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Protein

Signal peptide peptidase-like 2B

Gene

SPPL2B

Organism
Homo sapiens (Human)
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 ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17965014, PubMed:19114711, PubMed:22194595). 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 (PubMed:16829952, PubMed:16829951). May play a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus processed leader peptide gp18 of the envelope glycoprotein gp130 dependently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852).6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei359By similarity1
Active sitei421By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease

Enzyme and pathway databases

ReactomeiR-HSA-5357905 Regulation of TNFR1 signaling

Protein family/group databases

MEROPSiA22.004

Names & Taxonomyi

Protein namesi
Recommended name:
Signal peptide peptidase-like 2B1 PublicationImported (EC:3.4.23.-)
Short name:
SPP-like 2B1 Publication
Short name:
SPPL2b1 Publication
Alternative name(s):
Intramembrane protease 41 Publication
Short name:
IMP-41 Publication
Presenilin homologous protein 4
Short name:
PSH4
Presenilin-like protein 1
Gene namesi
Name:SPPL2B1 PublicationImported
Synonyms:IMP41 Publication, KIAA1532, PSL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000005206.16
HGNCiHGNC:30627 SPPL2B
MIMi608239 gene
neXtProtiNX_Q8TCT7

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 – 174Lumenal1 PublicationAdd BLAST149
Transmembranei175 – 195HelicalSequence analysisAdd BLAST21
Topological domaini196 – 221CytoplasmicSequence analysisAdd BLAST26
Transmembranei222 – 244HelicalSequence analysisAdd BLAST23
Topological domaini245 – 248LumenalSequence analysis4
Transmembranei249 – 271HelicalSequence analysisAdd BLAST23
Topological domaini272 – 293CytoplasmicSequence analysisAdd BLAST22
Transmembranei294 – 314HelicalSequence analysisAdd BLAST21
Topological domaini315 – 319LumenalSequence analysis5
Transmembranei320 – 340HelicalSequence analysisAdd BLAST21
Topological domaini341 – 348CytoplasmicSequence analysis8
Transmembranei349 – 369HelicalSequence analysisAdd BLAST21
Topological domaini370 – 412Lumenal1 PublicationAdd BLAST43
Transmembranei413 – 433HelicalSequence analysisAdd BLAST21
Topological domaini434 – 445CytoplasmicSequence analysisAdd BLAST12
Transmembranei446 – 466HelicalSequence analysisAdd BLAST21
Topological domaini467 – 470LumenalSequence analysis4
Transmembranei471 – 491HelicalSequence analysisAdd BLAST21
Topological domaini492 – 592Cytoplasmic1 PublicationAdd BLAST101

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi421D → A: Loss of intramembrane-cleaving activity toward ITM2B, TNF and the simian foamy virus envelope glycoprotein gp130. 4 Publications1

Organism-specific databases

DisGeNETi56928
OpenTargetsiENSG00000005206

Polymorphism and mutation databases

BioMutaiSPPL2B
DMDMi97537015

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 251 PublicationAdd BLAST25
ChainiPRO_000007390926 – 592Signal peptide peptidase-like 2BAdd BLAST567

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi129N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated (PubMed:15385547, PubMed:15998642).2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8TCT7
MaxQBiQ8TCT7
PeptideAtlasiQ8TCT7
PRIDEiQ8TCT7
ProteomicsDBi74160
74161 [Q8TCT7-2]
74163 [Q8TCT7-4]
TopDownProteomicsiQ8TCT7-4 [Q8TCT7-4]

PTM databases

iPTMnetiQ8TCT7
PhosphoSitePlusiQ8TCT7

Expressioni

Tissue specificityi

Expressed predominantly in adrenal cortex and mammary gland.1 Publication

Gene expression databases

BgeeiENSG00000005206 Expressed in 172 organ(s), highest expression level in right uterine tube
ExpressionAtlasiQ8TCT7 baseline and differential
GenevisibleiQ8TCT7 HS

Organism-specific databases

HPAiCAB005592
HPA039292

Interactioni

Subunit structurei

Monomer (PubMed:15998642, PubMed:16873890). Homodimer (PubMed:15998642, PubMed:16873890). Interacts with ITM2B (PubMed:17965014). Interacts with TNF (PubMed:16829951). Interacts with the simian foamy virus envelope glycoprotein gp130 and its processed leader peptide gp18LP; preferentially interacts with the leader peptide gp18LP (PubMed:23132852).5 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121255, 127 interactors
IntActiQ8TCT7, 3 interactors
MINTiQ8TCT7

Structurei

3D structure databases

ProteinModelPortaliQ8TCT7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini71 – 149PAAdd BLAST79

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi472 – 474PAL3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi350 – 357Poly-Leu8
Compositional biasi509 – 551Pro-richAdd BLAST43

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

GeneTreeiENSGT00530000062920
HOVERGENiHBG024193
InParanoidiQ8TCT7
KOiK09597
OMAiFSNQIPL
OrthoDBiEOG091G05NG
PhylomeDBiQ8TCT7

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 (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Experimental confirmation may be lacking for some isoforms.

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q8TCT7-1) [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
MAAAVAAALA RLLAAFLLLA AQVACEYGMV HVVSQAGGPE GKDYCILYNP
60 70 80 90 100
QWAHLPHDLS KASFLQLRNW TASLLCSAAD LPARGFSNQI PLVARGNCTF
110 120 130 140 150
YEKVRLAQGS GARGLLIVSR ERLVPPGGNK TQYDEIGIPV ALLSYKDMLD
160 170 180 190 200
IFTRFGRTVR AALYAPKEPV LDYNMVIIFI MAVGTVAIGG YWAGSRDVKK
210 220 230 240 250
RYMKHKRDDG PEKQEDEAVD VTPVMTCVFV VMCCSMLVLL YYFYDLLVYV
260 270 280 290 300
VIGIFCLASA TGLYSCLAPC VRRLPFGKCR IPNNSLPYFH KRPQARMLLL
310 320 330 340 350
ALFCVAVSVV WGVFRNEDQW AWVLQDALGI AFCLYMLKTI RLPTFKACTL
360 370 380 390 400
LLLVLFLYDI FFVFITPFLT KSGSSIMVEV ATGPSDSATR EKLPMVLKVP
410 420 430 440 450
RLNSSPLALC DRPFSLLGFG DILVPGLLVA YCHRFDIQVQ SSRVYFVACT
460 470 480 490 500
IAYGVGLLVT FVALALMQRG QPALLYLVPC TLVTSCAVAL WRRELGVFWT
510 520 530 540 550
GSGFAKVLPP SPWAPAPADG PQPPKDSATP LSPQPPSEEP ATSPWPAEQS
560 570 580 590
PKSRTSEEMG AGAPMREPGS PAESEGRDQA QPSPVTQPGA SA
Length:592
Mass (Da):64,644
Last modified:May 16, 2006 - v2
Checksum:i0F49370F16D36AA0
GO
Isoform 2 (identifier: Q8TCT7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     320-592: Missing.

Show »
Length:319
Mass (Da):35,295
Checksum:i5EFEEB110C4C7D7B
GO
Isoform 4 (identifier: Q8TCT7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     506-511: KVLPPS → VNTSLL
     512-592: Missing.

Show »
Length:511
Mass (Da):56,431
Checksum:i6B496A9879E9D57F
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZ50A0A087WZ50_HUMAN
Signal peptide peptidase-like 2B
SPPL2B
291Annotation score:
A0A087WT77A0A087WT77_HUMAN
Signal peptide peptidase-like 2B
SPPL2B
165Annotation score:
A0A087WZ93A0A087WZ93_HUMAN
Signal peptide peptidase-like 2B
SPPL2B
139Annotation score:
A0A087WWL4A0A087WWL4_HUMAN
Signal peptide peptidase-like 2B
SPPL2B
81Annotation score:

Sequence cautioni

The sequence AAC05601 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAG45441 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA96056 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAB96951 differs from that shown. Probable cloning artifact.Curated
The sequence CAB96951 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059780574S → P. Corresponds to variant dbSNP:rs10402284Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005204320 – 592Missing in isoform 2. 1 PublicationAdd BLAST273
Alternative sequenceiVSP_009221506 – 511KVLPPS → VNTSLL in isoform 4. 1 Publication6
Alternative sequenceiVSP_009222512 – 592Missing in isoform 4. 1 PublicationAdd BLAST81

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ345027 mRNA Translation: CAC87788.1
AJ420897 mRNA Translation: CAD13134.1
AY169315 mRNA Translation: AAO12540.1
AB040965 mRNA Translation: BAA96056.1 Different initiation.
AC004410 Genomic DNA Translation: AAC05601.1 Sequence problems.
AC005258 Genomic DNA Translation: AAG45441.1 Different initiation.
CH471139 Genomic DNA Translation: EAW69383.1
CH471139 Genomic DNA Translation: EAW69388.1
BC001788 mRNA Translation: AAH01788.2
BC028391 mRNA Translation: AAH28391.2
BC093046 mRNA Translation: AAH93046.1
AL365405 mRNA Translation: CAB96951.1 Sequence problems.
CCDSiCCDS74252.1 [Q8TCT7-1]
CCDS74253.1 [Q8TCT7-4]
RefSeqiNP_001070706.1, NM_001077238.1 [Q8TCT7-4]
NP_694533.1, NM_152988.2 [Q8TCT7-1]
UniGeneiHs.744026

Genome annotation databases

EnsembliENST00000610743; ENSP00000478510; ENSG00000005206 [Q8TCT7-4]
ENST00000613503; ENSP00000478298; ENSG00000005206 [Q8TCT7-1]
ENST00000618220; ENSP00000480813; ENSG00000005206 [Q8TCT7-2]
GeneIDi56928
KEGGihsa:56928
UCSCiuc032hjm.2 human [Q8TCT7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSPP2B_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT7
Secondary accession number(s): D6W609
, O60365, Q567S3, Q8IUH9, Q9BUY6, Q9H3M4, Q9NPN2, Q9P1Z6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 16, 2006
Last modified: September 12, 2018
This is version 149 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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