POK18_HUMAN
ID POK18_HUMAN Reviewed; 812 AA.
AC Q9QC07; Q6QAI9; Q96PI5;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Endogenous retrovirus group K member 18 Pol protein;
DE AltName: Full=HERV-K(C1a) Pol protein;
DE AltName: Full=HERV-K110 Pol protein;
DE AltName: Full=HERV-K18 Pol protein;
DE AltName: Full=HERV-K_1q23.3 provirus ancestral Pol protein;
DE Includes:
DE RecName: Full=Reverse transcriptase;
DE EC=2.7.7.49;
DE Includes:
DE RecName: Full=Ribonuclease H;
DE Short=RNase H;
DE EC=3.1.26.4;
GN Name=ERVK-18;
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=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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11672541; DOI=10.1016/s1074-7613(01)00212-6;
RA Stauffer Y., Marguerat S., Meylan F., Ucla C., Sutkowski N., Huber B.T.,
RA Pelet T., Conrad B.;
RT "Interferon-alpha induced endogenous superantigen: a model linking
RT environment and autoimmunity.";
RL Immunity 15:591-601(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-613.
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 76-156.
RA Contreras-Galindo R.A., Chompre G., Gonzalez M., Noel R.J. Jr.;
RT "The human immunodeficiency virus type 1 (HIV-1) Tat protein activates a
RT replication-competent human endogenous retrovirus type K in astrocytes.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
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.
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=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00408};
CC -!- DOMAIN: The LPQG and YXDD motifs are catalytically important and
CC conserved among many retroviruses.
CC -!- MISCELLANEOUS: This protein is synthesized as Gag-Pro and Gag-Pro-Pol
CC polyprotein precursors. These polyproteins are thought, by similarity
CC with type-B retroviruses, to be generated by -1 frameshifts occurring
CC at the Gag-Pro and Pro-Pol genes boundaries.
CC -!- MISCELLANEOUS: Exact N-terminus of this protein has not been formally
CC described.
CC -!- MISCELLANEOUS: Intragenic, in the first intron of CD48 gene.
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; premature stop codon after the RNase H domain.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL60056.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB56603.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; Y18890; CAB56603.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF333072; AAL60056.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL121985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY550203; AAS46612.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9QC07; -.
DR SMR; Q9QC07; -.
DR BioMuta; HGNC:39025; -.
DR DMDM; 52000844; -.
DR MassIVE; Q9QC07; -.
DR PeptideAtlas; Q9QC07; -.
DR PRIDE; Q9QC07; -.
DR GeneCards; ERVK-18; -.
DR HGNC; HGNC:39025; ERVK-18.
DR neXtProt; NX_Q9QC07; -.
DR PhylomeDB; Q9QC07; -.
DR Pharos; Q9QC07; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9QC07; protein.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0035613; F:RNA stem-loop binding; IBA:GO_Central.
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:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015074; P:DNA integration; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; IEA:UniProt.
DR Gene3D; 1.10.10.200; -; 1.
DR Gene3D; 3.30.420.10; -; 2.
DR Gene3D; 3.30.70.270; -; 2.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR017856; Integrase-like_N.
DR InterPro; IPR001584; Integrase_cat-core.
DR InterPro; IPR003308; Integrase_Zn-bd_dom_N.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR002156; RNaseH_domain.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR000477; RT_dom.
DR InterPro; IPR010661; RVT_thumb.
DR Pfam; PF02022; Integrase_Zn; 1.
DR Pfam; PF00075; RNase_H; 1.
DR Pfam; PF00665; rve; 1.
DR Pfam; PF00078; RVT_1; 1.
DR Pfam; PF06817; RVT_thumb; 1.
DR SUPFAM; SSF46919; SSF46919; 1.
DR SUPFAM; SSF53098; SSF53098; 2.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS50994; INTEGRASE; 1.
DR PROSITE; PS50879; RNASE_H_1; 1.
DR PROSITE; PS50878; RT_POL; 1.
DR PROSITE; PS50876; ZF_INTEGRASE; 1.
PE 3: Inferred from homology;
KW DNA-binding; Endonuclease; ERV; Hydrolase; Metal-binding;
KW Multifunctional enzyme; Nuclease; Nucleotidyltransferase;
KW Reference proteome; RNA-directed DNA polymerase; Transferase;
KW Transposable element; Zinc; Zinc-finger.
FT CHAIN 1..812
FT /note="Endogenous retrovirus group K member 18 Pol protein"
FT /id="PRO_0000186767"
FT DOMAIN 57..245
FT /note="Reverse transcriptase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00405"
FT DOMAIN 460..590
FT /note="RNase H type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT DOMAIN 637..803
FT /note="Integrase catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00457"
FT ZN_FING 587..628
FT /note="Integrase-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT MOTIF 161..164
FT /note="LPQG"
FT MOTIF 195..198
FT /note="YXDD"
FT BINDING 469
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT BINDING 469
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT BINDING 497
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT BINDING 517
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT BINDING 582
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00408"
FT BINDING 596
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 600
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 624
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT BINDING 627
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00450"
FT CONFLICT 171
FT /note="I -> L (in Ref. 1; CAB56603)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="R -> C (in Ref. 3; AL121985)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="D -> N (in Ref. 2; AAL60056)"
FT /evidence="ECO:0000305"
FT CONFLICT 643..662
FT /note="VCVLMHYGKWMSHMYLHLGR -> GLCPNALWQMDVTHVPSFGK (in
FT Ref. 2; AAL60056)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="C -> W (in Ref. 2; AAL60056)"
FT /evidence="ECO:0000305"
FT CONFLICT 705
FT /note="E -> K (in Ref. 2; AAL60056)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 812 AA; 91948 MW; 6E25F504DD1F0183 CRC64;
NKSRKRRNRV SFLGVTTVEP PKPIPLTWKT EKLVWVNQWP LPKQKLEALH LLANEQLEKG
HIEPSFSPWN SPVFVIQKKS SKWRMLTDLR AVNAVIQPMG PLQPGLPSPA MIPKDWPLII
IDLKDCFFTI PLAEQDCEKF AFTIPAINNK EPATRFQWKV LPQGMLNSPT ICQTFVGRAL
QPVRDKFSDC YIIHYFDDIL CAAETKDKLI DCYTFLQAEV ANAGLAIASD KIQTSTPFHY
LGMQIENRKI KPQKIEIRKD TLKTLNDFQK LLGDINWIRP TLGIPTYAMS NLFSILRGDS
DLNSKRMLTP EATKEIKLVE EKIQSAQINR IDPLAPLQLL IFATAHSPTG IIIQNTDLVE
WSFLPHSTVK TFTLYLDQIA TLIGPTRLRI IKLCGNDPDK IVVPLTKEQV RQAFINSGAW
QIGLANFVGI IDNHYPKTKI FQFLKLTTWI LPKITRREPL ENALTVFTDG SSNGKVAYTG
PKERVIKTPY QSAQRAELVA VITVLQDFDQ PINIISDSAY VVQATRDVET ALIKYSMDDQ
LNQLFNLLQQ TVRKRNFPFY ITHIRAHTNL PGPLTKANEQ ADLLVSSAFI KAQELHALTH
VNAAGLKNKF DVTWKQAKDI VQHCTQCQVL DLPTQEAGVN PEVCVLMHYG KWMSHMYLHL
GRLSYVHVTV DTYSHFMCAT CQTGESTSHV KKHLLSCFAV MGVPEKIKTD NGPGYCSKAF
QKFLSQWKIS HTTGIPYNSQ GQAIVERTNR TLKTQLVKQK EGGDSKECTT PQMQLNLALY
TLNFLNIYRN QTTTSAEHLT GKKNSPHEGK LI
