ENK6_HUMAN
ID ENK6_HUMAN Reviewed; 699 AA.
AC Q69384; Q8TD93; Q9UBU4; Q9YNA5; Q9YNA9;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Endogenous retrovirus group K member 6 Env polyprotein;
DE AltName: Full=EnvK2 protein;
DE AltName: Full=Envelope polyprotein;
DE AltName: Full=HERV-K(C7) envelope protein;
DE AltName: Full=HERV-K(HML-2.HOM) envelope protein;
DE AltName: Full=HERV-K108 envelope protein;
DE AltName: Full=HERV-K_7p22.1 provirus ancestral Env polyprotein;
DE Contains:
DE RecName: Full=Surface protein;
DE Short=SU;
DE Contains:
DE RecName: Full=Transmembrane protein;
DE Short=TM;
DE Flags: Precursor;
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].
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-674.
RA Reus K., Stuhr T., Mayer J., Meese E.U.;
RT "Haplotype analysis of human endogenous retroviruses: a genetic variant of
RT HERV-K(HML-2.HOM) with an intact YXDD motif of reverse transcriptase.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11401426; DOI=10.1006/geno.2001.6473;
RA Sugimoto J., Matsuura N., Kinjo Y., Takasu N., Oda T., Jinno Y.;
RT "Transcriptionally active HERV-K genes: identification, isolation, and
RT chromosomal mapping.";
RL Genomics 72:137-144(2001).
RN [8]
RP CHARACTERIZATION.
RX PubMed=12970426; DOI=10.1128/jvi.77.19.10414-10422.2003;
RA de Parseval N., Lazar V., Casella J.-F., Benit L., Heidmann T.;
RT "Survey of human genes of retroviral origin: identification and
RT transcriptome of the genes with coding capacity for complete envelope
RT proteins.";
RL J. Virol. 77:10414-10422(2003).
RN [9]
RP FUNCTION.
RX PubMed=14557543; DOI=10.1073/pnas.2132646100;
RA Blaise S., de Parseval N., Benit L., Heidmann T.;
RT "Genomewide screening for fusogenic human endogenous retrovirus envelopes
RT identifies syncytin 2, a gene conserved on primate evolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13013-13018(2003).
RN [10]
RP SUBGENOMIC RNA.
RX PubMed=12629516; DOI=10.1038/sj.onc.1206241;
RA Wang-Johanning F., Frost A.R., Jian B., Epp L., Lu D.W., Johanning G.L.;
RT "Quantitation of HERV-K env gene expression and splicing in human breast
RT cancer.";
RL Oncogene 22:1528-1535(2003).
CC -!- FUNCTION: Retroviral envelope proteins mediate receptor recognition and
CC membrane fusion during early infection. Endogenous envelope proteins
CC may have kept, lost or modified their original function during
CC evolution. This endogenous envelope protein has lost its original
CC fusogenic properties. {ECO:0000269|PubMed:14557543}.
CC -!- FUNCTION: SU mediates receptor recognition. {ECO:0000250}.
CC -!- FUNCTION: TM anchors the envelope heterodimer to the viral membrane
CC through one transmembrane domain. The other hydrophobic domain, called
CC fusion peptide, mediates fusion of the viral membrane with the target
CC cell membrane (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: The surface (SU) and transmembrane (TM) proteins form a
CC heterodimer. SU and TM are attached by noncovalent interactions or by a
CC labile interchain disulfide bond (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protein]: Cell membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Surface protein]: Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Note=The surface protein is
CC not anchored to the membrane, but localizes to the extracellular
CC surface through its binding to TM. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Endogenous retrovirus group K member 6 Env
CC polyprotein]: Virion {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, and peripheral blood
CC lymphocytes. {ECO:0000269|PubMed:11401426}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield the mature SU and TM
CC proteins. {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 -!- MISCELLANEOUS: ERVK-6 has a type 2 genome. The HERV-K(HML-2) family
CC contains type 1 and type 2 genomes depending on the absence or presence
CC of 292 nucleotides at the 5'-end of the env gene resulting in Env
CC proteins of distinct sizes. Despite their overall retroviral envelope
CC structure HERV-K(HML-2) type 1 envelope proteins lack a predictable
CC signal sequence. Subgenomic RNA transcripts coding for full-length
CC envelope proteins have been detected for both type of genomes.
CC -!- SIMILARITY: Belongs to the beta type-B retroviral envelope protein
CC family. HERV class-II K(HML-2) env subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA76880.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA76886.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X82272; CAA57723.1; -; mRNA.
DR EMBL; AF164614; AAD51798.1; -; Genomic_DNA.
DR EMBL; AF074086; AAD21098.1; -; Genomic_DNA.
DR EMBL; AF074086; AAF88168.1; -; Genomic_DNA.
DR EMBL; Y17832; CAA76880.1; ALT_INIT; Genomic_DNA.
DR EMBL; Y17834; CAA76886.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF490464; AAM09525.1; -; Genomic_DNA.
DR AlphaFoldDB; Q69384; -.
DR IntAct; Q69384; 1.
DR iPTMnet; Q69384; -.
DR PhosphoSitePlus; Q69384; -.
DR BioMuta; HGNC:13915; -.
DR DMDM; 47605629; -.
DR jPOST; Q69384; -.
DR MassIVE; Q69384; -.
DR PeptideAtlas; Q69384; -.
DR PRIDE; Q69384; -.
DR GeneCards; ERVK-6; -.
DR HGNC; HGNC:13915; ERVK-6.
DR MIM; 605626; gene.
DR neXtProt; NX_Q69384; -.
DR PhylomeDB; Q69384; -.
DR Pharos; Q69384; Tdark.
DR PRO; PR:Q69384; -.
DR Proteomes; UP000005640; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR InterPro; IPR000328; GP41-like.
DR InterPro; IPR029104; HERV-K_env.
DR Pfam; PF00517; GP41; 1.
DR Pfam; PF13804; HERV-K_env_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Disulfide bond; ERV;
KW Glycoprotein; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transposable element; Viral envelope protein; Virion.
FT SIGNAL 1..89
FT /evidence="ECO:0000255"
FT CHAIN 90..699
FT /note="Endogenous retrovirus group K member 6 Env
FT polyprotein"
FT /id="PRO_0000008500"
FT CHAIN 90..465
FT /note="Surface protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008501"
FT CHAIN 466..699
FT /note="Transmembrane protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008502"
FT TOPO_DOM 90..632
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 633..653
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 654..699
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..486
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT COMPBIAS 10..24
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 465..466
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 554
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 585
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 172
FT /note="L -> I (in Ref. 5; CAA76886)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="P -> Q (in Ref. 5; CAA76880)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="H -> L (in Ref. 5; CAA76886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 699 AA; 79218 MW; 3844DA6D80D76DFC CRC64;
MNPSEMQRKA PPRRRRHRNR APLTHKMNKM VTSEEQMKLP STKKAEPPTW AQLKKLTQLA
TKYLENTKVT QTPESMLLAA LMIVSMVVSL PMPAGAAAAN YTYWAYVPFP PLIRAVTWMD
NPTEVYVNDS VWVPGPIDDR CPAKPEEEGM MINISIGYHY PPICLGRAPG CLMPAVQNWL
VEVPTVSPIC RFTYHMVSGM SLRPRVNYLQ DFSYQRSLKF RPKGKPCPKE IPKESKNTEV
LVWEECVANS AVILQNNEFG TIIDWAPRGQ FYHNCSGQTQ SCPSAQVSPA VDSDLTESLD
KHKHKKLQSF YPWEWGEKGI STPRPKIVSP VSGPEHPELW RLTVASHHIR IWSGNQTLET
RDRKPFYTID LNSSLTVPLQ SCVKPPYMLV VGNIVIKPDS QTITCENCRL LTCIDSTFNW
QHRILLVRAR EGVWIPVSMD RPWEASPSVH ILTEVLKGVL NRSKRFIFTL IAVIMGLIAV
TATAAVAGVA LHSSVQSVNF VNDWQKNSTR LWNSQSSIDQ KLANQINDLR QTVIWMGDRL
MSLEHRFQLQ CDWNTSDFCI TPQIYNESEH HWDMVRRHLQ GREDNLTLDI SKLKEQIFEA
SKAHLNLVPG TEAIAGVADG LANLNPVTWV KTIGSTTIIN LILILVCLFC LLLVCRCTQQ
LRRDSDHRER AMMTMAVLSK RKGGNVGKSK RDQIVTVSV
