REC6_HUMAN
ID REC6_HUMAN Reviewed; 105 AA.
AC Q69383;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=Endogenous retrovirus group K member 6 Rec protein;
DE AltName: Full=Central open reading frame;
DE Short=c-orf;
DE Short=cORF;
DE AltName: Full=Endogenous retrovirus K protein 6;
DE AltName: Full=HERV-K(C7) Rec protein;
DE AltName: Full=HERV-K(HML-2.HOM) Rec protein;
DE AltName: Full=HERV-K108 Rec protein;
DE AltName: Full=HERV-K_7p22.1 provirus Rec protein;
DE AltName: Full=K-Rev;
DE AltName: Full=Rev-like protein;
DE AltName: Full=Rev/Rex homolog;
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 [MRNA], AND CHARACTERIZATION.
RX PubMed=7983704; DOI=10.1128/jvi.69.1.141-149.1995;
RA Loewer R., Toenjes R.R., Korbmacher C., Kurth R., Loewer J.;
RT "Identification of a Rev-related protein by analysis of spliced transcripts
RT of the human endogenous retroviruses HTDV/HERV-K.";
RL J. Virol. 69:141-149(1995).
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=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 [4]
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 [5]
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 [6]
RP CHARACTERIZATION.
RX PubMed=9060628; DOI=10.1128/jvi.71.4.2747-2756.1997;
RA Toenjes R.R., Limbach C., Loewer R., Kurth R.;
RT "Expression of human endogenous retrovirus type K envelope glycoprotein in
RT insect and mammalian cells.";
RL J. Virol. 71:2747-2756(1997).
RN [7]
RP DIVERSITY, AND EXPRESSION.
RX PubMed=15063128; DOI=10.1016/j.virol.2004.01.023;
RA Mayer J., Ehlhardt S., Seifert M., Sauter M., Mueller-Lantzsch N.,
RA Mehraein Y., Zang K.-D., Meese E.U.;
RT "Human endogenous retrovirus HERV-K(HML-2) proviruses with Rec protein
RT coding capacity and transcriptional activity.";
RL Virology 322:190-198(2004).
RN [8]
RP FUNCTION.
RX PubMed=10516058; DOI=10.1128/jvi.73.11.9496-9507.1999;
RA Magin C., Loewer R., Loewer J.;
RT "cORF and RcRE, the Rev/Rex and RRE/RxRE homologues of the human endogenous
RT retrovirus family HTDV/HERV-K.";
RL J. Virol. 73:9496-9507(1999).
RN [9]
RP FUNCTION, INTERACTION WITH XPO1, AND RNA-BINDING.
RX PubMed=10557333; DOI=10.1073/pnas.96.23.13404;
RA Yang J., Bogerd H.P., Peng S., Wiegand H.L., Truant R., Cullen B.R.;
RT "An ancient family of human endogenous retroviruses encodes a functional
RT homolog of the HIV-1 Rev protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:13404-13408(1999).
RN [10]
RP NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF LEU-53; LEU-56 AND LEU-59.
RX PubMed=10683442; DOI=10.1016/s0014-5793(00)01197-2;
RA Boese A., Sauter M., Mueller-Lantzsch N.;
RT "A rev-like NES mediates cytoplasmic localization of HERV-K cORF.";
RL FEBS Lett. 468:65-67(2000).
RN [11]
RP NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF ARG-13; ARG-14; ARG-16;
RP ARG-18 AND ARG-20.
RX PubMed=10936083; DOI=10.1006/viro.2000.0438;
RA Magin C., Hesse J., Loewer J., Loewer R.;
RT "Corf, the Rev/Rex homologue of HTDV/HERV-K, encodes an arginine-rich
RT nuclear localization signal that exerts a trans-dominant phenotype when
RT mutated.";
RL Virology 274:11-16(2000).
RN [12]
RP FUNCTION, AND MUTAGENESIS.
RX PubMed=11000203; DOI=10.1128/jvi.74.20.9353-9361.2000;
RA Bogerd H.P., Wiegand H.L., Yang J., Cullen B.R.;
RT "Mutational definition of functional domains within the Rev homolog encoded
RT by human endogenous retrovirus K.";
RL J. Virol. 74:9353-9361(2000).
RN [13]
RP FUNCTION, INTERACTION WITH ZNF145, AND TRANSFORMING POTENTIAL.
RX PubMed=10980608; DOI=10.1038/sj.onc.1203794;
RA Boese A., Sauter M., Galli U., Best B., Herbst H., Mayer J., Kremmer E.,
RA Roemer K., Mueller-Lantzsch N.;
RT "Human endogenous retrovirus protein cORF supports cell transformation and
RT associates with the promyelocytic leukemia zinc finger protein.";
RL Oncogene 19:4328-4336(2000).
RN [14]
RP HOMOOLIGOMERIZATION.
RX PubMed=11287007; DOI=10.1016/s0014-5793(01)02280-3;
RA Boese A., Galli U., Geyer M., Sauter M., Mueller-Lantzsch N.;
RT "The Rev/Rex homolog HERV-K cORF multimerizes via a C-terminal domain.";
RL FEBS Lett. 493:117-121(2001).
RN [15]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=11105755; DOI=10.1017/s135583820000100x;
RA Yang J., Bogerd H.P., Le S.-Y., Cullen B.R.;
RT "The human endogenous retrovirus K Rev response element coincides with a
RT predicted RNA folding region.";
RL RNA 6:1551-1564(2000).
RN [16]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=11581404; DOI=10.1128/jvi.75.21.10359-10371.2001;
RA Magin-Lachmann C., Hahn S., Strobel H., Held U., Loewer J., Loewer R.;
RT "Rec (formerly Corf) function requires interaction with a complex, folded
RT RNA structure within its responsive element rather than binding to a
RT discrete specific binding site.";
RL J. Virol. 75:10359-10371(2001).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=12083821; DOI=10.1006/viro.2002.1428;
RA Andersson A.-C., Venables P.J.W., Toenjes R.R., Scherer J., Eriksson L.,
RA Larsson E.;
RT "Developmental expression of HERV-R (ERV3) and HERV-K in human tissue.";
RL Virology 297:220-225(2002).
CC -!- FUNCTION: Retroviral replication requires the nuclear export and
CC translation of unspliced, singly-spliced and multiply-spliced
CC derivatives of the initial genomic transcript. Rec interacts with a
CC highly structured RNA element (RcRE) present in the viral 3'LTR and
CC recruits the cellular nuclear export machinery. This permits export to
CC the cytoplasm of unspliced genomic or incompletely spliced subgenomic
CC viral transcripts. {ECO:0000269|PubMed:10516058,
CC ECO:0000269|PubMed:10557333, ECO:0000269|PubMed:10980608,
CC ECO:0000269|PubMed:11000203, ECO:0000269|PubMed:11105755,
CC ECO:0000269|PubMed:11581404}.
CC -!- SUBUNIT: Forms homodimers, homotrimers, and homotetramers via a C-
CC terminal domain. Associates with XPO1 and with ZNF145.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Note=Shuttles
CC between the nucleus and the cytoplasm. When in the nucleus, resides in
CC the nucleolus.
CC -!- TISSUE SPECIFICITY: Expressed at higher level in placenta, expressed at
CC lower level in several organs and cell lines.
CC {ECO:0000269|PubMed:12083821}.
CC -!- MISCELLANEOUS: Despite functional similarity, Rec shares almost no
CC sequence homology with HIV-1 Rev and HTLV-1 Rex.
CC -!- MISCELLANEOUS: Two proviruses inserted as tandem repeats in most of
CC individuals tested. Both proviral genomes encode identical Rec
CC proteins.
CC -!- MISCELLANEOUS: This Rec protein is encoded by a human specific
CC provirus.
CC -!- MISCELLANEOUS: Has a type 2 genome. The HERV-K(HML-2) family contains
CC type 1 and type 2 genomes depending on the absence or presence of 292
CC nucleotides at the 5'-end of the env gene. Rec proteins are translated
CC from a doubly spliced transcript expressed exclusively by HERV-K(HML-2)
CC type 2 proviral genomes. The first exon comprises the 87 N-terminal
CC amino acids of the HERV-K(HML-2) type 2 envelope protein. The second
CC exon (18 amino acids) is positioned in the 3' part of the proviral
CC genome.
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DR EMBL; X82271; CAA57722.1; -; mRNA.
DR EMBL; X82272; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF164614; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF074086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y17832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y17834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF490464; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; Q69383; -.
DR SMR; Q69383; -.
DR BioMuta; HGNC:13915; -.
DR MassIVE; Q69383; -.
DR GeneCards; ERVK-6; -.
DR HGNC; HGNC:13915; ERVK-6.
DR MIM; 605626; gene.
DR neXtProt; NX_Q69383; -.
DR PhylomeDB; Q69383; -.
DR Pharos; Q69383; Tbio.
DR Proteomes; UP000005640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0006406; P:mRNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW Cytoplasm; ERV; mRNA transport; Nucleus; Reference proteome; RNA-binding;
KW Transport; Transposable element.
FT CHAIN 1..105
FT /note="Endogenous retrovirus group K member 6 Rec protein"
FT /id="PRO_0000186775"
FT REGION 1..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 13..20
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 50..59
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 10..24
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 4..6
FT /note="SEM->AAA: No loss of function."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 13..15
FT /note="RRR->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 13
FT /note="R->A: Total loss of function and dominant negative
FT effect; when associated with A-14; A-16; A-18 and A-20."
FT /evidence="ECO:0000269|PubMed:10936083"
FT MUTAGEN 14
FT /note="R->A: Total loss of function and dominant negative
FT effect; when associated with A-13; A-16; A-18 and A-20."
FT /evidence="ECO:0000269|PubMed:10936083"
FT MUTAGEN 16
FT /note="R->A: Total loss of function and dominant negative
FT effect; when associated with A-13; A-14; A-18 and A-20."
FT /evidence="ECO:0000269|PubMed:10936083"
FT MUTAGEN 18
FT /note="R->A: Total loss of function and dominant negative
FT effect; when associated with A-13; A-14; A-16 and A-20."
FT /evidence="ECO:0000269|PubMed:10936083"
FT MUTAGEN 19..20
FT /note="NR->AA: No loss of function."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 20
FT /note="R->A: Total loss of function and dominant negative
FT effect; when associated with A-13; A-14; A-16 and A-18."
FT /evidence="ECO:0000269|PubMed:10936083"
FT MUTAGEN 30..32
FT /note="MVT->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 37..39
FT /note="MKL->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 42..44
FT /note="TKK->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 48..50
FT /note="PTW->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 53..55
FT /note="LKK->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 53
FT /note="L->A: Exclusive nuclear localization; when
FT associated with A-56 and A-59."
FT /evidence="ECO:0000269|PubMed:10683442"
FT MUTAGEN 56
FT /note="L->A: Exclusive nuclear localization; when
FT associated with A-53 and A-59."
FT /evidence="ECO:0000269|PubMed:10683442"
FT MUTAGEN 59..61
FT /note="LAT->AAA: Partial loss of function."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 59
FT /note="L->A: Exclusive nuclear localization; when
FT associated with A-53 and A-56."
FT /evidence="ECO:0000269|PubMed:10683442"
FT MUTAGEN 66..68
FT /note="NTK->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 76..78
FT /note="MLL->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 82..84
FT /note="MIV->AAA: Total loss of function and dominant
FT negative effect."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 86..88
FT /note="MVS->AAA: Partial loss of function."
FT /evidence="ECO:0000269|PubMed:11000203"
FT MUTAGEN 93..95
FT /note="NSS->AAA: No loss of function."
FT /evidence="ECO:0000269|PubMed:11000203"
SQ SEQUENCE 105 AA; 11828 MW; 9935AF374750102F CRC64;
MNPSEMQRKA PPRRRRHRNR APLTHKMNKM VTSEEQMKLP STKKAEPPTW AQLKKLTQLA
TKYLENTKVT QTPESMLLAA LMIVSMVSAG VPNSSEETAT IENGP
