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Protein

Signal peptide peptidase-like 2B

Gene

Sppl2b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing. Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus. May play a role in the regulation of innate and adaptive immunity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei352By similarity1
Active sitei414By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease

Enzyme and pathway databases

ReactomeiR-MMU-5357905. Regulation of TNFR1 signaling.

Protein family/group databases

MEROPSiA22.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal peptide peptidase-like 2BBy similarity (EC:3.4.23.-)
Short name:
SPP-like 2BBy similarity
Short name:
SPPL2bBy similarity
Gene namesi
Name:Sppl2bBy similarityImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1920468. Sppl2b.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 168LumenalBy similarityAdd BLAST149
Transmembranei169 – 189HelicalSequence analysisAdd BLAST21
Topological domaini190 – 216CytoplasmicSequence analysisAdd BLAST27
Transmembranei217 – 237HelicalSequence analysisAdd BLAST21
Topological domaini238 – 239LumenalSequence analysis2
Transmembranei240 – 260HelicalSequence analysisAdd BLAST21
Topological domaini261 – 286CytoplasmicSequence analysisAdd BLAST26
Transmembranei287 – 307HelicalSequence analysisAdd BLAST21
Topological domaini308 – 312LumenalSequence analysis5
Transmembranei313 – 333HelicalSequence analysisAdd BLAST21
Topological domaini334 – 341CytoplasmicSequence analysis8
Transmembranei342 – 362HelicalSequence analysisAdd BLAST21
Topological domaini363 – 405LumenalBy similarityAdd BLAST43
Transmembranei406 – 426HelicalSequence analysisAdd BLAST21
Topological domaini427 – 438CytoplasmicSequence analysisAdd BLAST12
Transmembranei439 – 459HelicalSequence analysisAdd BLAST21
Topological domaini460 – 463LumenalSequence analysis4
Transmembranei464 – 484HelicalSequence analysisAdd BLAST21
Topological domaini485 – 578CytoplasmicBy similarityAdd BLAST94

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19By similarityAdd BLAST19
ChainiPRO_000023607620 – 578Signal peptide peptidase-like 2BAdd BLAST559

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi91N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi123N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ3TD49.
PaxDbiQ3TD49.
PeptideAtlasiQ3TD49.
PRIDEiQ3TD49.

PTM databases

iPTMnetiQ3TD49.
PhosphoSitePlusiQ3TD49.
SwissPalmiQ3TD49.

Expressioni

Gene expression databases

BgeeiENSMUSG00000035206.
CleanExiMM_3110056O03RIK.
ExpressionAtlasiQ3TD49. baseline and differential.
GenevisibleiQ3TD49. MM.

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with ITM2B and TNF.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000036289.

Structurei

3D structure databases

ProteinModelPortaliQ3TD49.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini61 – 145PAAdd BLAST85

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi465 – 467PAL3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi343 – 348Poly-Leu6

Domaini

The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP.By similarity

Sequence similaritiesi

Belongs to the peptidase A22B family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2442. Eukaryota.
ENOG410ZP52. LUCA.
GeneTreeiENSGT00530000062920.
HOGENOMiHOG000231496.
HOVERGENiHBG024193.
InParanoidiQ3TD49.
KOiK09597.
OMAiFSNQIPL.
OrthoDBiEOG091G05NG.
PhylomeDBiQ3TD49.
TreeFamiTF319186.

Family and domain databases

InterProiView protein in InterPro
IPR003137. PA_domain.
IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR033149. SPPL2B.
PANTHERiPTHR12174. PTHR12174. 1 hit.
PTHR12174:SF39. PTHR12174:SF39. 1 hit.
PfamiView protein in Pfam
PF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
SMARTiView protein in SMART
SM00730. PSN. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3TD49-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAARLAAAL LLLAAQVACE FGVLRVVSQT SRTRSRDYCI LYNPQWAHLP
60 70 80 90 100
HDLSKVSLLK LRDLSTTQLC SYLDVPAEDF TNQIALVARG NCTFYEKVRL
110 120 130 140 150
AQGSGAHGLL IVSKEKLVPP GGNKTQYEEI SIPVALLSHR DLQDIFRRFG
160 170 180 190 200
REVMVALYAP SEPVMDYNMV IIFVMAVGTV AIGGYWAGSH DVKKYMKHKR
210 220 230 240 250
DDGPEKQEDE AVDVTPVMIC VFVVMCCFML VLLYYFYDRL VYVIIGIFCL
260 270 280 290 300
ASSTGLYSCL APFVRKLPFC TCRVPDNNLP YFHKRPQARM LLLALFCVTV
310 320 330 340 350
SVVWGIFRNE DQWAWVLQDT LGIAFCLYML KTIRLPTFKA CTLLLLVLFI
360 370 380 390 400
YDIFFVFITP FLTKSGNSIM VEVATGPSNS STHEKLPMVL KVPRLNTSPL
410 420 430 440 450
SLCDRPFSLL GFGDILVPGL LVAYCHRFDI QVQSSRIYFV ACTIAYGLGL
460 470 480 490 500
LVTFVALVLM QRGQPALLYL VPCTLLTSCT VALWRRELGA FWTGSGFAKD
510 520 530 540 550
APQTPWAATQ GPVPPKAVGS SLSEQPPSEE LAKSPLSTEE AGAADPAKDP
560 570
DNPVASPLSP SNGDEAQPIP VVKPETSA
Length:578
Mass (Da):63,824
Last modified:May 16, 2006 - v2
Checksum:i864ED8504F5B6873
GO
Isoform 2 (identifier: Q3TD49-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     499-504: KDAPQT → VNTSLL
     505-578: Missing.

Note: No experimental confirmation available.
Show »
Length:504
Mass (Da):56,433
Checksum:i89C11B32AA660C09
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti151R → H in BAE38734 (PubMed:16141072).Curated1
Sequence conflicti194K → KR in BAE41755 (PubMed:16141072).Curated1
Sequence conflicti319D → G in BAE41755 (PubMed:16141072).Curated1
Sequence conflicti514P → R in BAE38734 (PubMed:16141072).Curated1
Sequence conflicti541A → T in BAE38734 (PubMed:16141072).Curated1
Sequence conflicti549D → N in BAE38734 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_018571499 – 504KDAPQT → VNTSLL in isoform 2. 1 Publication6
Alternative sequenceiVSP_018572505 – 578Missing in isoform 2. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK148109 mRNA. Translation: BAE28349.1.
AK166364 mRNA. Translation: BAE38734.1.
AK170375 mRNA. Translation: BAE41755.1.
BC052094 mRNA. Translation: AAH52094.1.
CCDSiCCDS35988.1. [Q3TD49-1]
RefSeqiNP_780404.2. NM_175195.3. [Q3TD49-1]
UniGeneiMm.3285.

Genome annotation databases

EnsembliENSMUST00000035597; ENSMUSP00000036289; ENSMUSG00000035206. [Q3TD49-1]
GeneIDi73218.
KEGGimmu:73218.
UCSCiuc007gfb.1. mouse. [Q3TD49-1]
uc007gfd.1. mouse. [Q3TD49-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSPP2B_MOUSE
AccessioniPrimary (citable) accession number: Q3TD49
Secondary accession number(s): Q3TLQ8, Q3UG60, Q80VZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: December 20, 2017
This is version 95 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families