Q9N2K0 (ENH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: HERV-H_2q24.3 provirus ancestral Env polyprotein Alternative name(s): Env protein HERV-H/p62 Env protein HERV-H19 Env protein HERV-Hcl.3 Envelope polyprotein HERV-H/env62 Cleaved into the following 2 chains: Surface protein Short name=SU Transmembrane protein Short name=TM
Organism	Homo sapiens (Human) [Reference proteome]
Taxonomic identifier	9606 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	584 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 original fusogenic properties but has immunosuppressive properties in vivo. Ref.4 Ref.5 SU mediates receptor recognition By similarity. 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.4 Ref.5
Subunit structure	The surface (SU) and transmembrane (TM) proteins form a heterodimer. SU and TM are attached by noncovalent interactions or by a labile interchain disulfide bond By similarity.
Subcellular location	Virion. Transmembrane protein: Cell membrane; Single-pass membrane protein Potential.
Tissue specificity	Low expression in skin and testis. No expression in several cell lines. Ref.6
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. 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	Envelope protein HERV-H19 and HERV-H/p62 are allelic variants of the same provirus.
Miscellaneous	Ortholog in Pan troglodytes. HERV-H family subgenomic RNAs have been observed. This provirus is intergenic, the closest flanking genes being TAIP2 and GALNT3.
Sequence similarities	Belongs to the gamma type-C retroviral envelope protein family. HERV class-I H env subfamily.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Viral envelope protein Virion
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome ERV Reference proteome Transposable element
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell viral envelope Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Chain	36 – 584	549	HERV-H_2q24.3 provirus ancestral Env polyprotein		PRO_0000008460
	Chain	36 – 387	352	Surface protein By similarity		PRO_0000008461
	Chain	388 – 584	197	Transmembrane protein By similarity		PRO_0000008462
Regions
	Topological domain	36 – 523	488	Extracellular Potential
	Transmembrane	524 – 544	21	Helical; Potential
	Topological domain	545 – 584	40	Cytoplasmic Potential
	Region	388 – 408	21	Fusion peptide By similarity
	Motif	64 – 67	4	CXXC By similarity
	Motif	454 – 470	17	CKS-17 By similarity
	Motif	471 – 479	9	CX6CC By similarity
Sites
	Site	387 – 388	2	Cleavage By similarity
Amino acid modifications
	Glycosylation	10	1	N-linked (GlcNAc...) Potential
	Glycosylation	47	1	N-linked (GlcNAc...) Potential
	Glycosylation	199	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	265	1	N-linked (GlcNAc...) Potential
	Glycosylation	283	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
	Glycosylation	370	1	N-linked (GlcNAc...) Potential
	Glycosylation	483	1	N-linked (GlcNAc...) Potential
	Disulfide bond	471 ↔ 478		By similarity
Natural variations
	Natural variant	81	1	V → L in allele HERV-H19. Ref.1 Ref.2 Ref.3		VAR_017799
	Natural variant	150	1	F → L in allele HERV-H19. Ref.1 Ref.2		VAR_017800
Experimental info
	Sequence conflict	80	1	A → T in AAL11491. Ref.3
	Sequence conflict	98	1	F → C in AAL11491. Ref.3
	Sequence conflict	316	1	T → A in AAL11491. Ref.3
	Sequence conflict	319	1	S → G in AAC79121. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9N2K0 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C03D260B5A60BDAB	FASTA	584	64,318
	10 20 30 40 50 60 MIFAGKAPSN TSTLMKFYSL LLYSLLFSFP FLCHPLPLPS YLHHTINLTH SLLAASNPSL 70 80 90 100 110 120 VNNCWLCISL SSSAYTAVPA VQTDWATSPI SLHLRTSFNS PHLYPPEELI YFLDRSSKTS 130 140 150 160 170 180 PDISHQQAAA LLRTYLKNLS PYINSTPPIF GPLTTQTTIP VAAPLCISWQ RPTGIPLGNL 190 200 210 220 230 240 SPSRCSFTLH LRSPTTNINE TIGAFQLHIT DKPSINTDKL KNISSNYCLG RHLPCISLHP 250 260 270 280 290 300 WLSSPCSSDS PPRPSSCLLI PSPENNSERL LVDTRRFLIH HENRTFPSTQ LPHQSPLQPL 310 320 330 340 350 360 TAAALAGSLG VWVQDTPFST PSHLFTLHLQ FCLAQGLFFL CGSSTYMCLP ANWTGTCTLV 370 380 390 400 410 420 FLTPKIQFAN GTEELPVPLM TPTQQKRVIP LIPLMVGLGL SASTVALGTG IAGISTSVMT 430 440 450 460 470 480 FRSLSNDFSA SITDISQTLS VLQAQVDSLA AVVLQNRRGL DLLTAEKGGL CIFLNEECCF 490 500 510 520 530 540 YLNQSGLVYD NIKKLKDRAQ KLANQASNYA EPPWALSNWM SWVLPIVSPL IPIFLLLLFG 550 560 570 580 PCIFRLVSQF IQNRIQAITN HSIRQMFLLT SPQYHPLPQD LPSA

References

[1]	"Isolation of a human endogenous retroviral HERV-H element with an open env reading frame." Lindeskog M., Mager D.L., Blomberg J. Virology 258:441-450(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-81 AND LEU-150.
[2]	"Characterization of the three HERV-H proviruses with an open envelope reading frame encompassing the immunosuppressive domain and evolutionary history in primates." de Parseval N., Casella J.-F., Gressin L., Heidmann T. Virology 279:558-569(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-81 AND LEU-150.
[3]	"Full-length HERV-H elements with env SU open reading frames in the human genome." Jern P., Lindeskog M., Karlsson D., Blomberg J. AIDS Res. Hum. Retroviruses 18:671-676(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-402, VARIANT LEU-81.
[4]	"The full-length envelope of an HERV-H human endogenous retrovirus has immunosuppressive properties." Mangeney M., de Parseval N., Thomas G., Heidmann T. J. Gen. Virol. 82:2515-2518(2001) [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.

Web resources

Human Endogenous Retrovirus Database (HERVd)

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF108843 Genomic DNA. Translation: AAD34324.1. U88902 Genomic DNA. Translation: AAC79121.1. AJ289709 Genomic DNA. Translation: CAB94192.1. AY050297 Genomic DNA. Translation: AAL11491.1.
IPI	IPI00400839.
PIR	B44282.
3D structure databases
ProteinModelPortal	Q9N2K0.
ModBase	Search...
Polymorphism databases
DMDM	44887889.
Proteomic databases
PRIDE	Q9N2K0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
neXtProt	NX_Q9N2K0.
Phylogenomic databases
HOVERGEN	HBG017290.
Gene expression databases
Genevestigator	Q9N2K0.
Family and domain databases
InterPro	IPR018154. TLV/ENV_coat_polyprotein. [Graphical view]
PANTHER	PTHR10424. PTHR10424. 1 hit.
Pfam	PF00429. TLV_coat. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	35541855.

Entry information

Entry name

ENH1_HUMAN

Accession

Primary (citable) accession number: Q9N2K0
Secondary accession number(s): O00354, Q96L63, Q9UNM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.