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Q14264 (ENR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
HERV-R_7q21.2 provirus ancestral Env polyprotein
Alternative name(s):
ERV-3 envelope protein
Short name=ERV3 envelope protein
ERV3-1 envelope protein
Envelope polyprotein
HERV-R envelope protein
Short name=ERV-R envelope protein

Cleaved into the following 2 chains:

  1. Surface protein
    Short name=SU
  2. Transmembrane protein
    Short name=TM
Gene names
Name:ERV3-1
Synonyms:ERV3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length604 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 endogenous envelope protein has lost its fusogenic properties. It can inhibit cell growth through decrease expression of cyclin B1 and increased expression of p21 in vitro. Ref.3 Ref.4 Ref.5

SU mediates receptor recognition By similarity. Ref.3 Ref.4 Ref.5

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. Ref.3 Ref.4 Ref.5

Subunit structure

The surface (SU) and transmembrane (TM) proteins form a heterodimer. SU and TM are attached by non-covalent interactions or by a labile interchain disulfide bond By similarity.

Subcellular location

Virion.

Tissue specificity

Expressed at higher level in adrenal, sebaceous glands and placenta. Expressed at lower level in bone marrow, brain, breast, colon, heart, kidney, liver, lung, ovary, PBL, prostate, skin, spleen, testis, thymus, thyroid, trachea. Ref.6

Developmental stage

Highly expressed in primitive adrenal cortex and placenta. Expressed at lower level in developing nervous tissues, tongue, heart, gut, kidney, columna vertebralis and liver. Ref.7

Domain

Contains the CKS-17 immunosuppressive domain present in many retroviral envelope proteins. As a synthetic peptide, it inhibits immune function in vitro and in vivo By similarity.

Post-translational modification

Specific enzymatic cleavages in vivo yield the mature SU and TM proteins By similarity. Has been mainly detected in vivo as an 65 kDa unprocessed polyprotein precursor.

The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion By similarity.

Polymorphism

This envelope gene is polymorphic with at least five different alleles. A mutation introducing a premature stop codon instead of amino acid 223 is present in approximately 1% of the Caucasian population.

Miscellaneous

HERV-R_7q21.2 genomic and subgenomic RNAs have been observed.

This provirus is intergenic, the closest flanking genes being ZNF117 and FLJ25037.

Sequence similarities

Belongs to the gamma type-C retroviral envelope protein family. HERV class-I R env subfamily.

Caution

CKS-17 sequence does not match the minimal active consensus.

Truncated; premature stop codon upstream of the fusion peptide on TM.

Ontologies

Keywords
   Cellular componentViral envelope protein
Virion
   Coding sequence diversityPolymorphism
   DomainSignal
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical termComplete proteome
ERV
Reference proteome
Transposable element
Gene Ontology (GO)
   Cellular_componentviral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 604582HERV-R_7q21.2 provirus ancestral Env polyprotein
PRO_0000008477
Chain23 – 471449Surface protein By similarity
PRO_0000008478
Chain472 – 604133Transmembrane protein By similarity
PRO_0000008479

Regions

Motif165 – 1684CXXC By similarity
Motif548 – 56417CKS-17 By similarity
Motif565 – 57410CX6CC By similarity

Sites

Site471 – 4722Cleavage By similarity

Amino acid modifications

Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation1051N-linked (GlcNAc...) Potential
Glycosylation2011N-linked (GlcNAc...) Potential
Glycosylation3161N-linked (GlcNAc...) Potential
Glycosylation3691N-linked (GlcNAc...) Potential
Glycosylation3821N-linked (GlcNAc...) Potential
Glycosylation3991N-linked (GlcNAc...) Potential
Glycosylation5271N-linked (GlcNAc...) Potential
Glycosylation5691N-linked (GlcNAc...) Potential

Natural variations

Natural variant901T → I. Ref.2 Ref.9
Corresponds to variant rs6460219 [ dbSNP | Ensembl ].
VAR_017801
Natural variant1921C → Y. Ref.8 Ref.9
Corresponds to variant rs34639489 [ dbSNP | Ensembl ].
VAR_017802
Natural variant2361Y → C. Ref.8 Ref.9
Corresponds to variant rs71539632 [ dbSNP | Ensembl ].
VAR_017803
Natural variant4811N → S. Ref.2 Ref.9
Corresponds to variant rs4618579 [ dbSNP | Ensembl ].
VAR_017804
Natural variant5221L → P. Ref.8
VAR_017805
Natural variant5691N → S. Ref.2 Ref.8 Ref.9
Corresponds to variant rs4717229 [ dbSNP | Ensembl ].
VAR_017806

Experimental info

Sequence conflict2181A → T in AAA88027. Ref.2
Sequence conflict2261G → D in AAA88027. Ref.2
Sequence conflict2511F → L in AAA88027. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q14264 [UniParc].

Last modified March 1, 2004. Version 2.
Checksum: C426D9193857D4BD

FASTA60467,942
        10         20         30         40         50         60 
MLGMNMLLIT LFLLLPLSML KGEPWEGCLH CTHTTWSGNI MTKTLLYHTY YECAGTCLGT 

        70         80         90        100        110        120 
CTHNQTTYSV CDPGRGQPYV CYDPKSSPGT WFEIHVGSKE GDLLNQTKVF PSGKDVVSLY 

       130        140        150        160        170        180 
FDVCQIVSMG SLFPVIFSSM EYYSSCHKNR YAHPACSTDS PVTTCWDCTT WSTNQQSLGP 

       190        200        210        220        230        240 
IMLTKIPLEP DCKTSTCNSV NLTILEPDQP IWTTGLKAPL GARVSGEEIG PGAYVYLYII 

       250        260        270        280        290        300 
KKTRTRSTQQ FRVFESFYEH VNQKLPEPPP LASNLFAQLA ENIASSLHVA SCYVCGGMNM 

       310        320        330        340        350        360 
GDQWPWEARE LMPQDNFTLT ASSLEPAPSS QSIWFLKTSI IGKFCIARWG KAFTDPVGEL 

       370        380        390        400        410        420 
TCLGQQYYNE TLGKTLWRGK SNNSESPHPS PFSRFPSLNH SWYQLEAPNT WQAPSGLYWI 

       430        440        450        460        470        480 
CGPQAYRQLP AKWSGACVLG TIRPSFFLMP LKQGEALGYP IYDETKRKSK RGITIGDWKD 

       490        500        510        520        530        540 
NEWPPERIIQ YYGPATWAED GMWGYRTPVY MLNRIIRLQA VLEIITNETA GALNLLAQQA 

       550        560        570        580        590        600 
TKMRNVIYQN RLALDYLLAQ EEGVCGKFNL TNCCLELDDE GKVIKEITAK IQKLAHIPVQ 


TWKG 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"The nucleotide sequence of the env gene from the human provirus ERV3 and isolation and characterization of an ERV3-specific cDNA."
Cohen M., Powers M., O'Connell C., Kato N.
Virology 147:449-458(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-604, VARIANTS ILE-90; SER-481 AND SER-569.
[3]"Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function."
Venables P.J.W., Brookes S.M., Griffiths D., Weiss R.A., Boyd M.T.
Virology 211:589-592(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"The cellular mechanism by which the human endogenous retrovirus ERV-3 env gene affects proliferation and differentiation in a human placental trophoblast model, BeWo."
Lin L., Xu B., Rote N.S.
Placenta 21:73-78(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution."
Blaise S., de Parseval N., Benit L., Heidmann T.
Proc. Natl. Acad. Sci. U.S.A. 100:13013-13018(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins."
de Parseval N., Lazar V., Casella J.-F., Benit L., Heidmann T.
J. Virol. 77:10414-10422(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Developmental expression of HERV-R (ERV3) and HERV-K in human tissue."
Andersson A.-C., Venables P.J.W., Toenjes R.R., Scherer J., Eriksson L., Larsson E.
Virology 297:220-225(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[8]"Physiological knockout of the envelope gene of the single-copy ERV-3 human endogenous retrovirus in a fraction of the Caucasian population."
de Parseval N., Heidmann T.
J. Virol. 72:3442-3445(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TYR-192; CYS-236; PRO-522 AND SER-569.
[9]"Large number of polymorphic nucleotides and a termination codon in the env gene of the endogenous human retrovirus ERV3."
Rasmussen H.B., Clausen J.
Dis. Markers 14:127-133(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-90; TYR-192; CYS-236; SER-481 AND SER-569.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC073210 Genomic DNA. No translation available.
M12140 Genomic DNA. Translation: AAA88027.1.
RefSeqNP_001007254.2. NM_001007253.3.
UniGeneHs.250693.

3D structure databases

ProteinModelPortalQ14264.
SMRQ14264. Positions 489-593.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108395. 1 interaction.
STRING9606.ENSP00000391594.

PTM databases

PhosphoSiteQ14264.

Polymorphism databases

DMDM44887883.

Proteomic databases

PaxDbQ14264.
PeptideAtlasQ14264.
PRIDEQ14264.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394323; ENSP00000391594; ENSG00000213462.
GeneID2086.
KEGGhsa:2086.
UCSCuc011kdr.2. human.

Organism-specific databases

CTD2086.
GeneCardsGC07M064451.
HGNCHGNC:3454. ERV3-1.
HPAHPA017209.
neXtProtNX_Q14264.
PharmGKBPA27866.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG126753.
HOGENOMHOG000112377.
HOVERGENHBG048920.
OMAWEARELM.
OrthoDBEOG7W6WK7.

Gene expression databases

BgeeQ14264.
CleanExHS_ERV3.
GenevestigatorQ14264.

Family and domain databases

InterProIPR018154. TLV/ENV_coat_polyprotein.
[Graphical view]
PANTHERPTHR10424. PTHR10424. 1 hit.
ProtoNetSearch...

Other

GeneWikiERV3.
NextBio8469.
PROQ14264.

Entry information

Entry nameENR1_HUMAN
AccessionPrimary (citable) accession number: Q14264
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: February 19, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM