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P90495 (MIR1_HHV8P) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase MIR1

EC=6.3.2.-
Alternative name(s):
IE1B protein
Modulator of immune recognition 1
ORF K3
Gene names
Name:K3
OrganismHuman herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus) [Reference proteome]
Taxonomic identifier868565 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length333 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase which promotes ubiquitination and subsequent degradation of host MHC-I and CD1D molecules, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes. Binds target molecules through transmembrane interaction. E3 ubiquitin-protein ligases accept ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfer it to target protein. The result of this ubiquitination is the enhancement of the endocytosis of the target chain and the delivery to the lysosome, where it is proteolytically destroyed. Induces ubiquitination not only on lysines, but also on cysteine residues. Ref.6 Ref.7 Ref.8 Ref.10 Ref.11

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Binds human MHC-I and CD1D Probable.

Subcellular location

Host cell membrane; Multi-pass membrane protein. Host endoplasmic reticulum. Note: Probably exerts its effects at the plasma membrane during viral infection. Ref.7

Miscellaneous

Specific for HLA-A, HLA-B, HLA-C and HLA-E alleles.

Sequence similarities

Contains 1 RING-CH-type zinc finger.

Ontologies

Keywords
   Biological processHost-virus interaction
Inhibition of host innate immune response by virus
Inhibition of host interferon receptors by virus
Inhibition of host interferon signaling pathway by virus
Ubl conjugation pathway
Viral immunoevasion
   Cellular componentHost cell membrane
Host endoplasmic reticulum
Host membrane
Membrane
   Developmental stageEarly protein
   DomainTransmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendocytosis involved in viral entry into host cell

Inferred from mutant phenotype PubMed 23460925. Source: CACAO

modulation by virus of host protein ubiquitination

Inferred from mutant phenotype PubMed 23460925. Source: CACAO

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 23460925. Source: CACAO

suppression by virus of host adaptive immune response

Inferred from mutant phenotype PubMed 23460925. Source: CACAO

suppression by virus of host interferon receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P889412EBI-6149947,EBI-7922689From a different organism.
P889512EBI-6149947,EBI-7923148From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 333333E3 ubiquitin-protein ligase MIR1
PRO_0000221389

Regions

Topological domain1 – 8282Cytoplasmic Potential
Transmembrane83 – 10321Helical; Potential
Topological domain104 – 12118Extracellular Potential
Transmembrane122 – 14221Helical; Potential
Topological domain143 – 333191Cytoplasmic Potential
Zinc finger1 – 6060RING-CH-type

Sites

Metal binding121Zinc
Metal binding241Zinc
Metal binding261Zinc
Metal binding341Zinc
Metal binding371Zinc
Metal binding501Zinc
Metal binding531Zinc

Experimental info

Mutagenesis411W → A: Loss of ubiquitination activity and degradation of class I molecules. Ref.9
Sequence conflict195 – 20410Missing in AAB62674. Ref.3
Sequence conflict195 – 20410Missing in ABD28858. Ref.5
Sequence conflict2811A → V in AAB62674. Ref.3
Sequence conflict3101P → L in ABD28858. Ref.5

Secondary structure

......... 333
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P90495 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: C9CCE79B87D3F553

FASTA33336,005
        10         20         30         40         50         60 
MEDEDVPVCW ICNEELGNER FRACGCTGEL ENVHRSCLST WLTISRNTAC QICGVVYNTR 

        70         80         90        100        110        120 
VVWRPLREMT LLPRLTYQEG LELIVFIFIM TLGAAGLAAA TWVWLYIVGG HDPEIDHVAA 

       130        140        150        160        170        180 
AAYYVFFVFY QLFVVFGLGA FFHMMRHVGR AYAAVNTRVE VFPYRPRPTS PECAVEEIEL 

       190        200        210        220        230        240 
QEILPRGDNQ DEEGPAGAAP GDQNGPAGAA PGDQDGPADG APVHRDSEES VDEAAGYKEA 

       250        260        270        280        290        300 
GEPTHNDGRD DNVEPTAVGC DCNNLGAERY RATYCGGYVG AQSGDGAYSV SCHNKAGPSS 

       310        320        330 
LVDILPQGLP GGGYGSMGVI RKRSAVSSAL MFH 

« Hide

References

« Hide 'large scale' references
[1]"A single 13-kilobase divergent locus in the Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genome contains nine open reading frames that are homologous to or related to cellular proteins."
Nicholas J., Ruvolo V., Zong J., Ciufo D., Guo H.-G., Reitz M.S., Hayward G.S.
J. Virol. 71:1963-1974(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Transcription pattern of human herpesvirus 8 open reading frame k3 in primary effusion lymphoma and kaposi's sarcoma."
Rimessi P., Bonaccorsi A., Sturzl M., Fabris M., Brocca-Cofano E., Caputo A., Melucci-Vigo G., Falchi M., Cafaro A., Cassai E., Ensoli B., Monini P.
J. Virol. 75:7161-7174(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The genome of human herpesvirus 8 cloned from Kaposi's sarcoma."
Neipel F., Albrecht J.-C., Ensser A., Huang Y.-Q., Li J.J., Friedman-Kien A.E., Fleckenstein B.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8)."
Russo J.J., Bohenzky R.A., Chien M.-C., Chen J., Yan M., Maddalena D., Parry J.P., Peruzzi D., Edelman I.S., Chang Y., Moore P.S.
Proc. Natl. Acad. Sci. U.S.A. 93:14862-14867(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Kaposi's sarcoma-associated herpesvirus immune modulation: an overview."
Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.
J. Gen. Virol. 87:1781-1804(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis."
Coscoy L., Ganem D.
Proc. Natl. Acad. Sci. U.S.A. 97:8051-8056(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins."
Ishido S., Wang C., Lee B.-S., Cohen G.B., Jung J.U.
J. Virol. 74:5300-5309(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]"A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition."
Coscoy L., Sanchez D.J., Ganem D.
J. Cell Biol. 155:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation."
Hewitt E.W., Duncan L., Mufti D., Baker J., Stevenson P.G., Lehner P.J.
EMBO J. 21:2418-2429(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN HLA-A, DOMAIN RINGV-TYPE ZINC-FINGER, MUTAGENESIS OF TRP-41.
[10]"Regulation of CD1d expression and function by a herpesvirus infection."
Sanchez D.J., Gumperz J.E., Ganem D.
J. Clin. Invest. 115:1369-1378(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase."
Cadwell K., Coscoy L.
Science 309:127-130(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal domain reveals a Novel E2-binding C4HC3-type RING domain."
Dodd R.B., Allen M.D., Brown S.E., Sanderson C.M., Duncan L.M., Lehner P.J., Bycroft M., Read R.J.
J. Biol. Chem. 279:53840-53847(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-60.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U75698 Genomic DNA. Translation: AAC57091.1.
AF307516 mRNA. Translation: AAK83788.1.
AF307517 mRNA. Translation: AAK83789.1.
AF307518 mRNA. Translation: AAK83790.1.
AF307519 mRNA. Translation: AAK83791.1.
U71365 Genomic DNA. Translation: AAC34939.1.
U83350 Genomic DNA. Translation: AAC56950.1.
U93872 Genomic DNA. Translation: AAB62674.1.
AF148805 Genomic DNA. Translation: ABD28858.1.
RefSeqYP_001129360.1. NC_009333.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VYXNMR-A1-60[»]
ProteinModelPortalP90495.
SMRP90495. Positions 1-60.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP90495. 16 interactions.
MINTMINT-2824800.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID4961486.

Phylogenomic databases

ProtClustDBCLSP2511820.

Enzyme and pathway databases

UniPathwayUPA00143.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF12906. RINGv. 1 hit.
[Graphical view]
SMARTSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP90495.

Entry information

Entry nameMIR1_HHV8P
AccessionPrimary (citable) accession number: P90495
Secondary accession number(s): O40920, Q2HRC5
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: May 1, 1997
Last modified: February 19, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways