SYNA_MOUSE
ID SYNA_MOUSE Reviewed; 617 AA.
AC Q5G5D5;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Syncytin-A {ECO:0000303|PubMed:15644441};
DE Contains:
DE RecName: Full=Surface protein {ECO:0000303|PubMed:15644441};
DE Short=SU {ECO:0000303|PubMed:15644441};
DE Contains:
DE RecName: Full=Transmembrane protein {ECO:0000303|PubMed:15644441};
DE Short=TM {ECO:0000303|PubMed:15644441};
DE Flags: Precursor;
GN Name=Syna {ECO:0000312|MGI:MGI:2684898};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:AAW62446.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAW62446.1};
RX PubMed=15644441; DOI=10.1073/pnas.0406509102;
RA Dupressoir A., Marceau G., Vernochet C., Benit L., Kanellopoulos C.,
RA Sapin V., Heidmann T.;
RT "Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope
RT genes of retroviral origin conserved in Muridae.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:725-730(2005).
RN [2] {ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000312|EMBL:AAI38920.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17762178; DOI=10.1159/000107535;
RA Gong R., Huang L., Shi J., Luo K., Qiu G., Feng H., Tien P., Xiao G.;
RT "Syncytin-A mediates the formation of syncytiotrophoblast involved in mouse
RT placental development.";
RL Cell. Physiol. Biochem. 20:517-526(2007).
RN [5] {ECO:0000305}
RP FUNCTION, AND SUBUNIT.
RX PubMed=17105734; DOI=10.1074/jbc.m606353200;
RA Peng X., Pan J., Gong R., Liu Y., Kang S., Feng H., Qiu G., Guo D.,
RA Tien P., Xiao G.;
RT "Functional characterization of syncytin-A, a newly murine endogenous virus
RT envelope protein. Implication for its fusion mechanism.";
RL J. Biol. Chem. 282:381-389(2007).
RN [6] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF ARG-493.
RX PubMed=18077339; DOI=10.1073/pnas.0707873105;
RA Mangeney M., Renard M., Schlecht-Louf G., Bouallaga I., Heidmann O.,
RA Letzelter C., Richaud A., Ducos B., Heidmann T.;
RT "Placental syncytins: Genetic disjunction between the fusogenic and
RT immunosuppressive activity of retroviral envelope proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20534-20539(2007).
RN [7] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18448564; DOI=10.1242/dev.020099;
RA Simmons D.G., Natale D.R., Begay V., Hughes M., Leutz A., Cross J.C.;
RT "Early patterning of the chorion leads to the trilaminar trophoblast cell
RT structure in the placental labyrinth.";
RL Development 135:2083-2091(2008).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19564597; DOI=10.1073/pnas.0902925106;
RA Dupressoir A., Vernochet C., Bawa O., Harper F., Pierron G., Opolon P.,
RA Heidmann T.;
RT "Syncytin-A knockout mice demonstrate the critical role in placentation of
RT a fusogenic, endogenous retrovirus-derived, envelope gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12127-12132(2009).
RN [9] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=22032925; DOI=10.1073/pnas.1112304108;
RA Dupressoir A., Vernochet C., Harper F., Guegan J., Dessen P., Pierron G.,
RA Heidmann T.;
RT "A pair of co-opted retroviral envelope syncytin genes is required for
RT formation of the two-layered murine placental syncytiotrophoblast.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:E1164-E1173(2011).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=27589388; DOI=10.1371/journal.pgen.1006289;
RA Redelsperger F., Raddi N., Bacquin A., Vernochet C., Mariot V., Gache V.,
RA Blanchard-Gutton N., Charrin S., Tiret L., Dumonceaux J., Dupressoir A.,
RA Heidmann T.;
RT "Genetic evidence that captured retroviral envelope syncytins contribute to
RT myoblast fusion and muscle sexual dimorphism in mice.";
RL PLoS Genet. 12:E1006289-E1006289(2016).
CC -!- FUNCTION: This endogenous retroviral envelope protein has retained its
CC original fusogenic properties (PubMed:15644441, PubMed:17762178,
CC PubMed:18077339, PubMed:19564597, PubMed:27589388). Together with Synb,
CC participates in trophoblast fusion and the formation of a syncytium
CC during placenta morphogenesis (PubMed:19564597). Syna is essential for
CC placental development and is specifically required for formation of
CC syncytiotrophoblast layer I (SynT-I) (PubMed:19564597). Promotes muscle
CC myoblast fusion (PubMed:27589388). Does not have immunosuppressive
CC activity (PubMed:18077339). {ECO:0000269|PubMed:15644441,
CC ECO:0000269|PubMed:17762178, ECO:0000269|PubMed:18077339,
CC ECO:0000269|PubMed:19564597, ECO:0000269|PubMed:27589388}.
CC -!- SUBUNIT: The mature protein consists of a trimer of SU-TM heterodimers
CC (Probable). The SU-TM heterodimers are attached by a labile interchain
CC disulfide bond (By similarity). {ECO:0000250|UniProtKB:Q9UQF0,
CC ECO:0000305|PubMed:17105734}.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protein]: Cell membrane
CC {ECO:0000305|PubMed:17762178}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Surface protein]: Cell membrane {ECO:0000305};
CC Peripheral membrane protein {ECO:0000305}. Note=The surface protein is
CC not anchored to the membrane, but localizes to the extracellular
CC surface through its binding to TM. {ECO:0000250|UniProtKB:Q9UQF0}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta where it localizes to
CC syncytiotrophoblasts of the labyrinthine zona (PubMed:15644441).
CC Specifically localizes to syncytiotrophoblast layer I (SynT-I)
CC (PubMed:18448564). Also detected at very low levels in hippocampus,
CC brain, testis and ovary (PubMed:15644441).
CC {ECO:0000269|PubMed:15644441}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the placental labyrinth from stage
CC 8.5 dpc onwards. {ECO:0000269|PubMed:15644441,
CC ECO:0000269|PubMed:18448564}.
CC -!- PTM: Synthesized as an inactive precursor that is heavily N-
CC glycosylated and processed likely by furin in the Golgi to yield the
CC mature SU and TM proteins. The cleavage site between SU and TM requires
CC the minimal sequence [KR]-X-[KR]-R. {ECO:0000250|UniProtKB:Q9UQF0}.
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.
CC {ECO:0000250|UniProtKB:Q9UQF0}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal with no survival beyond stage
CC 14.5 dpc (PubMed:19564597). Embryos show retarded growth but otherwise
CC have no significant morphological defects (PubMed:19564597). Placental
CC development is abnormal with significantly reduced vascularization of
CC extraembryonic tissues (PubMed:19564597). In the placental labyrinth,
CC there is an expansion of trophoblast cells which reduces available
CC space for fetal blood vessels (PubMed:19564597). Trophoblast cells fail
CC to fuse and form syncytiotrophoblast layer I (SynT-I), however
CC development of syncytiotrophoblast layer II (SynT-II) is not
CC significantly affected (PubMed:19564597). Double knockouts of Syna and
CC Synb are embryonic lethal at stage 9.5 dpc to 10.5 dpc, indicating a
CC more severe phenotype than the Syna single knockout (PubMed:22032925).
CC {ECO:0000269|PubMed:19564597, ECO:0000269|PubMed:22032925}.
CC -!- MISCELLANEOUS: The mouse genome contains a high percentage of proviral-
CC like elements, also called endogenous retroviruses (ERVs) that are the
CC genomic traces of ancient infections of the germline by exogenous
CC retroviruses. Although most of these elements are defective, some have
CC conserved a functional envelope (env) gene, most probably diverted by
CC the host for its benefit. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the gamma type-C retroviral envelope protein
CC family. {ECO:0000305}.
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DR EMBL; AY849973; AAW62446.1; -; Genomic_DNA.
DR EMBL; AC166938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC138919; AAI38920.1; -; mRNA.
DR CCDS; CCDS19721.1; -.
DR RefSeq; NP_001013773.1; NM_001013751.2.
DR RefSeq; XP_006504467.1; XM_006504404.3.
DR RefSeq; XP_006504469.1; XM_006504406.3.
DR RefSeq; XP_011239176.1; XM_011240874.2.
DR RefSeq; XP_011239177.1; XM_011240875.2.
DR RefSeq; XP_011239179.1; XM_011240877.2.
DR AlphaFoldDB; Q5G5D5; -.
DR SMR; Q5G5D5; -.
DR STRING; 10090.ENSMUSP00000116437; -.
DR GlyGen; Q5G5D5; 3 sites.
DR PaxDb; Q5G5D5; -.
DR PRIDE; Q5G5D5; -.
DR DNASU; 214292; -.
DR Ensembl; ENSMUST00000149604; ENSMUSP00000116437; ENSMUSG00000085957.
DR GeneID; 214292; -.
DR KEGG; mmu:214292; -.
DR UCSC; uc008zwk.2; mouse.
DR CTD; 214292; -.
DR MGI; MGI:2684898; Syna.
DR VEuPathDB; HostDB:ENSMUSG00000085957; -.
DR eggNOG; ENOG502SD08; Eukaryota.
DR GeneTree; ENSGT00940000163436; -.
DR HOGENOM; CLU_506176_0_0_1; -.
DR InParanoid; Q5G5D5; -.
DR OMA; MYSARTL; -.
DR OrthoDB; 451884at2759; -.
DR PhylomeDB; Q5G5D5; -.
DR TreeFam; TF332233; -.
DR BioGRID-ORCS; 214292; 5 hits in 72 CRISPR screens.
DR PRO; PR:Q5G5D5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q5G5D5; protein.
DR Bgee; ENSMUSG00000085957; Expressed in placenta and 47 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0060711; P:labyrinthine layer development; IMP:MGI.
DR GO; GO:0007520; P:myoblast fusion; IMP:MGI.
DR GO; GO:0000768; P:syncytium formation by plasma membrane fusion; IDA:MGI.
DR InterPro; IPR018154; TLV/ENV_coat_polyprotein.
DR PANTHER; PTHR10424; PTHR10424; 1.
DR Pfam; PF00429; TLV_coat; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Developmental protein;
KW Disulfide bond; ERV; Glycoprotein; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..617
FT /note="Syncytin-A"
FT /id="PRO_5009343953"
FT CHAIN 18..416
FT /note="Surface protein"
FT /evidence="ECO:0000305"
FT /id="PRO_0000440573"
FT CHAIN 417..617
FT /note="Transmembrane protein"
FT /evidence="ECO:0000305"
FT /id="PRO_0000440574"
FT TOPO_DOM 18..544
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 545..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..617
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 420..440
FT /note="Fusion peptide"
FT /evidence="ECO:0000305"
FT MOTIF 44..47
FT /note="CXXC"
FT /evidence="ECO:0000305"
FT MOTIF 497..505
FT /note="CX6CC"
FT /evidence="ECO:0000305"
FT SITE 416..417
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9UQF0"
FT CARBOHYD 27
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..505
FT /note="Interchain (between SU and TM chains, or C-47 with
FT C-505); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q9UQF0"
FT DISULFID 44..47
FT /evidence="ECO:0000250|UniProtKB:P23064"
FT DISULFID 497..504
FT /evidence="ECO:0000250|UniProtKB:P60508"
FT MUTAGEN 493
FT /note="R->K: No effect on fusogenic activity. Confers
FT immunosuppressive activity not found in the wild type
FT protein."
FT /evidence="ECO:0000269|PubMed:18077339"
SQ SEQUENCE 617 AA; 68657 MW; 24B203C30B2C8E2A CRC64;
MVRPWVFCLL LFPCSSAYSD SWMPLVNLTQ HLLQEANSSF SSNCWVCLSI QTQRSLAMPA
PLRTWTETPM KLRIMYSART LSGPYPITDL ERRLQNFQPL TPHSSFVNPD QRAIAFLQIT
SVTGILPILS RITSVRYPDD HVYESAQRPI WGSLSTQTIL TSQAPLCISR FFKNSNHATF
VGKLPASLCN HTFQLSPSAN HQSIDLSSSY AFAPLMAMPG SKWRNPLRFS GPPSLNSGMP
HYSCPIDDIH CHTYPTTPWR SCPSFPASTC YNLTLFEPDN SSHPITLSVD TTYFKIKLQG
HKDPYPLFQY QPLMGAALSG QYSIWEYEPT VKKNGGITPN IFSHLVSLTY SFCLNSSGVF
FLCGNSTYVC LPANWSGVCT LVFQYPDIEL LPNNQTISVP LFATVPSSVP ASRRKRALPL
LPLLAGLGIA SALGLGIAGI TTSTVYFQQL SKALSDSLDE IATSIISLQD QIDSLAGVVL
QNRRALDLIV AERGGTCLFL QEECCFYINQ SGVVRHAARK LRERASELGT SSSSWIQWLG
LGPWLPSWLT SLMAPILFIL VLLVFRPCLL NCLTHSVSRR MSSFIHTTTE GHVDKILLLR
ESQYKRLPQE PPEEDAV
