Reviewed, UniProtKB/Swiss-Prot P05089 (ARGI1_HUMAN)

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

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	322 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.
Pathway	Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.
Subunit structure	Homotrimer. Ref.9 Ref.11
Subcellular location	Cytoplasm. Ref.9
Induction	By arginine or homoarginine.
Involvement in disease	Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia. Ref.13 Ref.15
Sequence similarities	Belongs to the arginase family.

Ontologies

Keywords
Biological process	Arginine metabolism Urea cycle
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	Manganese Metal-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	arginine catabolic process Ref.1 Traceable author statement. Source: ProtInc urea cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.1 Traceable author statement. Source: ProtInc
Molecular function	arginase activity Ref.1 Traceable author statement. Source: ProtInc manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P05089-1)

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.

Isoform 2 (identifier: P05089-2)

Also known as: Erythroid variant;

The sequence of this isoform differs from the canonical sequence as follows:
     43-43: Q → QVTQNFLIL

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Isoform 3 (identifier: P05089-3)

The sequence of this isoform differs from the canonical sequence as follows:
     204-289: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 322

322

Arginase-1

PRO_0000173693

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

230

1

Phosphoserine By similarity

Natural variations

Alternative sequence

43

1

Q → QVTQNFLIL in isoform 2.

VSP_009330

Alternative sequence

204 – 289

86

Missing in isoform 3.

VSP_009331

Natural variant

11

1

I → T in ARGIN; 12% of wild-type activity.

VAR_015594

Natural variant

138

1

G → V in ARGIN.

VAR_015595

Natural variant

235

1

G → R in ARGIN.

VAR_000674

Natural variant

290

1

T → S Could be a polymorphism. Ref.14

VAR_000675

Experimental info

Sequence conflict

48

1

K → E in AAL71547. Ref.3

Sequence conflict

86

1

E → Q in AAA51776. Ref.1

Sequence conflict

202

1

E → K in AAL71547. Ref.3

Secondary structure

1

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322

Helix Strand Turn

Details...

Beta strand

7 – 13

7

Helix

22 – 26

5

Helix

27 – 33

7

Helix

36 – 42

7

Beta strand

46 – 52

7

Helix

70 – 89

20

Beta strand

93 – 99

7

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

Turn

153 – 155

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

221 – 223

3

Beta strand

227 – 232

6

Helix

233 – 235

3

Turn

238 – 240

3

Beta strand

243 – 246

4

Helix

254 – 267

14

Beta strand

270 – 276

7

Helix

280 – 282

3

Helix

286 – 303

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 8F3BE2652243F622	FASTA	322	34,735
	10 20 30 40 50 60 MSAKSRTIGI IGAPFSKGQP RGGVEEGPTV LRKAGLLEKL KEQECDVKDY GDLPFADIPN 70 80 90 100 110 120 DSPFQIVKNP RSVGKASEQL AGKVAEVKKN GRISLVLGGD HSLAIGSISG HARVHPDLGV 130 140 150 160 170 180 IWVDAHTDIN TPLTTTSGNL HGQPVSFLLK ELKGKIPDVP GFSWVTPCIS AKDIVYIGLR 190 200 210 220 230 240 DVDPGEHYIL KTLGIKYFSM TEVDRLGIGK VMEETLSYLL GRKKRPIHLS FDVDGLDPSF 250 260 270 280 290 300 TPATGTPVVG GLTYREGLYI TEEIYKTGLL SGLDIMEVNP SLGKTPEEVT RTVNTAVAIT 310 320 LACFGLAREG NHKPIDYLNP PK
	Isoform 2 (Erythroid variant). Checksum: 3547D8B6C254179B	FASTA	330	35,664
	10 20 30 40 50 60 MSAKSRTIGI IGAPFSKGQP RGGVEEGPTV LRKAGLLEKL KEQVTQNFLI LECDVKDYGD 70 80 90 100 110 120 LPFADIPNDS PFQIVKNPRS VGKASEQLAG KVAEVKKNGR ISLVLGGDHS LAIGSISGHA 130 140 150 160 170 180 RVHPDLGVIW VDAHTDINTP LTTTSGNLHG QPVSFLLKEL KGKIPDVPGF SWVTPCISAK 190 200 210 220 230 240 DIVYIGLRDV DPGEHYILKT LGIKYFSMTE VDRLGIGKVM EETLSYLLGR KKRPIHLSFD 250 260 270 280 290 300 VDGLDPSFTP ATGTPVVGGL TYREGLYITE EIYKTGLLSG LDIMEVNPSL GKTPEEVTRT 310 320 330 VNTAVAITLA CFGLAREGNH KPIDYLNPPK
	Isoform 3. Checksum: 79F02C69B700AB67	FASTA	236	25,356
	10 20 30 40 50 60 MSAKSRTIGI IGAPFSKGQP RGGVEEGPTV LRKAGLLEKL KEQECDVKDY GDLPFADIPN 70 80 90 100 110 120 DSPFQIVKNP RSVGKASEQL AGKVAEVKKN GRISLVLGGD HSLAIGSISG HARVHPDLGV 130 140 150 160 170 180 IWVDAHTDIN TPLTTTSGNL HGQPVSFLLK ELKGKIPDVP GFSWVTPCIS AKDIVYIGLR 190 200 210 220 230 DVDPGEHYIL KTLGIKYFSM TEVTRTVNTA VAITLACFGL AREGNHKPID YLNPPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and nucleotide sequence of cDNA for human liver arginase." Haraguchi Y., Takiguchi M., Amaya Y., Kawamoto S., Matsuda I., Mori M. Proc. Natl. Acad. Sci. U.S.A. 84:412-415(1987) [PubMed: 3540966] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Human liver-type arginase gene: structure of the gene and analysis of the promoter region." Takiguchi M., Haraguchi Y., Mori M. Nucleic Acids Res. 16:8789-8802(1988) [PubMed: 3174433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[3]	Lee Y.T., Miller J.L. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Erythroblast.
[4]	"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 3).
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 3). Tissue: Liver and Skeletal muscle.
[7]	"Expression of human liver arginase in Escherichia coli. Purification and properties of the product." Ikemoto M., Tabata M., Miyake T., Kono T., Mori M., Totani M., Murachi T. Biochem. J. 270:697-703(1990) [PubMed: 2241902] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-13, CHARACTERIZATION. Tissue: Liver.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response." Di Costanzo L., Sabio G., Mora A., Rodriguez P.C., Ochoa A.C., Centeno F., Christianson D.W. Proc. Natl. Acad. Sci. U.S.A. 102:13058-13063(2005) [PubMed: 16141327] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.29 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR 2(S)-AMINO-6-BORONOHEXANOIC ACID, SUBCELLULAR LOCATION, SUBUNIT.
[10]	"Expression, purification, assay, and crystal structure of perdeuterated human arginase I." Di Costanzo L., Moulin M., Haertlein M., Meilleur F., Christianson D.W. Arch. Biochem. Biophys. 465:82-89(2007) [PubMed: 17562323] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR 2(S)-AMINO-6-BORONOHEXANOIC ACID, MASS SPECTROMETRY.
[11]	"Crystal structure of human arginase I complexed with thiosemicarbazide reveals an unusual thiocarbonyl mu-sulfide ligand in the binuclear manganese cluster." Di Costanzo L., Pique M.E., Christianson D.W. J. Am. Chem. Soc. 129:6388-6389(2007) [PubMed: 17469833] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THIOSEMICARBAZIDE, SUBUNIT.
[12]	"Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I." Zakharian T.Y., Di Costanzo L., Christianson D.W. Org. Biomol. Chem. 6:3240-3243(2008) [PubMed: 18802628] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR (2S)-2-AMINO-7,8-EPOXYOCTANOIC ACID.
[13]	"Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia." Uchino T., Haraguchi Y., Aparicio J.M., Mizutani N., Higashikawa M., Naitoh H., Mori M., Matsuda I. Am. J. Hum. Genet. 51:1406-1412(1992) [PubMed: 1463019] [Abstract] Cited for: VARIANT ARGIN ARG-235.
[14]	"Molecular genetic study of human arginase deficiency." Grody W.W., Klein D., Dodson A.E., Kern R.M., Wissmann P.B., Goodman B.K., Bassand P., Marescau B., Kang S.-S., Leonard J.V., Cederbaum S.D. Am. J. Hum. Genet. 50:1281-1290(1992) [PubMed: 1598908] [Abstract] Cited for: VARIANT SER-290.
[15]	"Molecular basis of phenotypic variation in patients with argininemia." Uchino T., Snyderman S.E., Lambert M., Qureshi I.A., Shapira S.K., Sansaricq C., Smit L.M.E., Jakobs C., Matsuda I. Hum. Genet. 96:255-260(1995) [PubMed: 7649538] [Abstract] Cited for: VARIANTS ARGIN THR-11 AND VAL-138.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Arginase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M14502 mRNA. Translation: AAA51776.1.
X12662 , X12663, X12664, X12665, X12666, X12667, X12668, X12669 Genomic DNA. Translation: CAA31188.1.
AY074488 mRNA. Translation: AAL71547.1.
BT006741 mRNA. Translation: AAP35387.1.
AL121575 Genomic DNA. Translation: CAB92071.1.
AL121575 Genomic DNA. Translation: CAI23317.1.
AL121575 Genomic DNA. Translation: CAI23318.1.
BC005321 mRNA. Translation: AAH05321.1.
BC020653 mRNA. Translation: AAH20653.1.

IPI

IPI00038356.
IPI00291560.
IPI00398768.

PIR

A26370. S02132.

RefSeq

NP_000036.2.

UniGene

Hs.440934

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WVA	X-ray	1.94	A/B	1-322	[»]
1WVB	X-ray	2.30	A/B	1-322	[»]
2AEB	X-ray	1.29	A/B	1-322	[»]
2PHA	X-ray	1.90	A/B	1-322	[»]
2PHO	X-ray	1.95	A/B	1-322	[»]
2PLL	X-ray	1.90	A/B	1-322	[»]
2ZAV	X-ray	1.70	A/B	1-322	[»]
3DJ8	X-ray	1.51	A/B	1-322	[»]
3E6K	X-ray	2.10	A/B	1-322	[»]
3E6V	X-ray	1.72	A/B	1-322	[»]
3F80	X-ray	1.60	A/B	1-322	[»]

ModBase

Search...

PTM databases

PhosphoSite

P05089.

Proteomic databases

PRIDE

P05089.

Genome annotation databases

Ensembl

ENSG00000118520. Homo sapiens. [Contig view]

GeneID

383.

KEGG

hsa:383.

UCSC

uc003qcp.1. human.
uc010kfm.1. human.

Organism-specific databases

GeneCards

GC06P131936.

H-InvDB

HIX0006220.

HGNC

HGNC:663. ARG1.

HPA

CAB009434.
HPA003595.

MIM

207800. phenotype.
608313. gene.

Orphanet

90. Argininemia.

PharmGKB

PA24947.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P05089.

OMA

P05089. QIVKNPR.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-11284.

BRENDA

3.5.3.1. 247.

Pathway_Interaction_DB

il4_2pathway. IL4-mediated signaling events.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

P05089.

Bgee

P05089.

CleanEx

HS_ARG1.

GermOnline

ENSG00000118520. Homo sapiens.

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

DrugBank

DB00129. L-Ornithine.

NextBio

1603.

SOURCE

Search...

Entry information

Entry name

ARGI1_HUMAN

Accession

Primary (citable) accession number: P05089
Secondary accession number(s): A6NEA0 , Q5JWT5, Q5JWT6, Q8TE72, Q9BS50

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 11, 2001
Last modified:	July 7, 2009
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)