparatus {ECO:0000269|PubMed:16829952}.
CC       Membrane {ECO:0000269|PubMed:15385547}; Multi-pass membrane
CC       protein {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC         Comment=Experimental confirmation may be lacking for some
CC         isoforms.;
CC       Name=1;
CC         IsoId=Q8TCT6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8TCT6-2; Sequence=VSP_005206;
CC       Name=3;
CC         IsoId=Q8TCT6-3; Sequence=VSP_005205;
CC   -!- TISSUE SPECIFICITY: Widely expressed (PubMed:15385547). Expressed
CC       in the brain (PubMed:11978763). {ECO:0000269|PubMed:11978763,
CC       ECO:0000269|PubMed:15385547}.
CC   -!- DOMAIN: The first transmembrane domain may act as a type I signal
CC       anchor (PubMed:15385547). The catalytic loops is exposed toward
CC       the lumen (PubMed:15385547). The PAL motif is required for normal
CC       active site conformation. The catalytic domains embedded in the
CC       membrane are in the opposite orientation to that of the presenilin
CC       protein family (By similarity). {ECO:0000250|UniProtKB:P49768,
CC       ECO:0000269|PubMed:15385547}.
CC   -!- PTM: Not 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=BAC11290.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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DR   EMBL; AJ345030; CAC87791.1; -; mRNA.
DR   EMBL; AJ420898; CAD13135.1; -; mRNA.
DR   EMBL; AY169313; AAO12538.1; -; mRNA.
DR   EMBL; AB252457; BAF30928.1; -; mRNA.
DR   EMBL; CH471054; EAW98220.1; -; Genomic_DNA.
DR   EMBL; BC009551; AAH09551.1; -; mRNA.
DR   EMBL; BC025781; AAH25781.1; -; mRNA.
DR   EMBL; BC073910; AAH73910.1; -; mRNA.
DR   EMBL; BC101625; AAI01626.1; -; mRNA.
DR   EMBL; BC101627; AAI01628.1; -; mRNA.
DR   EMBL; AK074916; BAC11290.1; ALT_INIT; mRNA.
DR   CCDS; CCDS9208.1; -. [Q8TCT6-2]
DR   RefSeq; NP_620584.2; NM_139015.4. [Q8TCT6-2]
DR   UniGene; Hs.507087; -.
DR   UniGene; Hs.683964; -.
DR   ProteinModelPortal; Q8TCT6; -.
DR   BioGrid; 125743; 17.
DR   STRING; 9606.ENSP00000288680; -.
DR   MEROPS; A22.005; -.
DR   SwissPalm; Q8TCT6; -.
DR   BioMuta; SPPL3; -.
DR   DMDM; 25008979; -.
DR   MaxQB; Q8TCT6; -.
DR   PaxDb; Q8TCT6; -.
DR   PeptideAtlas; Q8TCT6; -.
DR   PRIDE; Q8TCT6; -.
DR   Ensembl; ENST00000353487; ENSP00000288680; ENSG00000157837. [Q8TCT6-2]
DR   GeneID; 121665; -.
DR   KEGG; hsa:121665; -.
DR   UCSC; uc001tzd.4; human. [Q8TCT6-1]
DR   CTD; 121665; -.
DR   DisGeNET; 121665; -.
DR   GeneCards; SPPL3; -.
DR   HGNC; HGNC:30424; SPPL3.
DR   HPA; HPA004194; -.
DR   HPA; HPA059958; -.
DR   MIM; 608240; gene.
DR   neXtProt; NX_Q8TCT6; -.
DR   OpenTargets; ENSG00000157837; -.
DR   eggNOG; KOG2443; Eukaryota.
DR   eggNOG; ENOG410XTES; LUCA.
DR   GeneTree; ENSGT00530000062920; -.
DR   HOGENOM; HOG000243413; -.
DR   HOVERGEN; HBG023986; -.
DR   InParanoid; Q8TCT6; -.
DR   KO; K09598; -.
DR   OMA; ELWEGPA; -.
DR   OrthoDB; EOG091G0EHF; -.
DR   PhylomeDB; Q8TCT6; -.
DR   TreeFam; TF323842; -.
DR   ChiTaRS; SPPL3; human.
DR   GeneWiki; UNQ1887; -.
DR   GenomeRNAi; 121665; -.
DR   PRO; PR:Q8TCT6; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000157837; -.
DR   ExpressionAtlas; Q8TCT6; baseline and differential.
DR   Genevisible; Q8TCT6; HS.
DR   GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; ISS: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:0005765; C:lysosomal membrane; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; 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:0033619; P:membrane protein proteolysis; IDA:UniProtKB.
DR   GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IMP:UniProtKB.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR   GO; GO:0051533; P:positive regulation of NFAT protein import into nucleus; IMP:UniProtKB.
DR   GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR   GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:UniProtKB.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR   InterPro; IPR007369; Peptidase_A22B_SPP.
DR   InterPro; IPR006639; Preselin/SPP.
DR   PANTHER; PTHR12174; PTHR12174; 1.
DR   Pfam; PF04258; Peptidase_A22B; 1.
DR   SMART; SM00730; PSN; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW   Golgi apparatus; Hydrolase; Membrane; Protease; Reference proteome;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN         1    385       Signal peptide peptidase-like 3.
FT                                /FTId=PRO_0000073912.
FT   TOPO_DOM      1      8       Lumenal. {ECO:0000269|PubMed:15385547}.
FT   TRANSMEM      9     29       Helical. {ECO:0000255}.
FT   TOPO_DOM     30     75       Cytoplasmic.
FT                                {ECO:0000269|PubMed:15385547}.
FT   TRANSMEM     76     96       Helical. {ECO:0000255}.
FT   TOPO_DOM     97     98       Lumenal. {ECO:0000255}.
FT   TRANSMEM     99    119       Helical. {ECO:0000255}.
FT   TOPO_DOM    120    137       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    138    160       Helical. {ECO:0000255}.
FT   TOPO_DOM    161    165       Lumenal. {ECO:0000255}.
FT   TRANSMEM    166    186       Helical. {ECO:0000255}.
FT   TOPO_DOM    187    191       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    192    212       Helical. {ECO:0000255}.
FT   TOPO_DOM    213    263       Lumenal. {ECO:0000269|PubMed:15385547}.
FT   TRANSMEM    264    284       Helical. {ECO:0000255}.
FT   TOPO_DOM    285    312       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    313    333       Helical. {ECO:0000255}.
FT   TOPO_DOM    334    340       Lumenal. {ECO:0000255}.
FT   TRANSMEM    341    361       Helical. {ECO:0000255}.
FT   TOPO_DOM    362    385       Cytoplasmic.
FT                                {ECO:0000269|PubMed:15385547}.
FT   MOTIF       342    344       PAL.
FT   COMPBIAS    375    380       Poly-Ser.
FT   ACT_SITE    201    201       {ECO:0000250|UniProtKB:P49810}.
FT   ACT_SITE    272    272       {ECO:0000250|UniProtKB:P49810}.
FT   VAR_SEQ       1    216       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_005205.
FT   VAR_SEQ      59     82       EQEPIIGFQPMDSTRARFLPMGAC -> NSTNNSIQTIDST
FT                                QALFLPIGAS (in isoform 2).
FT                                {ECO:0000303|PubMed:12077416,
FT                                ECO:0000303|PubMed:12139484,
FT                                ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_005206.
FT   MUTAGEN     201    201       D->A: Does not affect complex
FT                                glycosylation pattern of cellular
FT                                glycoproteins; when associated with A-
FT                                272. {ECO:0000269|PubMed:25354954}.
FT   MUTAGEN     272    272       D->A: Loss of intramembrane-cleaving
FT                                activity toward the simian foamy virus
FT                                envelope glycoprotein gp130. Does not
FT                                affect complex glycosylation pattern of
FT                                cellular glycoproteins; when associated
FT                                with A-201. {ECO:0000269|PubMed:23132852,
FT                                ECO:0000269|PubMed:25354954}.
FT   CONFLICT    140    140       F -> Y (in Ref. 7; BAC11290).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT        67    373       ipfam:Peptidase_A22B [T]
FT   MYHIT        65    362       ismart:PSN [T]
SQ   SEQUENCE   385 AA;  42563 MW;  BF829565E14A2996 CRC64;
     MAEQTYSWAY SLVDSSQVST FLISILLIVY GSFRSLNMDF ENQDKEKDSN SSSGSFNGEQ
     EPIIGFQPMD STRARFLPMG ACVSLLVMFF FFDSVQVVFT ICTAVLATIA FAFLLLPMCQ
     YLTRPCSPQN KISFGCCGRF TAAELLSFSL SVMLVLIWVL TGHWLLMDAL AMGLCVAMIA
     FVRLPSLKVS CLLLSGLLIY DVFWVFFSAY IFNSNVMVKV ATQPADNPLD VLSRKLHLGP
     NVGRDVPRLS LPGKLVFPSS TGSHFSMLGI GDIVMPGLLL CFVLRYDNYK KQASGDSCGA
     PGPANISGRM QKVSYFHCTL IGYFVGLLTA TVASRIHRAA QPALLYLVPF TLLPLLTMAY
     LKGDLRRMWS EPFHSKSSSS RFLEV
//