VPK6_HUMAN
ID VPK6_HUMAN Reviewed; 156 AA.
AC Q9Y6I0; Q9UKH5;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Endogenous retrovirus group K member 6 Pro protein;
DE AltName: Full=HERV-K(C7) Pro protein;
DE AltName: Full=HERV-K(HML-2.HOM) Pro protein;
DE AltName: Full=HERV-K108 Pro protein;
DE AltName: Full=HERV-K_7p22.1 provirus ancestral Pro protein;
DE EC=3.4.23.50;
DE AltName: Full=Protease;
DE AltName: Full=Proteinase;
DE Short=PR;
GN Name=ERVK-6; Synonyms=ERVK6;
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=10080172; DOI=10.1038/6766;
RA Mayer J., Sauter M., Racz A., Scherer D., Mueller-Lantzsch N., Meese E.U.;
RT "An almost-intact human endogenous retrovirus K on human chromosome 7.";
RL Nat. Genet. 21:257-258(1999).
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 [GENOMIC DNA].
RX PubMed=11401447; DOI=10.1006/geno.2000.6488;
RA Reus K., Mayer J., Sauter M., Scherer D., Mueller-Lantzsch N., Meese E.U.;
RT "Genomic organization of the human endogenous retrovirus HERV-K(HML-2.HOM)
RT (ERVK6) on chromosome 7.";
RL Genomics 72:314-320(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10516026; DOI=10.1128/jvi.73.11.9187-9195.1999;
RA Toenjes R.R., Czauderna F., Kurth R.;
RT "Genome wide screening, cloning, chromosomal assignment and expression of
RT full-length human endogenous retrovirus type K (HERV-K).";
RL J. Virol. 73:9187-9195(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
CC -!- FUNCTION: Retroviral proteases have roles in the processing of the
CC primary 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.
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;
CC -!- SUBUNIT: Active as a homodimer. {ECO:0000250}.
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=Q9Y6I0-1; 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 (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Two human-specific proviruses are inserted as tandem
CC repeats with a shared LTR in most individuals tested. The telomeric
CC copy is referred here as 'provirus 41574'. The centromeric copy is
CC referred here as 'provirus 41575'.
CC -!- SIMILARITY: Belongs to the peptidase A2 family. HERV class-II K(HML-2)
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Pro proteins of ERVK-6 tandem proviruses have been initially
CC reported as being identical (AAF88166 and AAD21096). However, the same
CC Pro proteins sequences, when translated from the human genome draft
CC (AC072054), show one conflict with respect to each other.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD21096.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAF88166.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF074086; AAD21096.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF074086; AAF88166.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF164614; AAD51797.1; ALT_SEQ; Genomic_DNA.
DR EMBL; Y17832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y17834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC072054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; Q9Y6I0; -.
DR SMR; Q9Y6I0; -.
DR MEROPS; A02.011; -.
DR BioMuta; HGNC:13915; -.
DR DMDM; 52000882; -.
DR PRIDE; Q9Y6I0; -.
DR GeneCards; ERVK-6; -.
DR HGNC; HGNC:13915; ERVK-6.
DR MIM; 605626; gene.
DR neXtProt; NX_Q9Y6I0; -.
DR PharmGKB; PA134987951; -.
DR PhylomeDB; Q9Y6I0; -.
DR Pharos; Q9Y6I0; 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 3: Inferred from homology;
KW Aspartyl protease; Autocatalytic cleavage; ERV; Hydrolase; Protease;
KW Reference proteome; Ribosomal frameshifting; Transposable element.
FT CHAIN 1..156
FT /note="Endogenous retrovirus group K member 6 Pro protein"
FT /id="PRO_0000199537"
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 CONFLICT 121
FT /note="K -> T (in Ref. 5; in provirus 41574)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 156 AA; 16972 MW; 2E5AD1DF2B057E2A CRC64;
WASQVSENRP VCKAIIQGKQ FEGLVDTGAD VSIIALNQWP KNWPKQKAVT GLVGIGTASE
VYQSTEILHC LGPDNQESTV QPMITSIPLN LWGRDLLQQW GAEITMPAPS YSPTSQKIMT
KMGYIPGKGL GKNEDGIKIP VEAKINQERE GIGNPC
