Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Arginase-2, mitochondrial

Gene

ARG2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to NO synthase. Since NO synthase is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase II plays a role in both male and female sexual arousal. It is therefore a potential target for the treatment of male and female sexual arousal disorders.1 Publication

Catalytic activityi

L-arginine + H2O = L-ornithine + urea.

Cofactori

Mn2+PROSITE-ProRule annotation1 PublicationNote: Binds 2 manganese ions per subunit.PROSITE-ProRule annotation1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi120 – 1201Manganese 1
Metal bindingi143 – 1431Manganese 1
Metal bindingi143 – 1431Manganese 2
Metal bindingi145 – 1451Manganese 2
Metal bindingi147 – 1471Manganese 1
Binding sitei202 – 2021SubstrateBy similarity
Metal bindingi251 – 2511Manganese 1
Metal bindingi251 – 2511Manganese 2
Metal bindingi253 – 2531Manganese 2
Binding sitei296 – 2961SubstrateBy similarity

GO - Molecular functioni

  1. arginase activity Source: Reactome
  2. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. arginine metabolic process Source: UniProtKB-KW
  2. cellular nitrogen compound metabolic process Source: Reactome
  3. nitric oxide biosynthetic process Source: ProtInc
  4. small molecule metabolic process Source: Reactome
  5. striated muscle contraction Source: Ensembl
  6. urea cycle Source: Reactome
  7. ureteric bud development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Arginine metabolism, Urea cycle

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS01388-MONOMER.
BRENDAi3.5.3.1. 2681.
ReactomeiREACT_847. Urea cycle.
SABIO-RKP78540.
UniPathwayiUPA00158; UER00270.

Names & Taxonomyi

Protein namesi
Recommended name:
Arginase-2, mitochondrial (EC:3.5.3.1)
Alternative name(s):
Kidney-type arginase
Non-hepatic arginase
Type II arginase
Gene namesi
Name:ARG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:664. ARG2.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial matrix Source: Reactome
  2. mitochondrion Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24948.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2222MitochondrionSequence AnalysisAdd
BLAST
Chaini23 – 354332Arginase-2, mitochondrialPRO_0000002084Add
BLAST

Proteomic databases

MaxQBiP78540.
PaxDbiP78540.
PeptideAtlasiP78540.
PRIDEiP78540.

PTM databases

PhosphoSiteiP78540.

Expressioni

Tissue specificityi

Expressed most strongly in kidney and prostate, much less strongly in the brain, skeletal muscle, placenta, lung, mammary gland, macrophage, uterus, testis and gut, but apparently not in the liver, heart and pancreas.

Gene expression databases

BgeeiP78540.
CleanExiHS_ARG2.
ExpressionAtlasiP78540. baseline and differential.
GenevestigatoriP78540.

Organism-specific databases

HPAiCAB009435.
HPA000663.

Interactioni

Subunit structurei

Homotrimer.1 Publication

Protein-protein interaction databases

BioGridi106879. 2 interactions.
STRINGi9606.ENSP00000261783.

Structurei

Secondary structure

1
354
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi25 – 306Combined sources
Helixi42 – 443Combined sources
Helixi45 – 517Combined sources
Helixi54 – 607Combined sources
Beta strandi64 – 707Combined sources
Turni83 – 853Combined sources
Helixi89 – 10820Combined sources
Beta strandi112 – 1165Combined sources
Helixi120 – 1223Combined sources
Helixi123 – 13311Combined sources
Beta strandi138 – 1458Combined sources
Turni151 – 1533Combined sources
Helixi159 – 1613Combined sources
Helixi163 – 1664Combined sources
Helixi169 – 1746Combined sources
Helixi190 – 1923Combined sources
Beta strandi193 – 1986Combined sources
Helixi203 – 2119Combined sources
Beta strandi215 – 2184Combined sources
Helixi219 – 2257Combined sources
Helixi227 – 23913Combined sources
Beta strandi240 – 2423Combined sources
Beta strandi246 – 2516Combined sources
Helixi252 – 2543Combined sources
Turni257 – 2593Combined sources
Beta strandi262 – 2654Combined sources
Helixi273 – 28513Combined sources
Beta strandi289 – 2957Combined sources
Helixi299 – 3013Combined sources
Beta strandi302 – 3043Combined sources
Helixi305 – 32218Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PQ3X-ray2.70A/B/C/D/E/F24-329[»]
4HZEX-ray1.60A/B/C24-329[»]
4I06X-ray1.80A/B/C24-329[»]
4IE2X-ray2.21A/B/C24-329[»]
4IE3X-ray2.35A/B/C24-329[»]
4IXUX-ray1.90A/B/C24-329[»]
4IXVX-ray2.30A/B/C24-329[»]
ProteinModelPortaliP78540.
SMRiP78540. Positions 24-329.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78540.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni145 – 1495Substrate bindingBy similarity
Regioni156 – 1583Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the arginase family.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0010.
GeneTreeiENSGT00530000063082.
HOGENOMiHOG000204319.
HOVERGENiHBG003030.
InParanoidiP78540.
KOiK01476.
OMAiIATCFGQ.
OrthoDBiEOG747PJ5.
PhylomeDBiP78540.
TreeFamiTF300034.

Family and domain databases

Gene3Di3.40.800.10. 1 hit.
InterProiIPR014033. Arginase.
IPR006035. Ureohydrolase.
IPR023696. Ureohydrolase_domain.
IPR020855. Ureohydrolase_Mn_BS.
[Graphical view]
PANTHERiPTHR11358. PTHR11358. 1 hit.
PfamiPF00491. Arginase. 1 hit.
[Graphical view]
PIRSFiPIRSF036979. Arginase. 1 hit.
PRINTSiPR00116. ARGINASE.
TIGRFAMsiTIGR01229. rocF_arginase. 1 hit.
PROSITEiPS01053. ARGINASE_1. 1 hit.
PS51409. ARGINASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P78540-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLRGSLSRL LQTRVHSILK KSVHSVAVIG APFSQGQKRK GVEHGPAAIR
60 70 80 90 100
EAGLMKRLSS LGCHLKDFGD LSFTPVPKDD LYNNLIVNPR SVGLANQELA
110 120 130 140 150
EVVSRAVSDG YSCVTLGGDH SLAIGTISGH ARHCPDLCVV WVDAHADINT
160 170 180 190 200
PLTTSSGNLH GQPVSFLLRE LQDKVPQLPG FSWIKPCISS ASIVYIGLRD
210 220 230 240 250
VDPPEHFILK NYDIQYFSMR DIDRLGIQKV MERTFDLLIG KRQRPIHLSF
260 270 280 290 300
DIDAFDPTLA PATGTPVVGG LTYREGMYIA EEIHNTGLLS ALDLVEVNPQ
310 320 330 340 350
LATSEEEAKT TANLAVDVIA SSFGQTREGG HIVYDQLPTP SSPDESENQA

RVRI
Length:354
Mass (Da):38,578
Last modified:May 1, 1997 - v1
Checksum:i1624FAC7D515C68B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti240 – 2401G → R.
Corresponds to variant rs17104534 [ dbSNP | Ensembl ].
VAR_033520

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86724 mRNA. Translation: BAA13158.1.
U75667 mRNA. Translation: AAB39855.1.
U82256 mRNA. Translation: AAC51664.1.
AY074489 mRNA. Translation: AAL71548.1.
CR536550 mRNA. Translation: CAG38787.1.
AK312484 mRNA. Translation: BAG35387.1.
CH471061 Genomic DNA. Translation: EAW80943.1.
BC001350 mRNA. Translation: AAH01350.1.
BC008464 mRNA. Translation: AAH08464.1.
BC029050 mRNA. Translation: AAH29050.1.
CCDSiCCDS9785.1.
RefSeqiNP_001163.1. NM_001172.3.
UniGeneiHs.226007.

Genome annotation databases

EnsembliENST00000261783; ENSP00000261783; ENSG00000081181.
GeneIDi384.
KEGGihsa:384.
UCSCiuc001xjs.3. human.

Polymorphism databases

DMDMi2492935.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Arginase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86724 mRNA. Translation: BAA13158.1.
U75667 mRNA. Translation: AAB39855.1.
U82256 mRNA. Translation: AAC51664.1.
AY074489 mRNA. Translation: AAL71548.1.
CR536550 mRNA. Translation: CAG38787.1.
AK312484 mRNA. Translation: BAG35387.1.
CH471061 Genomic DNA. Translation: EAW80943.1.
BC001350 mRNA. Translation: AAH01350.1.
BC008464 mRNA. Translation: AAH08464.1.
BC029050 mRNA. Translation: AAH29050.1.
CCDSiCCDS9785.1.
RefSeqiNP_001163.1. NM_001172.3.
UniGeneiHs.226007.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PQ3X-ray2.70A/B/C/D/E/F24-329[»]
4HZEX-ray1.60A/B/C24-329[»]
4I06X-ray1.80A/B/C24-329[»]
4IE2X-ray2.21A/B/C24-329[»]
4IE3X-ray2.35A/B/C24-329[»]
4IXUX-ray1.90A/B/C24-329[»]
4IXVX-ray2.30A/B/C24-329[»]
ProteinModelPortaliP78540.
SMRiP78540. Positions 24-329.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106879. 2 interactions.
STRINGi9606.ENSP00000261783.

Chemistry

BindingDBiP78540.
ChEMBLiCHEMBL1795148.
DrugBankiDB00125. L-Arginine.
DB00129. L-Ornithine.

PTM databases

PhosphoSiteiP78540.

Polymorphism databases

DMDMi2492935.

Proteomic databases

MaxQBiP78540.
PaxDbiP78540.
PeptideAtlasiP78540.
PRIDEiP78540.

Protocols and materials databases

DNASUi384.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261783; ENSP00000261783; ENSG00000081181.
GeneIDi384.
KEGGihsa:384.
UCSCiuc001xjs.3. human.

Organism-specific databases

CTDi384.
GeneCardsiGC14P068086.
HGNCiHGNC:664. ARG2.
HPAiCAB009435.
HPA000663.
MIMi107830. gene.
neXtProtiNX_P78540.
PharmGKBiPA24948.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0010.
GeneTreeiENSGT00530000063082.
HOGENOMiHOG000204319.
HOVERGENiHBG003030.
InParanoidiP78540.
KOiK01476.
OMAiIATCFGQ.
OrthoDBiEOG747PJ5.
PhylomeDBiP78540.
TreeFamiTF300034.

Enzyme and pathway databases

UniPathwayiUPA00158; UER00270.
BioCyciMetaCyc:HS01388-MONOMER.
BRENDAi3.5.3.1. 2681.
ReactomeiREACT_847. Urea cycle.
SABIO-RKP78540.

Miscellaneous databases

ChiTaRSiARG2. human.
EvolutionaryTraceiP78540.
GenomeRNAii384.
NextBioi1607.
PROiP78540.
SOURCEiSearch...

Gene expression databases

BgeeiP78540.
CleanExiHS_ARG2.
ExpressionAtlasiP78540. baseline and differential.
GenevestigatoriP78540.

Family and domain databases

Gene3Di3.40.800.10. 1 hit.
InterProiIPR014033. Arginase.
IPR006035. Ureohydrolase.
IPR023696. Ureohydrolase_domain.
IPR020855. Ureohydrolase_Mn_BS.
[Graphical view]
PANTHERiPTHR11358. PTHR11358. 1 hit.
PfamiPF00491. Arginase. 1 hit.
[Graphical view]
PIRSFiPIRSF036979. Arginase. 1 hit.
PRINTSiPR00116. ARGINASE.
TIGRFAMsiTIGR01229. rocF_arginase. 1 hit.
PROSITEiPS01053. ARGINASE_1. 1 hit.
PS51409. ARGINASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line."
    Gotoh T., Sonoki T., Nagasaki A., Terada K., Takiguchi M., Mori M.
    FEBS Lett. 395:119-122(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cloning and characterization of the human type II arginase gene."
    Vockley J.G., Jenkinson C.P., Shukla H., Kern R.M., Grody W.W., Cederbaum S.D.
    Genomics 38:118-123(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Human type II arginase: sequence analysis and tissue-specific expression."
    Morris S.M. Jr., Bhamidipati D., Kepka-Lenhart D.
    Gene 193:157-161(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  4. Lee Y.T., Miller J.L.
    Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Erythroblast.
  5. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Hippocampus.
  7. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain, Lung, Muscle, Prostate and Testis.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "Human arginase II: crystal structure and physiological role in male and female sexual arousal."
    Cama E., Colleluori D.M., Emig F.A., Shin H., Kim S.W., Kim N.N., Traish A.M., Ash D.E., Christianson D.W.
    Biochemistry 42:8445-8451(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 24-329 IN COMPLEX WITH MANGANESE IONS AND S-2-(BORONOETHYL)-L-CYSTEINE, COFACTOR, SUBUNIT, FUNCTION.

Entry informationi

Entry nameiARGI2_HUMAN
AccessioniPrimary (citable) accession number: P78540
Secondary accession number(s): B2R690, Q6FHY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: April 1, 2015
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.