P59632 (AP3A_CVHSA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein 3a

Alternative name(s):
Accessory protein 3a
Protein U274
Protein X1

Gene names

ORF Names:

3a

Organism

Human SARS coronavirus (SARS-CoV) (Severe acute respiratory syndrome coronavirus)

Taxonomic identifier

227859 [NCBI]

Taxonomic lineage

Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Betacoronavirus

Virus host

Homo sapiens (Human) [TaxID: 9606]
Paguma larvata (Masked palm civet) [TaxID: 9675]

Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Ref.20 Ref.21 Ref.24
Subunit structure	Homotetramer composed of two homodimers linked non covalently. Interacts with M, S and E proteins. Also interacts with the accessory protein 7a. Ref.16 Ref.17 Ref.24
Subcellular location	Virion. Host Golgi apparatus membrane; Multi-pass membrane protein. Host cell membrane; Multi-pass membrane protein. Secreted. Host cytoplasm. Note: The cell surface expressed protein can undergo endocytosis. The protein is secreted in association with membranous structures. Ref.16 Ref.17 Ref.19 Ref.23
Domain	The second or the third transmembrane region are responsible for Golgi localization.
Post-translational modification	Exists in both O-glycosylated and non-glycosylated forms. The glycosylated form is associated with the virion. Ref.22

Ontologies

Keywords
Biological process	Apoptosis 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 Ion transport Transport Viral immunoevasion
Cellular component	Host Golgi apparatus Host cell membrane Host cytoplasm Host membrane Membrane Secreted Virion
Domain	Transmembrane Transmembrane helix
Molecular function	Ionic channel Viral ionic channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	host cell Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Non-traceable author statement. Source: UniProtKB virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ion channel activity 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
	Chain	1 – 274	274	Protein 3a		PRO_0000106131
Regions
	Topological domain	1 – 34	34	Extracellular Probable
	Transmembrane	35 – 55	21	Helical; Potential
	Topological domain	56 – 78	23	Cytoplasmic Potential
	Transmembrane	79 – 99	21	Helical; Potential
	Topological domain	100 – 104	5	Extracellular Potential
	Transmembrane	105 – 125	21	Helical; Potential
	Topological domain	126 – 274	149	Cytoplasmic Probable
	Compositional bias	83 – 86	4	Poly-Leu
	Compositional bias	267 – 270	4	Poly-Thr
Sites
	Site	133	1	Involved in polymerization
Amino acid modifications
	Glycosylation	27	1	O-linked (GalNAc...); by host Potential
	Glycosylation	28	1	O-linked (GalNAc...); by host Probable
	Glycosylation	32	1	O-linked (GalNAc...); by host Probable
	Glycosylation	34	1	O-linked (GalNAc...); by host Potential
Natural variations
	Natural variant	11	1	G → R in strain: Isolate Tor2, Isolate BJ02 and Isolate BJ03.
	Natural variant	20	1	I → T in strain: Isolate Shanghai LY.
	Natural variant	29	1	V → A in strain: Isolate Shanghai QXC1.
	Natural variant	101	1	M → K in strain: Isolate HKU-39849.
	Natural variant	129	1	L → F in strain: Isolate TWK.
	Natural variant	136	1	K → Q in strain: Isolate BJ01.
	Natural variant	171	1	E → A in strain: Isolate GD01.
	Natural variant	193	1	R → W in strain: Isolate GD01.
	Natural variant	222	1	D → N in strain: Isolate Shanghai QXC1.
Experimental info
	Mutagenesis	27	1	S → G: Complete loss of O-glycosylation; when associated with A-28; A-32 and A-34. Ref.22
	Mutagenesis	28	1	T → A: Complete loss of O-glycosylation; when associated with A-27; A-32 and A-34. Ref.22
	Mutagenesis	32	1	T → A: Complete loss of O-glycosylation; when associated with A-27; A-28 and A-34. Ref.22
	Mutagenesis	34	1	T → A: Complete loss of O-glycosylation; when associated with A-27; A-28 and A-32. Ref.22
	Mutagenesis	81	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	117	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	121	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	127	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	130	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	133	1	C → A: Almost complete loss of polimerization ability. Ref.24
	Mutagenesis	148	1	C → A: No effect on polymerization. Ref.24
	Mutagenesis	157	1	C → A: No effect on polymerization. Ref.24

Sequences

	Sequence		Length	Mass (Da)
	P59632 [UniParc]. Last modified April 23, 2003. Version 1. Checksum: E48C7D44A4DE34FE	FASTA	274	30,903
	10 20 30 40 50 60 MDLFMRFFTL GSITAQPVKI DNASPASTVH ATATIPLQAS LPFGWLVIGV AFLAVFQSAT 70 80 90 100 110 120 KIIALNKRWQ LALYKGFQFI CNLLLLFVTI YSHLLLVAAG MEAQFLYLYA LIYFLQCINA 130 140 150 160 170 180 CRIIMRCWLC WKCKSKNPLL YDANYFVCWH THNYDYCIPY NSVTDTIVVT EGDGISTPKL 190 200 210 220 230 240 KEDYQIGGYS EDRHSGVKDY VVVHGYFTEV YYQLESTQIT TDTGIENATF FIFNKLVKDP 250 260 270 PNVQIHTIDG SSGVANPAMD PIYDEPTTTT SVPL

References

[1]	"Characterization of a novel coronavirus associated with severe acute respiratory syndrome." Rota P.A., Oberste M.S., Monroe S.S., Nix W.A., Campagnoli R., Icenogle J.P., Penaranda S., Bankamp B., Maher K., Chen M.-H., Tong S., Tamin A., Lowe L., Frace M., DeRisi J.L., Chen Q., Wang D., Erdman D.D. , Peret T.C.T., Burns C., Ksiazek T.G., Rollin P.E., Sanchez A., Liffick S., Holloway B., Limor J., McCaustland K., Olsen-Rasmussen M., Fouchier R., Guenther S., Osterhaus A.D.M.E., Drosten C., Pallansch M.A., Anderson L.J., Bellini W.J. Science 300:1394-1399(2003) [PubMed: 12730500] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Urbani.
[2]	"The genome sequence of the SARS-associated coronavirus." Marra M.A., Jones S.J.M., Astell C.R., Holt R.A., Brooks-Wilson A., Butterfield Y.S.N., Khattra J., Asano J.K., Barber S.A., Chan S.Y., Cloutier A., Coughlin S.M., Freeman D., Girn N., Griffith O.L., Leach S.R., Mayo M., McDonald H. , Montgomery S.B., Pandoh P.K., Petrescu A.S., Robertson A.G., Schein J.E., Siddiqui A., Smailus D.E., Stott J.M., Yang G.S., Plummer F., Andonov A., Artsob H., Bastien N., Bernard K., Booth T.F., Bowness D., Czub M., Drebot M., Fernando L., Flick R., Garbutt M., Gray M., Grolla A., Jones S., Feldmann H., Meyers A., Kabani A., Li Y., Normand S., Stroher U., Tipples G.A., Tyler S., Vogrig R., Ward D., Watson B., Brunham R.C., Krajden M., Petric M., Skowronski D.M., Upton C., Roper R.L. Science 300:1399-1404(2003) [PubMed: 12730501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Tor2.
[3]	"Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome." Tsui S.K.W., Chim S.S.C., Lo Y.M.D. N. Engl. J. Med. 349:187-188(2003) [PubMed: 12853594] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate CUHK-Su10 and Isolate CUHK-W1.
[4]	"The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39)." Zeng F.Y., Chan C.W., Chan M.N., Chen J.D., Chow K.Y.C., Hon C.C.C., Hui R.K.H., Li J., Li V.Y.Y., Wang C.Y., Wang P.Y., Guan Y., Zheng B., Poon L.L.M., Chan K.H., Yuen K.Y., Peiris J.S.M., Leung F.C. Exp. Biol. Med. 228:866-873(2003) [PubMed: 12876307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate HKU-39849.
[5]	Qin E., Zhu Q., Yu M., Fan B., Chang G., Si B., Yang B., Peng W., Jiang T., Liu B., Deng Y., Liu H., Zhang Y., Wang C., Li Y., Gan Y., Li X., Lu F. , Tan G., Yang R., Cao W.S., Wang J., Chen W., Cong L., Deng Y., Dong W., Han Y., Hu W., Lei M., Li C., Li G., Li G., Li H., Li S., Li S., Li W., Li W., Lin W., Liu J., Liu Z., Lu H., Ni P., Qi Q., Sun Y., Tang L., Tong Z., Wang J., Wang X., Wu Q., Xi Y., Xu Z., Yang L., Ye C., Ye J., Zhang B., Zhang F., Zhang J., Zhang X., Zhou J., Yang H. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate BJ01, Isolate BJ02, Isolate BJ03, Isolate BJ04 and Isolate GD01.
[6]	"The complete genome of SARS coronavirus clone TW1." Yeh S.-H., Kao C.-L., Tsai C.-Y., Liu C.-J., Chen D.-S., Chen P.-J. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TW1.
[7]	"SARS virus is a close relative of type II coronaviruses." Eickmann M., Becker S., Klenk H.-D., Doerr H.W., Stadler K., Censini S., Guidotti S., Masignani V., Scarselli M., Mora M., Donati C., Han J., Song H.C., Abrignani S., Covacci A., Rappuoli R. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate FRA.
[8]	Thiel V., Hertzig T., Putics A., Ivanov K.A., Schelle B., Bayer S., Scheiner B., Weinand H., Weissbrich B., Ziebuhr J. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Frankfurt 1.
[9]	Chang J.-G.C., Lin T.-H., Chen C.-M., Lin C.-S., Chan W.-L., Shih M.-C. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Taiwan TC1, Isolate Taiwan TC2 and Isolate Taiwan TC3.
[10]	"The complete genome of SARS coronavirus TWH." Shu H.Y., Wu K.M., Tsai S.F. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate TWH, Isolate TWJ, Isolate TWK, Isolate TWS and Isolate TWY.
[11]	Canducci F., Clementi M., Poli G., Vicenzi E. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate HSR 1.
[12]	Balotta C., Corvasce S., Violin M., Galli M., Moroni M., Vigevani G.M., Ruan Y.J., Salemi M. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate AS.
[13]	"Analysis of SARS coronavirus genome in Shanghai isolates." Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate Shanghai QXC1.
[14]	Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-125. Strain: Isolate Shanghai LY.
[15]	"Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus." Yu C.-J., Chen Y.-C., Hsiao C.-H., Kuo T.-C., Chang S.C., Lu C.-Y., Wei W.-C., Lee C.-H., Huang L.-M., Chang M.-F., Ho H.-N., Lee F.-J.S. FEBS Lett. 565:111-116(2004) [PubMed: 15135062] [Abstract] Cited for: IDENTIFICATION.
[16]	"A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis." Tan Y.-J., Teng E., Shen S., Tan T.H.P., Goh P.-Y., Fielding B.C., Ooi E.-E., Tan H.-C., Lim S.G., Hong W. J. Virol. 78:6723-6734(2004) [PubMed: 15194747] [Abstract] Cited for: SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION WITH M PROTEIN; E PROTEIN; SPIKE GLYCOPROTEIN AND ACCESSORY PROTEIN 7A.
[17]	"Subcellular localization and membrane association of SARS-CoV 3a protein." Yuan X., Li J., Shan Y., Yang Z., Zhao Z., Chen B., Yao Z., Dong B., Wang S., Chen J., Cong Y. Virus Res. 109:191-202(2005) [PubMed: 15763150] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH M AND E PROTEINS.
[18]	"The severe acute respiratory syndrome coronavirus 3a is a novel structural protein." Shen S., Lin P.S., Chao Y.C., Zhang A., Yang X., Lim S.G., Hong W., Tan Y.J. Biochem. Biophys. Res. Commun. 330:286-292(2005) [PubMed: 15781262] [Abstract] Cited for: CHARACTERIZATION.
[19]	"Severe acute respiratory syndrome coronavirus 3a protein is a viral structural protein." Ito N., Mossel E.C., Narayanan K., Popov V.L., Huang C., Inoue T., Peters C.J., Makino S. J. Virol. 79:3182-3186(2005) [PubMed: 15709039] [Abstract] Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION.
[20]	"The severe acute respiratory syndrome coronavirus 3a protein up-regulates expression of fibrinogen in lung epithelial cells." Tan Y.J., Tham P.Y., Chan D.Z., Chou C.-F., Shen S., Fielding B.C., Tan T.H., Lim S.G., Hong W. J. Virol. 79:10083-10087(2005) [PubMed: 16014971] [Abstract] Cited for: FUNCTION.
[21]	"The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells." Law P.T., Wong C.H., Au T.C., Chuck C.P., Kong S.K., Chan P.K., To K.F., Lo A.W., Chan J.Y., Suen Y.K., Chan H.Y., Fung K.P., Waye M.M., Sung J.J., Lo Y.M.D., Tsui S.K.W. J. Gen. Virol. 86:1921-1930(2005) [PubMed: 15958670] [Abstract] Cited for: FUNCTION.
[22]	"Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M." Oostra M., de Haan C.A., de Groot R.J., Rottier P.J.M. J. Virol. 80:2326-2336(2006) [PubMed: 16474139] [Abstract] Cited for: GLYCOSYLATION, MUTAGENESIS OF SER-27; THR-28; THR-32 AND THR-34.
[23]	"Severe acute respiratory syndrome coronavirus 3a protein is released in membranous structures from 3a protein-expressing cells and infected cells." Huang C., Narayanan K., Ito N., Peters C.J., Makino S. J. Virol. 80:210-217(2006) [PubMed: 16352545] [Abstract] Cited for: SUBCELLULAR LOCATION.
[24]	"Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release." Lu W., Zheng B.-J., Xu K., Schwarz W., Du L., Wong C.K.L., Chen J., Duan S., Deubel V., Sun B. Proc. Natl. Acad. Sci. U.S.A. 103:12540-12545(2006) [PubMed: 16894145] [Abstract] Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-81; CYS-117; CYS-121; CYS-127; CYS-130; CYS-133; CYS-148 AND CYS-157.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY278741 Genomic RNA. Translation: AAP13446.1. AY274119 Genomic RNA. Translation: AAP41038.1. AY282752 Genomic RNA. No translation available. AY278554 Genomic RNA. Translation: AAP13568.1. AY278491 Genomic RNA. No translation available. AY278487 Genomic RNA. No translation available. AY278488 Genomic RNA. Translation: AAP30031.1. AY278489 Genomic RNA. Translation: AAP51228.1. AY278490 Genomic RNA. No translation available. AY279354 Genomic RNA. No translation available. AY291451 Genomic RNA. Translation: AAP37018.1. AY310120 Genomic RNA. Translation: AAP50486.1. AY291315 Genomic RNA. Translation: AAP33698.1. AY338174 Genomic RNA. Translation: AAQ01598.1. AY338175 Genomic RNA. Translation: AAQ01610.1. AY348314 Genomic RNA. Translation: AAP97883.1. AP006557 Genomic RNA. Translation: BAC81349.1. AP006558 Genomic RNA. Translation: BAC81363.1. AP006559 Genomic RNA. Translation: BAC81377.1. AP006560 Genomic RNA. Translation: BAC81391.1. AP006561 Genomic RNA. Translation: BAC81405.1. AY323977 Genomic RNA. Translation: AAP72975.1. AY427439 Genomic RNA. Translation: AAQ94061.1. AY463059 Genomic RNA. Translation: AAP82984.2. AY322207 Genomic RNA. Translation: AAP82969.1.
3D structure databases
ModBase	Search...
Protein family/group databases
TCDB	1.A.57.1.1. human SARS caronavirus viroporin (SARS-VP).
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR024407. SARS_coronavirus_Orf3/3a. [Graphical view]
Pfam	PF11289. DUF3092. 1 hit. [Graphical view]
ProDom	PD719245. PD719245. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...

Entry information

Entry name

AP3A_CVHSA

Accession

Primary (citable) accession number: P59632
Secondary accession number(s): Q7T6R6 , Q7TA10, Q7TA18, Q7TFB0, Q7TLD0, Q80BV5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	April 23, 2003
Last modified:	October 19, 2011
This is version 58 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program