SPP2B_MOUSE
ID SPP2B_MOUSE Reviewed; 578 AA.
AC Q3TD49; Q3TLQ8; Q3UG60; Q80VZ6;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Signal peptide peptidase-like 2B {ECO:0000250|UniProtKB:Q8TCT7};
DE Short=SPP-like 2B {ECO:0000250|UniProtKB:Q8TCT7};
DE Short=SPPL2b {ECO:0000250|UniProtKB:Q8TCT7};
DE EC=3.4.23.-;
DE Flags: Precursor;
GN Name=Sppl2b {ECO:0000250|UniProtKB:Q8TCT7, ECO:0000312|MGI:MGI:1920468};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Dendritic cell, Mammary gland, and Melanoma;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-578 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=21896273; DOI=10.1016/j.febslet.2011.08.043;
RA Behnke J., Schneppenheim J., Koch-Nolte F., Haag F., Saftig P.,
RA Schroder B.;
RT "Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late
RT endosomes by a tyrosine motif in its C-terminal tail.";
RL FEBS Lett. 585:2951-2957(2011).
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. Catalyzes the
CC intramembrane cleavage of the anchored fragment of shed TNF-alpha
CC (TNF), which promotes the release of the intracellular domain (ICD) for
CC signaling to the nucleus. May play a role in the regulation of innate
CC and adaptive immunity. {ECO:0000250|UniProtKB:Q8TCT7}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with ITM2B and TNF.
CC {ECO:0000250|UniProtKB:Q8TCT7}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21896273};
CC Multi-pass membrane protein {ECO:0000305}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q8TCT7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8TCT7}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q8TCT7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8TCT7}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8TCT7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8TCT7}. Membrane
CC {ECO:0000250|UniProtKB:Q8TCT7}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8TCT7}; Lumenal side
CC {ECO:0000250|UniProtKB:Q8TCT7}. Note=targeted through the entire
CC secretory pathway to endosomes/lysosomes.
CC {ECO:0000250|UniProtKB:Q8TCT7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3TD49-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3TD49-2; Sequence=VSP_018571, VSP_018572;
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. {ECO:0000250|UniProtKB:Q8TCT7}.
CC -!- SIMILARITY: Belongs to the peptidase A22B family. {ECO:0000305}.
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DR EMBL; AK148109; BAE28349.1; -; mRNA.
DR EMBL; AK166364; BAE38734.1; -; mRNA.
DR EMBL; AK170375; BAE41755.1; -; mRNA.
DR EMBL; BC052094; AAH52094.1; -; mRNA.
DR CCDS; CCDS35988.1; -. [Q3TD49-1]
DR RefSeq; NP_780404.2; NM_175195.3. [Q3TD49-1]
DR AlphaFoldDB; Q3TD49; -.
DR BioGRID; 215843; 1.
DR STRING; 10090.ENSMUSP00000036289; -.
DR MEROPS; A22.004; -.
DR GlyGen; Q3TD49; 2 sites.
DR iPTMnet; Q3TD49; -.
DR PhosphoSitePlus; Q3TD49; -.
DR SwissPalm; Q3TD49; -.
DR EPD; Q3TD49; -.
DR MaxQB; Q3TD49; -.
DR PaxDb; Q3TD49; -.
DR PeptideAtlas; Q3TD49; -.
DR PRIDE; Q3TD49; -.
DR ProteomicsDB; 257355; -. [Q3TD49-1]
DR ProteomicsDB; 257356; -. [Q3TD49-2]
DR Antibodypedia; 3352; 73 antibodies from 15 providers.
DR DNASU; 73218; -.
DR Ensembl; ENSMUST00000035597; ENSMUSP00000036289; ENSMUSG00000035206. [Q3TD49-1]
DR GeneID; 73218; -.
DR KEGG; mmu:73218; -.
DR UCSC; uc007gfb.1; mouse. [Q3TD49-1]
DR UCSC; uc007gfd.1; mouse. [Q3TD49-2]
DR CTD; 56928; -.
DR MGI; MGI:1920468; Sppl2b.
DR VEuPathDB; HostDB:ENSMUSG00000035206; -.
DR eggNOG; KOG2442; Eukaryota.
DR GeneTree; ENSGT00940000158753; -.
DR HOGENOM; CLU_023799_2_1_1; -.
DR InParanoid; Q3TD49; -.
DR OMA; VIAPVNC; -.
DR OrthoDB; 535101at2759; -.
DR PhylomeDB; Q3TD49; -.
DR TreeFam; TF319186; -.
DR BRENDA; 3.4.23.B24; 3474.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR BioGRID-ORCS; 73218; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q3TD49; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3TD49; protein.
DR Bgee; ENSMUSG00000035206; Expressed in embryonic brain and 248 other tissues.
DR ExpressionAtlas; Q3TD49; baseline and differential.
DR Genevisible; Q3TD49; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; ISS:UniProtKB.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; ISS:UniProtKB.
DR GO; GO:0033619; P:membrane protein proteolysis; ISS:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; ISS:UniProtKB.
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..19
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT CHAIN 20..578
FT /note="Signal peptide peptidase-like 2B"
FT /id="PRO_0000236076"
FT TOPO_DOM 20..168
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..239
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..286
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..312
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..405
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT TRANSMEM 406..426
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 427..438
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 439..459
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..463
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..578
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT DOMAIN 61..145
FT /note="PA"
FT REGION 502..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 465..467
FT /note="PAL"
FT ACT_SITE 352
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT ACT_SITE 414
FT /evidence="ECO:0000250|UniProtKB:P49810"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 499..504
FT /note="KDAPQT -> VNTSLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018571"
FT VAR_SEQ 505..578
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018572"
FT CONFLICT 151
FT /note="R -> H (in Ref. 1; BAE38734)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="K -> KR (in Ref. 1; BAE41755)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="D -> G (in Ref. 1; BAE41755)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="P -> R (in Ref. 1; BAE38734)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="A -> T (in Ref. 1; BAE38734)"
FT /evidence="ECO:0000305"
FT CONFLICT 549
FT /note="D -> N (in Ref. 1; BAE38734)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 578 AA; 63824 MW; 864ED8504F5B6873 CRC64;
MAAARLAAAL LLLAAQVACE FGVLRVVSQT SRTRSRDYCI LYNPQWAHLP HDLSKVSLLK
LRDLSTTQLC SYLDVPAEDF TNQIALVARG NCTFYEKVRL AQGSGAHGLL IVSKEKLVPP
GGNKTQYEEI SIPVALLSHR DLQDIFRRFG REVMVALYAP SEPVMDYNMV IIFVMAVGTV
AIGGYWAGSH DVKKYMKHKR DDGPEKQEDE AVDVTPVMIC VFVVMCCFML VLLYYFYDRL
VYVIIGIFCL ASSTGLYSCL APFVRKLPFC TCRVPDNNLP YFHKRPQARM LLLALFCVTV
SVVWGIFRNE DQWAWVLQDT LGIAFCLYML KTIRLPTFKA CTLLLLVLFI YDIFFVFITP
FLTKSGNSIM VEVATGPSNS STHEKLPMVL KVPRLNTSPL SLCDRPFSLL GFGDILVPGL
LVAYCHRFDI QVQSSRIYFV ACTIAYGLGL LVTFVALVLM QRGQPALLYL VPCTLLTSCT
VALWRRELGA FWTGSGFAKD APQTPWAATQ GPVPPKAVGS SLSEQPPSEE LAKSPLSTEE
AGAADPAKDP DNPVASPLSP SNGDEAQPIP VVKPETSA
