Q53FA7 (QORX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Quinone oxidoreductase PIG3
EC=1.-.-.-

Alternative name(s):
Tumor protein p53-inducible protein 3
p53-induced gene 3 protein

Gene names

Name:	TP53I3
Synonyms:	PIG3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	332 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the generation of reactive oxygen species (ROS). Has low NADPH-dependent naphtoquinone reductase activity, with a preference for 1,2-naphtoquinone over 1,4-naphtoquinone. Has low NADPH-dependent diamine reductase activity (in vitro). Ref.11
Subunit structure	Homodimer. Ref.11
Induction	Isoform 1 and isoform 2 are both activated by p53/TP53, doxorubicin, etoposide and ionizing radiation. Isoform 2 is highly activated by UV radiation. Ref.1
Sequence similarities	Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
Biophysicochemical properties	Kinetic parameters: KM=215 µM for 1,2-naphtoquinone Ref.11
Sequence caution	The sequence AAC39535.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	NADP metabolic process Inferred from direct assay Ref.11. Source: UniProtKB induction of apoptosis by oxidative stress Non-traceable author statement. Source: UniProtKB
Molecular function	NADPH binding Inferred from direct assay Ref.11. Source: UniProtKB NADPH:quinone reductase activity Inferred from direct assay Ref.11. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.11. Source: UniProtKB quinone binding Inferred from direct assay Ref.11. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: UV radiation favors the production of isoform 2.

Isoform 1 (identifier: Q53FA7-1)

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.

Note: Major isoform under normal light conditions.

Isoform 2 (identifier: Q53FA7-2)

Also known as: PIG3AS;

The sequence of this isoform differs from the canonical sequence as follows:
     207-248: GAGVNLILDC...GLMGGGDING → VQANAGECFH...LPSDRNPGGP
     249-332: Missing.

Note: Major isoform under UV light exposure. Undergoes rapid proteolytic degradation by the proteasome.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 332

332

Quinone oxidoreductase PIG3

PRO_0000160917

Regions

Nucleotide binding

148 – 154

7

NADP

Nucleotide binding

173 – 177

5

NADP

Nucleotide binding

264 – 266

3

NADP

Sites

Binding site

41

1

NADP

Binding site

192

1

NADP

Binding site

322

1

NADP

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.9

Modified residue

321

1

N6-acetyllysine Ref.10

Natural variations

Alternative sequence

207 – 248

42

GAGVN…GDING → VQANAGECFHGANSASLLHG GPPTSAAGSGQNLPSDRNPG GP in isoform 2.

VSP_015783

Alternative sequence

249 – 332

84

Missing in isoform 2.

VSP_015784

Natural variant

180

1

M → K in a breast cancer sample; somatic mutation. Ref.12

VAR_033032

Natural variant

223

1

E → K.
Corresponds to variant rs35176319 [ dbSNP | Ensembl ].

VAR_048201

Experimental info

Mutagenesis

51

1

Y → A: Loss of enzyme activity. Ref.11

Mutagenesis

51

1

Y → F: Increased enzyme activity. Ref.11

Mutagenesis

151

1

S → V: Loss of enzyme activity. Ref.11

Sequence conflict

36

1

A → AA in AAC39535. Ref.1

Sequence conflict

263

1

T → A in BAD97102. Ref.4

Sequence conflict

315 – 332

18

KYMEA…LELPQ → STWRPTRT in AAC39528. Ref.1

Secondary structure

1

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332

Helix Strand Turn

Details...

Beta strand

1 – 8

8

Helix

12 – 14

3

Beta strand

15 – 21

7

Beta strand

29 – 38

10

Helix

41 – 47

7

Beta strand

59 – 61

3

Beta strand

63 – 72

10

Beta strand

85 – 89

5

Beta strand

95 – 102

8

Helix

103 – 105

3

Beta strand

106 – 108

3

Helix

115 – 118

4

Helix

122 – 132

11

Turn

133 – 135

3

Beta strand

143 – 148

6

Helix

152 – 163

12

Beta strand

167 – 173

7

Helix

175 – 184

10

Beta strand

187 – 191

5

Turn

192 – 194

3

Helix

197 – 204

8

Turn

205 – 207

3

Beta strand

210 – 217

8

Helix

219 – 221

3

Helix

222 – 228

7

Beta strand

229 – 237

9

Beta strand

246 – 248

3

Helix

250 – 256

7

Beta strand

260 – 263

4

Helix

271 – 284

14

Helix

286 – 289

4

Beta strand

301 – 306

6

Helix

307 – 309

3

Helix

310 – 318

9

Beta strand

323 – 329

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: C5A33C46B3F96473	FASTA	332	35,536
	10 20 30 40 50 60 MLAVHFDKPG GPENLYVKEV AKPSPGEGEV LLKVAASALN RADLMQRQGQ YDPPPGASNI 70 80 90 100 110 120 LGLEASGHVA ELGPGCQGHW KIGDTAMALL PGGGQAQYVT VPEGLLMPIP EGLTLTQAAA 130 140 150 160 170 180 IPEAWLTAFQ LLHLVGNVQA GDYVLIHAGL SGVGTAAIQL TRMAGAIPLV TAGSQKKLQM 190 200 210 220 230 240 AEKLGAAAGF NYKKEDFSEA TLKFTKGAGV NLILDCIGGS YWEKNVNCLA LDGRWVLYGL 250 260 270 280 290 300 MGGGDINGPL FSKLLFKRGS LITSLLRSRD NKYKQMLVNA FTEQILPHFS TEGPQRLLPV 310 320 330 LDRIYPVTEI QEAHKYMEAN KNIGKIVLEL PQ
	Isoform 2 (PIG3AS) [UniParc]. Checksum: 8899613C763DDDDC	FASTA	248	25,402
	10 20 30 40 50 60 MLAVHFDKPG GPENLYVKEV AKPSPGEGEV LLKVAASALN RADLMQRQGQ YDPPPGASNI 70 80 90 100 110 120 LGLEASGHVA ELGPGCQGHW KIGDTAMALL PGGGQAQYVT VPEGLLMPIP EGLTLTQAAA 130 140 150 160 170 180 IPEAWLTAFQ LLHLVGNVQA GDYVLIHAGL SGVGTAAIQL TRMAGAIPLV TAGSQKKLQM 190 200 210 220 230 240 AEKLGAAAGF NYKKEDFSEA TLKFTKVQAN AGECFHGANS ASLLHGGPPT SAAGSGQNLP SDRNPGGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A model for p53-induced apoptosis." Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B. Nature 389:300-306(1997) [PubMed: 9305847] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INDUCTION BY TP53. Tissue: Colon cancer.
[2]	"UV-dependent alternative splicing uncouples p53 activity and PIG3 gene function through rapid proteolytic degradation." Nicholls C.D., Shields M.A., Lee P.W.K., Robbins S.M., Beattie T.L. J. Biol. Chem. 279:24171-24178(2004) [PubMed: 15067011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Mammary tumor.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Gastric mucosa.
[5]	NIEHS SNPs program Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Muscle.
[9]	Bienvenut W.V., Vousden K.H., Lukashchuk N. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-33; 163-176; 184-203; 259-267; 297-303 AND 326-332, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-321, MASS SPECTROMETRY.
[11]	"Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase PIG3." Porte S., Valencia E., Yakovtseva E.A., Borras E., Shafqat N., Debreczeny J.E., Pike A.C.W., Oppermann U., Farres J., Fita I., Pares X. J. Biol. Chem. 284:17194-17205(2009) [PubMed: 19349281] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-51 AND SER-151.
[12]	"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas." Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L. Breast Cancer Res. 9:R5-R5(2007) [PubMed: 17224074] [Abstract] Cited for: VARIANT LYS-180.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF010309 mRNA. Translation: AAC39528.1.
AF010317 Genomic DNA. Translation: AAC39535.1. Sequence problems.
AY371700 mRNA. Translation: AAQ90166.1.
BT007149 mRNA. Translation: AAP35813.1.
AK223382 mRNA. Translation: BAD97102.1.
DQ232851 Genomic DNA. Translation: ABB02183.1.
AC008073 Genomic DNA. Translation: AAY14665.1.
CH471053 Genomic DNA. Translation: EAX00762.1.
CH471053 Genomic DNA. Translation: EAX00763.1.
CH471053 Genomic DNA. Translation: EAX00766.1.
BC000474 mRNA. Translation: AAH00474.1.

IPI

IPI00384643.
IPI00418440.

RefSeq

NP_001193731.1. NM_001206802.2.
NP_004872.2. NM_004881.4.
NP_671713.1. NM_147184.3.

UniGene

Hs.50649.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2J8Z	X-ray	2.50	A	1-332	[»]
2OBY	X-ray	3.00	A/B/C/D/E	1-332	[»]

ProteinModelPortal

Q53FA7.

SMR

Q53FA7. Positions 1-332.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q53FA7. 4 interactions.

STRING

Q53FA7.

PTM databases

PhosphoSite

Q53FA7.

Polymorphism databases

DMDM

76789665.

Proteomic databases

PeptideAtlas

Q53FA7.

PRIDE

Q53FA7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000238721; ENSP00000238721; ENSG00000115129.
ENST00000335934; ENSP00000337834; ENSG00000115129.

GeneID

9540.

KEGG

hsa:9540.

UCSC

uc002rex.1. human.
uc002rey.1. human.

Organism-specific databases

CTD

9540.

GeneCards

GC02M024300.

HGNC

HGNC:19373. TP53I3.

HPA

CAB017479.
HPA022012.
HPA028742.

MIM

605171. gene.

neXtProt

NX_Q53FA7.

PharmGKB

PA134923704.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04698.

GeneTree

ENSGT00550000074483.

HOGENOM

HBG753318.

HOVERGEN

HBG097584.

InParanoid

Q53FA7.

OMA

IPEVWLT.

OrthoDB

EOG4G7C00.

PhylomeDB

Q53FA7.

Gene expression databases

ArrayExpress

Q53FA7.

Bgee

Q53FA7.

CleanEx

HS_TP53I3.

Genevestigator

Q53FA7.

GermOnline

ENSG00000115129. Homo sapiens.

Family and domain databases

InterPro

IPR013149. ADH_C.
IPR013154. ADH_GroES-like.
IPR002085. ADH_SF_Zn-type.
IPR011032. GroES-like.
IPR016040. NAD(P)-bd_dom.
IPR014189. Quinone_OxRdtase_PIG3.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K10133.

PANTHER

PTHR11695. ADH_Sf_Zn. 1 hit.
PTHR11695:SF28. Quinone_oxidored_PIG3. 1 hit.

Pfam

PF08240. ADH_N. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
[Graphical view]

SUPFAM

SSF50129. GroES_like. 1 hit.

TIGRFAMs

TIGR02824. Quinone_pig3. 1 hit.

PROSITE

PS01162. QOR_ZETA_CRYSTAL. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

35770.

SOURCE

Search...

Entry information

Entry name

QORX_HUMAN

Accession

Primary (citable) accession number: Q53FA7
Secondary accession number(s): D6W533 , O14679, O14685, Q38G78, Q6JLE7, Q9BWB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	September 27, 2005
Last modified:	January 25, 2012
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.