P16753 (PPR_HCMVA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protease precursor
Short name=pPR

Alternative name(s):
Capsid protein P40

Cleaved into the following 2 chains:

1. Assemblin
   EC=3.4.21.97
   Alternative name(s):
   Protease
2. Assembly protein

Gene names

Name:	UL80
Synonyms:	APNG

Organism

Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) [Complete proteome]

Taxonomic identifier

10360 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Betaherpesvirinae › Cytomegalovirus › Human cytomegalovirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	708 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	Protease precursor plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein UL86 in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as protein UL86 forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein UL86. Cleavages products are evicted from the capsid before or during DNA packaging By similarity. Assemblin is a protease essential for virion assembly in the nucleus. Catalyzes the cleavage of the assembly protein after complete capsid formation. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging By similarity. Assembly protein plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein UL86. Multimerizes in the nucleus such as protein UL86 forms the icosahedral T=16 capsid. Cleaved by assemblin after capsid completion. The cleavages products are evicted from the capsid before or during DNA packaging By similarity.
Catalytic activity	Cleaves -Ala-|-Ser- and -Ala-|-Ala- bonds in the scaffold protein.
Subunit structure	Protease precursor homomultimerizes and interacts with major capsid protein UL86. Assemblin exists in a monomer-dimer equilibrium with the dimer being the active species. Assembly protein homomultimerizes and interacts with major capsid protein UL86 By similarity. Ref.6
Subcellular location	Protease precursor: Host cytoplasm. Assemblin: Host nucleus. Assembly protein: Host nucleus.
Domain	Region of interaction between pPR and pAP is called Amino conserved domain (ACD). The region of interaction with major capsid protein is called carboxyl conserved domain (CCD) By similarity.
Post-translational modification	Protease precursor is cleaved by assemblin after completion of icosahedral capsid formation. Cleavages occur at two or more sites: release and tail site By similarity. Capsid assembly protein is phosphorylated.
Sequence similarities	Belongs to the peptidase S21 family.
Sequence caution	The sequence CAA35354.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Host cytoplasm Host nucleus
Coding sequence diversity	Alternative promoter usage
Molecular function	Hydrolase Protease Serine protease Viral capsid scaffolding protein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform Protease precursor (identifier: P16753-1)

Also known as: pPR; UL80a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform pAP (identifier: P16753-2)

Also known as: Assembly protein; UL80.5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-335: Missing.

Isoform UL80.4 protein (identifier: P16753-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-392: Missing.

Isoform UL80.3 protein (identifier: P16753-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-477: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 708

708

Protease precursor

PRO_0000027284

Chain

1 – 256

256

Assemblin

PRO_0000027285

Chain

257 – 708

452

Assembly protein By similarity

PRO_0000027286

Regions

Region

369 – 388

20

Interaction with pAP

Region

688 – 708

21

Interaction with major capsid protein

Motif

510 – 515

6

Nuclear localization signal 1

Motif

537 – 543

7

Nuclear localization signal 2

Sites

Active site

63

1

Charge relay system

Active site

132

1

Charge relay system

Active site

157

1

Charge relay system

Site

256 – 257

2

Cleavage; by assemblin; Release site

Site

643 – 644

2

Cleavage; by assemblin; Maturation site

Site

675 – 676

2

Cleavage; by assemblin; Tail site

Natural variations

Alternative sequence

1 – 477

477

Missing in isoform UL80.3 protein.

VSP_037425

Alternative sequence

1 – 392

392

Missing in isoform UL80.4 protein.

VSP_037424

Alternative sequence

1 – 335

335

Missing in isoform pAP.

VSP_037423

Secondary structure

1

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708

Helix Strand Turn

Details...

Helix

4 – 10

7

Beta strand

14 – 22

9

Helix

30 – 32

3

Helix

36 – 42

7

Beta strand

58 – 61

4

Beta strand

64 – 78

15

Beta strand

81 – 88

8

Helix

91 – 101

11

Helix

105 – 108

4

Beta strand

112 – 115

4

Helix

119 – 127

9

Beta strand

130 – 133

4

Beta strand

138 – 140

3

Beta strand

158 – 163

6

Beta strand

165 – 168

4

Beta strand

172 – 175

4

Helix

177 – 181

5

Beta strand

184 – 186

3

Helix

189 – 199

11

Helix

200 – 204

5

Helix

218 – 229

12

Helix

234 – 244

11

Helix

249 – 251

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Protease precursor (pPR) (UL80a) [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 32A993D6586824C9	FASTA	708	73,852
	10 20 30 40 50 60 MTMDEQQSQA VAPVYVGGFL ARYDQSPDEA ELLLPRDVVE HWLHAQGQGQ PSLSVALPLN 70 80 90 100 110 120 INHDDTAVVG HVAAMQSVRD GLFCLGCVTS PRFLEIVRRA SEKSELVSRG PVSPLQPDKV 130 140 150 160 170 180 VEFLSGSYAG LSLSSRRCDD VEAATSLSGS ETTPFKHVAL CSVGRRRGTL AVYGRDPEWV 190 200 210 220 230 240 TQRFPDLTAA DRDGLRAQWQ RCGSTAVDAS GDPFRSDSYG LLGNSVDALY IRERLPKLRY 250 260 270 280 290 300 DKQLVGVTER ESYVKASVSP EAACDIKAAS AERSGDSRSQ AATPAAGARV PSSSPSPPVE 310 320 330 340 350 360 PPSPVQPPAL PASPSVLPAE SPPSLSPSEP AEAASMSHPL SAAVPAATAP PGATVAGASP 370 380 390 400 410 420 AVSSLAWPHD GVYLPKDAFF SLLGASRSAV PVMYPGAVAA PPSASPAPLP LPSYPASYGA 430 440 450 460 470 480 PVVGYDQLAA RHFADYVDPH YPGWGRRYEP APSLHPSYPV PPPPSPAYYR RRDSPGGMDE 490 500 510 520 530 540 PPSGWERYDG GHRGQSQKQH RHGGSGGHNK RRKETAAASS SSSDEDLSFP GEAEHGRARK 550 560 570 580 590 600 RLKSHVNSDG GSGGHAGSNQ QQQQRYDELR DAIHELKRDL FAARQSSTLL SAALPSAASS 610 620 630 640 650 660 SPTTTTVCTP TGELTSGGGE TPTALLSGGA KVAERAQAGV VNASCRLATA SGSEAATAGP 670 680 690 700 STAGSSSCPA SVVLAAAAAQ AAAASQSPPK DMVDLNRRIF VAALNKLE
	Isoform pAP (Assembly protein) (UL80.5) [UniParc]. Checksum: E98A2DA99A5E1597	FASTA	373	38,252
	10 20 30 40 50 60 MSHPLSAAVP AATAPPGATV AGASPAVSSL AWPHDGVYLP KDAFFSLLGA SRSAVPVMYP 70 80 90 100 110 120 GAVAAPPSAS PAPLPLPSYP ASYGAPVVGY DQLAARHFAD YVDPHYPGWG RRYEPAPSLH 130 140 150 160 170 180 PSYPVPPPPS PAYYRRRDSP GGMDEPPSGW ERYDGGHRGQ SQKQHRHGGS GGHNKRRKET 190 200 210 220 230 240 AAASSSSSDE DLSFPGEAEH GRARKRLKSH VNSDGGSGGH AGSNQQQQQR YDELRDAIHE 250 260 270 280 290 300 LKRDLFAARQ SSTLLSAALP SAASSSPTTT TVCTPTGELT SGGGETPTAL LSGGAKVAER 310 320 330 340 350 360 AQAGVVNASC RLATASGSEA ATAGPSTAGS SSCPASVVLA AAAAQAAAAS QSPPKDMVDL 370 NRRIFVAALN KLE
	Isoform UL80.4 protein [UniParc]. Checksum: 7E2E5EC4F9E51BF5	FASTA	316	32,700
	10 20 30 40 50 60 MYPGAVAAPP SASPAPLPLP SYPASYGAPV VGYDQLAARH FADYVDPHYP GWGRRYEPAP 70 80 90 100 110 120 SLHPSYPVPP PPSPAYYRRR DSPGGMDEPP SGWERYDGGH RGQSQKQHRH GGSGGHNKRR 130 140 150 160 170 180 KETAAASSSS SDEDLSFPGE AEHGRARKRL KSHVNSDGGS GGHAGSNQQQ QQRYDELRDA 190 200 210 220 230 240 IHELKRDLFA ARQSSTLLSA ALPSAASSSP TTTTVCTPTG ELTSGGGETP TALLSGGAKV 250 260 270 280 290 300 AERAQAGVVN ASCRLATASG SEAATAGPST AGSSSCPASV VLAAAAAQAA AASQSPPKDM 310 VDLNRRIFVA ALNKLE
	Isoform UL80.3 protein [UniParc]. Checksum: 19D7AC8C58798835	FASTA	231	23,601
	10 20 30 40 50 60 MDEPPSGWER YDGGHRGQSQ KQHRHGGSGG HNKRRKETAA ASSSSSDEDL SFPGEAEHGR 70 80 90 100 110 120 ARKRLKSHVN SDGGSGGHAG SNQQQQQRYD ELRDAIHELK RDLFAARQSS TLLSAALPSA 130 140 150 160 170 180 ASSSPTTTTV CTPTGELTSG GGETPTALLS GGAKVAERAQ AGVVNASCRL ATASGSEAAT 190 200 210 220 230 AGPSTAGSSS CPASVVLAAA AAQAAAASQS PPKDMVDLNR RIFVAALNKL E

References

[1]	"Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169." Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R., Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A., Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G. Curr. Top. Microbiol. Immunol. 154:125-169(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome." Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:17-28(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION.
[3]	Erratum Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:1053-1053(2003)
[4]	"Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome." Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J., Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W., Shenk T., Smith R.D., Nelson J.A. J. Virol. 78:10960-10966(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[5]	Erratum Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J., Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W., Shenk T., Smith R.D., Nelson J.A. J. Virol. 78:13395-13395(2004)
[6]	"Human cytomegalovirus capsid assembly protein precursor (pUL80.5) interacts with itself and with the major capsid protein (pUL86) through two different domains." Wood L.J., Baxter M.K., Plafker S.M., Gibson W. J. Virol. 71:179-190(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MULTIMERIZATION, INTERACTION WITH UL86.
[7]	"Structure and formation of the cytomegalovirus virion." Gibson W. Curr. Top. Microbiol. Immunol. 325:187-204(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW, ISOFORM UL80.4 PROTEIN AND UL80.3 PROTEIN.
[8]	"A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease." Tong L., Qian C., Massariol M.-J., Bonneau P.R., Cordingley M.G., Lagace L. Nature 383:272-275(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF PROTEASE.
[9]	"Unique fold and active site in cytomegalovirus protease." Qiu X., Culp J.S., Dilella A.G., Hellmig B., Hoog S.S., Janson C.A., Smith W.W., Abdel-Meguid S.A. Nature 383:275-279(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF PROTEASE.
[10]	"Three-dimensional structure of human cytomegalovirus protease." Shieh H.-S., Kurumbail R.G., Stevens A.M., Stegeman R.A., Sturman E.J., Pak J.Y., Wittwer A.J., Palmier M.O., Wiegand R.C., Holwerda B.C., Stallings W.C. Nature 383:279-282(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF PROTEASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X17403 Genomic DNA. Translation: CAA35353.1.
X17403 Genomic DNA. Translation: CAA35354.1. Different initiation.
BK000394 Genomic DNA. Translation: DAA00177.1.
BK000394 Genomic DNA. Translation: DAA00178.1.

PIR

QQBEB8. S09843.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CMV	X-ray	2.27	A/B	1-256	[»]
1ID4	X-ray	2.20	A/B	1-256	[»]
1IEC	X-ray	2.20	A/B	1-256	[»]
1IED	X-ray	2.00	A/B	1-256	[»]
1IEF	X-ray	2.30	A/B	1-256	[»]
1IEG	X-ray	2.00	A/B	1-256	[»]
1JQ6	X-ray	2.30	A	1-256	[»]
1JQ7	X-ray	3.00	A/B	1-256	[»]
1LAY	X-ray	2.50	A	1-256	[»]
1NJT	X-ray	2.50	A/B/C/D	1-256	[»]
1NJU	X-ray	2.70	A/B/C/D	1-256	[»]
1NKK	X-ray	2.60	A/B/C/D	1-256	[»]
1NKM	X-ray	2.70	A/B	1-256	[»]
1WPO	X-ray	2.00	A/B	1-256	[»]
2WPO	X-ray	2.70	A/B/C/D	1-256	[»]

ProteinModelPortal

P16753.

SMR

P16753. Positions 4-256.

ModBase

Search...

Protein family/group databases

MEROPS

S21.002.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.20.16.10. 1 hit.

InterPro

IPR001847. Peptidase_S21.
[Graphical view]

Pfam

PF00716. Peptidase_S21. 1 hit.
[Graphical view]

PRINTS

PR00236. HSVCAPSIDP40.

SUPFAM

SSF50789. Peptidase_S21. 1 hit.

ProtoNet

Search...

Other

BindingDB

P16753.

ChEMBL

CHEMBL3771.

EvolutionaryTrace

P16753.

Entry information

Entry name

PPR_HCMVA

Accession

Primary (citable) accession number: P16753
Secondary accession number(s): Q69030, Q7M6L0, Q7M6L1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	April 3, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program