ENW1_HUMAN » Syncytin-1

ENW1_HUMAN » Syncytin-1
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
ENW1_HUMAN » Syncytin-1 » Endogenous retrovirus group W member 1;Env-W;Envelope polyprotein gPr73;Enverin;HERV-7q Envelope protein;HERV-W envelope protein;Syncytin;Syncytin-1;
Hydrophobic Thickness 38.8 ± 7.2 Å
Tilt Angle 30 ± 0°
ΔGtransfer -34.0 kcal/mol
ΔGfold -18.5 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 447-476 (444-478)
Pathways none
PDB none
OPM none
Complexes none
Interactions none
Domains

AA: 56-477, PDBID: 1xnl, Subunit A, Seq Identity:48%, ENV polyprotein (coat polyprotein)

UniProt annotation for ENW1_HUMAN » Syncytin-1
FUNCTION: 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. May induce fusion through binding of SLC1A4 and SLC1A5 (PubMed, PubMed, PubMed).

FUNCTION: Endogenous envelope proteins may have kept, lost or modified their original function during evolution. Retroviral envelope proteins mediate receptor recognition and membrane fusion during early infection. The surface protein (SU) mediates receptor recognition, while the transmembrane protein (TM) acts as a class I viral fusion protein. The protein may have at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of membranes.

SUBUNIT: The mature envelope protein (Env) consists of a trimer of SU-TM heterodimers attached probably by a labile interchain disulfide bond. Interacts with the C-type lectin CD209/DC-SIGN.

TISSUE SPECIFICITY: Expressed at higher level in placental syncytiotrophoblast. Expressed at intermediate level in testis. Seems also to be found at low level in adrenal tissue, bone marrow, breast, colon, kidney, ovary, prostate, skin, spleen, thymus, thyroid, brain and trachea. Both mRNA and protein levels are significantly increased in the brain of individuals with multiple sclerosis, particularly in astrocytes and microglia.

DEVELOPMENTAL STAGE: In placenta, detected at higher level during early pregnancy and at lower level during late pregnancy.

DOMAIN: The cytoplasmic region is essential for the fusiogenic function.

DOMAIN: The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo (By similarity).

MISCELLANEOUS: Probably involved in the development of multiple sclerosis (MS). MS is a neurodegenerative disease characterized by the gradual accumulation of focal plaques of demyelination particularly in the periventricular areas of the brain. It leads to physical and cognitive disabilities. Viral particles or intracellular RNA of HERV-W family members have been detected in tissue from patients with multiple sclerosis or schizophrenia.

MISCELLANEOUS: Orthologs in Pan troglodytes, Gorilla gorilla, Pongo pygmaeus and Hylobates moloch.

MISCELLANEOUS: It can make pseudotypes with HIV-1 virions and confer infectivity. Can also induce cellular resistance to spleen necrosis virus in vitro.

MISCELLANEOUS: HERV-W family subgenomic RNAs have been observed.

MISCELLANEOUS: This provirus is intergenic, the closest flanking genes being ODAG and PEX1.

MISCELLANEOUS: 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.

UniProt features for ENW1_HUMAN » Syncytin-1
SIGNAL 1 20 Potential.
CHAIN 21 538 HERV-W_7q21.2 provirus ancestral Env polyprotein.
CHAIN 21 317 Surface protein.
CHAIN 318 538 Transmembrane protein.
REGION 320 340 Fusion peptide (Potential).
REGION 380 396 Immunosuppression (By similarity).
REGION 465 484 Essential for the fusiogenic function.
MOTIF 186 189 CXXC (By similarity).
MOTIF 397 405 CX6CC (By similarity).
SITE 317 318 Cleavage.
DISULFID 186 405 Interchain (between SU and TM chains, or C-189 with C-405); alternate (By similarity).
DISULFID 186 189 Alternate (By similarity).
DISULFID 397 404 By similarity.
Amino Acid Sequence for ENW1_HUMAN » Syncytin-1
MALPYHIFLF TVLLPSFTLT APPPCRCMTS SSPYQEFLWR MQRPGNIDAP SYRSLSKGTP TFTAHTHMPR NCYHSATLCM HANTHYWTGK MINPSCPGGL GVTVCWTYFT QTGMSDGGGV QDQAREKHVK EVISQLTRVH GTSSPYKGLD LSKLHETLRT HTRLVSLFNT TLTGLHEVSA QNPTNCWICL PLNFRPYVSI PVPEQWNNFS TEINTTSVLV GPLVSNLEIT HTSNLTCVKF SNTTYTTNSQ CIRWVTPPTQ IVCLPSGIFF VCGTSAYRCL NGSSESMCFL SFLVPPMTIY TEQDLYSYVI SKPRNKRVPI LPFVIGAGVL GALGTGIGGI TTSTQFYYKL SQELNGDMER VADSLVTLQD QLNSLAAVVL QNRRALDLLT AERGGTCLFL GEECCYYVNQ SGIVTEKVKE IRDRIQRRAE ELRNTGPWGL LSQWMPWILP FLGPLAAIIL LLLFGPCIFN LLVNFVSSRI EAVKLQMEPK MQSKTKIYRR PLDRPASPRS DVNDIKGTPP EEISAAQPLL RPNSAGSS