Reviewed, UniProtKB/Swiss-Prot P07824 (ARGI1_RAT)

Names and origin

Protein names

Recommended name:
    Arginase-1
    EC=3.5.3.1
Alternative name(s):
    Type I arginase
    Liver-type arginase

Gene names

Name:

Arg1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	L-arginine + H2O = L-ornithine + urea.
Cofactor	Binds 2 manganese ions per subunit. Ref.8 Ref.10
Enzyme regulation	Inactivated by diethyl pyrocarbonate (DEPC).
Pathway	Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.
Subunit structure	Homotrimer.
Subcellular location	Cytoplasm.
Tissue specificity	Detected in liver (at protein level). Ref.10
Induction	By arginine or homoarginine.
Sequence similarities	Belongs to the arginase family.
Biophysicochemical properties	Kinetic parameters: KM=1.4 mM for arginine

Ontologies

Keywords
Biological process	Arginine metabolism Urea cycle
Cellular component	Cytoplasm
Ligand	Manganese Metal-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	arginine metabolic process Inferred from direct assay. Source: RGD female pregnancy Inferred from expression pattern. Source: RGD response to wounding Inferred from expression pattern. Source: RGD urea cycle Inferred from direct assay. Source: RGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from direct assay. Source: RGD
Molecular function	arginase activity Inferred from direct assay. Source: RGD manganese ion binding 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 – 323

323

Arginase-1

PRO_0000173697

Regions

Region

126 – 130

5

Substrate binding

Region

137 – 139

3

Substrate binding

Sites

Metal binding

101

1

Manganese 1

Metal binding

124

1

Manganese 1

Metal binding

124

1

Manganese 2

Metal binding

126

1

Manganese 2

Metal binding

128

1

Manganese 1

Metal binding

232

1

Manganese 1

Metal binding

232

1

Manganese 2

Metal binding

234

1

Manganese 2

Binding site

183

1

Substrate

Amino acid modifications

Modified residue

3

1

Phosphoserine By similarity

Modified residue

230

1

Phosphoserine By similarity

Experimental info

Mutagenesis

101

1

H → E: Reduced catalytic activity. No effect on manganese binding. Ref.8

Mutagenesis

128

1

D → E or N: Reduced manganese binding and strongly reduced catalytic activity. Ref.8

Mutagenesis

141

1

H → A, C or D: Strongly reduced catalytic activity. Minor effect on affinity for arginine. Ref.10

Mutagenesis

141

1

H → N: Reduced affinity for arginine and reduced catalytic activity. Ref.10

Mutagenesis

232

1

D → A: Loss of one manganese ion and strongly reduced catalytic activity. Ref.8

Mutagenesis

232

1

D → C: Reduced manganese binding and strongly reduced catalytic activity. Ref.8

Mutagenesis

234

1

D → A, E or H: Reduced manganese binding and strongly reduced catalytic activity. Ref.8

Mutagenesis

235

1

G → A: 56% of wild-type activity. Ref.4

Mutagenesis

235

1

G → R: Loss of manganese-binding and activity. Ref.4

Sequence conflict

298

1

A → P in AAA40761. Ref.1

Sequence conflict

298

1

A → P in AAA40760. Ref.1

Secondary structure

1

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323

Helix Strand Turn

Details...

Beta strand

8 – 12

5

Helix

22 – 26

5

Helix

27 – 33

7

Helix

36 – 40

5

Beta strand

43 – 45

3

Beta strand

47 – 52

6

Helix

70 – 89

20

Beta strand

93 – 97

5

Helix

101 – 103

3

Helix

104 – 114

11

Beta strand

119 – 126

8

Turn

132 – 134

3

Helix

140 – 142

3

Helix

144 – 148

5

Helix

150 – 152

3

Helix

171 – 173

3

Beta strand

174 – 179

6

Helix

184 – 193

10

Beta strand

196 – 199

4

Helix

200 – 206

7

Helix

208 – 220

13

Beta strand

227 – 232

6

Helix

233 – 235

3

Turn

238 – 240

3

Beta strand

244 – 246

3

Helix

254 – 267

14

Beta strand

270 – 276

7

Helix

286 – 303

18

Sequences

	Sequence		Length	Mass (Da)
	P07824-1 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: 5A92CB0931F9A053	FASTA	323	34,973
	10 20 30 40 50 60 MSSKPKPIEI IGAPFSKGQP RGGVEKGPAA LRKAGLVEKL KETEYNVRDH GDLAFVDVPN 70 80 90 100 110 120 DSPFQIVKNP RSVGKANEQL AAVVAETQKN GTISVVLGGD HSMAIGSISG HARVHPDLCV 130 140 150 160 170 180 IWVDAHTDIN TPLTTSSGNL HGQPVAFLLK ELKGKFPDVP GFSWVTPCIS AKDIVYIGLR 190 200 210 220 230 240 DVDPGEHYII KTLGIKYFSM TEVDKLGIGK VMEETFSYLL GRKKRPIHLS FDVDGLDPVF 250 260 270 280 290 300 TPATGTPVVG GLSYREGLYI TEEIYKTGLL SGLDIMEVNP TLGKTPEEVT RTVNTAVALT 310 320 LSCFGTKREG NHKPETDYLK PPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide sequence of cDNA and deduced amino acid sequence of rat liver arginase." Kawamoto S., Amaya Y., Murakami K., Tokunaga F., Iwanaga S., Kobayashi K., Saheki T., Kimura S., Mori M. J. Biol. Chem. 262:6280-6283(1987) [PubMed: 3571256] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Structural organization of the gene for rat liver-type arginase." Ohtake A., Takiguchi M., Shigeto Y., Amaya Y., Kawamoto S., Mori M. J. Biol. Chem. 263:2245-2249(1988) [PubMed: 2892837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Liver.
[3]	"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: Liver.
[4]	"Functional consequences of the G235R mutation in liver arginase leading to hyperargininemia." Lavulo L.T., Emig F.A., Ash D.E. Arch. Biochem. Biophys. 399:49-55(2002) [PubMed: 11883902] [Abstract] Cited for: MUTAGENESIS OF GLY-235.
[5]	"Structure of a unique binuclear manganese cluster in arginase." Kanyo Z.F., Scolnick L.R., Ash D.E., Christianson D.W. Nature 383:554-557(1996) [PubMed: 8849731] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[6]	"Altering the binuclear manganese cluster of arginase diminishes thermostability and catalytic function." Scolnick L.R., Kanyo Z.F., Cavalli R.C., Ash D.E., Christianson D.W. Biochemistry 36:10558-10565(1997) [PubMed: 9265637] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[7]	"Arginase-boronic acid complex highlights a physiological role in erectile function." Cox J.D., Kim N.N., Traish A.M., Christianson D.W. Nat. Struct. Biol. 6:1043-1047(1999) [PubMed: 10542097] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[8]	"Structural and functional importance of first-shell metal ligands in the binuclear manganese cluster of arginase I." Cama E., Emig F.A., Ash D.E., Christianson D.W. Biochemistry 42:7748-7758(2003) [PubMed: 12820884] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 6-319 OF MUTANTS ASN-101; GLU-101; ASN-128; GLU-128; ALA-232; CYS-232 AND GLU-234 IN COMPLEXES WITH MANGANESE IONS, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-101; ASP-128; ASP-232 AND ASP-234.
[9]	"Design of amino acid aldehydes as transition-state analogue inhibitors of arginase." Shin H., Cama E., Christianson D.W. J. Am. Chem. Soc. 126:10278-10284(2004) [PubMed: 15315440] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 6-319 IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR (S)-2-AMINO-7-OXOHEPTANOIC ACID.
[10]	"Probing the role of the hyper-reactive histidine residue of arginase." Colleluori D.M., Reczkowski R.S., Emig F.A., Cama E., Cox J.D., Scolnick L.R., Compher K., Jude K., Han S., Viola R.E., Christianson D.W., Ash D.E. Arch. Biochem. Biophys. 444:15-26(2005) [PubMed: 16266687] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 6-319 OF MUTANTS ALA-141; ASN-141; ASP-141 AND CYS-141 IN COMPLEX WITH MANGANESE IONS, COFACTOR, MUTAGENESIS OF HIS-141, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

J02720 mRNA. Translation: AAA40761.1.
M17931 , M17924, M17925, M17926, M17927, M17928, M17929, M17930 Genomic DNA. Translation: AAA40760.1.
BC091158 mRNA. Translation: AAH91158.1.

IPI

IPI00327518.

PIR

A26702.

RefSeq

NP_058830.2.

UniGene

Rn.9857

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D3V	X-ray	1.70	A/B	1-323	[»]
1HQ5	X-ray	2.30	A/B	1-323	[»]
1HQF	X-ray	2.90	A/B/C	1-323	[»]
1HQG	X-ray	2.00	A/B/C	1-323	[»]
1HQH	X-ray	2.80	A/B/C	1-323	[»]
1HQX	X-ray	3.00	A/B/C	1-323	[»]
1P8M	X-ray	2.84	A/B/C	6-319	[»]
1P8N	X-ray	2.90	A/B/C	6-319	[»]
1P8O	X-ray	2.96	A/B/C	6-319	[»]
1P8P	X-ray	2.50	A/B/C	6-319	[»]
1P8Q	X-ray	2.95	A/B/C	6-319	[»]
1P8R	X-ray	2.50	A/B	6-313	[»]
1P8S	X-ray	3.20	A/B/C	6-319	[»]
1R1O	X-ray	2.80	A/B/C	1-323	[»]
1RLA	X-ray	2.10	A/B/C	1-323	[»]
1T4P	X-ray	2.60	A/B/C	6-319	[»]
1T4R	X-ray	2.60	A/B/C	6-319	[»]
1T4S	X-ray	2.80	A/B/C	6-319	[»]
1T4T	X-ray	2.20	A/B/C	6-319	[»]
1T5F	X-ray	2.20	A/B/C	6-319	[»]
1T5G	X-ray	2.40	A/B/C	6-319	[»]
1TA1	X-ray	2.50	A/B/C	6-319	[»]
1TBH	X-ray	2.70	A/B/C	6-319	[»]
1TBJ	X-ray	2.80	A/B/C	6-319	[»]
1TBL	X-ray	3.10	A/B/C	6-319	[»]
1ZPE	X-ray	1.70	A/B/C	6-319	[»]
1ZPG	X-ray	1.90	A/B/C	6-319	[»]
2RLA	X-ray	3.00	A/B/C	1-323	[»]
3E8Q	X-ray	2.90	A/B/C	1-323	[»]
3E8Z	X-ray	2.00	A/B/C	1-323	[»]
3E9B	X-ray	2.15	A/B/C	1-323	[»]
3RLA	X-ray	2.54	A/B/C	1-323	[»]
4RLA	X-ray	2.94	A/B/C	1-323	[»]
5RLA	X-ray	2.74	A/B/C	1-323	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P07824.

Proteomic databases

PRIDE

P07824.

Genome annotation databases

Ensembl

ENSRNOT00000017911; ENSRNOP00000017911; ENSRNOG00000013304; Rattus norvegicus. [Genome view]

GeneID

29221.

KEGG

rno:29221.

NMPDR

fig|10116.3.peg.244.

UCSC

NM_017134. rat.

Organism-specific databases

CTD

29221.

RGD

2150. Arg1.

Phylogenomic databases

HOVERGEN

P07824.

Enzyme and pathway databases

BRENDA

3.5.3.1. 248.

Gene expression databases

ArrayExpress

P07824.

Genevestigator

P07824.

GermOnline

ENSRNOG00000013304. Rattus norvegicus.

Family and domain databases

InterPro

IPR005924. Arginase.
IPR014033. Arginase_sub.
IPR006035. Ureohydrolase.
[Graphical view]

Gene3D

G3DSA:3.40.800.10. Ureohydrolase. 1 hit.

PANTHER

PTHR11358:SF2. Arginase_sub. 1 hit.
PTHR11358. Ureohydrolase. 1 hit.

Pfam

PF00491. Arginase. 1 hit.
[Graphical view]

PRINTS

PR00116. ARGINASE.

TIGRFAMs

TIGR01229. rocF_arginase. 1 hit.

PROSITE

PS01053. ARGINASE_1. 1 hit.
PS51409. ARGINASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

608419.

Entry information

Entry name

ARGI1_RAT

Accession

Primary (citable) accession number: P07824
Secondary accession number(s): Q5BK93

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	April 1, 1990
Last modified:	October 13, 2009
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)