POK9_HUMAN
ID POK9_HUMAN Reviewed; 1117 AA.
AC P63128; Q9UKH4;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Endogenous retrovirus group K member 9 Pol protein;
DE AltName: Full=HERV-K(C6) Gag-Pol protein;
DE AltName: Full=HERV-K109 Gag-Pol protein;
DE AltName: Full=HERV-K_6q14.1 provirus ancestral Gag-Pol polyprotein;
DE Includes:
DE RecName: Full=Protease;
DE EC=3.4.23.50;
DE AltName: Full=PR;
DE AltName: Full=Retropepsin;
DE Includes:
DE RecName: Full=Reverse transcriptase/ribonuclease H;
DE EC=2.7.7.49;
DE EC=2.7.7.7;
DE EC=3.1.26.4;
DE AltName: Full=p66 RT;
GN Name=ERVK-9;
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=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).
CC -!- FUNCTION: The products of the Gag polyproteins of infectious
CC retroviruses perform highly complex orchestrated tasks during the
CC assembly, budding, maturation, and infection stages of the viral
CC replication cycle. During viral assembly, the proteins form membrane
CC associations and self-associations that ultimately result in budding of
CC an immature virion from the infected cell. Gag precursors also function
CC during viral assembly to selectively bind and package two plus strands
CC of genomic RNA. Endogenous Gag proteins may have kept, lost or modified
CC their original function during evolution (By similarity).
CC {ECO:0000250}.
CC -!- FUNCTION: Early post-infection, the reverse transcriptase converts the
CC viral RNA genome into double-stranded viral DNA. The RNase H domain of
CC the reverse transcriptase performs two functions. It degrades the RNA
CC template and specifically removes the RNA primer from the RNA/DNA
CC hybrid. Following nuclear import, the integrase catalyzes the insertion
CC of the linear, double-stranded viral DNA into the host cell chromosome.
CC Endogenous Pol proteins may have kept, lost or modified their original
CC function during evolution (By similarity). {ECO:0000250}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.49; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00405};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Note=Cytoplasmic membrane (in a
CC transfection system). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Comment=This protein is synthesized as a Gag polypeptide and as a
CC Gag-Pro-Pol polyprotein. The later is the precursor of the Pro and
CC Pol proteins. It is thought, by similarity with type-B retroviruses,
CC to be generated by -1 frameshifts occurring at the Gag-Pro and
CC Pro-Pol genes boundaries.;
CC Name=1;
CC IsoId=P63128-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P63126-1; Sequence=External;
CC -!- DOMAIN: The LPQG motifs are catalytically important and conserved among
CC many retroviruses.
CC -!- DOMAIN: HERV-K Gag polyprotein contains regions homologous to the
CC matrix (MA), capsid (CA) and nucleocapsid (NC) proteins from infectious
CC retroviruses. Evidence suggests that HERV-K(HML-2) Gag polyprotein can
CC be cleaved into mature MA, CA and NC under certain circumstances.
CC However, the exact boundaries as well as the size of processed Gag
CC proteins have not been precisely determined yet.
CC -!- PTM: Myristoylation is essential for retroviral assembly. Alteration of
CC the glycine residue leads to a block in the budding of particles and an
CC accumulation of Gag inside the cell (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages may yield mature proteins.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the beta type-B retroviral polymerase family.
CC HERV class-II K(HML-2) pol subfamily. {ECO:0000305}.
CC -!- CAUTION: Truncated; frameshift leads to premature stop codon.
CC {ECO:0000305}.
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DR EMBL; AF164615; AAD51799.1; ALT_SEQ; Genomic_DNA.
DR PDB; 6SA9; X-ray; 1.80 A; A/B=282-433.
DR PDBsum; 6SA9; -.
DR AlphaFoldDB; P63128; -.
DR SMR; P63128; -.
DR IntAct; P63128; 1.
DR iPTMnet; P63128; -.
DR PhosphoSitePlus; P63128; -.
DR BioMuta; HGNC:39005; -.
DR DMDM; 118572691; -.
DR jPOST; P63128; -.
DR MassIVE; P63128; -.
DR PeptideAtlas; P63128; -.
DR PRIDE; P63128; -.
DR GeneCards; ERVK-9; -.
DR HGNC; HGNC:39005; ERVK-9.
DR neXtProt; NX_P63128; -.
DR PhylomeDB; P63128; -.
DR Pharos; P63128; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; P63128; protein.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-EC.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003964; F:RNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0016032; P:viral process; IEA:InterPro.
DR CDD; cd05482; HIV_retropepsin_like; 1.
DR CDD; cd07557; trimeric_dUTPase; 1.
DR Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.150.490; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR Gene3D; 2.70.40.10; -; 1.
DR Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR003322; B_retro_matrix.
DR InterPro; IPR038124; B_retro_matrix_sf.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR029054; dUTPase-like.
DR InterPro; IPR036157; dUTPase-like_sf.
DR InterPro; IPR033704; dUTPase_trimeric.
DR InterPro; IPR000467; G_patch_dom.
DR InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR000721; Gag_p24_N.
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 InterPro; IPR008916; Retrov_capsid_C.
DR InterPro; IPR008919; Retrov_capsid_N.
DR InterPro; IPR010999; Retrovr_matrix.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF00692; dUTPase; 1.
DR Pfam; PF01585; G-patch; 1.
DR Pfam; PF02337; Gag_p10; 1.
DR Pfam; PF00607; Gag_p24; 1.
DR Pfam; PF19317; Gag_p24_C; 1.
DR Pfam; PF00077; RVP; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF00098; zf-CCHC; 1.
DR SMART; SM00443; G_patch; 1.
DR SMART; SM00343; ZnF_C2HC; 2.
DR SUPFAM; SSF47836; SSF47836; 1.
DR SUPFAM; SSF47943; SSF47943; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF51283; SSF51283; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR SUPFAM; SSF57756; SSF57756; 2.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS50174; G_PATCH; 1.
DR PROSITE; PS50878; RT_POL; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; ERV; Hydrolase; Lipoprotein; Membrane;
KW Metal-binding; Multifunctional enzyme; Myristate; Nucleotidyltransferase;
KW Protease; Reference proteome; Repeat; Ribosomal frameshifting; RNA-binding;
KW RNA-directed DNA polymerase; Transferase; Transposable element; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..1117
FT /note="Endogenous retrovirus group K member 9 Pol protein"
FT /id="PRO_0000186764"
FT DOMAIN 58..195
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 800..875
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT DOMAIN 890..936
FT /note="G-patch"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00092"
FT ZN_FING 544..561
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 580..597
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 165..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..253
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 805
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 312..325
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 330..342
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 347..357
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 360..383
FT /evidence="ECO:0007829|PDB:6SA9"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 405..408
FT /evidence="ECO:0007829|PDB:6SA9"
FT HELIX 413..428
FT /evidence="ECO:0007829|PDB:6SA9"
SQ SEQUENCE 1117 AA; 123620 MW; F7614F482B4117DD CRC64;
MGQTKSKIKS KYASYLSFIK ILLKRGGVKV STKNLIKLFQ IIEQFCPWFP EQGTLDLKDW
KRIGKELKQA GRKGNIIPLT VWNDWAIIKA ALEPFQTEED SISVSDAPGS GIIDCNEKTR
KKSQKETESL HCEYVAEPVM AQSTQNVDYN QLQEVIYPET LKLEGKGPEL VGPSESKPRG
TSPLPAGQVP VTLQPQKQVK ENKTQPPVAY QYWPPAELQY RPPPESQYGY PGMPPAPQGR
APYPQPPTRR LNPTAPPSRQ GSELHEIIDK SRKEGDTEAW QFPVTLEPMP PGEGAQEGEP
PTVEARYKSF SIKILKDMKE GVKQYGPNSP YMRTLLDSIA HGHRLIPYDW EILAKSSLSP
SQFLQFKTWW IDGVQEQVRR NRAANPPVNI DADQLLGIGQ NWSTISQQAL MQNEAIEQVR
AICLRAWEKI QDPGSTCPSF NTVRQGSKEP YPDFVARLQD VAQKSIADEK ARKVIVELMA
YENANPECQS AIKPLKGKVP AGSDVISEYV KACDGIGGAM HKAMLMAQAI TGVVLGGQVR
TFGGKCYNCG QIGHLKKNCP VLNKQNITIQ ATTTGREPPD LCPRCKKGKH WASQCRSKFD
KNGQPLSGNE QRGQPQAPQQ TGAFPIQPFV PQGFQGQQPP LSQVFQGISQ LPQYNNCPPP
QVAVQQVDLC TIQAVSLLPG EPPQKIPTGV YGPLPEGTVG LILGRSSLNL KGVQIHTSVV
DSDYKGEIQL VISSSVPWSA SPGDRIAQLL LLPYIKGGNS EIKRIGGLGS TDPTGKAAYW
ASQVSENRPV CKAIIQGKQF EGLVDTGADV SIIALNQWPK NWPKQKAVTG LVGIGTASEV
YQSMEILHCL GPDNQESTVQ PMITSIPLNL WGRDLLQQWG AEITMPAPLY SPTSQKIMTK
RGYIPGKGLG KNEDGIKIPF EAKINQKREG IGYPFLGAAT IEPPKPIPLT WKTEKPVWVN
QWPLPKQKLE ALHLLANEQL EKGHIEPSFS PWNSPVFVIQ KKSGKWRMLT DLRAVNAVIQ
PMGPLQPGLP SPAMIPKDWP LIIIDLKDCF FTIPLAEQDC EKFAFTIPAI NNKEPATRFQ
WKVLPQGMLN SPTICQTFVG RALQPVKVFR LLYYSLY
