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Literature for peptidase A22.003: impas 1 peptidase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Literature Substrates Inhibitors

(Topics flags: A Assay, S Structure, P Specificity, K Knockout, V Review, M Mutation, I Inhibitor, R Splicing. To select only the references relevant to a single topic, click the link above. See explanation.)

    2026
  1. Tomida,S., Kawahara,R., Bienes,K.M., Tokoro,Y., Yamasaki,T. and Kizuka,Y.
    Signal peptide peptidase (SPP)- and SPP-like 3 (SPPL3)-dependent shedding of alpha1,6-fucosyltransferase (FUT8) differentially affects core fucosylation
    J Biol Chem (2026) , 111209-111209. PubMed  Europe PubMed DOI
    2. 2025
  2. Cao,Y., Xie,Q., Zheng,Q., Zhang,J., Yao,M., Du,Z., Zhang,L., Hu,T., Zhao,Y., Du,J., Li,Y., Feng,Y., Melgiri,N.D., Zhao,X., Huang,R. and Sun,Y.
    Macrophage HM13/SPP Enhances Foamy Macrophage Formation and Atherogenesis
    Adv Sci (Weinh) (2025) , e2412498-e2412498. PubMed  Europe PubMed DOI
  3. Huang,G., Guo,X., Wang,J., Ge,X., Kong,F., Shen,Z., Wang,X., Yan,C., Lei,J., Shi,Y. and Zhou,R.
    Structural insights into human signal peptide peptidase
    Proc Natl Acad Sci U S A (2025) 122, e2528340122-e2528340122. PubMed  Europe PubMed DOI  PMC  EPMC
  4. Qiao,W., Xie,X., Shi,P.Y., Ooi,Y.S. and Carette,J.E.
    Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses
    Proc Natl Acad Sci U S A (2025) 122, e2421573122-e2421573122. PubMed  Europe PubMed DOI
  5. Tever,O.K., Mentrup,T., Chinn,I.K., Ishikuma,H., Fluhrer,R., Schmitz,M., Wehner,R., Behrendt,R., Chinen,J. and Schroder,B.
    The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis
    Cell Mol Life Sci (2025) 82, 107-107. PubMed  Europe PubMed DOI  PMC  EPMC
    6. 2024
  6. Avci,D., Heidasch,R., Costa,M., Luchtenborg,C., Kale,D., Brugger,B. and Lemberg,M.K.
    Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase
    J Biol Chem (2024) 300, 105644-105644. PubMed  Europe PubMed DOI  PMC  EPMC
  7. Feng,Y.T., Yang,C.Y., Wu,L., Wang,Y.C., Shen,G.W. and Lin,P.
    BmSPP is a virus resistance gene in Bombyx mori
    Front Immunol (2024) 15, 1377270-1377270. PubMed  Europe PubMed DOI  PMC  EPMC
  8. Mentrup,T., Leinung,N., Patel,M., Fluhrer,R. and Schroder,B.
    The role of SPP/SPPL intramembrane proteases in membrane protein homeostasis
    FEBS J (2024) 291, 25-44. PubMed  Europe PubMed DOI  V
  9. Voorthuijzen,F., Stroobandt,C., van Criekinge,W., Goovaerts,T. and De Meyer,T.
    Loss-of-Imprinting of HM13 Leads to Poor Prognosis in Clear Cell Renal Cell Carcinoma
    Biomolecules (2024) 14 PubMed  Europe PubMed DOI  PMC  EPMC
    10. 2023
  10. Hoppner,S., Schroder,B. and Fluhrer,R.
    Structure and function of SPP/SPPL proteases: insights from biochemical evidence and predictive modeling
    FEBS J (2023) 290, 5456-5474. PubMed  Europe PubMed DOI
  11. Yang,J., Zhai,N., Chen,Y., Wang,L., Chen,R. and Pan,H.
    A signal peptide peptidase is required for ER-symbiosome proximal association and protein secretion
    Nat Commun (2023) 14, 4355-4355. PubMed  Europe PubMed DOI  PMC  EPMC
    12. 2022
  12. Schwake,C., Hyon,M. and Chishti,A.H.
    Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
    Expert Opin Ther Targets (2022) 26, 261-273. PubMed  Europe PubMed DOI  V
    13. 2021
  13. Hirano,J., Yoshio,S., Sakai,Y., Songling,L., Suzuki,T., Itoh,Y., Zhang,H., Chen,D.V., Haga,S., Oomori,H., Kodama,T., Maeda,Y., Ono,Y., Takahashi,Y., Standley,D.M., Yamamoto,M., Moriishi,K., Moriya,K., Kanto,T., Takehara,T., Koike,K., Matsuura,Y. and Okamoto,T.
    Hepatitis C virus modulates signal peptide peptidase to alter host protein processing
    Proc Natl Acad Sci U S A (2021) 118 PubMed  Europe PubMed DOI  PMC  EPMC
  14. Wang,S., Jaggi,U., Yu,J. and Ghiasi,H.
    Blocking HSV-1 glycoprotein K binding to signal peptide peptidase reduces virus infectivity in vitro and in vivo
    PLoS Pathog (2021) 17, e1009848-e1009848. PubMed  Europe PubMed DOI  PMC  EPMC
    15. 2019
  15. Avci,D., Malchus,N.S., Heidasch,R., Lorenz,H., Richter,K., Nessling,M. and Lemberg,M.K.
    The intramembrane protease SPP impacts morphology of the endoplasmic reticulum by triggering degradation of morphogenic proteins
    J Biol Chem (2019) 294, 2786-2800. PubMed  Europe PubMed DOI
  16. Hsu,F.F., Chou,Y.T., Chiang,M.T., Li,F.A., Yeh,C.T., Lee,W.H. and Chau,L.Y.
    Signal peptide peptidase promotes tumor progression via facilitating FKBP8 degradation
    Oncogene (2019) 38, 1688-1701. PubMed  Europe PubMed DOI
  17. Wang,S. and Ghiasi,H.
    Absence of signal peptide peptidase, an essential HSV-1 glycoprotein K (gK) binding partner, reduces virus infectivity in vivo
    J Virol (2019) 93, e01309-19-e01309-19. PubMed  Europe PubMed DOI  K
    18. 2017
  18. Grigorenko,A.P., Moliaka,Y.K., Plotnikova,O.V., Smirnov,A., Nikishina,V.A., Goltsov,A.Y., Gusev,F., Andreeva,T.V., Nelson,O., Bezprozvanny,I. and Rogaev,E.I.
    Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer's disease
    Oncotarget (2017) 8, 82006-82026. PubMed  Europe PubMed DOI  M
  19. Guan,J., Zhang,J., Yuan,S., Yang,B., Clark,K.D., Ling,E. and Huang,W.
    Analysis of the functions of the signal peptidase complex in the midgut of Tribolium castaneum
    Arch Insect Biochem Physiol (2017) 97 PubMed  Europe PubMed DOI
  20. Hirano,J., Okamoto,T., Sugiyama,Y., Suzuki,T., Kusakabe,S., Tokunaga,M., Fukuhara,T., Sasai,M., Tougan,T., Matsunaga,Y., Yamashita,K., Sakai,Y., Yamamoto,M., Horii,T., Standley,D.M., Moriishi,K., Moriya,K., Koike,K. and Matsuura,Y.
    Characterization of SPP inhibitors suppressing propagation of HCV and protozoa
    Proc Natl Acad Sci U S A (2017) 114, E10782-E10782. PubMed  Europe PubMed DOI  I
  21. Schaefer,B., Moriishi,K. and Behrends,S.
    Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase
    PLoS ONE (2017) 12, e0188344-e0188344. PubMed  Europe PubMed DOI  PMC  EPMC
  22. Wei,J.W., Cai,J.Q., Fang,C., Tan,Y.L., Huang,K., Yang,C., Chen,Q., Jiang,C.L. and Kang,C.S.
    Signal peptide peptidase, encoded by HM13, contributes to tumor progression by affecting EGFRvIII secretion profiles in glioblastoma
    CNS Neurosci Ther (2017) 23, 257-265. PubMed  Europe PubMed DOI
    23. 2014
  23. Allen,S.J., Mott,K.R. and Ghiasi,H.
    Inhibitors of signal peptide peptidase (SPP) affect HSV-1 infectivity in vitro and in vivo
    Exp Eye Res (2014) 123, 8-15. PubMed  Europe PubMed DOI  I
  24. Boname,J.M., Bloor,S., Wandel,M.P., Nathan,J.A., Antrobus,R., Dingwell,K.S., Thurston,T.L., Smith,D.L., Smith,J.C., Randow,F. and Lehner,P.J.
    Cleavage by signal peptide peptidase is required for the degradation of selected tail-anchored proteins
    J Cell Biol (2014) 205, 847-862. PubMed  Europe PubMed DOI  PMC  EPMC  K
  25. Chen,C.Y., Malchus,N.S., Hehn,B., Stelzer,W., Avci,D., Langosch,D. and Lemberg,M.K.
    Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u
    EMBO J (2014) 33, 2492-2506. PubMed  Europe PubMed DOI
    26. 2013
  26. Oliveira,C.C., Querido,B., Sluijter,M., de Groot,A.F., van der Zee,R., Rabelink,M.J., Hoeben,R.C., Ossendorp,F., van der Burg,S.H. and van Hall,T.
    New role of signal peptide peptidase to liberate C-terminal peptides for MHC class I presentation
    J Immunol (2013) 191, 4020-4028. PubMed  Europe PubMed DOI
    27. 2012
  27. Lu,S.H., Jeon,A.H., Schmitt-Ulms,G., Qamar,S., Dodd,R., McDonald,B., Li,Y., Meadows,W., Cox,K., Bohm,C., Chen,F., Fraser,P. and St George-Hyslop,P.
    Vigilin interacts with signal peptide peptidase
    Proteome Sci (2012) 10, 33-33. PubMed  Europe PubMed DOI
  28. Wolfe,M.S.
    Signal peptide peptidase
    [ISSN:978-0-12-407744-7] (2012) 3, 281-284. DOI
    29. 2011
  29. Miyashita,H., Maruyama,Y., Isshiki,H., Osawa,S., Ogura,T., Mio,K., Sato,C., Tomita,T. and Iwatsubo,T.
    Three-dimensional structure of the signal peptide peptidase
    J Biol Chem (2011) 286, 26188-26197. PubMed  Europe PubMed DOI  S
    30. 2010
  30. Lee,S.O., Cho,K., Cho,S., Kim,I., Oh,C. and Ahn,K.
    Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation
    EMBO J (2010) 29, 363-375. PubMed  Europe PubMed DOI
  31. Schroder,B. and Saftig,P.
    Molecular insights into mechanisms of intramembrane proteolysis through signal peptide peptidase (SPP)
    Biochem J (2010) 427, e1-e3. PubMed  Europe PubMed DOI
  32. Schrul,B., Kapp,K., Sinning,I. and Dobberstein,B.
    Signal peptide peptidase (SPP) assembles with substrates and misfolded membrane proteins into distinct oligomeric complexes
    Biochem J (2010) 427, 523-534. PubMed  Europe PubMed DOI
    33. 2009
  33. Golde,T.E., Wolfe,M.S. and Greenbaum,D.C.
    Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins
    Semin Cell Dev Biol (2009) 20, 225-230. PubMed  Europe PubMed DOI  V
  34. Han,S., Green,L. and Schnell,D.J.
    The signal peptide peptidase is required for pollen function in Arabidopsis
    Plant Physiol (2009) 149, 1289-1301. PubMed  Europe PubMed DOI  PMC  EPMC
  35. Tamura,T., Kuroda,M., Oikawa,T., Kyozuka,J., Terauchi,K., Ishimaru,Y., Abe,K. and Asakura,T.
    Signal peptide peptidases are expressed in the shoot apex of rice, localized to the endoplasmic reticulum
    Plant Cell Rep (2009) 28, 1615-1621. PubMed  Europe PubMed DOI
  36. Wolfe,M.S.
    Intramembrane-cleaving proteases
    J Biol Chem (2009) 284, 13969-13973. PubMed  Europe PubMed DOI  PMC  EPMC
    37. 2008
  37. El Hage,F., Stroobant,V., Vergnon,I., Baurain,J.F., Echchakir,H., Lazar,V., Chouaib,S., Coulie,P.G. and Mami-Chouaib,F.
    Preprocalcitonin signal peptide generates a cytotoxic T lymphocyte-defined tumor epitope processed by a proteasome-independent pathway
    Proc Natl Acad Sci U S A (2008) 105, 10119-10124. PubMed  Europe PubMed DOI  PMC  EPMC
  38. Okamoto,K., Mori,Y., Komoda,Y., Okamoto,T., Okochi,M., Takeda,M., Suzuki,T., Moriishi,K. and Matsuura,Y.
    Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation
    J Virol (2008) 82, 8349-8361. PubMed  Europe PubMed DOI  PMC  EPMC  P  I
  39. Robakis,T., Bak,B., Lin,S.H., Bernard,D.J. and Scheiffele,P.
    An internal signal sequence directs intramembrane proteolysis of a cellular immunoglobulin domain protein
    J Biol Chem (2008) 283, 36369-36376. PubMed  Europe PubMed DOI  PMC  EPMC
  40. Sato,T., Ananda,K., Cheng,C.I., Suh,E.J., Narayanan,S. and Wolfe,M.S.
    Distinct pharmacological effects of inhibitors of signal peptide peptidase and gamma-secretase
    J Biol Chem (2008) 283, 33287-33295. PubMed  Europe PubMed DOI  PMC  EPMC  I
  41. Targett-Adams,P., Hope,G., Boulant,S. and McLauchlan,J.
    Maturation of hepatitis C virus core protein by signal peptide peptidase is required for virus production
    J Biol Chem (2008) 283, 16850-16859. PubMed  Europe PubMed DOI
    42. 2007
  42. Chang,H.T., Kao,Y.L., Wu,C.M., Fan,T.C., Lai,Y.K., Huang,K.L., Chang,Y.S., Tsai,J.J. and Chang,M.D.
    Signal peptide of eosinophil cationic protein upregulates transforming growth factor-alpha expression in human cells
    J Cell Biochem (2007) 100, 1266-1275. PubMed  Europe PubMed DOI
  43. Narayanan,S., Sato,T. and Wolfe,M.S.
    A C-terminal region of signal peptide peptidase defines a functional domain for intramembrane aspartic protease catalysis
    J Biol Chem (2007) 282, 20172-20179. PubMed  Europe PubMed DOI
    44. 2006
  44. Ait-Goughoulte,M., Hourioux,C., Patient,R., Trassard,S., Brand,D. and Roingeard,P.
    Core protein cleavage by signal peptide peptidase is required for hepatitis C virus-like particle assembly
    J Gen Virol (2006) 87, 855-860. PubMed  Europe PubMed DOI  PMC  EPMC
  45. [YEAR:15-4-2006]Dev,K.K., Chatterjee,S., Osinde,M., Stauffer,D., Morgan,H., Kobialko,M., Dengler,U., Rueeger,H., Martoglio,B. and Rovelli,G.
    Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals
    Eur J Pharmacol (15-4-2006) 540, 10-17. PubMed  Europe PubMed DOI  I
  46. Heimann,M., Roman-Sosa,G., Martoglio,B., Thiel,H.J. and Rumenapf,T.
    Core protein of pestiviruses is processed at the C terminus by signal peptide peptidase
    J Virol (2006) 80, 1915-1921. PubMed  Europe PubMed DOI  PMC  EPMC  I
  47. Hope,R.G., McElwee,M.J. and McLauchlan,J.
    Efficient cleavage by signal peptide peptidase requires residues within the signal peptide between the core and E1 proteins of hepatitis C virus strain J1
    J Gen Virol (2006) 87, 623-627. PubMed  Europe PubMed DOI  P
  48. Nyborg,A.C., Herl,L., Berezovska,O., Thomas,A.V., Ladd,T.B., Jansen,K., Hyman,B.T. and Golde,T.E.
    Signal peptide peptidase (SPP) dimer formation as assessed by fluorescence lifetime imaging microscopy (FLIM) in intact cells
    Mol Neurodegener (2006) 1, 16-16. PubMed  Europe PubMed DOI  PMC  EPMC
  49. [YEAR:18-7-2006]Sato,T., Nyborg,A.C., Iwata,N., Diehl,T.S., Saido,T.C., Golde,T.E. and Wolfe,M.S.
    Signal peptide peptidase: biochemical properties and modulation by nonsteroidal antiinflammatory drugs
    Biochemistry (18-7-2006) 45, 8649-8656. PubMed  Europe PubMed DOI
  50. [YEAR:1-8-2006]Targett-Adams,P., Schaller,T., Hope,G., Lanford,R.E., Lemon,S.M., Martin,A. and McLauchlan,J.
    Signal peptide peptidase cleavage of GB virus B core protein is required for productive infection in vivo
    J Biol Chem (1-8-2006) 281, 29221-29227. PubMed  Europe PubMed DOI
  51. Urny,J., Hermans-Borgmeyer,I. and Schaller,H.C.
    Cell-surface expression of a new splice variant of the mouse signal peptide peptidase
    Biochim Biophys Acta (2006) 1759, 159-165. PubMed  Europe PubMed DOI  R
  52. [YEAR:18-7-2006]Vauloup-Fellous,C., Pene,V., Garaud-Aunis,J., Harper,F., Bardin,S., Suire,Y., Pichard,E., Schmitt,A., Sogni,P., Pierron,G., Briand,P. and Rosenberg,A.R.
    Signal peptide peptidase-catalyzed cleavage of hepatitis C virus core protein is dispensable for virus budding but destabilizes the viral capsid
    J Biol Chem (18-7-2006) 281, 27679-27692. PubMed  Europe PubMed DOI
    53. 2005
  53. [YEAR:16-2-2005]Casso,D.J., Tanda,S., Biehs,B., Martoglio,B. and Kornberg,T.B.
    Drosophila signal peptide peptidase is an essential protease for larval development
    Genetics (16-2-2005) 170, 139-148. PubMed  Europe PubMed DOI  PMC  EPMC
  54. Majeau,N., Gagne,V., Bolduc,M. and Leclerc,D.
    Signal peptide peptidase promotes the formation of hepatitis C virus non-enveloped particles and is captured on the viral membrane during assembly
    J Gen Virol (2005) 86, 3055-3064. PubMed  Europe PubMed DOI
    55. 2004
  55. [YEAR:21-9-2004]Friedmann,E., Lemberg,M.K., Weihofen,A., Dev,K.K., Dengler,U., Rovelli,G. and Martoglio,B.
    Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins
    J Biol Chem (21-9-2004) 279, 50790-50798. PubMed  Europe PubMed DOI
  56. [YEAR:30-4-2004]Lemberg,M.K. and Martoglio,B.
    On the mechanism of SPP-catalysed intramembrane proteolysis; conformational control of peptide bond hydrolysis in the plane of the membrane
    FEBS Lett (30-4-2004) 564, 213-218. PubMed  Europe PubMed DOI
  57. [YEAR:16-1-2004]Moliaka,Y.K., Grigorenko,A., Madera,D. and Rogaev,E.I.
    Impas 1 possesses endoproteolytic activity against multipass membrane protein substrate cleaving the presenilin 1 holoprotein
    FEBS Lett (16-1-2004) 557, 185-192. PubMed  Europe PubMed DOI
  58. [YEAR:12-7-2004]Nyborg,A.C., Jansen,K., Ladd,T.B., Fauq,A. and Golde,T.E.
    A signal peptide peptidase (SPP) reporter activity assay based on the cleavage of type II membrane protein substrates provides further evidence for an inverted orientation of the SPP active site relative to presenilin
    J Biol Chem (12-7-2004) 279, 43148-43156. PubMed  Europe PubMed DOI  A
  59. [YEAR:5-1-2004]Nyborg,A.C., Kornilova,A.Y., Jansen,K., Ladd,T.B., Wolfe,M.S. and Golde,T.E.
    Signal peptide peptidase forms a homodimer that is labeled by an active site-directed gamma-secretase inhibitor
    J Biol Chem (5-1-2004) 279, 15153-15160. PubMed  Europe PubMed DOI  I
  60. Okamoto,K., Moriishi,K., Miyamura,T. and Matsuura,Y.
    Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein
    J Virol (2004) 78, 6370-6380. PubMed  Europe PubMed DOI  PMC  EPMC
  61. [YEAR:17-9-2004]Wu,C.M. and Chang,M.D.
    Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase
    Biochem Biophys Res Commun (17-9-2004) 322, 585-592. PubMed  Europe PubMed DOI
    62. 2003
  62. Urny,J., Hermans-Borgmeyer,I., Gercken,G. and Schaller,H.C.
    Expression of the presenilin-like signal peptide peptidase (SPP) in mouse adult brain and during development
    Gene Expr Patterns (2003) 3, 685-691. PubMed  Europe PubMed DOI
  63. [YEAR:9-5-2003]Weihofen,A., Lemberg,M.K., Friedmann,E., Rueeger,H., Schmitz,A., Paganetti,P., Rovelli,G. and Martoglio,B.
    Targeting presenilin-type aspartic protease signal peptide peptidase with gamma-secretase inhibitors
    J Biol Chem (9-5-2003) 278, 16528-16533. PubMed  Europe PubMed DOI  I
    64. 2002
  64. Grigorenko,A.P., Moliaka,Y.K., Korovaitseva,G.I. and Rogaev,E.I.
    Novel class of polytopic proteins with domains associated with putative protease activity
    Biochemistry (Mosc) (2002) 67, 826-835. PubMed  Europe PubMed DOI
  65. Lemberg,M.K. and Martoglio,B.
    Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis
    Mol Cell (2002) 10, 735-744. PubMed  Europe PubMed DOI
  66. [YEAR:1-8-2002]McLauchlan,J., Lemberg,M.K., Hope,G. and Martoglio,B.
    Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets
    EMBO J (1-8-2002) 21, 3980-3988. PubMed  Europe PubMed DOI  PMC  EPMC  I
  67. [YEAR:21-6-2002]Weihofen,A., Binns,K., Lemberg,M.K., Ashman,K. and Martoglio,B.
    Identification of signal peptide peptidase, a presenilin-type aspartic protease
    Science (21-6-2002) 296, 2215-2218. PubMed  Europe PubMed DOI  I
    68. 2001
  68. [YEAR:1-12-2001]Lemberg,M.K., Bland,F.A., Weihofen,A., Braud,V.M. and Martoglio,B.
    Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes
    J Immunol (1-12-2001) 167, 6441-6446. PubMed  Europe PubMed  I
    69. 1995
  69. [YEAR:25-8-1995]Lyko,F., Martoglio,B., Jungnickel,B., Rapoport,T.A. and Dobberstein,B.
    Signal sequence processing in rough microsomes
    J Biol Chem (25-8-1995) 270, 19873-19878. PubMed  Europe PubMed DOI

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