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Q9NX46 (ARHL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Poly(ADP-ribose) glycohydrolase ARH3

EC=3.2.1.143
Alternative name(s):
ADP-ribosylhydrolase 3
[Protein ADP-ribosylarginine] hydrolase-like protein 2
Gene names
Name:ADPRHL2
Synonyms:ARH3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length363 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase. Poly(ADP-ribose) metabolism may be required for maintenance of the normal function of neuronal cells. Generates ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds. Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3 is the only PAR hydrolyzing enzyme in mitochondria. Ref.8

Catalytic activity

Hydrolyzes poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose. Ref.11

Cofactor

Binds 2 magnesium ions per subunit. Ref.8

Enzyme regulation

Activity is enhanced by magnesium. Ref.8

Subunit structure

Monomer By similarity.

Subcellular location

Cytoplasm. Mitochondrion matrix. Nucleus Ref.8 Ref.9 Ref.11.

Tissue specificity

Ubiquitous. Ref.8

Sequence similarities

Belongs to the ADP-ribosylglycohydrolase family.

Sequence caution

The sequence AAK14922.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityPolymorphism
   DomainTransit peptide
   LigandMagnesium
Metal-binding
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentmitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

poly(ADP-ribose) glycohydrolase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2727Mitochondrion Potential
Chain28 – 363336Poly(ADP-ribose) glycohydrolase ARH3
PRO_0000277613

Regions

Compositional bias2 – 109Poly-Ala

Sites

Metal binding411Magnesium 2
Metal binding761Magnesium 1
Metal binding771Magnesium 1
Metal binding781Magnesium 1
Metal binding3141Magnesium 2
Metal binding3161Magnesium 1
Metal binding3161Magnesium 2
Metal binding3171Magnesium 2
Binding site2541Substrate By similarity

Natural variations

Natural variant2091E → K. Ref.5
Corresponds to variant rs2236387 [ dbSNP | Ensembl ].
VAR_030579

Experimental info

Mutagenesis411E → A or Q: Significant loss of activity. Ref.14
Mutagenesis77 – 782DD → NN: Complete loss of activity. Ref.14
Mutagenesis771D → N: Complete loss of activity. Ref.14
Mutagenesis1481S → A: Complete loss of activity. Ref.14
Mutagenesis1491Y → A: Significant loss of activity. Ref.14
Mutagenesis1511N → A: Partial loss of activity. Ref.14
Mutagenesis1821H → Q: Complete loss of activity. Ref.14
Mutagenesis238 – 2392EE → QQ: Slight reduction in activity. Ref.8
Mutagenesis261 – 2622EE → QQ: Slight reduction in activity. Ref.8
Mutagenesis3141D → E: Complete loss of activity. Ref.14
Mutagenesis3141D → N: Significant loss of activity. Ref.14
Mutagenesis3171T → A: Complete loss of activity. Ref.14
Mutagenesis3171T → S: Partial loss of activity. Ref.14
Sequence conflict1091K → E in CAG33518. Ref.4

Secondary structure

................................................. 363
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NX46 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 5FD99F59F27CD29F

FASTA36338,947
        10         20         30         40         50         60 
MAAAAMAAAA GGGAGAARSL SRFRGCLAGA LLGDCVGSFY EAHDTVDLTS VLRHVQSLEP 

        70         80         90        100        110        120 
DPGTPGSERT EALYYTDDTA MARALVQSLL AKEAFDEVDM AHRFAQEYKK DPDRGYGAGV 

       130        140        150        160        170        180 
VTVFKKLLNP KCRDVFEPAR AQFNGKGSYG NGGAMRVAGI SLAYSSVQDV QKFARLSAQL 

       190        200        210        220        230        240 
THASSLGYNG AILQALAVHL ALQGESSSEH FLKQLLGHME DLEGDAQSVL DARELGMEER 

       250        260        270        280        290        300 
PYSSRLKKIG ELLDQASVTR EEVVSELGNG IAAFESVPTA IYCFLRCMEP DPEIPSAFNS 

       310        320        330        340        350        360 
LQRTLIYSIS LGGDTDTIAT MAGAIAGAYY GMDQVPESWQ QSCEGYEETD ILAQSLHRVF 


QKS 

« Hide

References

« Hide 'large scale' references
[1]"The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse."
Glowacki G., Braren R., Firner K., Nissen M., Kuehl M., Reche P., Bazan J.F., Cetkovic-Cvrlje M., Leiter E., Haag F., Koch-Nolte F.
Protein Sci. 11:1657-1670(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"A novel gene expressed in human liver cancer tissue."
Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver cancer.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Suzuki Y., Sugano S., 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], VARIANT LYS-209.
Tissue: Thyroid.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[8]"Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase."
Oka S., Kato J., Moss J.
J. Biol. Chem. 281:705-713(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION, COFACTOR, MUTAGENESIS OF 77-ASP--ASP-78; 238-GLU--GLU-239 AND 261-GLU--GLU-262.
[9]"Functional localization of two poly(ADP-ribose)-degrading enzymes to the mitochondrial matrix."
Niere M., Kernstock S., Koch-Nolte F., Ziegler M.
Mol. Cell. Biol. 28:814-824(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase (PARG) isoforms, is responsible for degradation of mitochondrial matrix-associated poly(ADP-ribose)."
Niere M., Mashimo M., Agledal L., Dolle C., Kasamatsu A., Kato J., Moss J., Ziegler M.
J. Biol. Chem. 287:16088-16102(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[12]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation."
Mueller-Dieckmann C., Kernstock S., Lisurek M., von Kries J.P., Haag F., Weiss M.S., Koch-Nolte F.
Proc. Natl. Acad. Sci. U.S.A. 103:15026-15031(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 19-363, MUTAGENESIS OF GLU-41; ASP-77; SER-148; TYR-149; ASN-151; HIS-182; ASP-314 AND THR-317.
[15]"The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase."
Slade D., Dunstan M.S., Barkauskaite E., Weston R., Lafite P., Dixon N., Ahel M., Leys D., Ahel I.
Nature 477:616-620(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 19-363, SUBSTRATE-BINDING SITE, METAL-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ313333 Genomic DNA. Translation: CAC85940.1.
AJ427295 mRNA. Translation: CAD20316.1.
AF212236 mRNA. Translation: AAK14922.1. Frameshift.
AK000453 mRNA. Translation: BAA91174.1.
CR457237 mRNA. Translation: CAG33518.1.
AK223037 mRNA. Translation: BAD96757.1.
AL138787 Genomic DNA. Translation: CAC21453.1.
BC014169 mRNA. Translation: AAH14169.1.
CCDSCCDS402.1.
RefSeqNP_060295.1. NM_017825.2.
UniGeneHs.18021.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FOZX-ray1.60A19-363[»]
2FP0X-ray2.05A/B19-363[»]
2G4KX-ray1.82A18-363[»]
ProteinModelPortalQ9NX46.
SMRQ9NX46. Positions 19-363.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120276. 3 interactions.
IntActQ9NX46. 2 interactions.
MINTMINT-1420706.
STRING9606.ENSP00000362273.

PTM databases

PhosphoSiteQ9NX46.

Polymorphism databases

DMDM74753038.

Proteomic databases

MaxQBQ9NX46.
PaxDbQ9NX46.
PeptideAtlasQ9NX46.
PRIDEQ9NX46.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373178; ENSP00000362273; ENSG00000116863.
GeneID54936.
KEGGhsa:54936.
UCSCuc001bzt.3. human.

Organism-specific databases

CTD54936.
GeneCardsGC01P036554.
HGNCHGNC:21304. ADPRHL2.
HPAHPA027104.
HPA027141.
MIM610624. gene.
neXtProtNX_Q9NX46.
PharmGKBPA134903576.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1397.
HOGENOMHOG000225333.
HOVERGENHBG080863.
InParanoidQ9NX46.
KOK11687.
OMAYKKDPDR.
OrthoDBEOG7D2FFB.
PhylomeDBQ9NX46.
TreeFamTF324754.

Enzyme and pathway databases

BRENDA3.2.1.143. 2681.

Gene expression databases

ArrayExpressQ9NX46.
BgeeQ9NX46.
CleanExHS_ADPRHL2.
GenevestigatorQ9NX46.

Family and domain databases

InterProIPR005502. Ribosyl_crysJ1.
[Graphical view]
PfamPF03747. ADP_ribosyl_GH. 1 hit.
[Graphical view]
SUPFAMSSF101478. SSF101478. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9NX46.
GeneWikiADPRHL2.
GenomeRNAi54936.
NextBio58054.
PROQ9NX46.
SOURCESearch...

Entry information

Entry nameARHL2_HUMAN
AccessionPrimary (citable) accession number: Q9NX46
Secondary accession number(s): Q53G94, Q6IAB8, Q9BY47
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries