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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)DescriptionActionsGraphical viewLength
Topological domaini16 – 478ExtracellularSequence analysisAdd BLAST463
Transmembranei479 – 499HelicalSequence analysisAdd BLAST21
Topological domaini500 – 538CytoplasmicSequence analysisAdd BLAST39

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Viral envelope protein, Virion

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000244476.

Polymorphism and mutation databases

BioMutaiERVFRD-1.
DMDMi44887864.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 15Sequence analysisAdd BLAST15
ChainiPRO_000000843916 – 538Syncytin-2Add BLAST523
ChainiPRO_000000844016 – 350Surface proteinBy similarityAdd BLAST335
ChainiPRO_0000008441351 – 538Transmembrane proteinBy similarityAdd BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi133N-linked (GlcNAc...)Sequence analysis1
Glycosylationi146N-linked (GlcNAc...)Sequence analysis1
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Glycosylationi220N-linked (GlcNAc...)Sequence analysis1
Glycosylationi241N-linked (GlcNAc...)Sequence analysis1
Glycosylationi247N-linked (GlcNAc...)Sequence analysis1
Glycosylationi312N-linked (GlcNAc...)Sequence analysis1
Glycosylationi332N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi431 ↔ 4381 Publication
Glycosylationi443N-linked (GlcNAc...)Sequence analysis1

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)DescriptionActionsGraphical viewLength
Sitei350 – 351CleavageBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP60508.
PeptideAtlasiP60508.
PRIDEiP60508.
TopDownProteomicsiP60508.

PTM databases

iPTMnetiP60508.
PhosphoSitePlusiP60508.

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

BgeeiENSG00000244476.
GenevisibleiP60508. HS.

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 interactor.
STRINGi9606.ENSP00000420174.

Structurei

Secondary structure

1538
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi395 – 423Combined sources29
Helixi425 – 427Combined sources3
Helixi430 – 433Combined sources4

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP60508.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni354 – 374Fusion peptideBy similarityAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi43 – 46CXXCBy similarity4
Motifi414 – 430CKS-17By similarityAdd BLAST17
Motifi431 – 439CX6CCBy similarity9

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.
OrthoDBiEOG091G04WY.
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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Y4MX-ray1.60A/B/C391-443[»]
ProteinModelPortaliP60508.
SMRiP60508.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi135715. 1 interactor.
STRINGi9606.ENSP00000420174.

PTM databases

iPTMnetiP60508.
PhosphoSitePlusiP60508.

Polymorphism and mutation databases

BioMutaiERVFRD-1.
DMDMi44887864.

Proteomic databases

PaxDbiP60508.
PeptideAtlasiP60508.
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.
MIMi610524. gene.
neXtProtiNX_P60508.
OpenTargetsiENSG00000244476.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JCYM. Eukaryota.
ENOG4111CG7. LUCA.
GeneTreeiENSGT00770000120690.
HOVERGENiHBG096013.
InParanoidiP60508.
OMAiPNITFPQ.
OrthoDBiEOG091G04WY.
PhylomeDBiP60508.
TreeFamiTF332233.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000244476.
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...

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: November 2, 2016
This is version 119 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.