SPP2B_RAT
ID SPP2B_RAT Reviewed; 577 AA.
AC Q5PQL3;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
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|RGD:1308556};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
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:0000250|UniProtKB:Q3TD49};
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 -!- 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; BC087132; AAH87132.1; -; mRNA.
DR RefSeq; NP_001014222.1; NM_001014200.1.
DR AlphaFoldDB; Q5PQL3; -.
DR STRING; 10116.ENSRNOP00000050649; -.
DR GlyGen; Q5PQL3; 1 site.
DR PhosphoSitePlus; Q5PQL3; -.
DR PaxDb; Q5PQL3; -.
DR PRIDE; Q5PQL3; -.
DR GeneID; 362828; -.
DR KEGG; rno:362828; -.
DR UCSC; RGD:1308556; rat.
DR CTD; 56928; -.
DR RGD; 1308556; Sppl2b.
DR VEuPathDB; HostDB:ENSRNOG00000057881; -.
DR eggNOG; KOG2442; Eukaryota.
DR HOGENOM; CLU_023799_2_1_1; -.
DR InParanoid; Q5PQL3; -.
DR OMA; VIAPVNC; -.
DR OrthoDB; 535101at2759; -.
DR PhylomeDB; Q5PQL3; -.
DR TreeFam; TF319186; -.
DR Reactome; R-RNO-5357905; Regulation of TNFR1 signaling.
DR PRO; PR:Q5PQL3; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000057881; Expressed in pancreas and 19 other tissues.
DR Genevisible; Q5PQL3; RN.
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: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 2: Evidence at transcript level;
KW Cell membrane; Endosome; Glycoprotein; Golgi apparatus; Hydrolase;
KW Lysosome; Membrane; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT CHAIN 20..577
FT /note="Signal peptide peptidase-like 2B"
FT /id="PRO_0000236077"
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..577
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT7"
FT DOMAIN 49..149
FT /note="PA"
FT REGION 502..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 465..467
FT /note="PAL"
FT COMPBIAS 557..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ SEQUENCE 577 AA; 63737 MW; 3247629232E44CE0 CRC64;
MAAARLAASL LLLAAQVACE FGVLRVVPQS GGTRGRDYCI LYNPQWAHLP HDLNKVSLLK
LRDLSTTQLC SHLDVPVEDF TNQIALVARG NCTFYEKVRL AQGSGAHGLL IVSKERLVPP
RGNKTQYEEI SIPVALLSHR DLQDIFRRFG HEVMVALYAP SEPVMDYNMV IIFIMAVGTV
ALGGYWAGSH DVKKYMKHKR DDVPEKQEDE AVDVTPVMIC VFVVMCCFML VLLYYFYDRL
VYVIIGIFCL ASSTGLYSCL APCVRKLPFC TCRVPDNNLP YFHKRPQARM LLLALFCVTV
SVVWGVFRNE DQWAWVLQDT LGIAFCLYML RTIRLPTFKA CTLLLLVLFV YDIFFVFITP
YLTKSGNSIM VEVATGPSNS STHEKLPMVL KVPRLNTSPL SLCDRPFSLL GFGDILVPGL
LVAYCHRFDI QVQSSRIYFV ACTIAYGLGL LVTFVALVLM RHGQPALLYL VPCTLLTSCT
VALWRREMGA FWTGSGFADA PQTPWAAPQG PVPPKDVDAS LSEQPRGEEL AQSPLATEEA
GATDPAKDPD SPVAGPLSPS NGDQVQPIPV VTPGTSA
