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Endogenous retrovirus group K member 18 Env polyprotein (Envelope polyprotein) (HERV-K(C1a) envelope protein) (HERV-K110 envelope protein) (HERV-K18 envelope protein) (HERV-K18 superantigen) (HERV-K_1q23.3 provirus ancestral Env polyprotein) (IDDMK1,2 22 envelope protein) (IDDMK1,2 22 superantigen) [Cleaved into: Surface protein (SU); Transmembrane protein (TM)]

 ENK18_HUMAN             Reviewed;         560 AA.
O42043; O95280; Q96PI3; Q96PI6; Q9QC06;
24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
24-MAY-2004, sequence version 2.
20-JUN-2018, entry version 88.
RecName: Full=Endogenous retrovirus group K member 18 Env polyprotein;
AltName: Full=Envelope polyprotein;
AltName: Full=HERV-K(C1a) envelope protein;
AltName: Full=HERV-K110 envelope protein;
AltName: Full=HERV-K18 envelope protein;
AltName: Full=HERV-K18 superantigen;
AltName: Full=HERV-K_1q23.3 provirus ancestral Env polyprotein;
AltName: Full=IDDMK1,2 22 envelope protein;
AltName: Full=IDDMK1,2 22 superantigen;
Contains:
RecName: Full=Surface protein;
Short=SU;
Contains:
RecName: Full=Transmembrane protein;
Short=TM;
Name=ERVK-18;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE HERV-K18.2).
PubMed=10516026;
Toenjes R.R., Czauderna F., Kurth R.;
"Genome wide screening, cloning, chromosomal assignment and expression
of full-length human endogenous retrovirus type K (HERV-K).";
J. Virol. 73:9187-9195(1999).
[2]
NUCLEOTIDE SEQUENCE (ALLELE HERV-K18.3), INDUCTION, AND
CHARACTERIZATION.
PubMed=11672541; DOI=10.1016/S1074-7613(01)00212-6;
Stauffer Y., Marguerat S., Meylan F., Ucla C., Sutkowski N.,
Huber B.T., Pelet T., Conrad B.;
"Interferon-alpha induced endogenous superantigen: a model linking
environment and autoimmunity.";
Immunity 15:591-601(2001).
[3]
NUCLEOTIDE SEQUENCE (ALLELE HERV-K18.1).
PubMed=9244304; DOI=10.1016/S0092-8674(00)80338-4;
Conrad B., Weissmahr R.N., Boeni J., Arcari R., Schuepbach J.,
Mach B.;
"A human endogenous retroviral superantigen as candidate autoimmune
gene in type I diabetes.";
Cell 90:303-313(1997).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE HERV-K18.1).
PubMed=9778243; DOI=10.1016/S0092-8674(00)81777-8;
Lan M.S., Mason A., Coutant R., Chen Q.-Y., Vargas A., Rao J.,
Gomez R., Chalew S., Garry R., Maclaren N.K.;
"HERV-K10s and immune-mediated (type 1) diabetes.";
Cell 95:14-16(1998).
[5]
NUCLEOTIDE SEQUENCE (ALLELE HERV-K18.1).
PubMed=10496080; DOI=10.1007/s100380050173;
Hasuike S., Miura K., Miyoshi O., Miyamoto T., Niikawa N., Jinno Y.,
Ishikawa M.;
"Isolation and localization of an IDDMK1,2-22-related human endogenous
retroviral gene, and identification of a CA repeat marker at its
locus.";
J. Hum. Genet. 44:343-347(1999).
[6]
CHARACTERIZATION.
PubMed=11672540; DOI=10.1016/S1074-7613(01)00210-2;
Sutkowski N., Conrad B., Thorley-Lawson D.A., Huber B.T.;
"Epstein-Barr virus transactivates the human endogenous retrovirus
HERV-K18 that encodes a superantigen.";
Immunity 15:579-589(2001).
[7]
CHARACTERIZATION.
PubMed=11982593; DOI=10.1046/j.1365-2249.2002.01735.x;
Herve C.A., Lugli E.B., Brand A., Griffiths D.J., Venables P.J.W.;
"Autoantibodies to human endogenous retrovirus-K are frequently
detected in health and disease and react with multiple epitopes.";
Clin. Exp. Immunol. 128:75-82(2002).
[8]
CHARACTERIZATION.
PubMed=11841850; DOI=10.1016/S0165-2478(01)00340-6;
Azar G.A., Thibodeau J.;
"Human endogenous retrovirus IDDMK(1,2)22 and mouse mammary tumor
virus superantigens differ in their ability to stimulate murine T cell
hybridomas.";
Immunol. Lett. 81:87-91(2002).
[9]
POLYMORPHISM.
PubMed=11776384; DOI=10.1007/s100380170005;
Kinjo Y., Matsuura N., Yokota Y., Ohtsu S., Nomoto K., Komiya I.,
Sugimoto J., Jinno Y., Takasu N.;
"Identification of nonsynonymous polymorphisms in the superantigen-
coding region of IDDMK1,2 22 and a pilot study on the association
between IDDMK1,2 22 and type 1 diabetes.";
J. Hum. Genet. 46:712-716(2001).
[10]
POLYMORPHISM.
PubMed=14988274; DOI=10.2337/diabetes.53.3.852;
Marguerat S., Wang W.Y.S., Todd J.A., Conrad B.;
"Association of human endogenous retrovirus K-18 polymorphisms with
type 1 diabetes.";
Diabetes 53:852-854(2004).
[11]
SUBGENOMIC RNA.
PubMed=12629516; DOI=10.1038/sj.onc.1206241;
Wang-Johanning F., Frost A.R., Jian B., Epp L., Lu D.W.,
Johanning G.L.;
"Quantitation of HERV-K env gene expression and splicing in human
breast cancer.";
Oncogene 22:1528-1535(2003).
-!- FUNCTION: Retroviral envelope proteins mediate receptor
recognition and membrane fusion during early infection. Endogenous
envelope proteins may have kept, lost or modified their original
function during evolution. This envelope protein has
superantigenic properties.
-!- FUNCTION: SU mediates receptor recognition. {ECO:0000250}.
-!- FUNCTION: TM anchors the envelope heterodimer to the viral
membrane through one transmembrane domain. The other hydrophobic
domain, called fusion peptide, mediates fusion of the viral
membrane with the target cell membrane (By similarity).
{ECO:0000250}.
-!- SUBUNIT: The surface (SU) and transmembrane (TM) proteins form a
heterodimer. SU and TM are attached by noncovalent interactions or
by a labile interchain disulfide bond (By similarity).
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Transmembrane protein: Cell membrane
{ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Surface protein: Cell membrane
{ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=The
surface protein is not anchored to the membrane, but localizes to
the extracellular surface through its binding to TM.
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Endogenous retrovirus group K member 18 Env
polyprotein: Virion {ECO:0000250}.
-!- TISSUE SPECIFICITY: Expressed at higher level in the thymus.
Expressed at lower level in peripheral blood lymphocytes.
-!- DEVELOPMENTAL STAGE: High expression in thymocytes. Neither
expressed nor inducible in mature T-cells. Inducible in CD2
negative peripheral blood lymphocytes.
-!- INDUCTION: Induced by type I interferons and by Epstein-Barr virus
(EBV). {ECO:0000269|PubMed:11672541}.
-!- PTM: Specific enzymatic cleavages in vivo yield the mature SU and
TM proteins. {ECO:0000250}.
-!- POLYMORPHISM: This envelope gene is polymorphic with at least
three different alleles (called HERV-K18.1, HERV-K18.2 and HERV-
K18.3). A polymorphism introducing a premature stop codon in
position 154 is present in allele HERV-K18.1 resulting in a
truncated SU protein. The sequence shown is that of HERV-K18.2.
{ECO:0000305}.
-!- POLYMORPHISM: Some positive evidence of genetic association found
between allele HERV-K18.3 and type 1 diabetes.
{ECO:0000269|PubMed:11672541, ECO:0000269|PubMed:11776384,
ECO:0000269|PubMed:14988274}.
-!- MISCELLANEOUS: Orthologs in Pan troglodytes and Gorilla gorilla.
-!- MISCELLANEOUS: Has a type 1 genome. The HERV-K(HML-2) family
contains type 1 and type 2 genomes depending on the absence or
presence of 292 nucleotides at the 5'-end of the env gene
resulting in Env proteins of distinct sizes. Despite their overall
retroviral envelope structure HERV-K(HML-2) type 1 envelope
proteins lack a predictable signal sequence. Subgenomic RNA
transcripts coding for full-length envelope proteins have been
detected for both type of genomes.
-!- MISCELLANEOUS: Autoantibodies reactive to this envelope are
detectable in sera from healthy donors and individuals with
autoimmune diseases.
-!- MISCELLANEOUS: Intragenic, in the first intron of CD48 gene.
-!- SIMILARITY: Belongs to the beta type-B retroviral envelope protein
family. HERV class-II K(HML-2) env subfamily. {ECO:0000305}.
-!- CAUTION: No predictable signal peptide. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; Y18890; CAB56604.1; -; Genomic_DNA.
EMBL; AF012336; AAC58456.1; -; Genomic_DNA.
EMBL; AF333069; AAL16777.1; -; Genomic_DNA.
EMBL; AF333072; AAL60057.1; -; Genomic_DNA.
EMBL; AF333073; AAL16780.1; -; Genomic_DNA.
EMBL; AF012337; AAC58457.1; -; Genomic_DNA.
EMBL; AF084864; AAC68893.1; -; Genomic_DNA.
EMBL; AF134984; AAD33055.1; -; Genomic_DNA.
iPTMnet; O42043; -.
PhosphoSitePlus; O42043; -.
PRIDE; O42043; -.
ProteomicsDB; 48759; -.
DisGeNET; 100775105; -.
GeneCards; ERVK-18; -.
H-InvDB; HIX0019571; -.
HGNC; HGNC:39025; ERVK-18.
neXtProt; NX_O42043; -.
HOVERGEN; HBG051479; -.
PhylomeDB; O42043; -.
Proteomes; UP000005640; Unplaced.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
CDD; cd09909; HIV-1-like_HR1-HR2; 1.
InterPro; IPR000328; GP41-like.
InterPro; IPR029104; HERV-K_env.
Pfam; PF00517; GP41; 1.
Pfam; PF13804; HERV-K_env_2; 1.
1: Evidence at protein level;
Cell membrane; Cleavage on pair of basic residues; Complete proteome;
Disulfide bond; ERV; Membrane; Polymorphism; Reference proteome;
Transmembrane; Transmembrane helix; Transposable element;
Viral envelope protein; Virion.
CHAIN 1 560 Endogenous retrovirus group K member 18
Env polyprotein.
/FTId=PRO_0000008515.
CHAIN 1 354 Surface protein. {ECO:0000250}.
/FTId=PRO_0000008516.
CHAIN 355 560 Transmembrane protein. {ECO:0000250}.
/FTId=PRO_0000008517.
TRANSMEM 522 542 Helical. {ECO:0000255}.
REGION 355 375 Fusion peptide. {ECO:0000255}.
SITE 354 355 Cleavage. {ECO:0000250}.
VARIANT 97 97 C -> Y (in allele HERV-K18.1 and allele
HERV-K18.3).
{ECO:0000269|PubMed:10496080,
ECO:0000269|PubMed:10516026,
ECO:0000269|PubMed:11672541,
ECO:0000269|PubMed:9778243}.
/FTId=VAR_018642.
VARIANT 155 560 Missing (in allele HERV-K18.1).
{ECO:0000269|PubMed:10496080,
ECO:0000269|PubMed:9244304,
ECO:0000269|PubMed:9778243}.
/FTId=VAR_018643.
VARIANT 272 272 V -> I (in allele HERV-K18.3).
{ECO:0000269|PubMed:11672541}.
/FTId=VAR_018644.
VARIANT 348 348 V -> I (in allele HERV-K18.3).
{ECO:0000269|PubMed:11672541}.
/FTId=VAR_018645.
VARIANT 534 534 V -> I (in allele HERV-K18.3).
{ECO:0000269|PubMed:11672541}.
/FTId=VAR_018646.
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


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