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Protein

Syncytin-2

Gene

ERVFRD-1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This endogenous retroviral envelope protein has retained its original fusogenic properties and participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis. The interaction with MFSD2A is apparently important for this process (PubMed:18988732).1 Publication
Endogenous envelope proteins may have kept, lost or modified their original function during evolution but this one can still make pseudotypes with MLV, HIV-1 or SIV-1 virions and confer infectivity. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein mediates receptor recognition, while the transmembrane protein 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 (PubMed:14694139).1 Publication

GO - Biological processi

  • syncytium formation Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Syncytin-2
Alternative name(s):
Endogenous retrovirus group FRD member 1
Envelope polyprotein
HERV-FRD
HERV-FRD_6p24.1 provirus ancestral Env polyprotein
Cleaved into the following 2 chains:
Surface protein
Short name:
SU
Transmembrane protein
Short name:
TM
Gene namesi
Name:ERVFRD-1
Synonyms:ERVFRDE1
ORF Names:UNQ6191/PRO20218
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:33823. ERVFRD-1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini16 – 478463ExtracellularSequence analysisAdd
BLAST
Transmembranei479 – 49921HelicalSequence analysisAdd
BLAST
Topological domaini500 – 53839CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Viral envelope protein, Virion

Pathology & Biotechi

Polymorphism and mutation databases

BioMutaiERVFRD-1.
DMDMi44887864.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1515Sequence analysisAdd
BLAST
Chaini16 – 538523Syncytin-2PRO_0000008439Add
BLAST
Chaini16 – 350335Surface proteinBy similarityPRO_0000008440Add
BLAST
Chaini351 – 538188Transmembrane proteinBy similarityPRO_0000008441Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi133 – 1331N-linked (GlcNAc...)Sequence analysis
Glycosylationi146 – 1461N-linked (GlcNAc...)Sequence analysis
Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence analysis
Glycosylationi220 – 2201N-linked (GlcNAc...)Sequence analysis
Glycosylationi241 – 2411N-linked (GlcNAc...)Sequence analysis
Glycosylationi247 – 2471N-linked (GlcNAc...)Sequence analysis
Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence analysis
Glycosylationi332 – 3321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi431 ↔ 4381 Publication
Glycosylationi443 – 4431N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Specific enzymatic cleavages in vivo yield the mature SU and TM proteins.By similarity
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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei350 – 3512CleavageBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiP60508.
PaxDbiP60508.
PRIDEiP60508.
TopDownProteomicsiP60508.

PTM databases

iPTMnetiP60508.
PhosphoSiteiP60508.

Expressioni

Tissue specificityi

Expressed at higher level in placenta. Expressed at lower level in adrenal, bone marrow, brain, breast, colon, kidney, lung, ovary, peripheral blood lymphocytes, prostate, skin, spleen, testis, thymus, thyroid, trachea.1 Publication

Gene expression databases

BgeeiP60508.
GenevisibleiP60508. HS.

Organism-specific databases

HPAiHPA011812.

Interactioni

Subunit structurei

The surface and transmembrane proteins form a heterodimer. They are attached by non-covalent interactions or by a labile interchain disulfide bond (By similarity). Interacts with MFSD2A.By similarity1 Publication

Protein-protein interaction databases

BioGridi135715. 1 interaction.
STRINGi9606.ENSP00000420174.

Structurei

Secondary structure

1
538
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi395 – 42329Combined sources
Helixi425 – 4273Combined sources
Helixi430 – 4334Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y4MX-ray1.60A/B/C391-443[»]
ProteinModelPortaliP60508.
SMRiP60508. Positions 391-443.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60508.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni354 – 37421Fusion peptideBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi43 – 464CXXCBy similarity
Motifi414 – 43017CKS-17By similarityAdd
BLAST
Motifi431 – 4399CX6CCBy similarity

Domaini

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).By similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410JCYM. Eukaryota.
ENOG4111CG7. LUCA.
GeneTreeiENSGT00770000120690.
HOVERGENiHBG096013.
InParanoidiP60508.
OMAiPNITFPQ.
OrthoDBiEOG70ZZQM.
PhylomeDBiP60508.
TreeFamiTF332233.

Family and domain databases

InterProiIPR018154. TLV/ENV_coat_polyprotein.
[Graphical view]
PANTHERiPTHR10424. PTHR10424. 1 hit.
PfamiPF00429. TLV_coat. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P60508-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLLLLVLIL TPSLAAYRHP DFPLLEKAQQ LLQSTGSPYS TNCWLCTSSS
60 70 80 90 100
TETPGTAYPA SPREWTSIEA ELHISYRWDP NLKGLMRPAN SLLSTVKQDF
110 120 130 140 150
PDIRQKPPIF GPIFTNINLM GIAPICVMAK RKNGTNVGTL PSTVCNVTFT
160 170 180 190 200
VDSNQQTYQT YTHNQFRHQP RFPKPPNITF PQGTLLDKSS RFCQGRPSSC
210 220 230 240 250
STRNFWFRPA DYNQCLQISN LSSTAEWVLL DQTRNSLFWE NKTKGANQSQ
260 270 280 290 300
TPCVQVLAGM TIATSYLGIS AVSEFFGTSL TPLFHFHIST CLKTQGAFYI
310 320 330 340 350
CGQSIHQCLP SNWTGTCTIG YVTPDIFIAP GNLSLPIPIY GNSPLPRVRR
360 370 380 390 400
AIHFIPLLAG LGILAGTGTG IAGITKASLT YSQLSKEIAN NIDTMAKALT
410 420 430 440 450
TMQEQIDSLA AVVLQNRRGL DMLTAAQGGI CLALDEKCCF WVNQSGKVQD
460 470 480 490 500
NIRQLLNQAS SLRERATQGW LNWEGTWKWF SWVLPLTGPL VSLLLLLLFG
510 520 530
PCLLNLITQF VSSRLQAIKL QTNLSAGRHP RNIQESPF
Length:538
Mass (Da):59,523
Last modified:March 1, 2004 - v1
Checksum:iAC4229CB43129F06
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358244 mRNA. Translation: AAQ88611.1.
AK123938 mRNA. Translation: BAC85731.1.
AL136139 Genomic DNA. No translation available.
BC068585 mRNA. Translation: AAH68585.1.
CCDSiCCDS4519.1.
RefSeqiNP_997465.1. NM_207582.2.
UniGeneiHs.631996.

Genome annotation databases

EnsembliENST00000472091; ENSP00000420174; ENSG00000244476.
ENST00000542862; ENSP00000444461; ENSG00000244476.
GeneIDi405754.
KEGGihsa:405754.
UCSCiuc003mzt.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358244 mRNA. Translation: AAQ88611.1.
AK123938 mRNA. Translation: BAC85731.1.
AL136139 Genomic DNA. No translation available.
BC068585 mRNA. Translation: AAH68585.1.
CCDSiCCDS4519.1.
RefSeqiNP_997465.1. NM_207582.2.
UniGeneiHs.631996.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y4MX-ray1.60A/B/C391-443[»]
ProteinModelPortaliP60508.
SMRiP60508. Positions 391-443.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi135715. 1 interaction.
STRINGi9606.ENSP00000420174.

PTM databases

iPTMnetiP60508.
PhosphoSiteiP60508.

Polymorphism and mutation databases

BioMutaiERVFRD-1.
DMDMi44887864.

Proteomic databases

EPDiP60508.
PaxDbiP60508.
PRIDEiP60508.
TopDownProteomicsiP60508.

Protocols and materials databases

DNASUi405754.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000472091; ENSP00000420174; ENSG00000244476.
ENST00000542862; ENSP00000444461; ENSG00000244476.
GeneIDi405754.
KEGGihsa:405754.
UCSCiuc003mzt.4. human.

Organism-specific databases

CTDi405754.
GeneCardsiERVFRD-1.
HGNCiHGNC:33823. ERVFRD-1.
HPAiHPA011812.
MIMi610524. gene.
neXtProtiNX_P60508.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JCYM. Eukaryota.
ENOG4111CG7. LUCA.
GeneTreeiENSGT00770000120690.
HOVERGENiHBG096013.
InParanoidiP60508.
OMAiPNITFPQ.
OrthoDBiEOG70ZZQM.
PhylomeDBiP60508.
TreeFamiTF332233.

Miscellaneous databases

EvolutionaryTraceiP60508.
GeneWikiiHERV-FRD.
GenomeRNAii405754.
PROiP60508.
SOURCEiSearch...

Gene expression databases

BgeeiP60508.
GenevisibleiP60508. HS.

Family and domain databases

InterProiIPR018154. TLV/ENV_coat_polyprotein.
[Graphical view]
PANTHERiPTHR10424. PTHR10424. 1 hit.
PfamiPF00429. TLV_coat. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  3. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  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. "Identification of an envelope protein from the FRD family of human endogenous retroviruses (HERV-FRD) conferring infectivity and functional conservation among simians."
    Blaise S., Ruggieri A., Dewannieux M., Cosset F.-L., Heidmann T.
    J. Virol. 78:1050-1054(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "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.
  8. "A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2."
    Esnault C., Priet S., Ribet D., Vernochet C., Bruls T., Lavialle C., Weissenbach J., Heidmann T.
    Proc. Natl. Acad. Sci. U.S.A. 105:17532-17537(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MFSD2A.
  9. "A novel human endogenous retroviral protein inhibits cell-cell fusion."
    Sugimoto J., Sugimoto M., Bernstein H., Jinno Y., Schust D.
    Sci. Rep. 3:1462-1462(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Crystal structure of a pivotal domain of human syncytin-2, a 40 million years old endogenous retrovirus fusogenic envelope gene captured by primates."
    Renard M., Varela P.F., Letzelter C., Duquerroy S., Rey F.A., Heidmann T.
    J. Mol. Biol. 352:1029-1034(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 391-443, DISULFIDE BOND.

Entry informationi

Entry nameiSYCY2_HUMAN
AccessioniPrimary (citable) accession number: P60508
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: June 8, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

HERV-FRD subgenomic RNA has been observed.
Ortholog in old-world and new-world monkeys, but not in prosimians.
The human genome contains a high percentage of proviral-like elements, also called endogenous retroviruses (ERVs) that are the genomic traces of ancient infections of the germline by exogenous retroviruses. Although most of these elements are defective, some have conserved a functional envelope (env) gene, most probably diverted by the host for its benefit.

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, ERV, Reference proteome, Transposable element

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.