ENR1_HUMAN
ID ENR1_HUMAN Reviewed; 604 AA.
AC Q14264;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Endogenous retrovirus group 3 member 1 Env polyprotein;
DE AltName: Full=ERV-3 envelope protein;
DE Short=ERV3 envelope protein;
DE AltName: Full=ERV3-1 envelope protein;
DE AltName: Full=Envelope polyprotein;
DE AltName: Full=HERV-R envelope protein;
DE Short=ERV-R envelope protein;
DE AltName: Full=HERV-R_7q21.2 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=ERV3-1; Synonyms=ERV3;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-604, AND VARIANTS ILE-90; SER-481
RP AND SER-569.
RX PubMed=3840930; DOI=10.1016/0042-6822(85)90147-3;
RA Cohen M., Powers M., O'Connell C., Kato N.;
RT "The nucleotide sequence of the env gene from the human provirus ERV3 and
RT isolation and characterization of an ERV3-specific cDNA.";
RL Virology 147:449-458(1985).
RN [3]
RP FUNCTION.
RX PubMed=7645262; DOI=10.1006/viro.1995.1442;
RA Venables P.J.W., Brookes S.M., Griffiths D., Weiss R.A., Boyd M.T.;
RT "Abundance of an endogenous retroviral envelope protein in placental
RT trophoblasts suggests a biological function.";
RL Virology 211:589-592(1995).
RN [4]
RP FUNCTION.
RX PubMed=10692254; DOI=10.1053/plac.1999.0443;
RA Lin L., Xu B., Rote N.S.;
RT "The cellular mechanism by which the human endogenous retrovirus ERV-3 env
RT gene affects proliferation and differentiation in a human placental
RT trophoblast model, BeWo.";
RL Placenta 21:73-78(2000).
RN [5]
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 [6]
RP TISSUE SPECIFICITY.
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 [7]
RP DEVELOPMENTAL STAGE.
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).
RN [8]
RP VARIANTS TYR-192; CYS-236; PRO-522 AND SER-569, AND POLYMORPHISM.
RX PubMed=9525678; DOI=10.1128/jvi.72.4.3442-3445.1998;
RA de Parseval N., Heidmann T.;
RT "Physiological knockout of the envelope gene of the single-copy ERV-3 human
RT endogenous retrovirus in a fraction of the Caucasian population.";
RL J. Virol. 72:3442-3445(1998).
RN [9]
RP VARIANTS ILE-90; TYR-192; CYS-236; SER-481 AND SER-569, AND POLYMORPHISM.
RX PubMed=10427470; DOI=10.1155/1998/958379;
RA Rasmussen H.B., Clausen J.;
RT "Large number of polymorphic nucleotides and a termination codon in the env
RT gene of the endogenous human retrovirus ERV3.";
RL Dis. Markers 14:127-133(1998).
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 fusogenic
CC properties. It can inhibit cell growth through decrease expression of
CC cyclin B1 and increased expression of p21 in vitro.
CC {ECO:0000269|PubMed:10692254, ECO:0000269|PubMed:14557543,
CC ECO:0000269|PubMed:7645262}.
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 non-covalent interactions or by
CC a labile interchain disulfide bond (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion.
CC -!- TISSUE SPECIFICITY: Expressed at higher level in adrenal, sebaceous
CC glands and placenta. Expressed at lower level in bone marrow, brain,
CC breast, colon, heart, kidney, liver, lung, ovary, PBL, prostate, skin,
CC spleen, testis, thymus, thyroid, trachea.
CC {ECO:0000269|PubMed:12970426}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in primitive adrenal cortex and
CC placenta. Expressed at lower level in developing nervous tissues,
CC tongue, heart, gut, kidney, columna vertebralis and liver.
CC {ECO:0000269|PubMed:12083821}.
CC -!- DOMAIN: Contains the CKS-17 immunosuppressive domain present in many
CC retroviral envelope proteins. As a synthetic peptide, it inhibits
CC immune function in vitro and in vivo (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield the mature SU and TM
CC proteins (By similarity). Has been mainly detected in vivo as an 65 kDa
CC unprocessed polyprotein precursor. {ECO:0000250}.
CC -!- PTM: The CXXC motif is highly conserved across a broad range of
CC retroviral envelope proteins. It is thought to participate in the
CC formation of a labile disulfide bond possibly with the CX6CC motif
CC present in the transmembrane protein. Isomerization of the intersubunit
CC disulfide bond to an SU intrachain disulfide bond is thought to occur
CC upon receptor recognition in order to allow membrane fusion (By
CC similarity). {ECO:0000250}.
CC -!- POLYMORPHISM: This envelope gene is polymorphic with at least five
CC different alleles. A mutation introducing a premature stop codon
CC instead of amino acid 223 is present in approximately 1% of the
CC Caucasian population (PubMed:9525678). {ECO:0000269|PubMed:10427470,
CC ECO:0000269|PubMed:3840930, ECO:0000269|PubMed:9525678}.
CC -!- MISCELLANEOUS: HERV-R_7q21.2 genomic and subgenomic RNAs have been
CC observed.
CC -!- MISCELLANEOUS: This provirus is intergenic, the closest flanking genes
CC being ZNF117 and FLJ25037.
CC -!- SIMILARITY: Belongs to the gamma type-C retroviral envelope protein
CC family. HERV class-I R env subfamily. {ECO:0000305}.
CC -!- CAUTION: CKS-17 sequence does not match the minimal active consensus.
CC {ECO:0000305}.
CC -!- CAUTION: Truncated; premature stop codon upstream of the fusion peptide
CC on TM. {ECO:0000305}.
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DR EMBL; AC073210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M12140; AAA88027.1; -; Genomic_DNA.
DR CCDS; CCDS47595.1; -.
DR RefSeq; NP_001007254.2; NM_001007253.3.
DR AlphaFoldDB; Q14264; -.
DR BioGRID; 108395; 2.
DR IntAct; Q14264; 1.
DR STRING; 9606.ENSP00000391594; -.
DR GlyConnect; 1202; 3 N-Linked glycans (1 site).
DR GlyGen; Q14264; 9 sites, 3 N-linked glycans (1 site).
DR iPTMnet; Q14264; -.
DR PhosphoSitePlus; Q14264; -.
DR BioMuta; ERV3-1; -.
DR DMDM; 44887883; -.
DR MassIVE; Q14264; -.
DR PaxDb; Q14264; -.
DR PeptideAtlas; Q14264; -.
DR PRIDE; Q14264; -.
DR ProteomicsDB; 59954; -.
DR TopDownProteomics; Q14264; -.
DR Antibodypedia; 55905; 105 antibodies from 20 providers.
DR DNASU; 2086; -.
DR Ensembl; ENST00000394323.3; ENSP00000391594.1; ENSG00000213462.5.
DR GeneID; 2086; -.
DR KEGG; hsa:2086; -.
DR MANE-Select; ENST00000394323.3; ENSP00000391594.1; NM_001007253.4; NP_001007254.2.
DR UCSC; uc011kdr.3; human.
DR CTD; 2086; -.
DR DisGeNET; 2086; -.
DR GeneCards; ERV3-1; -.
DR HGNC; HGNC:3454; ERV3-1.
DR HPA; ENSG00000213462; Low tissue specificity.
DR neXtProt; NX_Q14264; -.
DR OpenTargets; ENSG00000213462; -.
DR PharmGKB; PA27866; -.
DR VEuPathDB; HostDB:ENSG00000213462; -.
DR eggNOG; ENOG502SX29; Eukaryota.
DR GeneTree; ENSGT00940000165291; -.
DR HOGENOM; CLU_037390_0_0_1; -.
DR InParanoid; Q14264; -.
DR OMA; LEAPNTW; -.
DR OrthoDB; 389221at2759; -.
DR PhylomeDB; Q14264; -.
DR PathwayCommons; Q14264; -.
DR SignaLink; Q14264; -.
DR BioGRID-ORCS; 2086; 8 hits in 1024 CRISPR screens.
DR GeneWiki; ERV3; -.
DR GenomeRNAi; 2086; -.
DR Pharos; Q14264; Tbio.
DR PRO; PR:Q14264; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q14264; protein.
DR Bgee; ENSG00000213462; Expressed in adrenal tissue and 97 other tissues.
DR InterPro; IPR018154; TLV/ENV_coat_polyprotein.
DR PANTHER; PTHR10424; PTHR10424; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; ERV; Glycoprotein;
KW Reference proteome; Signal; Transposable element; Viral envelope protein;
KW Virion.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..604
FT /note="Endogenous retrovirus group 3 member 1 Env
FT polyprotein"
FT /id="PRO_0000008477"
FT CHAIN 23..471
FT /note="Surface protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008478"
FT CHAIN 472..604
FT /note="Transmembrane protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008479"
FT MOTIF 165..168
FT /note="CXXC"
FT /evidence="ECO:0000250"
FT MOTIF 548..564
FT /note="CKS-17"
FT /evidence="ECO:0000250"
FT MOTIF 565..574
FT /note="CX6CC"
FT /evidence="ECO:0000250"
FT SITE 471..472
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 527
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 90
FT /note="T -> I (in dbSNP:rs6460219)"
FT /evidence="ECO:0000269|PubMed:10427470,
FT ECO:0000269|PubMed:3840930"
FT /id="VAR_017801"
FT VARIANT 192
FT /note="C -> Y (in dbSNP:rs34639489)"
FT /evidence="ECO:0000269|PubMed:10427470,
FT ECO:0000269|PubMed:9525678"
FT /id="VAR_017802"
FT VARIANT 236
FT /note="Y -> C (in dbSNP:rs71539632)"
FT /evidence="ECO:0000269|PubMed:10427470,
FT ECO:0000269|PubMed:9525678"
FT /id="VAR_017803"
FT VARIANT 481
FT /note="N -> S (in dbSNP:rs4618579)"
FT /evidence="ECO:0000269|PubMed:10427470,
FT ECO:0000269|PubMed:3840930"
FT /id="VAR_017804"
FT VARIANT 522
FT /note="L -> P (in dbSNP:rs1406592674)"
FT /evidence="ECO:0000269|PubMed:9525678"
FT /id="VAR_017805"
FT VARIANT 569
FT /note="N -> S (in dbSNP:rs4717229)"
FT /evidence="ECO:0000269|PubMed:10427470,
FT ECO:0000269|PubMed:3840930, ECO:0000269|PubMed:9525678"
FT /id="VAR_017806"
FT CONFLICT 218
FT /note="A -> T (in Ref. 2; AAA88027)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="G -> D (in Ref. 2; AAA88027)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="F -> L (in Ref. 2; AAA88027)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 604 AA; 67942 MW; C426D9193857D4BD CRC64;
MLGMNMLLIT LFLLLPLSML KGEPWEGCLH CTHTTWSGNI MTKTLLYHTY YECAGTCLGT
CTHNQTTYSV CDPGRGQPYV CYDPKSSPGT WFEIHVGSKE GDLLNQTKVF PSGKDVVSLY
FDVCQIVSMG SLFPVIFSSM EYYSSCHKNR YAHPACSTDS PVTTCWDCTT WSTNQQSLGP
IMLTKIPLEP DCKTSTCNSV NLTILEPDQP IWTTGLKAPL GARVSGEEIG PGAYVYLYII
KKTRTRSTQQ FRVFESFYEH VNQKLPEPPP LASNLFAQLA ENIASSLHVA SCYVCGGMNM
GDQWPWEARE LMPQDNFTLT ASSLEPAPSS QSIWFLKTSI IGKFCIARWG KAFTDPVGEL
TCLGQQYYNE TLGKTLWRGK SNNSESPHPS PFSRFPSLNH SWYQLEAPNT WQAPSGLYWI
CGPQAYRQLP AKWSGACVLG TIRPSFFLMP LKQGEALGYP IYDETKRKSK RGITIGDWKD
NEWPPERIIQ YYGPATWAED GMWGYRTPVY MLNRIIRLQA VLEIITNETA GALNLLAQQA
TKMRNVIYQN RLALDYLLAQ EEGVCGKFNL TNCCLELDDE GKVIKEITAK IQKLAHIPVQ
TWKG
