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Q8IUH8

- SPP2C_HUMAN

UniProt

Q8IUH8 - SPP2C_HUMAN

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Protein
Signal peptide peptidase-like 2C
Gene
SPPL2C, IMP5
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 may be able to cleave type II membrane signal peptides in the hydrophobic plane of the membrane By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei386 – 3861 By similarity
Active sitei448 – 4481 By similarity

GO - Molecular functioni

  1. aspartic-type endopeptidase activity Source: InterPro
  2. protein homodimerization activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease

    Protein family/group databases

    MEROPSiA22.006.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Signal peptide peptidase-like 2C (EC:3.4.23.-)
    Short name:
    SPP-like 2C
    Short name:
    SPPL2c
    Alternative name(s):
    Intramembrane protease 5
    Short name:
    IMP-5
    Gene namesi
    Name:SPPL2C
    Synonyms:IMP5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:28902. SPPL2C.

    Subcellular locationi

    Membrane; Multi-pass membrane protein Inferred. Endoplasmic reticulum membrane; Multi-pass membrane protein 1 Publication

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini22 – 186165Lumenal Reviewed prediction
    Add
    BLAST
    Transmembranei187 – 20721Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini208 – 25346Cytoplasmic Reviewed prediction
    Add
    BLAST
    Transmembranei254 – 27421Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini275 – 2762Lumenal Reviewed prediction
    Transmembranei277 – 29721Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini298 – 31922Cytoplasmic Reviewed prediction
    Add
    BLAST
    Transmembranei320 – 34021Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini341 – 3466Lumenal Reviewed prediction
    Transmembranei347 – 36519Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini366 – 37611Cytoplasmic Reviewed prediction
    Add
    BLAST
    Transmembranei377 – 39721Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini398 – 43942Lumenal Reviewed prediction
    Add
    BLAST
    Transmembranei440 – 46021Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini461 – 47212Cytoplasmic Reviewed prediction
    Add
    BLAST
    Transmembranei473 – 49321Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini494 – 4952Lumenal Reviewed prediction
    Transmembranei496 – 51621Helical; Reviewed prediction
    Add
    BLAST
    Topological domaini517 – 684168Cytoplasmic Reviewed prediction
    Add
    BLAST

    GO - Cellular componenti

    1. endoplasmic reticulum 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
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121 Reviewed prediction
    Add
    BLAST
    Chaini22 – 684663Signal peptide peptidase-like 2C
    PRO_0000314797Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi100 – 1001N-linked (GlcNAc...) Inferred

    Post-translational modificationi

    Glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ8IUH8.
    PRIDEiQ8IUH8.

    Expressioni

    Tissue specificityi

    Ubiquitous.1 Publication

    Gene expression databases

    BgeeiQ8IUH8.
    GenevestigatoriQ8IUH8.

    Organism-specific databases

    HPAiHPA024444.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IUH8.
    SMRiQ8IUH8. Positions 89-175.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini83 – 16381PA
    Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi499 – 5013PAL

    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.

    Sequence similaritiesi

    Belongs to the peptidase A22B family.

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG268366.
    HOGENOMiHOG000231496.
    HOVERGENiHBG024193.
    InParanoidiQ8IUH8.
    KOiK14212.
    OMAiILWVAYR.
    OrthoDBiEOG769ZJ4.
    PhylomeDBiQ8IUH8.
    TreeFamiTF319186.

    Family and domain databases

    InterProiIPR007369. Peptidase_A22B_SPP.
    IPR006639. Preselin/SPP.
    IPR003137. Protease-assoc_domain.
    [Graphical view]
    PANTHERiPTHR12174. PTHR12174. 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.

    Q8IUH8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MACLGFLLPV GFLLLISTVA GGKYGVAHVV SENWSKDYCI LFSSDYITLP    50
    RDLHHAPLLP LYDGTKAPWC PGEDSPHQAQ LRSPSQRPLR QTTAMVMRGN 100
    CSFHTKGWLA QGQGAHGLLI VSRVSDQQCS DTTLAPQDPR QPLADLTIPV 150
    AMLHYADMLD ILSHTRGEAV VRVAMYAPPE PIIDYNMLVI FILAVGTVAA 200
    GGYWAGLTEA NRLQRRRARR GGGSGGHHQL QEAAAAEGAQ KEDNEDIPVD 250
    FTPAMTGVVV TLSCSLMLLL YFFYDHFVYV TIGIFGLGAG IGLYSCLSPL 300
    VCRLSLRQYQ RPPHSLWASL PLPLLLLASL CATVIIFWVA YRNEDRWAWL 350
    LQDTLGISYC LFVLHRVRLP TLKNCSSFLL ALLAFDVFFV FVTPFFTKTG 400
    ESIMAQVALG PAESSSHERL PMVLKVPRLR VSALTLCSQP FSILGFGDIV 450
    VPGFLVAYCC RFDVQVCSRQ IYFVACTVAY AVGLLVTFMA MVLMQMGQPA 500
    LLYLVSSTLL TSLAVAACRQ ELSLFWTGQG RAKMCGLGCA PSAGSRQKQE 550
    GAADAHTAST LERGTSRGAG DLDSNPGEDT TEIVTISENE ATNPEDRSDS 600
    SEGWSDAHLD PNELPFIPPG ASEELMPLMP MAMLIPLMPL MPPPSELGHV 650
    HAQAQAHETG LPWAGLHKRK GLKVRKSMST QAPL 684
    Length:684
    Mass (Da):74,503
    Last modified:November 24, 2009 - v3
    Checksum:i578DA60509765667
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti123 – 1231R → Q.
    Corresponds to variant rs17763658 [ dbSNP | Ensembl ].
    VAR_038048
    Natural varianti303 – 3031R → H.2 Publications
    Corresponds to variant rs242944 [ dbSNP | Ensembl ].
    VAR_038049
    Natural varianti461 – 4611R → P.
    Corresponds to variant rs12185233 [ dbSNP | Ensembl ].
    VAR_038050
    Natural varianti471 – 4711I → V.
    Corresponds to variant rs12185268 [ dbSNP | Ensembl ].
    VAR_038051
    Natural varianti601 – 6011S → P.
    Corresponds to variant rs12373123 [ dbSNP | Ensembl ].
    VAR_038052
    Natural varianti620 – 6201G → R.
    Corresponds to variant rs12373139 [ dbSNP | Ensembl ].
    VAR_038053
    Natural varianti626 – 6261M → V.1 Publication
    VAR_060590
    Natural varianti643 – 6431P → R.
    Corresponds to variant rs12373142 [ dbSNP | Ensembl ].
    VAR_038054
    Natural varianti659 – 6591T → I.
    Corresponds to variant rs16940694 [ dbSNP | Ensembl ].
    VAR_057147

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY169316 Genomic DNA. Translation: AAO12541.1.
    AC003662 Genomic DNA. No translation available.
    AC217770 Genomic DNA. No translation available.
    AC217771 Genomic DNA. No translation available.
    BC022041 mRNA. Translation: AAH22041.2.
    BC025401 mRNA. Translation: AAH25401.1.
    CCDSiCCDS32673.1.
    RefSeqiNP_787078.2. NM_175882.2.
    UniGeneiHs.144491.

    Genome annotation databases

    EnsembliENST00000329196; ENSP00000332488; ENSG00000185294.
    GeneIDi162540.
    KEGGihsa:162540.
    UCSCiuc010wka.2. human.

    Polymorphism databases

    DMDMi269849676.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY169316 Genomic DNA. Translation: AAO12541.1 .
    AC003662 Genomic DNA. No translation available.
    AC217770 Genomic DNA. No translation available.
    AC217771 Genomic DNA. No translation available.
    BC022041 mRNA. Translation: AAH22041.2 .
    BC025401 mRNA. Translation: AAH25401.1 .
    CCDSi CCDS32673.1.
    RefSeqi NP_787078.2. NM_175882.2.
    UniGenei Hs.144491.

    3D structure databases

    ProteinModelPortali Q8IUH8.
    SMRi Q8IUH8. Positions 89-175.
    ModBasei Search...

    Protein family/group databases

    MEROPSi A22.006.

    Polymorphism databases

    DMDMi 269849676.

    Proteomic databases

    PaxDbi Q8IUH8.
    PRIDEi Q8IUH8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000329196 ; ENSP00000332488 ; ENSG00000185294 .
    GeneIDi 162540.
    KEGGi hsa:162540.
    UCSCi uc010wka.2. human.

    Organism-specific databases

    CTDi 162540.
    GeneCardsi GC17P043923.
    H-InvDB HIX0013905.
    HGNCi HGNC:28902. SPPL2C.
    HPAi HPA024444.
    MIMi 608284. gene.
    neXtProti NX_Q8IUH8.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG268366.
    HOGENOMi HOG000231496.
    HOVERGENi HBG024193.
    InParanoidi Q8IUH8.
    KOi K14212.
    OMAi ILWVAYR.
    OrthoDBi EOG769ZJ4.
    PhylomeDBi Q8IUH8.
    TreeFami TF319186.

    Miscellaneous databases

    GenomeRNAii 162540.
    NextBioi 88197.
    PROi Q8IUH8.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8IUH8.
    Genevestigatori Q8IUH8.

    Family and domain databases

    InterProi IPR007369. Peptidase_A22B_SPP.
    IPR006639. Preselin/SPP.
    IPR003137. Protease-assoc_domain.
    [Graphical view ]
    PANTHERi PTHR12174. PTHR12174. 1 hit.
    Pfami PF02225. PA. 1 hit.
    PF04258. Peptidase_A22B. 1 hit.
    [Graphical view ]
    SMARTi SM00730. PSN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    « Hide 'large scale' publications
    1. "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 [GENOMIC DNA], VARIANT HIS-303.
    2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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], VARIANTS HIS-303 AND VAL-626.
      Tissue: Testis.
    4. "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: GLYCOSYLATION, TOPOLOGY, TISSUE SPECIFICITY.
    5. "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 nameiSPP2C_HUMAN
    AccessioniPrimary (citable) accession number: Q8IUH8
    Secondary accession number(s): Q8TC67, Q8WVZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: November 24, 2009
    Last modified: July 9, 2014
    This is version 76 of the entry and version 3 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 17
      Human chromosome 17: 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

    External Data

    Dasty 3

    Similar proteinsi