VPK10_HUMAN
ID VPK10_HUMAN Reviewed; 156 AA.
AC P10265; Q9UKH6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Endogenous retrovirus group K member 10 Pro protein;
DE AltName: Full=HERV-K10 Pro protein;
DE AltName: Full=HERV-K107 Pro protein;
DE AltName: Full=HERV-K_5q33.3 provirus ancestral Pro protein;
DE EC=3.4.23.50;
DE AltName: Full=Protease;
DE AltName: Full=Proteinase;
DE Short=PR;
GN Name=ERVK-10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3021993; DOI=10.1128/jvi.60.2.589-598.1986;
RA Ono M., Yasunaga T., Miyata T., Ushikubo H.;
RT "Nucleotide sequence of human endogenous retrovirus genome related to the
RT mouse mammary tumor virus genome.";
RL J. Virol. 60:589-598(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10469592; DOI=10.1016/s0960-9822(99)80390-x;
RA Barbulescu M., Turner G., Seaman M.I., Deinard A.S., Kidd K.K., Lenz J.;
RT "Many human endogenous retrovirus K (HERV-K) proviruses are unique to
RT humans.";
RL Curr. Biol. 9:861-868(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP CHARACTERIZATION.
RX PubMed=8627242; DOI=10.1099/0022-1317-77-2-375;
RA Schommer S., Sauter M., Krausslich H.G., Best B., Mueller-Lantzsch N.;
RT "Characterization of the human endogenous retrovirus K proteinase.";
RL J. Gen. Virol. 77:375-379(1996).
RN [5]
RP CHARACTERIZATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-26, PROTEIN
RP SEQUENCE OF N-TERMINUS, AND MASS SPECTROMETRY.
RX PubMed=9860826; DOI=10.1021/bi9818927;
RA Towler E.M., Gulnik S.V., Bhat T.N., Xie D., Gustschina E., Sumpter T.R.,
RA Robertson N., Jones C., Sauter M., Mueller-Lantzsch N., Debouck C.,
RA Erickson J.W.;
RT "Functional characterization of the protease of human endogenous
RT retrovirus, K10: can it complement HIV-1 protease?";
RL Biochemistry 37:17137-17144(1998).
RN [6]
RP CHARACTERIZATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-26, PROTEIN
RP SEQUENCE OF N-TERMINUS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11278433; DOI=10.1074/jbc.m008763200;
RA Kuhelj R., Rizzo C.J., Chang C.H., Jadhav P.K., Towler E.M., Korant B.D.;
RT "Inhibition of human endogenous retrovirus-K10 protease in cell-free and
RT cell-based assays.";
RL J. Biol. Chem. 276:16674-16682(2001).
CC -!- FUNCTION: Retroviral proteases have roles in processing of the primary
CC translation products and the maturation of the viral particle.
CC Endogenous Pro proteins may have kept, lost or modified their original
CC function during evolution. This endogenous protein has retained most of
CC the characteristics of retroviral proteases.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Processing at the authentic HIV-1 PR recognition site and
CC release of the mature p17 matrix and the p24 capsid protein, as a
CC result of the cleavage of the -SQNY-|-PIVQ- cleavage site.;
CC EC=3.4.23.50; Evidence={ECO:0000269|PubMed:11278433,
CC ECO:0000269|PubMed:9860826};
CC -!- ACTIVITY REGULATION: Resistant to a number of clinically useful HIV-1
CC PR inhibitors. Inhibited by cyclic urea SD146.
CC -!- SUBUNIT: Active as a homodimer.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=1;
CC Comment=This protein is synthesized as Gag-Pro and Gag-Pro-Pol
CC polyprotein. These polyproteins are thought, by similarity with
CC type-B retroviruses, to be generated by -1 frameshifts occurring at
CC the Gag-Pro and Pro-Pol genes boundaries.;
CC Name=1;
CC IsoId=P10265-1; Sequence=Displayed;
CC -!- PTM: Autoproteolytically processed at the N-terminus. Expected C-
CC terminal autoprocessing not detected. The sequence shown is that of the
CC processed Pro protein.
CC -!- MASS SPECTROMETRY: Mass=18230; Method=MALDI; Note=Reported mass
CC includes mass of a C-terminal His6 tag, expressed in E.coli.;
CC Evidence={ECO:0000269|PubMed:9860826};
CC -!- SIMILARITY: Belongs to the peptidase A2 family. HERV class-II K(HML-2)
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA88032.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M14123; AAA88032.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF164613; AAD51796.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC016577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; C24483; PRHUER.
DR AlphaFoldDB; P10265; -.
DR SMR; P10265; -.
DR MEROPS; A02.011; -.
DR iPTMnet; P10265; -.
DR PhosphoSitePlus; P10265; -.
DR BioMuta; HGNC:39004; -.
DR DMDM; 52001472; -.
DR GeneCards; ERVK-10; -.
DR HGNC; HGNC:39004; ERVK-10.
DR neXtProt; NX_P10265; -.
DR PhylomeDB; P10265; -.
DR BRENDA; 3.4.23.50; 2681.
DR Pharos; P10265; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd05482; HIV_retropepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR000467; G_patch_dom.
DR InterPro; IPR001995; Peptidase_A2_cat.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR034170; Retropepsin-like_cat_dom.
DR InterPro; IPR018061; Retropepsins.
DR Pfam; PF01585; G-patch; 1.
DR Pfam; PF00077; RVP; 1.
DR SMART; SM00443; G_patch; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS50174; G_PATCH; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Autocatalytic cleavage; Direct protein sequencing; ERV;
KW Hydrolase; Protease; Reference proteome; Ribosomal frameshifting;
KW Transposable element.
FT CHAIN 1..156
FT /note="Endogenous retrovirus group K member 10 Pro protein"
FT /id="PRO_0000199544"
FT DOMAIN 21..96
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT DOMAIN 111..156
FT /note="G-patch"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00092"
FT ACT_SITE 26
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT MUTAGEN 26
FT /note="D->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11278433,
FT ECO:0000269|PubMed:9860826"
SQ SEQUENCE 156 AA; 17108 MW; D2C94207A21DF68B CRC64;
WASQVSENRP VCKAIIQGKQ FEGLVDTGAD VSIIALNQWP KNWPKQKAVT GLVGIGTASE
VYQSMEILHC LGPDNQESTV QPMITSIPLN LWGRDLLQQW GAEITMPAPL YSPTSQKIMT
KMGYIPGKGL GKNEDGIKVP VEAKINQERE GIGYPF
