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Protein

Signal peptide peptidase-like 2A

Gene

Sppl2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 FASLG, 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. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD). May play a role in the regulation of innate and adaptive immunity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei355By similarity1
Active sitei416By 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

MEROPSiA22.007
TCDBi1.A.54.3.1 the presenilin er ca(2+) leak channel (presenilin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Signal peptide peptidase-like 2ABy similarity (EC:3.4.23.-)
Short name:
SPP-like 2ABy similarity
Short name:
SPPL2aBy similarity
Alternative name(s):
Intramembrane protease 3By similarity
Short name:
IMP-3By similarity
Presenilin-like protein 2
Gene namesi
Name:Sppl2aBy similarityImported
Synonyms:Imp3By similarity, Psl2
ORF Names:MNCb-3763
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1913802 Sppl2a

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 domaini26 – 175LumenalSequence analysisBy similarityAdd BLAST150
Transmembranei176 – 196HelicalSequence analysisAdd BLAST21
Topological domaini197 – 224CytoplasmicSequence analysisAdd BLAST28
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 247LumenalSequence analysis2
Transmembranei248 – 268HelicalSequence analysisAdd BLAST21
Topological domaini269 – 288CytoplasmicSequence analysisAdd BLAST20
Transmembranei289 – 309HelicalSequence analysisAdd BLAST21
Topological domaini310 – 315LumenalSequence analysis6
Transmembranei316 – 336HelicalSequence analysisAdd BLAST21
Topological domaini337 – 344CytoplasmicSequence analysis8
Transmembranei345 – 365HelicalSequence analysisAdd BLAST21
Topological domaini366 – 403LumenalBy similarityAdd BLAST38
Transmembranei404 – 424HelicalSequence analysisAdd BLAST21
Topological domaini425 – 440CytoplasmicSequence analysisAdd BLAST16
Transmembranei441 – 461HelicalSequence analysisAdd BLAST21
Topological domaini462 – 463LumenalSequence analysis2
Transmembranei464 – 484HelicalSequence analysisAdd BLAST21
Topological domaini485 – 523CytoplasmicBy similarityAdd BLAST39

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi498Y → A: Inhibits lysosomal/late endosomal targeting. 1 Publication1
Mutagenesisi506Y → A: Does not inhibit lysosomal/late endosomal targeting. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25By similarityAdd BLAST25
ChainiPRO_000007391126 – 523Signal peptide peptidase-like 2AAdd BLAST498

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi51N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi61N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi69N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi119N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9JJF9
PaxDbiQ9JJF9
PeptideAtlasiQ9JJF9
PRIDEiQ9JJF9

PTM databases

iPTMnetiQ9JJF9
PhosphoSitePlusiQ9JJF9
SwissPalmiQ9JJF9

Expressioni

Gene expression databases

BgeeiENSMUSG00000027366
CleanExiMM_2010106G01RIK
ExpressionAtlasiQ9JJF9 baseline and differential
GenevisibleiQ9JJF9 MM

Interactioni

Subunit structurei

Interacts with ITM2B.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9JJF9, 2 interactors
MINTiQ9JJF9
STRINGi10090.ENSMUSP00000028844

Structurei

3D structure databases

ProteinModelPortaliQ9JJF9
SMRiQ9JJF9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini70 – 155PAAdd BLAST86

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi466 – 468PAL3
Motifi498 – 501YXXo lysosomal targeting motif4

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). The C-terminal tail is necessary for lysosomal transport (PubMed:21896273).By similarity1 Publication

Sequence similaritiesi

Belongs to the peptidase A22B family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2442 Eukaryota
ENOG410ZP52 LUCA
GeneTreeiENSGT00530000062920
HOGENOMiHOG000231496
HOVERGENiHBG024193
InParanoidiQ9JJF9
KOiK09596
OMAiKKFWKGS
OrthoDBiEOG091G05NG
TreeFamiTF319186

Family and domain databases

InterProiView protein in InterPro
IPR003137 PA_domain
IPR007369 Peptidase_A22B_SPP
IPR006639 Preselin/SPP
IPR033151 SPPL2a
PANTHERiPTHR12174 PTHR12174, 1 hit
PTHR12174:SF34 PTHR12174:SF34, 1 hit
PfamiView protein in Pfam
PF02225 PA, 1 hit
PF04258 Peptidase_A22B, 1 hit
SMARTiView protein in SMART
SM00730 PSN, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9JJF9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLLHSLHAP AAALLWSCLL GLAAAQEAIL HASTNGVSSL SKDYCMYYNN
60 70 80 90 100
NWTRLPSSLE NATSLSLMNL TGTALCHLSD IPPDGIRNKA VVVHWGPCHF
110 120 130 140 150
LEKARIAQEG GAAALLIANN SVLIPSSRNK STFQNVTVLI AVITQKDFKD
160 170 180 190 200
MKETLGDDIT VKMYSPSWPN FDYTLVVIFV IAVFTVALGG YWSGLIELEN
210 220 230 240 250
MKSVEDAEDR ETRKKKDDYL TFSPLTVVVF VVICCIMIVL LYFFYRWLVY
260 270 280 290 300
VMIAIFCIAS SMSLYNCLSA LIHRMPCGQC TILCCGKNIK VSLIFLSGLC
310 320 330 340 350
ISVAVVWAVF RNEDRWAWIL QDILGIAFCL NLIKTMKLPN FMSCVILLGL
360 370 380 390 400
LLIYDVFFVF ITPFITKNGE SIMVELAAGP FENAEKLPVV IRVPKLMGYS
410 420 430 440 450
VMSVCSVPVS VLGFGDIIVP GLLIAYCRRF DVQTGSSIYY ISSTIAYAVG
460 470 480 490 500
MIITFVVLMV MKTGQPALLY LVPCTLITVS VVAWSRKEMK KFWKGSSYQV
510 520
MDHLDYSTNE ENPVTTDEQI VQQ
Length:523
Mass (Da):58,129
Last modified:July 27, 2011 - v2
Checksum:iA15109A71FCF25C4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti74A → P in AAH26578 (PubMed:19468303).Curated1
Sequence conflicti331 – 333NLI → PKV in AAH26578 (PubMed:19468303).Curated3
Sequence conflicti502D → G in BAA95032 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041547 mRNA Translation: BAA95032.1
AL732330, AL928836 Genomic DNA Translation: CAM14542.1
AL928836, AL732330 Genomic DNA Translation: CAM18333.1
CH466519 Genomic DNA Translation: EDL28169.1
BC026578 mRNA Translation: AAH26578.1
CCDSiCCDS16690.1
RefSeqiNP_075709.2, NM_023220.2
XP_011238039.1, XM_011239737.2
UniGeneiMm.269928

Genome annotation databases

EnsembliENSMUST00000028844; ENSMUSP00000028844; ENSMUSG00000027366
GeneIDi66552
KEGGimmu:66552
UCSCiuc008mej.2 mouse

Similar proteinsi

Entry informationi

Entry nameiSPP2A_MOUSE
AccessioniPrimary (citable) accession number: Q9JJF9
Secondary accession number(s): A2AI51, Q8R354
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 125 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

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