Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei355 – 3551By similarity
Active sitei416 – 4161By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 175150LumenalSequence analysisBy similarityAdd
BLAST
Transmembranei176 – 19621HelicalSequence analysisAdd
BLAST
Topological domaini197 – 22428CytoplasmicSequence analysisAdd
BLAST
Transmembranei225 – 24521HelicalSequence analysisAdd
BLAST
Topological domaini246 – 2472LumenalSequence analysis
Transmembranei248 – 26821HelicalSequence analysisAdd
BLAST
Topological domaini269 – 28820CytoplasmicSequence analysisAdd
BLAST
Transmembranei289 – 30921HelicalSequence analysisAdd
BLAST
Topological domaini310 – 3156LumenalSequence analysis
Transmembranei316 – 33621HelicalSequence analysisAdd
BLAST
Topological domaini337 – 3448CytoplasmicSequence analysis
Transmembranei345 – 36521HelicalSequence analysisAdd
BLAST
Topological domaini366 – 40338LumenalBy similarityAdd
BLAST
Transmembranei404 – 42421HelicalSequence analysisAdd
BLAST
Topological domaini425 – 44016CytoplasmicSequence analysisAdd
BLAST
Transmembranei441 – 46121HelicalSequence analysisAdd
BLAST
Topological domaini462 – 4632LumenalSequence analysis
Transmembranei464 – 48421HelicalSequence analysisAdd
BLAST
Topological domaini485 – 52339CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi498 – 4981Y → A: Inhibits lysosomal/late endosomal targeting. 1 Publication
Mutagenesisi506 – 5061Y → A: Does not inhibit lysosomal/late endosomal targeting. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525By similarityAdd
BLAST
Chaini26 – 523498Signal peptide peptidase-like 2APRO_0000073911Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi51 – 511N-linked (GlcNAc...)Sequence analysis
Glycosylationi61 – 611N-linked (GlcNAc...)Sequence analysis
Glycosylationi69 – 691N-linked (GlcNAc...)Sequence analysis
Glycosylationi119 – 1191N-linked (GlcNAc...)Sequence analysis
Glycosylationi129 – 1291N-linked (GlcNAc...)Sequence analysis
Glycosylationi135 – 1351N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9JJF9.
MaxQBiQ9JJF9.
PaxDbiQ9JJF9.
PeptideAtlasiQ9JJF9.
PRIDEiQ9JJF9.

PTM databases

iPTMnetiQ9JJF9.
PhosphoSiteiQ9JJF9.

Expressioni

Gene expression databases

BgeeiQ9JJF9.
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 interactions.
STRINGi10090.ENSMUSP00000028844.

Structurei

3D structure databases

ProteinModelPortaliQ9JJF9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini70 – 15586PAAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi466 – 4683PAL
Motifi498 – 5014YXXo lysosomal targeting motif

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.
OMAiPDCCSTP.
OrthoDBiEOG769ZJ4.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti74 – 741A → P in AAH26578 (PubMed:19468303).Curated
Sequence conflicti331 – 3333NLI → PKV in AAH26578 (PubMed:19468303).Curated
Sequence conflicti502 – 5021D → G in BAA95032 (Ref. 1) Curated

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_011239737.1.
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_011239737.1.
UniGeneiMm.269928.

3D structure databases

ProteinModelPortaliQ9JJF9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9JJF9. 2 interactions.
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.
PhosphoSiteiQ9JJF9.

Proteomic databases

EPDiQ9JJF9.
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.
OMAiPDCCSTP.
OrthoDBiEOG769ZJ4.
TreeFamiTF319186.

Miscellaneous databases

PROiQ9JJF9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JJF9.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of full-length cDNA clones from mouse brain cDNA library made by oligo-capping method."
    Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.
    Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-333.
    Tissue: Mammary tumor.
  5. "Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail."
    Behnke J., Schneppenheim J., Koch-Nolte F., Haag F., Saftig P., Schroder B.
    FEBS Lett. 585:2951-2957(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY, LYSOSOMAL TARGETING MOTIF, MUTAGENESIS OF TYR-498 AND TYR-506.

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: July 6, 2016
This is version 114 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.