P90495 (MIR1_HHV8P) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus) [Reference proteome]

Taxonomic identifier

868565 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Gammaherpesvirinae › Rhadinovirus › Human herpesvirus 8

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	333 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Host-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 component	Host cell membrane Host endoplasmic reticulum Host membrane Membrane
Developmental stage	Early protein
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway 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_component	host cell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 333

333

E3 ubiquitin-protein ligase MIR1

PRO_0000221389

Regions

Topological domain

1 – 82

82

Cytoplasmic Potential

Transmembrane

83 – 103

21

Helical; Potential

Topological domain

104 – 121

18

Extracellular Potential

Transmembrane

122 – 142

21

Helical; Potential

Topological domain

143 – 333

191

Cytoplasmic Potential

Zinc finger

1 – 60

60

RING-CH-type

Sites

Metal binding

12

1

Zinc

Metal binding

24

1

Zinc

Metal binding

26

1

Zinc

Metal binding

34

1

Zinc

Metal binding

37

1

Zinc

Metal binding

50

1

Zinc

Metal binding

53

1

Zinc

Experimental info

Mutagenesis

41

1

W → A: Loss of ubiquitination activity and degradation of class I molecules. Ref.9

Sequence conflict

195 – 204

10

Missing in AAB62674. Ref.3

Sequence conflict

195 – 204

10

Missing in ABD28858. Ref.5

Sequence conflict

281

1

A → V in AAB62674. Ref.3

Sequence conflict

310

1

P → L in ABD28858. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

333

Helix Strand Turn

Details...

Turn

10 – 13

4

Helix

29 – 31

3

Helix

35 – 45

11

Turn

51 – 53

3

Sequences

	Sequence		Length	Mass (Da)
	P90495 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: C9CCE79B87D3F553	FASTA	333	36,005
	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

References

	« Hide 'large scale' referencesShow '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.

RefSeq

YP_001129360.1. NC_009333.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VYX	NMR	-	A	1-60	[»]

ProteinModelPortal

P90495.

SMR

P90495. Positions 1-60.

ModBase

Search...

Protein-protein interaction databases

IntAct

P90495. 14 interactions.

MINT

MINT-2824800.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

4961486.

Phylogenomic databases

ProtClustDB

CLSP2511820.

Enzyme and pathway databases

UniPathway

UPA00143.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF12906. RINGv. 1 hit.
[Graphical view]

SMART

SM00744. RINGv. 1 hit.
[Graphical view]

PROSITE

PS51292. ZF_RING_CH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P90495.

Entry information

Entry name

MIR1_HHV8P

Accession

Primary (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:	April 3, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program