ID SPPL3_HUMAN Reviewed; 384 AA. AC Q8TCT6; Q3MJ04; Q8TAU4; Q96DD9; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 28-MAR-2018, sequence version 2. DT 24-JAN-2024, entry version 172. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). 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 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 aspartic RT 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 putative RT protease activity."; RL Biochemistry (Mosc.) 67:826-834(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Fetal brain; RA Kondo K., Heike T., Yorifuji T., Nishikomori R., Kawai M., Ma F., Ma L., RA Adachi S., Nakahata T.; RT "Proteolytic processing, N-glycosylation, and proteasomal degradation of RT human signal peptide peptidase-like protein 3: the YD and PAL motifs, but RT 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., 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] (ISOFORMS 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-384 (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., 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 [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 OF RP GLYCOSYLATION. 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, 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 homologues RT SPPL2b and SPPL3."; RL J. Biol. Chem. 280:39515-39523(2005). RN [11] RP FUNCTION, ACTIVITY 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 like RT 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 ACTIVITY REGULATION, INTERACTION WITH ENV, AND RP MUTAGENESIS OF ASP-271. 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 [14] RP FUNCTION, AND MUTAGENESIS OF ASP-200 AND ASP-271. 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 3 RT (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., Brase S., RA 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 mediating CC the proteolytic release and secretion of active site-containing CC ectodomains of glycan-modifiying glycosidase and glycosyltransferase CC enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, CC PubMed:25827571). Catalyzes the intramembrane cleavage of the envelope CC glycoprotein gp130 and/or the leader peptide gp18LP of the simian foamy CC virus independent of prior ectodomain shedding by furin or furin-like CC proprotein convertase (PC)-mediated cleavage proteolysis CC (PubMed:23132852). May also have the ability to serve as a shedding CC protease for subsequent intramembrane proteolysis by SPPL2A and SPPL2B CC of the envelope glycoprotein gp130 (PubMed:23132852). Plays a role in CC the regulation of cellular glycosylation processes (PubMed:25354954). CC Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT CC signaling cascades in lymphocytes by promoting the association of STIM1 CC and ORAI1 during store-operated calcium entry (SOCE) in a protease- CC independent manner (PubMed:25384971). {ECO:0000269|PubMed:16873890, CC ECO:0000269|PubMed:23132852, ECO:0000269|PubMed:25354954, CC ECO:0000269|PubMed:25384971, ECO:0000269|PubMed:25827571}. CC -!- ACTIVITY 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, PubMed:16873890). CC Homodimer (PubMed:15385547, PubMed:15998642, PubMed:16873890). CC Interacts with STIM1 (via the transmembrane region and the SOAR/CAD CC domain); the interaction promotes the binding of STIM1 to ORAI1 CC (PubMed:25384971). Interacts with the simian foamy virus envelope CC glycoprotein gp130 and its processed leader peptide gp18LP; CC preferentially interacts with the envelope glycoprotein gp130 CC (PubMed:23132852). {ECO:0000250|UniProtKB:Q9CUS9, CC ECO:0000269|PubMed:15385547, ECO:0000269|PubMed:15998642, CC ECO:0000269|PubMed:16873890, ECO:0000269|PubMed:23132852, CC 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}. Membrane CC {ECO:0000269|PubMed:15385547}; Multi-pass membrane protein CC {ECO:0000305}; Lumenal side {ECO:0000269|PubMed:15385547}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; CC IsoId=Q8TCT6-2; Sequence=Displayed; CC Name=3; CC IsoId=Q8TCT6-3; Sequence=VSP_005205; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:15385547). Expressed in CC 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 the CC lumen (PubMed:15385547). The PAL motif is required for normal active CC site conformation. The catalytic domains embedded in the membrane are CC in the opposite orientation to that of the presenilin protein family CC (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=Truncated N-terminus.; 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; 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 AlphaFoldDB; Q8TCT6; -. DR BioGRID; 125743; 889. DR IntAct; Q8TCT6; 16. DR STRING; 9606.ENSP00000288680; -. DR MEROPS; A22.005; -. DR iPTMnet; Q8TCT6; -. DR PhosphoSitePlus; Q8TCT6; -. DR SwissPalm; Q8TCT6; -. DR BioMuta; SPPL3; -. DR DMDM; 25008979; -. DR EPD; Q8TCT6; -. DR jPOST; Q8TCT6; -. DR MassIVE; Q8TCT6; -. DR MaxQB; Q8TCT6; -. DR PaxDb; 9606-ENSP00000288680; -. DR PeptideAtlas; Q8TCT6; -. DR ProteomicsDB; 74158; -. [Q8TCT6-2] DR ProteomicsDB; 74159; -. [Q8TCT6-3] DR Antibodypedia; 31508; 116 antibodies from 21 providers. DR DNASU; 121665; -. DR Ensembl; ENST00000353487.7; ENSP00000288680.4; ENSG00000157837.16. [Q8TCT6-2] DR GeneID; 121665; -. DR KEGG; hsa:121665; -. DR MANE-Select; ENST00000353487.7; ENSP00000288680.4; NM_139015.5; NP_620584.2. DR UCSC; uc001tzd.4; human. [Q8TCT6-2] DR AGR; HGNC:30424; -. DR CTD; 121665; -. DR DisGeNET; 121665; -. DR GeneCards; SPPL3; -. DR HGNC; HGNC:30424; SPPL3. DR HPA; ENSG00000157837; Low tissue specificity. DR MIM; 608240; gene. DR neXtProt; NX_Q8TCT6; -. DR OpenTargets; ENSG00000157837; -. DR VEuPathDB; HostDB:ENSG00000157837; -. DR eggNOG; KOG2443; Eukaryota. DR GeneTree; ENSGT00940000158101; -. DR HOGENOM; CLU_061449_0_0_1; -. DR InParanoid; Q8TCT6; -. DR OMA; VDYQWAY; -. DR OrthoDB; 5485941at2759; -. DR PhylomeDB; Q8TCT6; -. DR TreeFam; TF323842; -. DR PathwayCommons; Q8TCT6; -. DR SignaLink; Q8TCT6; -. DR BioGRID-ORCS; 121665; 45 hits in 1170 CRISPR screens. DR ChiTaRS; SPPL3; human. DR GeneWiki; UNQ1887; -. DR GenomeRNAi; 121665; -. DR Pharos; Q8TCT6; Tbio. DR PRO; PR:Q8TCT6; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q8TCT6; Protein. DR Bgee; ENSG00000157837; Expressed in upper arm skin and 189 other cell types or tissues. DR ExpressionAtlas; Q8TCT6; baseline and differential. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0098553; C:lumenal side of endoplasmic reticulum membrane; IDA:UniProtKB. 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:0032092; P:positive regulation of protein binding; ISS:UniProtKB. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:UniProtKB. DR GO; GO:0006465; P:signal peptide processing; IBA:GO_Central. 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; SIGNAL PEPTIDE PEPTIDASE; 1. DR PANTHER; PTHR12174:SF22; SIGNAL PEPTIDE PEPTIDASE-LIKE 3; 1. DR Pfam; PF04258; Peptidase_A22B; 1. DR SMART; SM00730; PSN; 1. DR Genevisible; Q8TCT6; HS. PE 1: Evidence at protein level; KW Alternative splicing; Endoplasmic reticulum; Golgi apparatus; Hydrolase; KW Membrane; Protease; Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..384 FT /note="Signal peptide peptidase-like 3" FT /id="PRO_0000073912" FT TOPO_DOM 1..8 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:15385547" FT TRANSMEM 9..29 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 30..74 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:15385547" FT TRANSMEM 75..95 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 96..97 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 98..118 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 119..136 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 137..159 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 160..164 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 165..185 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 186..190 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 191..211 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 212..262 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:15385547" FT TRANSMEM 263..283 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 284..311 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 312..332 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 333..339 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 340..360 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 361..384 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:15385547" FT MOTIF 341..343 FT /note="PAL" FT ACT_SITE 200 FT /evidence="ECO:0000250|UniProtKB:P49810" FT ACT_SITE 271 FT /evidence="ECO:0000250|UniProtKB:P49810" FT VAR_SEQ 1..215 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_005205" FT MUTAGEN 200 FT /note="D->A: Does not affect complex glycosylation pattern FT of cellular glycoproteins; when associated with A-271." FT /evidence="ECO:0000269|PubMed:25354954" FT MUTAGEN 271 FT /note="D->A: Loss of intramembrane-cleaving activity toward FT the simian foamy virus envelope glycoprotein gp130. Does FT not affect complex glycosylation pattern of cellular FT glycoproteins; when associated with A-200." FT /evidence="ECO:0000269|PubMed:23132852, FT ECO:0000269|PubMed:25354954" FT CONFLICT 59..81 FT /note="NSTNNSIQTIDSTQALFLPIGAS -> EQEPIIGFQPMDSTRARFLPMGAC FT (in Ref. 2; CAD13135)" FT /evidence="ECO:0000305" FT CONFLICT 139 FT /note="F -> Y (in Ref. 7; BAC11290)" FT /evidence="ECO:0000305" SQ SEQUENCE 384 AA; 42261 MW; 04D8C036355B32A1 CRC64; MAEQTYSWAY SLVDSSQVST FLISILLIVY GSFRSLNMDF ENQDKEKDSN SSSGSFNGNS TNNSIQTIDS TQALFLPIGA SVSLLVMFFF FDSVQVVFTI CTAVLATIAF AFLLLPMCQY LTRPCSPQNK ISFGCCGRFT AAELLSFSLS VMLVLIWVLT GHWLLMDALA MGLCVAMIAF VRLPSLKVSC LLLSGLLIYD VFWVFFSAYI FNSNVMVKVA TQPADNPLDV LSRKLHLGPN VGRDVPRLSL PGKLVFPSST GSHFSMLGIG DIVMPGLLLC FVLRYDNYKK QASGDSCGAP GPANISGRMQ KVSYFHCTLI GYFVGLLTAT VASRIHRAAQ PALLYLVPFT LLPLLTMAYL KGDLRRMWSE PFHSKSSSSR FLEV //