O73557 (Z_LASSJ) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RING finger protein Z
Short name=Protein Z

Alternative name(s):
Zinc-binding protein

Gene names

Name:

Z

Organism

Lassa virus (strain Mouse/Sierra Leone/Josiah/1976) (LASV) [Reference proteome]

Taxonomic identifier

11622 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Arenaviridae › Arenavirus › Old world arenaviruses › Lassa virus

Virus host

Homo sapiens (Human) [TaxID: 9606]
Mastomys natalensis (African soft-furred rat) (Praomys natalensis) [TaxID: 10112]

Protein attributes

Sequence length	99 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a crucial role in virion assembly and budding. Expressed late in the virus life cycle, it acts as an inhibitor of viral transcription and RNA synthesis by interacting with the viral polymerase L By similarity. Presumably recruits the NP encapsidated genome to cellular membranes at budding sites via direct interaction with NP. Plays critical roles in the final steps of viral release by interacting with host TSG101, a member of the vacuolar protein-sorting pathway and using other cellular host proteins involved in vesicle formation pathway. The budding of the virus progeny occurs after association of protein Z with the viral glycoprotein complex SSP-GP1-GP2 at the cell periphery, step that requires myristoylation of protein Z. Also selectively represses protein production by associating with host eIF4E. Ref.4 Ref.5
Subunit structure	Interacts with protein NP; this interaction probably directs the encapsidated genome to budding sites By similarity. Interacts (via RING domain) with polymerase L; this interaction inhibits viral transcription and replication By similarity. Interacts with the glycoprotein complex; this interaction plays a role in virion budding. Interacts with host eIF4E; this interaction results in eIF4E reduced affinity for its substrate, the 5'-m7 G cap structure. Interacts (via late-budding domain) with host TSG101; this interaction is essential for budding and release of viral particles. Interacts with host RPLP0; this interaction may serve to load ribosome-like particles inside the virion. Interacts with host PML; this interaction induces PML bodies redistribution in the cytoplasm upon viral infection. Ref.3 Ref.6 Ref.8 Ref.9
Subcellular location	Virion. Host cytoplasm › host perinuclear region. Host cell membrane; Lipid-anchor; Cytoplasmic side. Note: Mainly perinuclear. During budding, associates at the inner side of the plasma membrane of infected cells.
Domain	Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. Ring-finger protein Z contains two L domains: a PTAP/PSAP motif which interacts with the UEV domain of TSG101, and a PPXY motif which probably binds to the WW domains of HECT (homologous to E6-AP C-terminus) E3 ubiquitin ligases By similarity. Ref.4 Ref.8
Sequence similarities	Belongs to the arenaviridae Z protein family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Host-virus interaction Viral budding Viral budding via the host ESCRT complexes Virus exit from host cell
Cellular component	Host cell membrane Host cytoplasm Host membrane Membrane Virion
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Lipoprotein Myristate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	viral release from host cell Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: InterPro 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

Initiator methionine

1

1

Removed; by host

Chain

2 – 99

98

RING finger protein Z

PRO_0000079201

Regions

Zinc finger

31 – 67

37

RING-type; atypical

Motif

81 – 84

4

PTAP/PSAP motif

Motif

94 – 97

4

PPXY motif

Amino acid modifications

Lipidation

2

1

N-myristoyl glycine; by host Ref.7

Experimental info

Mutagenesis

2

1

G → A: Complete loss of myristoylation. Complete loss of virion budding. Ref.7

Mutagenesis

81 – 84

4

PTAP → ATAA: 50% decrease of virus budding. Ref.4

Mutagenesis

94 – 97

4

PPPY → AAAA: 90% decrease of virus budding. Ref.4

Mutagenesis

97

1

Y → A: 90% decrease of virus budding.

Secondary structure

1

.

.

.

.

.

.

.

.

.

99

Helix Strand Turn

Details...

Beta strand

39 – 43

5

Beta strand

48 – 50

3

Helix

51 – 56

6

Turn

57 – 60

4

Beta strand

61 – 64

4

Turn

65 – 68

4

Sequences

	Sequence		Length	Mass (Da)
	O73557 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: F68877962B65F045	FASTA	99	10,675
	10 20 30 40 50 60 MGNKQAKAPE SKDSPRASLI PDATHLGPQF CKSCWFENKG LVECNNHYLC LNCLTLLLSV 70 80 90 SNRCPICKMP LPTKLRPSAA PTAPPTGAAD SIRPPPYSP

References

[1]	"Completion of the Lassa fever virus sequence and identification of a RING finger open reading frame at the L RNA 5' End." Djavani M., Lukashevich I.S., Sanchez A., Nichol S.T., Salvato M.S. Virology 235:414-418(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	Hajjaj A., Chain P.S.G., Do L.H., Smith K.L., Imbro P.M., Malfatti S.A. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"An arenavirus RING (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the cytoplasm." Borden K.L., Campbell-Dwyer E.J., Salvato M.S. J. Virol. 72:758-766(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN PML.
[4]	"Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles." Strecker T., Eichler R., Meulen J., Weissenhorn W., Dieter Klenk H., Garten W., Lenz O. J. Virol. 77:10700-10705(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LATE-BUDDING DOMAIN, FUNCTION, MUTAGENESIS OF 81-PRO--PRO-84 AND 94-PRO--PRO-97.
[5]	"Cells expressing the RING finger Z protein are resistant to arenavirus infection." Cornu T.I., Feldmann H., de la Torre J.C. J. Virol. 78:2979-2983(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Characterization of the Lassa virus matrix protein Z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP)." Eichler R., Strecker T., Kolesnikova L., ter Meulen J., Weissenhorn W., Becker S., Klenk H.D., Garten W., Lenz O. Virus Res. 100:249-255(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NP.
[7]	"Myristoylation of the RING finger Z protein is essential for arenavirus budding." Perez M., Greenwald D.L., de la Torre J.C. J. Virol. 78:11443-11448(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION AT GLY-2, MUTAGENESIS OF GLY-2.
[8]	"Cellular factors required for Lassa virus budding." Urata S., Noda T., Kawaoka Y., Yokosawa H., Yasuda J. J. Virol. 80:4191-4195(2006) [PubMed] [Europe PMC] [Abstract] Cited for: LATE-BUDDING DOMAIN, INTERACTION WITH HUMAN TSG101.
[9]	"Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E." Volpon L., Osborne M.J., Capul A.A., de la Torre J.C., Borden K.L. Proc. Natl. Acad. Sci. U.S.A. 107:5441-5446(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR IN COMPEX WITH ZINC IONS, INTERACTION WITH HOST EIF4E.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U73035 Genomic RNA. Translation: AAC05818.2.
U73034 Genomic RNA. Translation: AAC05816.2.
AY628202 Genomic RNA. Translation: AAT49001.1.

RefSeq

NP_694871.1. NC_004297.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M1S	NMR	-	A	1-99	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58625N.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

956586.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR024183. RING_finger_Z_arenaviridae.
IPR003224. Znf_P11.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF03854. zf-P11. 1 hit.
[Graphical view]

PIRSF

PIRSF004030. Z_ArenaV. 1 hit.

PROSITE

PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O73557.

Entry information

Entry name

Z_LASSJ

Accession

Primary (citable) accession number: O73557

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 73 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program