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Q8TCT6

- SPPL3_HUMAN

UniProt

Q8TCT6 - SPPL3_HUMAN

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Protein
Signal peptide peptidase-like 3
Gene
SPPL3, IMP2, PSL4
Organism
Homo sapiens (Human)
Status
Reviewed - 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.1 Publication

Enzyme regulationi

Its proteolytic activity is blocked by signal peptide peptidase (SPP) inhibitors.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei201 – 2011 By similarity
Active sitei272 – 2721 By similarity

GO - Molecular functioni

  1. aspartic endopeptidase activity, intramembrane cleaving Source: UniProtKB
  2. protein homodimerization activity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

Protein family/group databases

MEROPSiA22.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Signal peptide peptidase-like 3 (EC:3.4.23.-)
Short name:
SPP-like 3
Alternative name(s):
Intramembrane protease 2
Short name:
IMP-2
Presenilin homologous protein 1
Short name:
PSH1
Presenilin-like protein 4
Gene namesi
Name:SPPL3
Synonyms:IMP2, PSL4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:30424. SPPL3.

Subcellular locationi

Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein
Note: Restricted to the early secretory compartment.2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88Lumenal Reviewed prediction
Transmembranei9 – 2921Helical; Reviewed prediction
Add
BLAST
Topological domaini30 – 7546Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei76 – 9621Helical; Reviewed prediction
Add
BLAST
Topological domaini97 – 982Lumenal Reviewed prediction
Transmembranei99 – 11921Helical; Reviewed prediction
Add
BLAST
Topological domaini120 – 13718Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei138 – 16023Helical; Reviewed prediction
Add
BLAST
Topological domaini161 – 1655Lumenal Reviewed prediction
Transmembranei166 – 18621Helical; Reviewed prediction
Add
BLAST
Topological domaini187 – 1915Cytoplasmic Reviewed prediction
Transmembranei192 – 21221Helical; Reviewed prediction
Add
BLAST
Topological domaini213 – 26351Lumenal Reviewed prediction
Add
BLAST
Transmembranei264 – 28421Helical; Reviewed prediction
Add
BLAST
Topological domaini285 – 31228Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei313 – 33321Helical; Reviewed prediction
Add
BLAST
Topological domaini334 – 3407Lumenal Reviewed prediction
Transmembranei341 – 36121Helical; Reviewed prediction
Add
BLAST
Topological domaini362 – 38524Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi-associated vesicle membrane Source: UniProtKB
  2. integral component of cytoplasmic side of endoplasmic reticulum membrane Source: UniProtKB
  3. integral component of lumenal side of endoplasmic reticulum membrane Source: UniProtKB
  4. rough endoplasmic reticulum Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 385385Signal peptide peptidase-like 3
PRO_0000073912Add
BLAST

Post-translational modificationi

Not glycosylated.

Proteomic databases

MaxQBiQ8TCT6.
PaxDbiQ8TCT6.
PRIDEiQ8TCT6.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

ArrayExpressiQ8TCT6.
GenevestigatoriQ8TCT6.

Organism-specific databases

HPAiHPA059958.

Interactioni

Subunit structurei

Monomer. Homodimer.1 Publication

Protein-protein interaction databases

BioGridi125743. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ8TCT6.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi342 – 3443PAL

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi375 – 3806Poly-Ser

Domaini

The PAL motif is required for normal active site conformation By similarity. 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.
The first transmembrane domain may act as a type I signal anchor.

Sequence similaritiesi

Belongs to the peptidase A22B family.

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG250196.
HOGENOMiHOG000243413.
HOVERGENiHBG023986.
InParanoidiQ8TCT6.
KOiK09598.
OMAiYKKQANG.
OrthoDBiEOG7NW69W.
PhylomeDBiQ8TCT6.
TreeFamiTF323842.

Family and domain databases

InterProiIPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERiPTHR12174. PTHR12174. 1 hit.
PfamiPF04258. Peptidase_A22B. 1 hit.
[Graphical view]
SMARTiSM00730. PSN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q8TCT6-1) [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

MAEQTYSWAY SLVDSSQVST FLISILLIVY GSFRSLNMDF ENQDKEKDSN    50
SSSGSFNGEQ EPIIGFQPMD STRARFLPMG ACVSLLVMFF FFDSVQVVFT 100
ICTAVLATIA FAFLLLPMCQ YLTRPCSPQN KISFGCCGRF TAAELLSFSL 150
SVMLVLIWVL TGHWLLMDAL AMGLCVAMIA FVRLPSLKVS CLLLSGLLIY 200
DVFWVFFSAY IFNSNVMVKV ATQPADNPLD VLSRKLHLGP NVGRDVPRLS 250
LPGKLVFPSS TGSHFSMLGI GDIVMPGLLL CFVLRYDNYK KQASGDSCGA 300
PGPANISGRM QKVSYFHCTL IGYFVGLLTA TVASRIHRAA QPALLYLVPF 350
TLLPLLTMAY LKGDLRRMWS EPFHSKSSSS RFLEV 385
Length:385
Mass (Da):42,563
Last modified:June 1, 2002 - v1
Checksum:iBF829565E14A2996
GO
Isoform 2 (identifier: Q8TCT6-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     59-82: EQEPIIGFQPMDSTRARFLPMGAC → NSTNNSIQTIDSTQALFLPIGAS

Show »
Length:384
Mass (Da):42,261
Checksum:i04D8C036355B32A1
GO
Isoform 3 (identifier: Q8TCT6-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.

Show »
Length:169
Mass (Da):18,478
Checksum:i7A97E2C1713CB938
GO

Sequence cautioni

The sequence BAC11290.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 216216Missing in isoform 3.
VSP_005205Add
BLAST
Alternative sequencei59 – 8224EQEPI…PMGAC → NSTNNSIQTIDSTQALFLPI GAS in isoform 2.
VSP_005206Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti140 – 1401F → Y in BAC11290. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ345030 mRNA. Translation: CAC87791.1.
AJ420898 mRNA. Translation: CAD13135.1.
AY169313 mRNA. Translation: AAO12538.1.
AB252457 mRNA. Translation: BAF30928.1.
CH471054 Genomic DNA. Translation: EAW98220.1.
BC009551 mRNA. Translation: AAH09551.1.
BC025781 mRNA. Translation: AAH25781.1.
BC073910 mRNA. Translation: AAH73910.1.
BC101625 mRNA. Translation: AAI01626.1.
BC101627 mRNA. Translation: AAI01628.1.
AK074916 mRNA. Translation: BAC11290.1. Different initiation.
CCDSiCCDS9208.1. [Q8TCT6-2]
RefSeqiNP_620584.2. NM_139015.4. [Q8TCT6-2]
UniGeneiHs.507087.
Hs.683964.

Genome annotation databases

EnsembliENST00000353487; ENSP00000288680; ENSG00000157837. [Q8TCT6-2]
GeneIDi121665.
KEGGihsa:121665.
UCSCiuc001tzc.3. human. [Q8TCT6-1]
uc001tzd.3. human. [Q8TCT6-2]

Polymorphism databases

DMDMi25008979.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ345030 mRNA. Translation: CAC87791.1 .
AJ420898 mRNA. Translation: CAD13135.1 .
AY169313 mRNA. Translation: AAO12538.1 .
AB252457 mRNA. Translation: BAF30928.1 .
CH471054 Genomic DNA. Translation: EAW98220.1 .
BC009551 mRNA. Translation: AAH09551.1 .
BC025781 mRNA. Translation: AAH25781.1 .
BC073910 mRNA. Translation: AAH73910.1 .
BC101625 mRNA. Translation: AAI01626.1 .
BC101627 mRNA. Translation: AAI01628.1 .
AK074916 mRNA. Translation: BAC11290.1 . Different initiation.
CCDSi CCDS9208.1. [Q8TCT6-2 ]
RefSeqi NP_620584.2. NM_139015.4. [Q8TCT6-2 ]
UniGenei Hs.507087.
Hs.683964.

3D structure databases

ProteinModelPortali Q8TCT6.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 125743. 3 interactions.

Protein family/group databases

MEROPSi A22.005.

Polymorphism databases

DMDMi 25008979.

Proteomic databases

MaxQBi Q8TCT6.
PaxDbi Q8TCT6.
PRIDEi Q8TCT6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000353487 ; ENSP00000288680 ; ENSG00000157837 . [Q8TCT6-2 ]
GeneIDi 121665.
KEGGi hsa:121665.
UCSCi uc001tzc.3. human. [Q8TCT6-1 ]
uc001tzd.3. human. [Q8TCT6-2 ]

Organism-specific databases

CTDi 121665.
GeneCardsi GC12M121231.
HGNCi HGNC:30424. SPPL3.
HPAi HPA059958.
MIMi 608240. gene.
neXtProti NX_Q8TCT6.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG250196.
HOGENOMi HOG000243413.
HOVERGENi HBG023986.
InParanoidi Q8TCT6.
KOi K09598.
OMAi YKKQANG.
OrthoDBi EOG7NW69W.
PhylomeDBi Q8TCT6.
TreeFami TF323842.

Miscellaneous databases

ChiTaRSi SPPL3. human.
GeneWikii UNQ1887.
GenomeRNAii 121665.
NextBioi 80798.
PROi Q8TCT6.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8TCT6.
Genevestigatori Q8TCT6.

Family and domain databases

InterProi IPR007369. Peptidase_A22B_SPP.
IPR006639. Preselin/SPP.
[Graphical view ]
PANTHERi PTHR12174. PTHR12174. 1 hit.
Pfami PF04258. Peptidase_A22B. 1 hit.
[Graphical view ]
SMARTi SM00730. PSN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a new protein family with homology to presenilins."
    Irmler M., Tomiuk S., Korner M.R., Hofmann K., Conradt M.
    Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Identification of signal peptide peptidase, a presenilin-type aspartic protease."
    Weihofen A., Binns K., Lemberg M.K., Ashman K., Martoglio B.
    Science 296:2215-2218(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Cervix carcinoma.
  3. "Novel class of polytopic proteins with domains associated with putative protease activity."
    Grigorenko A.P., Moliaka Y.K., Korovaitseva G.I., Rogaev E.I.
    Biochemistry (Mosc.) 67:826-834(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Blood.
  4. "Proteolytic processing, N-glycosylation, and proteasomal degradation of human signal peptide peptidase-like protein 3: the YD and PAL motifs, but not the GXGD motif, are critical for protein stability."
    Kondo K., Heike T., Yorifuji T., Nishikomori R., Kawai M., Ma F., Ma L., Adachi S., Nakahata T.
    Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fetal brain.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORMS 1; 2 AND 3).
    Tissue: Liver, Pancreas and Testis.
  7. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-385 (ISOFORM 2).
    Tissue: Teratocarcinoma.
  8. "Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins."
    Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., Martoglio B.
    J. Biol. Chem. 279:50790-50798(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY, TISSUE SPECIFICITY.
  9. "Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3."
    Krawitz P., Haffner C., Fluhrer R., Steiner H., Schmid B., Haass C.
    J. Biol. Chem. 280:39515-39523(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  10. "Intramembrane proteolytic cleavage by human signal peptide peptidase like 3 and malaria signal peptide peptidase."
    Nyborg A.C., Ladd T.B., Jansen K., Kukar T., Golde T.E.
    FASEB J. 20:1671-1679(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, HOMODIMERIZATION.
  11. "SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production."
    Friedmann E., Hauben E., Maylandt K., Schleeger S., Vreugde S., Lichtenthaler S.F., Kuhn P.H., Stauffer D., Rovelli G., Martoglio B.
    Nat. Cell Biol. 8:843-848(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiSPPL3_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT6
Secondary accession number(s): Q3MJ04, Q8TAU4, Q96DD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: June 1, 2002
Last modified: July 9, 2014
This is version 110 of the entry and version 1 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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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