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Information on EC 3.4.23.50 - human endogenous retrovirus K endopeptidase and Organism(s) Homo sapiens and UniProt Accession P10265
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3.4.23.50 human endogenous retrovirus K endopeptidaseSpecify your search results
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Processing at the authentic HIV-1 PR recognition site and release of the mature p17 matrix and the p24 capsid protein, as a result of the cleavage of the -SQNY-/-PIVQ- cleavage site.
Synonyms
herv-k pr, herv-k(hml-2) pro, herv-k protease, herv-k(hml-2) protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
endogenous retrovirus HERV-K10 putative protease
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HERV K10 endopeptidase
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HERV-K PR
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HERV-K protease
human endogenous retrovirus K retropepsin
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additional information
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the enzyme belongs to the human endogenous retrovirus family HERV-K/HML-5
HERV-K protease
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Processing at the authentic HIV-1 PR recognition site and release of the mature p17 matrix and the p24 capsid protein, as a result of the cleavage of the -SQNY-/-PIVQ- cleavage site.
the enzyme contains the aspartic protease triad Asp-Thr-Gly in the catalytic site
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
144114-21-6
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala + H2O
?
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?
2-aminobenzoyl-ATHQVY-(4-nitro)FVRKA + H2O
2-aminobenzoyl-ATHQVY + (4-nitro)FVRKA
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?
Gag polyprotein + H2O
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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?
Gag-Pol polyprotein + H2O
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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?
HERV-K Gag polyprotein + H2O
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processing of HERV-K Gag is dependent on the presence of the functional retroviral protease
HERV-K Gag is processed into matrix protein, a short spacer peptide, p15, capsid and nucelocapsid
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?
HIV-1 matrix-capsid polyprotein + H2O
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processing at the authentic HIV-1 PR recognition site
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?
HIV-1 matrix-capsid polyprotein + H2O
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cleavage also in presence of HIV-1 PR inhibitor
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additional information
?
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the results do not exclude the possibility that the HERV-K PR could complement an HIV-1 PR whoses function is impaired due to drugs or drug-resistant mutations, they clearly demomstrate that the HERV-K PR cannot substitute for the function of the wild-type HIV-1 PR
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?
additional information
?
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the enzyme probably functions in the processing of Gag precursor protein
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additional information
?
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the C-terminal 13-amino-acid extension of the enzyme might play a regulatory role
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additional information
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the N-terminal cleavage site for HERV-K capsid protein matches the sequence consistently found at the N-terminus of all retroviral capsid proteins. The other cleavage sites correspond well to the simplified version of a cleavage site as an amino acid stretch that is hydrophobic and both accessible and flexible, i.e. apparently the space between separately folded domainsof Gag
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Gag polyprotein + H2O
?
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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?
Gag-Pol polyprotein + H2O
?
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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?
additional information
?
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the results do not exclude the possibility that the HERV-K PR could complement an HIV-1 PR whoses function is impaired due to drugs or drug-resistant mutations, they clearly demomstrate that the HERV-K PR cannot substitute for the function of the wild-type HIV-1 PR
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?
additional information
?
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the enzyme probably functions in the processing of Gag precursor protein
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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the enzyme is highly resistant to all the HIV-1 PR inhibitors tested, including L-735,524, Ro31-8959, and ABT 538
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
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pH 5.0, 25°C, 13000 Da C-terminally truncated enzyme form
0.041
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
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pH 5.0, 25°C, 18000 Da enzyme form
0.001
Lys-Ala-Arg-Val-Tyr-Phe(NO2)-Glu-Ala-Nle-NH2
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pH 4.5, 11600 Da core domain
0.0103
Lys-Ala-Arg-Val-Tyr-Phe(NO2)-Glu-Ala-Nle-NH2
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pH 4.5, 18200 Da enzyme form
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.13
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
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pH 5.0, 25°C, 13000 Da C-terminally truncated enzyme form
1.37
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
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pH 5.0, 25°C, 18000 Da enzyme form
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). VPK10_HUMAN
156
0
17108
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
16470
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avarage molecular weight under near physiological conditions, sedimentation equilibrium analysis
17500
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2 * 17500, the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, structure overview
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
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2 * 17500, the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, structure overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
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the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, autoprocessing at the N-terminal sequence Lys-Ala-Ala-Tyr-Trp-Ala-Ser-Gln
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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a C-terminally truncated mutant enzyme shows increased affinity for the peptide substrates and increased sensitivity to peptidomimetic inhibitors compared to the wild-type enzyme
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 9
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room temperature, prolonged incubation, 60% remaining activity in presence or absence of 1 M NaCl, no autolysis
668800
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and C-terminally truncated mutant enzymes from Escherichia coli by ammonium sulfate fractionation, cation and anion exchange chromatography, and hydrophobic interaction chromatography, or recombinant C-terminally truncated mutant enzyme from inclusion bodies by dialysis and pepstatin A affinity chromatography followed by autoprocession to active, soluble enzme
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
213 amino acids of the 3'-end of the HERV-K protease open reading frame are expressed in Escherichia coli. Autocatalytic cleavage of the expressed polypeptide results in a catalytically active 18200 Da protein
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expression of a full-length and C-terminally truncated enzyme in Escherichia coli
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nucleotide sequence determination and analysis, detailed phylogenetic analysis of virus from primates and humans, and structural analysis of 100 HERV-K(HML-5) provirus sequences, reconstruction of a coding-competent HML-5 provirus, overview
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sequence determination and analysis, expression of wild-type and C-terminally truncated mutant enzymes in Escherichia coli
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targeting of the HERV-K PR to protease-deficient HIV-1 virions by expressing it as a Vpr fusion partner. The Vpr fusion proteins are sucessfully delivered to the HIV-1 virions, where the HERV-K PR not only autoprocesses itself to ist mature form, but also cleaves a number of HIV-1 polyproteins
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the enzyme is expressed either as a full-length native protein or as truncated protein in Escherichia coli
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the HERV-K113 sequence is cloned into a small plasmid vector. It is shown that based on a substantial LTR-promoter activity, full length messenger RNA and spliced env-, rec- and 1.5 kb (hel)-transcripts are produced. Envelope protein of HERV-K113 is synthesized as an 85 kDa precursor that is found partially processed. The accessory Rec protein is highly expressed and accumulates in the nucleus. Expression analysis reveals synthesis of the Gag precursor and the protease in lysates of transfected HEK-293T cells. The cloned HERV-K113 provirus is not replication competent
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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in the present study HIV-1 and HCV-1-positive plasma samples are screened for the presence of HERV-K(HML-2) RNA in an RT-PCR using HERV-K pol specific primers. Type 1 and type 2 HERV-K(HML- 2) viral RNA genomes are found to coexist in the same plasma of HIV-1 patients suggesting that HERV-K(HML-2) viral particles are induced in HIV-1-infected individuals
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ono M.; Yasunaga T.; Miyata T.; Ushikubo H.
Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome
J. Virol.
60
589-598
1986
Homo sapiens (P10265)
Towler, E.M.; Gulnik, S.V.; Bhat, T.N.; Xie, D.; Gustschina, E.; Sumpter, T.R.; Robertson, N.; Jones, C.; Sauter, M.; Mueller-Lantzsch, N.; Debouck, C.; Erickson, J.W.
Functional characterization of the protease of human endogenous retrovirus, K10: can it complement HIV-1 protease?
Biochemistry
37
17137-17144
1998
Homo sapiens
Kuhelj, R.; Rizzo, C.J.; Chang, C.H.; Jadhav, P.K.; Towler, E.M.; Korant, B.D.
Inhibition of human endogenous retrovirus-K10 protease in cell-free and cell-based assays
J. Biol. Chem.
276
16674-16682
2001
Homo sapiens
Padow, M.; Lai, L.; Fisher, R.J.; Zhou, Y.C.; Wu, X.; Kappes, J.C.; Towler, E.M.
Analysis of human immunodeficiency virus type 1 containing HERV-K protease
AIDS Res. Hum. Retroviruses
16
1973-1980
2000
Homo sapiens
Schommer, S.; Sauter, M.; Krausslich, H.G.; Best, B.; Mueller-Lantzsch, N.
Characterization of the human endogenous retrovirus K proteinase
J. Gen. Virol.
77
375-379
1996
Homo sapiens
Strisovsky, K.; Kraeusslich, H.
Human retrovirus K10 retropepsin
Handbook of Proteolytic Enzymes (Barrett, J. ; Rawlings, N. D. ; Woessner, J. F. , eds. )
1
182-184
2004
Homo sapiens
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Lavie, L.; Medstrand, P.; Schempp, W.; Meese, E.; Mayer, J.
Human endogenous retrovirus family HERV-K(HML-5): status, evolution, and reconstruction of an ancient betaretrovirus in the human genome
J. Virol.
78
8788-8798
2004
Homo sapiens
Contreras-Galindo, R.; Kaplan, M.H.; Markovitz, D.M.; Lorenzo, E.; Yamamura, Y.
Detection of HERV-K(HML-2) Viral RNA in Plasma of HIV Type 1-Infected Individuals
AIDS Res. Hum. Retroviruses
22
979-984
2006
Homo sapiens
Beimforde, N.; Hanke, K.; Ammar, I.; Kurth, R.; Bannert, N.
Molecular cloning and functional characterization of the human endogenous retrovirus K113
Virology
371
216-225
2008
Homo sapiens
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