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Information on EC 3.4.23.50 - human endogenous retrovirus K endopeptidase
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3.4.23.50 human endogenous retrovirus K endopeptidaseSpecify your search results
The enzyme appears in 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(hml-2) protease, herv-k protease, 
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SYNONYM 
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.
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.
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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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additional information
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hundreds of cellular proteins are potential substrates of enzyme HERV-K(HML-2) Pro
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additional information
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identification of human cellular proteins that are substrates of HERV-K(HML-2) Pro employing a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) procedure. Confirmation of cleavage of a majority of selected human proteins in vitro and in co-expression experiments in vivo, overview
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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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?
additional information
?
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hundreds of cellular proteins are potential substrates of enzyme HERV-K(HML-2) Pro
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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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pepstatin A
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a specific inhibitor of retroviral aspartate proteinases
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Infections
Functional characterization of the protease of human endogenous retrovirus, K10: can it complement HIV-1 protease?
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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
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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
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 8
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highest activity at pH 5.5, lowest activity at pH 8.0
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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hundreds of cellular proteins are potential substrates of enzyme HERV-K(HML-2) Pro. Thus, even low-level expression of HERV-K(HML-2) Pro affects levels of a diverse array of proteins and has a functional impact on cell biology and possible relevance for human diseases
Show AA Sequence and Transmembrane Helices (103 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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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
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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
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
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
proteolytic modification
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recombinant HML-2 Pro, harboring self-processing sites, self-processes from the precursor during the expression, purification, and renaturation steps
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
additional information
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two different, enzymatically inactive mutants of HML-2 Pro harboring mutations in catalytic motifs cannot be purified due to inefficient binding to pepstatin A affinity resin
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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
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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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cloning of HML-2 Pro including self-processing sites and in-frame flanking sequence, HML-2 Pro is prokaryotically expressed. HML-2 Pro self-processes from the precursor during the expression, purification, and renaturation steps. Coexpression of the enzyme with HA-tagged potential human substrate proteins HSPA90AA1, MAP2K2, and C15orf57 in HEK-293 cells. The HEK293T cells harvested after 5 h do not show evidence of processing of candidate proteins due to apoptotic processes
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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
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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)
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
-
brenda
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
brenda
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
brenda
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
brenda
Kraus, B.; Boller, K.; Reuter, A.; Schnierle, B.
Characterization of the human endogenous retrovirus K Gag protein: Identification of protease cleavage sites
Retrovirology
8
21
2011
Homo sapiens
brenda
Rigogliuso, G.; Biniossek, M.L.; Goodier, J.L.; Mayer, B.; Pereira, G.C.; Schilling, O.; Meese, E.; Mayer, J.
A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins
Mob. DNA
10
36
2019
Human endogenous retrovirus K
brenda
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