ENK18_HUMAN
ID ENK18_HUMAN Reviewed; 560 AA.
AC O42043; O95280; Q96PI3; Q96PI6; Q9QC06;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Endogenous retrovirus group K member 18 Env polyprotein;
DE AltName: Full=Envelope polyprotein;
DE AltName: Full=HERV-K(C1a) envelope protein;
DE AltName: Full=HERV-K110 envelope protein;
DE AltName: Full=HERV-K18 envelope protein;
DE AltName: Full=HERV-K18 superantigen;
DE AltName: Full=HERV-K_1q23.3 provirus ancestral Env polyprotein;
DE AltName: Full=IDDMK1,2 22 envelope protein;
DE AltName: Full=IDDMK1,2 22 superantigen;
DE Contains:
DE RecName: Full=Surface protein;
DE Short=SU;
DE Contains:
DE RecName: Full=Transmembrane protein;
DE Short=TM;
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] (ALLELE HERV-K18.2).
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 (ALLELE HERV-K18.3), INDUCTION, AND CHARACTERIZATION.
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 (ALLELE HERV-K18.1).
RX PubMed=9244304; DOI=10.1016/s0092-8674(00)80338-4;
RA Conrad B., Weissmahr R.N., Boeni J., Arcari R., Schuepbach J., Mach B.;
RT "A human endogenous retroviral superantigen as candidate autoimmune gene in
RT type I diabetes.";
RL Cell 90:303-313(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE HERV-K18.1).
RX PubMed=9778243; DOI=10.1016/s0092-8674(00)81777-8;
RA Lan M.S., Mason A., Coutant R., Chen Q.-Y., Vargas A., Rao J., Gomez R.,
RA Chalew S., Garry R., Maclaren N.K.;
RT "HERV-K10s and immune-mediated (type 1) diabetes.";
RL Cell 95:14-16(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE (ALLELE HERV-K18.1).
RX PubMed=10496080; DOI=10.1007/s100380050173;
RA Hasuike S., Miura K., Miyoshi O., Miyamoto T., Niikawa N., Jinno Y.,
RA Ishikawa M.;
RT "Isolation and localization of an IDDMK1,2-22-related human endogenous
RT retroviral gene, and identification of a CA repeat marker at its locus.";
RL J. Hum. Genet. 44:343-347(1999).
RN [6]
RP CHARACTERIZATION.
RX PubMed=11672540; DOI=10.1016/s1074-7613(01)00210-2;
RA Sutkowski N., Conrad B., Thorley-Lawson D.A., Huber B.T.;
RT "Epstein-Barr virus transactivates the human endogenous retrovirus HERV-K18
RT that encodes a superantigen.";
RL Immunity 15:579-589(2001).
RN [7]
RP CHARACTERIZATION.
RX PubMed=11982593; DOI=10.1046/j.1365-2249.2002.01735.x;
RA Herve C.A., Lugli E.B., Brand A., Griffiths D.J., Venables P.J.W.;
RT "Autoantibodies to human endogenous retrovirus-K are frequently detected in
RT health and disease and react with multiple epitopes.";
RL Clin. Exp. Immunol. 128:75-82(2002).
RN [8]
RP CHARACTERIZATION.
RX PubMed=11841850; DOI=10.1016/s0165-2478(01)00340-6;
RA Azar G.A., Thibodeau J.;
RT "Human endogenous retrovirus IDDMK(1,2)22 and mouse mammary tumor virus
RT superantigens differ in their ability to stimulate murine T cell
RT hybridomas.";
RL Immunol. Lett. 81:87-91(2002).
RN [9]
RP POLYMORPHISM.
RX PubMed=11776384; DOI=10.1007/s100380170005;
RA Kinjo Y., Matsuura N., Yokota Y., Ohtsu S., Nomoto K., Komiya I.,
RA Sugimoto J., Jinno Y., Takasu N.;
RT "Identification of nonsynonymous polymorphisms in the superantigen-coding
RT region of IDDMK1,2 22 and a pilot study on the association between IDDMK1,2
RT 22 and type 1 diabetes.";
RL J. Hum. Genet. 46:712-716(2001).
RN [10]
RP POLYMORPHISM.
RX PubMed=14988274; DOI=10.2337/diabetes.53.3.852;
RA Marguerat S., Wang W.Y.S., Todd J.A., Conrad B.;
RT "Association of human endogenous retrovirus K-18 polymorphisms with type 1
RT diabetes.";
RL Diabetes 53:852-854(2004).
RN [11]
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 envelope protein has superantigenic properties.
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 18 Env
CC polyprotein]: Virion {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at higher level in the thymus. Expressed
CC at lower level in peripheral blood lymphocytes.
CC -!- DEVELOPMENTAL STAGE: High expression in thymocytes. Neither expressed
CC nor inducible in mature T-cells. Inducible in CD2 negative peripheral
CC blood lymphocytes.
CC -!- INDUCTION: Induced by type I interferons and by Epstein-Barr virus
CC (EBV). {ECO:0000269|PubMed:11672541}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield the mature SU and TM
CC proteins. {ECO:0000250}.
CC -!- POLYMORPHISM: This envelope gene is polymorphic with at least three
CC different alleles (called HERV-K18.1, HERV-K18.2 and HERV-K18.3). A
CC polymorphism introducing a premature stop codon in position 154 is
CC present in allele HERV-K18.1 resulting in a truncated SU protein. The
CC sequence shown is that of HERV-K18.2. {ECO:0000305}.
CC -!- POLYMORPHISM: Some positive evidence of genetic association found
CC between allele HERV-K18.3 and type 1 diabetes.
CC {ECO:0000269|PubMed:11672541, ECO:0000269|PubMed:11776384,
CC ECO:0000269|PubMed:14988274}.
CC -!- MISCELLANEOUS: Orthologs in P.troglodytes and G.gorilla.
CC -!- MISCELLANEOUS: Has a type 1 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 resulting in Env proteins of
CC distinct sizes. Despite their overall retroviral envelope structure
CC HERV-K(HML-2) type 1 envelope proteins lack a predictable signal
CC sequence. Subgenomic RNA transcripts coding for full-length envelope
CC proteins have been detected for both type of genomes.
CC -!- MISCELLANEOUS: Autoantibodies reactive to this envelope are detectable
CC in sera from healthy donors and individuals with autoimmune diseases.
CC -!- MISCELLANEOUS: Intragenic, in the first intron of CD48 gene.
CC -!- SIMILARITY: Belongs to the beta type-B retroviral envelope protein
CC family. HERV class-II K(HML-2) env subfamily. {ECO:0000305}.
CC -!- CAUTION: No predictable signal peptide. {ECO:0000305}.
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DR EMBL; Y18890; CAB56604.1; -; Genomic_DNA.
DR EMBL; AF012336; AAC58456.1; -; Genomic_DNA.
DR EMBL; AF333069; AAL16777.1; -; Genomic_DNA.
DR EMBL; AF333072; AAL60057.1; -; Genomic_DNA.
DR EMBL; AF333073; AAL16780.1; -; Genomic_DNA.
DR EMBL; AF012337; AAC58457.1; -; Genomic_DNA.
DR EMBL; AF084864; AAC68893.1; -; Genomic_DNA.
DR EMBL; AF134984; AAD33055.1; -; Genomic_DNA.
DR AlphaFoldDB; O42043; -.
DR IntAct; O42043; 1.
DR iPTMnet; O42043; -.
DR PhosphoSitePlus; O42043; -.
DR BioMuta; HGNC:39025; -.
DR jPOST; O42043; -.
DR PeptideAtlas; O42043; -.
DR PRIDE; O42043; -.
DR GeneCards; ERVK-18; -.
DR HGNC; HGNC:39025; ERVK-18.
DR neXtProt; NX_O42043; -.
DR PhylomeDB; O42043; -.
DR Pharos; O42043; Tdark.
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 Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW Transposable element; Viral envelope protein; Virion.
FT CHAIN 1..560
FT /note="Endogenous retrovirus group K member 18 Env
FT polyprotein"
FT /id="PRO_0000008515"
FT CHAIN 1..354
FT /note="Surface protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008516"
FT CHAIN 355..560
FT /note="Transmembrane protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008517"
FT TRANSMEM 522..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 355..375
FT /note="Fusion peptide"
FT /evidence="ECO:0000255"
FT SITE 354..355
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT VARIANT 97
FT /note="C -> Y (in allele HERV-K18.1 and allele HERV-K18.3)"
FT /evidence="ECO:0000269|PubMed:10496080,
FT ECO:0000269|PubMed:10516026, ECO:0000269|PubMed:11672541,
FT ECO:0000269|PubMed:9778243"
FT /id="VAR_018642"
FT VARIANT 155..560
FT /note="Missing (in allele HERV-K18.1)"
FT /evidence="ECO:0000269|PubMed:10496080,
FT ECO:0000269|PubMed:9244304, ECO:0000269|PubMed:9778243"
FT /id="VAR_018643"
FT VARIANT 272
FT /note="V -> I (in allele HERV-K18.3)"
FT /evidence="ECO:0000269|PubMed:11672541"
FT /id="VAR_018644"
FT VARIANT 348
FT /note="V -> I (in allele HERV-K18.3)"
FT /evidence="ECO:0000269|PubMed:11672541"
FT /id="VAR_018645"
FT VARIANT 534
FT /note="V -> I (in allele HERV-K18.3)"
FT /evidence="ECO:0000269|PubMed:11672541"
FT /id="VAR_018646"
SQ SEQUENCE 560 AA; 63671 MW; 8A4565663901BC3A CRC64;
MVTPVTWMDN PIEVYVNDSV WVPGPTDDRC PAKPEEEGMM INISIGYHYP PICLGRAPGC
LMPAVQNWLV EVPTVSPNSR FTYHMVSGMS LRPRVNCLQD FSYQRSLKFR PKGKTCPKEI
PKGSKNTEVL VWEECVANSV VILQNNEFGT IIDWAPRGQF YHNCSGQTQS CPSAQVSPAV
DSDLTESLDK HKHKKLQSFY LWEWEEKGIS TPRPKIISPV SGPEHPELWR LTVASHHIRI
WSGNQTLETR YRKPFYTIDL NSILTVPLQS CVKPPYMLVV GNIVIKPASQ TITCENCRLF
TCIDSTFNWQ HRILLVRARE GMWIPVSTDR PWEASPSIHI LTEILKGVLN RSKRFIFTLI
AVIMGLIAVT ATAAVAGVAL HSSVQSVNFV NYWQKNSTRL WNSQSSIDQK LASQINDLRQ
TVIWMGDRLM TLEHHFQLQC DWNTSDFCIT PQIYNESEHH WDMVRRHLQG REDNLTLDIS
KLKEQIFEAS KAHLNLVPGT EAIAGVADGL ANLNPVTWIK TIRSTMIINL ILIVVCLFCL
LLVCRCTQQL RRDSDIENGP
