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Protein

Signal peptide peptidase-like 2A

Gene

Sppl2a

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 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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1913802. Sppl2a.

Subcellular locationi

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi61N-linked (GlcNAc...)Sequence analysis1
Glycosylationi69N-linked (GlcNAc...)Sequence analysis1
Glycosylationi119N-linked (GlcNAc...)Sequence analysis1
Glycosylationi129N-linked (GlcNAc...)Sequence analysis1
Glycosylationi135N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9JJF9.
PaxDbiQ9JJF9.
PeptideAtlasiQ9JJF9.
PRIDEiQ9JJF9.

PTM databases

iPTMnetiQ9JJF9.
PhosphoSitePlusiQ9JJF9.

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.
STRINGi10090.ENSMUSP00000028844.

Structurei

3D structure databases

ProteinModelPortaliQ9JJF9.
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.
OMAiMRYDWAG.
OrthoDBiEOG091G05NG.
TreeFamiTF319186.

Family and domain databases

InterProiIPR003137. PA_domain.
IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR033151. SPPL2a.
[Graphical view]
PANTHERiPTHR12174. PTHR12174. 1 hit.
PTHR12174:SF34. PTHR12174:SF34. 1 hit.
PfamiPF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTiSM00730. PSN. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9JJF9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9JJF9. 2 interactors.
STRINGi10090.ENSMUSP00000028844.

Protein family/group databases

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

PTM databases

iPTMnetiQ9JJF9.
PhosphoSitePlusiQ9JJF9.

Proteomic databases

MaxQBiQ9JJF9.
PaxDbiQ9JJF9.
PeptideAtlasiQ9JJF9.
PRIDEiQ9JJF9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi84888.
MGIiMGI:1913802. Sppl2a.

Phylogenomic databases

eggNOGiKOG2442. Eukaryota.
ENOG410ZP52. LUCA.
GeneTreeiENSGT00530000062920.
HOGENOMiHOG000231496.
HOVERGENiHBG024193.
InParanoidiQ9JJF9.
KOiK09596.
OMAiMRYDWAG.
OrthoDBiEOG091G05NG.
TreeFamiTF319186.

Enzyme and pathway databases

ReactomeiR-MMU-5357905. Regulation of TNFR1 signaling.

Miscellaneous databases

PROiQ9JJF9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027366.
CleanExiMM_2010106G01RIK.
ExpressionAtlasiQ9JJF9. baseline and differential.
GenevisibleiQ9JJF9. MM.

Family and domain databases

InterProiIPR003137. PA_domain.
IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR033151. SPPL2a.
[Graphical view]
PANTHERiPTHR12174. PTHR12174. 1 hit.
PTHR12174:SF34. PTHR12174:SF34. 1 hit.
PfamiPF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTiSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPP2A_MOUSE
AccessioniPrimary (citable) accession number: Q9JJF9
Secondary accession number(s): A2AI51, Q8R354
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 117 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.