Reviewed, UniProtKB/Swiss-Prot Q9NX46 (ARHL2_HUMAN)

Names and origin

Protein names

Recommended 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

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	363 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
Catalytic activity	Hydrolyzes poly(ADP-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-ribose.
Cofactor	Magnesium.
Enzyme regulation	Activity is enhanced by magnesium.
Subcellular location	CytoplasmBy similarity. Nucleus.
Tissue specificity	Ubiquitous.
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 component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure
Gene Ontology (GO)
None. [Check GOA]

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 363

363

Poly(ADP-ribose) glycohydrolase ARH3

Regions

Compositional bias

2 – 10

9

Poly-Ala

Sites

Metal binding

41

1

Magnesium 2

Metal binding

76

1

Magnesium 1

Metal binding

77

1

Magnesium 1

Metal binding

78

1

Magnesium 1

Metal binding

314

1

Magnesium 2

Metal binding

316

1

Magnesium 1

Metal binding

316

1

Magnesium 2

Metal binding

317

1

Magnesium 2

Natural variations

Natural variant

209

1

E → K: dbSNP rs2236387.

Experimental info

Mutagenesis

41

1

E → A or Q: Significant loss of activity

Mutagenesis

77 – 78

2

DD → NN: Complete loss of activity

Mutagenesis

77

1

D → N: Complete loss of activity

Mutagenesis

148

1

S → A: Complete loss of activity

Mutagenesis

149

1

Y → A: Significant loss of activity

Mutagenesis

151

1

N → A: Partial loss of activity

Mutagenesis

182

1

H → Q: Complete loss of activity

Mutagenesis

238 – 239

2

EE → QQ: Slight reduction in activity

Mutagenesis

261 – 262

2

EE → QQ: Slight reduction in activity

Mutagenesis

314

1

D → E: Complete loss of activity

Mutagenesis

314

1

D → N: Significant loss of activity

Mutagenesis

317

1

T → A: Complete loss of activity

Mutagenesis

317

1

T → S: Partial loss of activity

Sequence conflict

109

1

K → E in CAG33518. Ref.4

Secondary structure

1

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363

Helix Strand Turn

Details...

Helix

19 – 37

19

Helix

38 – 40

3

Helix

48 – 56

9

Helix

77 – 92

16

Helix

97 – 110

14

Helix

118 – 127

10

Helix

137 – 141

5

Turn

142 – 146

5

Helix

152 – 155

4

Helix

158 – 163

6

Helix

167 – 179

13

Helix

185 – 201

17

Helix

208 – 222

15

Helix

226 – 234

9

Helix

241 – 254

14

Beta strand

255 – 257

3

Helix

260 – 267

8

Beta strand

270 – 272

3

Helix

273 – 275

3

Helix

277 – 286

10

Helix

300 – 310

11

Helix

315 – 330

16

Helix

332 – 334

3

Helix

337 – 341

5

Helix

346 – 360

15

Sequences

	Sequence		Length	Mass (Da)
	Q9NX46-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 5FD99F59F27CD29F	FASTA	363	38,947
	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

References

	« Hide 'large scale' referencesShow '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: 12070318] [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. , 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: 14702039] [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. , 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: 16710414] [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: 15489334] [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: 16278211] [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]	"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: 17015823] [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.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_060295.1.

UniGene

Hs.18021

3D structure databases

PDBMSD

Entry

Method