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 2B

Gene

SPPL2B

Organism
Homo sapiens (Human)
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 (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

  • aspartic endopeptidase activity, intramembrane cleaving Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • membrane protein ectodomain proteolysis Source: UniProtKB
  • membrane protein intracellular domain proteolysis Source: UniProtKB
  • membrane protein proteolysis Source: UniProtKB
  • regulation of immune response Source: UniProtKB
  • signal peptide processing Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

Enzyme and pathway databases

BioCyciZFISH:ENSG00000005206-MONOMER.
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

HGNCiHGNC:30627. SPPL2B.

Subcellular locationi

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

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • centrosome Source: HPA
  • endosome membrane Source: UniProtKB
  • Golgi-associated vesicle membrane Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of cytoplasmic side of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of lumenal side of endoplasmic reticulum membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • plasma membrane Source: UniProtKB
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi129N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8TCT7.
MaxQBiQ8TCT7.
PeptideAtlasiQ8TCT7.
PRIDEiQ8TCT7.
TopDownProteomicsiQ8TCT7-4. [Q8TCT7-4]

PTM databases

iPTMnetiQ8TCT7.
PhosphoSitePlusiQ8TCT7.

Expressioni

Tissue specificityi

Expressed predominantly in adrenal cortex and mammary gland.1 Publication

Gene expression databases

ExpressionAtlasiQ8TCT7. baseline and differential.
GenevisibleiQ8TCT7. HS.

Organism-specific databases

HPAiHPA039292.

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 homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi121255. 99 interactors.
IntActiQ8TCT7. 3 interactors.

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.
OMAiELAMFWT.
OrthoDBiEOG091G05NG.
PhylomeDBiQ8TCT7.

Family and domain databases

InterProiIPR003137. PA_domain.
IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR033149. SPPL2B.
[Graphical view]
PANTHERiPTHR12174. PTHR12174. 1 hit.
PTHR12174:SF39. PTHR12174:SF39. 1 hit.
PfamiPF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTiSM00730. PSN. 1 hit.
[Graphical view]

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.
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.

Note: No experimental confirmation available.
Show »
Length:511
Mass (Da):56,431
Checksum:i6B496A9879E9D57F
GO

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 rs10402284dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8TCT7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121255. 99 interactors.
IntActiQ8TCT7. 3 interactors.

Protein family/group databases

MEROPSiA22.004.

PTM databases

iPTMnetiQ8TCT7.
PhosphoSitePlusiQ8TCT7.

Polymorphism and mutation databases

BioMutaiSPPL2B.
DMDMi97537015.

Proteomic databases

EPDiQ8TCT7.
MaxQBiQ8TCT7.
PeptideAtlasiQ8TCT7.
PRIDEiQ8TCT7.
TopDownProteomicsiQ8TCT7-4. [Q8TCT7-4]

Protocols and materials databases

DNASUi56928.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi56928.
DisGeNETi56928.
GeneCardsiSPPL2B.
H-InvDBHIX0158528.
HGNCiHGNC:30627. SPPL2B.
HPAiHPA039292.
MIMi608239. gene.
neXtProtiNX_Q8TCT7.
OpenTargetsiENSG00000005206.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00530000062920.
HOVERGENiHBG024193.
InParanoidiQ8TCT7.
KOiK09597.
OMAiELAMFWT.
OrthoDBiEOG091G05NG.
PhylomeDBiQ8TCT7.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000005206-MONOMER.
ReactomeiR-HSA-5357905. Regulation of TNFR1 signaling.

Miscellaneous databases

ChiTaRSiSPPL2B. human.
GeneWikiiSPPL2B.
GenomeRNAii56928.
PROiQ8TCT7.
SOURCEiSearch...

Gene expression databases

ExpressionAtlasiQ8TCT7. baseline and differential.
GenevisibleiQ8TCT7. HS.

Family and domain databases

InterProiIPR003137. PA_domain.
IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
IPR033149. SPPL2B.
[Graphical view]
PANTHERiPTHR12174. PTHR12174. 1 hit.
PTHR12174:SF39. PTHR12174:SF39. 1 hit.
PfamiPF02225. PA. 1 hit.
PF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTiSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPP2B_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT7
Secondary accession number(s): D6W609
, O60365, Q567S3, Q8IUH9, Q9BUY6, Q9H3M4, Q9NPN2, Q9P1Z6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 16, 2006
Last modified: November 2, 2016
This is version 136 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.