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Q8TCT6

- SPPL3_HUMAN

UniProt

Q8TCT6 - SPPL3_HUMAN

Protein

Signal peptide peptidase-like 3

Gene

SPPL3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    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 – 2011By similarity
    Active sitei272 – 2721By similarity

    GO - Molecular functioni

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

    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

    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

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    PTM / Processingi

    Molecule processing

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

    Protein-protein interaction databases

    BioGridi125743. 3 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8TCT6.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88LumenalSequence Analysis
    Topological domaini30 – 7546CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini97 – 982LumenalSequence Analysis
    Topological domaini120 – 13718CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini161 – 1655LumenalSequence Analysis
    Topological domaini187 – 1915CytoplasmicSequence Analysis
    Topological domaini213 – 26351LumenalSequence AnalysisAdd
    BLAST
    Topological domaini285 – 31228CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini334 – 3407LumenalSequence Analysis
    Topological domaini362 – 38524CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 2921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei76 – 9621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei99 – 11921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei138 – 16023HelicalSequence AnalysisAdd
    BLAST
    Transmembranei166 – 18621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei192 – 21221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei264 – 28421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei313 – 33321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei341 – 36121HelicalSequence AnalysisAdd
    BLAST

    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.By similarity
    The first transmembrane domain may act as a type I signal anchor.

    Sequence similaritiesi

    Belongs to the peptidase A22B family.Curated

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti140 – 1401F → Y in BAC11290. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 216216Missing in isoform 3. 1 PublicationVSP_005205Add
    BLAST
    Alternative sequencei59 – 8224EQEPI…PMGAC → NSTNNSIQTIDSTQALFLPI GAS in isoform 2. 4 PublicationsVSP_005206Add
    BLAST

    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

    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: October 1, 2014
    This is version 111 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