AZIN2_MOUSE
ID AZIN2_MOUSE Reviewed; 459 AA.
AC Q8BVM4; A2A823;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Antizyme inhibitor 2;
DE Short=AzI2;
DE AltName: Full=Arginine decarboxylase-like protein;
DE Short=ADC;
DE Short=ARGDC;
DE AltName: Full=Ornithine decarboxylase-like protein;
DE Short=ODC-like protein;
DE AltName: Full=ornithine decarboxylase paralog;
DE Short=ODC-p;
GN Name=Azin2; Synonyms=Adc, Odcp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH OAZ1; OAZ2 AND OAZ3,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16916800; DOI=10.1074/jbc.m602840200;
RA Lopez-Contreras A.J., Lopez-Garcia C., Jimenez-Cervantes C., Cremades A.,
RA Penafiel R.;
RT "Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor
RT devoid of ornithine and arginine decarboxylating activity.";
RL J. Biol. Chem. 281:30896-30906(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH OAZ1 AND OAZ3.
RX PubMed=18062773; DOI=10.1042/bj20071423;
RA Snapir Z., Keren-Paz A., Bercovich Z., Kahana C.;
RT "ODCp, a brain- and testis-specific ornithine decarboxylase paralogue,
RT functions as an antizyme inhibitor, although less efficiently than AzI1.";
RL Biochem. J. 410:613-619(2008).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18508777; DOI=10.1074/jbc.m801024200;
RA Lopez-Contreras A.J., Ramos-Molina B., Cremades A., Penafiel R.;
RT "Antizyme inhibitor 2 (AZIN2/ODCp) stimulates polyamine uptake in mammalian
RT cells.";
RL J. Biol. Chem. 283:20761-20769(2008).
RN [6]
RP FUNCTION, INTERACTION WITH OAZ3, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=18973822; DOI=10.1016/j.biocel.2008.09.029;
RA Lopez-Contreras A.J., Ramos-Molina B., Martinez-de-la-Torre M.,
RA Penafiel-Verdu C., Puelles L., Cremades A., Penafiel R.;
RT "Expression of antizyme inhibitor 2 in male haploid germinal cells suggests
RT a role in spermiogenesis.";
RL Int. J. Biochem. Cell Biol. 41:1070-1078(2009).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=19449338; DOI=10.1002/jcb.22168;
RA Lopez-Contreras A.J., Sanchez-Laorden B.L., Ramos-Molina B.,
RA de la Morena M.E., Cremades A., Penafiel R.;
RT "Subcellular localization of antizyme inhibitor 2 in mammalian cells:
RT Influence of intrinsic sequences and interaction with antizymes.";
RL J. Cell. Biochem. 107:732-740(2009).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=22562773; DOI=10.1007/s00726-012-1300-4;
RA Levillain O., Ramos-Molina B., Forcheron F., Penafiel R.;
RT "Expression and distribution of genes encoding for polyamine-metabolizing
RT enzymes in the different zones of male and female mouse kidneys.";
RL Amino Acids 43:2153-2163(2012).
RN [9]
RP REVIEW, AND CHARACTERIZATION.
RX PubMed=19956990; DOI=10.1007/s00726-009-0419-4;
RA Lopez-Contreras A.J., Ramos-Molina B., Cremades A., Penafiel R.;
RT "Antizyme inhibitor 2: molecular, cellular and physiological aspects.";
RL Amino Acids 38:603-611(2010).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23874910; DOI=10.1371/journal.pone.0069188;
RA Lopez-Garcia C., Ramos-Molina B., Lambertos A., Lopez-Contreras A.J.,
RA Cremades A., Penafiel R.;
RT "Antizyme inhibitor 2 hypomorphic mice. New patterns of expression in
RT pancreas and adrenal glands suggest a role in secretory processes.";
RL PLoS ONE 8:E69188-E69188(2013).
RN [11]
RP FUNCTION, INTERACTION WITH OAZ1, SUBUNIT, AND MUTAGENESIS OF LYS-116;
RP ALA-124; GLU-139; LEU-140 AND LYS-142.
RX PubMed=24967154; DOI=10.1016/j.fob.2014.05.004;
RA Ramos-Molina B., Lambertos A., Lopez-Contreras A.J., Kasprzak J.M.,
RA Czerwoniec A., Bujnicki J.M., Cremades A., Penafiel R.;
RT "Structural and degradative aspects of ornithine decarboxylase antizyme
RT inhibitor 2.";
RL FEBS Open Bio 4:510-521(2014).
CC -!- FUNCTION: Antizyme inhibitor (AZI) protein that positively regulates
CC ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an
CC enzymatically inactive ODC homolog that counteracts the negative effect
CC of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing
CC with ODC for antizyme-binding (PubMed:18062773, PubMed:18508777,
CC PubMed:18973822). Inhibits antizyme-dependent ODC degradation and
CC releases ODC monomers from their inactive complex with antizymes,
CC leading to formation of the catalytically active ODC homodimer and
CC restoring polyamine production (PubMed:16916800, PubMed:24967154).
CC Participates in the morphological integrity of the trans-Golgi network
CC (TGN) and functions as a regulator of intracellular secretory vesicle
CC trafficking (By similarity). {ECO:0000250|UniProtKB:Q96A70,
CC ECO:0000269|PubMed:16916800, ECO:0000269|PubMed:18062773,
CC ECO:0000269|PubMed:18508777, ECO:0000269|PubMed:18973822,
CC ECO:0000269|PubMed:24967154}.
CC -!- SUBUNIT: Monomer. Interacts with OAZ1, OAZ2 and OAZ3; this interaction
CC disrupts the interaction between the antizyme and ODC1. Does not form a
CC heterodimer with ODC1. {ECO:0000269|PubMed:16916800,
CC ECO:0000269|PubMed:18062773, ECO:0000269|PubMed:18973822,
CC ECO:0000269|PubMed:24967154}.
CC -!- INTERACTION:
CC Q8BVM4; Q9R109: Oaz3; NbExp=2; IntAct=EBI-9656869, EBI-4370103;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear region
CC {ECO:0000250}. Membrane. Cytoplasmic vesicle {ECO:0000250}. Endoplasmic
CC reticulum-Golgi intermediate compartment. Golgi apparatus, cis-Golgi
CC network. Golgi apparatus, trans-Golgi network {ECO:0000250}.
CC Cytoplasmic granule. Cell projection, axon {ECO:0000250}. Cell
CC projection, dendrite {ECO:0000250}. Perikaryon {ECO:0000250}.
CC Note=Detected as vesicle-like pattern in neurite outgrowths. Localizes
CC to the vesicular compartments of the secretory pathway, predominantly
CC in the trans-Golgi network (TGN). Localizes with vesicle-associated
CC membrane protein VAMP8 in the vicinity of the plasma membrane within
CC serotonin-containing secretory granules (By similarity). Colocalizes
CC with KDEL receptors in ER-Golgi intermediate compartment (ERGIC).
CC Translocates from the ERGIC structure to the cytoplasm in a antizyme-
CC dependent manner. Localizes with vesicle-associated membrane protein
CC VAMP8 in the vicinity of the plasma membrane within serotonin-
CC containing secretory granules. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the medulla and chromaffin cells of
CC the adrenal gland. Expressed in the Langerhans islets of the pancreas.
CC Expressed in the inner part of the seminiferous tubules and in
CC spermatozoa located in the lumen of the epididymis of the testis.
CC Expressed in the cortex, hippocampus and cerebellum of the brain.
CC Expressed in normal and neoplastic mast cells (MC) (at protein level).
CC Expressed in testis, pancreas and brain. Expressed throughout the
CC differentiation process from spermatids to spermatozoa in the inner
CC part of the seminiferous tubules. Expressed in the kidney: expressed in
CC the superficial (Cs) and the deep layer (Cd) of the cortex region and
CC in the outer stripe (OS), inner stripe (IS) and the inner medulla
CC papilla (IM) of the medulla region. {ECO:0000269|PubMed:16916800,
CC ECO:0000269|PubMed:18508777, ECO:0000269|PubMed:18973822,
CC ECO:0000269|PubMed:22562773, ECO:0000269|PubMed:23874910}.
CC -!- DOMAIN: The N-terminus domain is necessary for its localization to the
CC ER-Golgi intermediate compartment (ERGIC).
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation; a process
CC that is reduced in presence of antizymes. May also be degraded through
CC the lysosomal degradative pathway in a proteasomal-independent manner.
CC {ECO:0000269|PubMed:18062773}.
CC -!- MISCELLANEOUS: Gly-70 is present instead of the conserved Lys which
CC would otherwise be the covalent pyridoxal phosphate binding site.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family.
CC ODC antizyme inhibitor subfamily. {ECO:0000305}.
CC -!- CAUTION: The human ortholog was initially reported to have ornithine or
CC arginine decarboxylase activities, but it was later found to possess
CC neither of them. {ECO:0000305|PubMed:16916800}.
CC -!- CAUTION: Previously reported to be localized in the mitochondrion
CC (PubMed:16916800). However, it was not confirmed by later reports
CC (PubMed:18062773). {ECO:0000305|PubMed:16916800,
CC ECO:0000305|PubMed:18062773}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK077201; BAC36679.1; -; mRNA.
DR EMBL; AL607086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18678.1; -.
DR RefSeq; NP_766463.1; NM_172875.4.
DR AlphaFoldDB; Q8BVM4; -.
DR SMR; Q8BVM4; -.
DR IntAct; Q8BVM4; 3.
DR STRING; 10090.ENSMUSP00000030581; -.
DR PhosphoSitePlus; Q8BVM4; -.
DR MaxQB; Q8BVM4; -.
DR PaxDb; Q8BVM4; -.
DR PRIDE; Q8BVM4; -.
DR ProteomicsDB; 273644; -.
DR Antibodypedia; 31397; 81 antibodies from 20 providers.
DR DNASU; 242669; -.
DR Ensembl; ENSMUST00000030581; ENSMUSP00000030581; ENSMUSG00000028789.
DR Ensembl; ENSMUST00000106068; ENSMUSP00000101683; ENSMUSG00000028789.
DR GeneID; 242669; -.
DR KEGG; mmu:242669; -.
DR UCSC; uc008uvq.2; mouse.
DR CTD; 113451; -.
DR MGI; MGI:2442093; Azin2.
DR VEuPathDB; HostDB:ENSMUSG00000028789; -.
DR eggNOG; KOG0622; Eukaryota.
DR GeneTree; ENSGT00950000182995; -.
DR InParanoid; Q8BVM4; -.
DR OMA; CPEQPWH; -.
DR OrthoDB; 725914at2759; -.
DR PhylomeDB; Q8BVM4; -.
DR TreeFam; TF300760; -.
DR Reactome; R-MMU-351143; Agmatine biosynthesis.
DR BioGRID-ORCS; 242669; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q8BVM4; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8BVM4; protein.
DR Bgee; ENSMUSG00000028789; Expressed in seminiferous tubule of testis and 137 other tissues.
DR ExpressionAtlas; Q8BVM4; baseline and differential.
DR Genevisible; Q8BVM4; MM.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0005801; C:cis-Golgi network; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:1990005; C:granular vesicle; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; ISS:UniProtKB.
DR GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR GO; GO:0042978; F:ornithine decarboxylase activator activity; IDA:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0006591; P:ornithine metabolic process; IDA:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:1902269; P:positive regulation of polyamine transmembrane transport; IDA:UniProtKB.
DR GO; GO:0033387; P:putrescine biosynthetic process from ornithine; IBA:GO_Central.
DR GO; GO:0098629; P:trans-Golgi network membrane organization; ISS:UniProtKB.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR031173; Azin2.
DR InterPro; IPR022643; De-COase2_C.
DR InterPro; IPR022657; De-COase2_CS.
DR InterPro; IPR022644; De-COase2_N.
DR InterPro; IPR000183; Orn/DAP/Arg_de-COase.
DR InterPro; IPR002433; Orn_de-COase.
DR InterPro; IPR029066; PLP-binding_barrel.
DR PANTHER; PTHR11482; PTHR11482; 1.
DR PANTHER; PTHR11482:SF4; PTHR11482:SF4; 1.
DR Pfam; PF02784; Orn_Arg_deC_N; 1.
DR Pfam; PF00278; Orn_DAP_Arg_deC; 1.
DR PRINTS; PR01179; ODADCRBXLASE.
DR PRINTS; PR01182; ORNDCRBXLASE.
DR SUPFAM; SSF50621; SSF50621; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
DR PROSITE; PS00879; ODR_DC_2_2; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Golgi apparatus; Membrane;
KW Nucleus; Polyamine biosynthesis; Reference proteome; Transport;
KW Ubl conjugation.
FT CHAIN 1..459
FT /note="Antizyme inhibitor 2"
FT /id="PRO_0000149945"
FT REGION 117..140
FT /note="Necessary for polyamine uptake stimulation"
FT MUTAGEN 116
FT /note="K->A: Does not inhibit interaction with OAZ1.
FT Reduces interaction with OAZ1; when associated with A-142."
FT /evidence="ECO:0000269|PubMed:24967154"
FT MUTAGEN 124
FT /note="A->S: Does not inhibit interaction with OAZ1."
FT /evidence="ECO:0000269|PubMed:24967154"
FT MUTAGEN 139
FT /note="E->A: Strongly reduces interaction with OAZ1 and
FT unable to abrogate both the inhibitory effect of OAZ1 on
FT ornithine decarboxylase (ODC) activity and polyamine
FT uptake; when associated with A-140 and A-142."
FT /evidence="ECO:0000269|PubMed:24967154"
FT MUTAGEN 140
FT /note="L->A: Strongly reduces interaction with OAZ1 and
FT unable to abrogate both the inhibitory effect of OAZ1 on
FT ornithine decarboxylase (ODC) activity and polyamine
FT uptake; when associated with A-139 and A-142."
FT /evidence="ECO:0000269|PubMed:24967154"
FT MUTAGEN 142
FT /note="K->A: Does not inhibit interaction with OAZ1.
FT Reduces interaction with OAZ1; when associated with A-116.
FT Strongly reduces interaction with OAZ1 and unable to
FT abrogate the inhibitory effect of OAZ1 on ornithine
FT decarboxylase (ODC) activity and polyamine uptake; when
FT associated with A-139 and A-140."
FT /evidence="ECO:0000269|PubMed:24967154"
FT CONFLICT 317
FT /note="Y -> H (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 49503 MW; 4C8D3994B89ABAC5 CRC64;
MAGYLSESDF VMVEEGFSTR DLLEELTLGA SQATSGKVAA FFVADLGAVV RKHFCFLKHL
PRVRPFYAVG CNSSLGVLKV LAELGLGFSC ANKAEMELVQ HIGVPASKII CANPCKQVAQ
IKYAAKHGVR LLSFDNEVEL AKVVKSHPSA KMVLCIATQD SHSLNHLSLR FGASLKSCRH
LLENAKKSHV EVVGVSFHIG SGCPDPQAYA QSIADARLVF QMGEELGHTM NILDLGGGFP
GLEGAKVRFE EMASVINSAL DLYFPEGCGV DILAELGRYY VTSAFTVAVS IVAKREVLDQ
ASREEQTGAA PKSIVYYLDE GVYGVFNSVL FDNTCPTPAL QKKPSADQPL YSSSLWGPAV
EGCDCVAEGL WLPQLQVGDW LVFDNMGAYT VDTKSLLGGT QARRVTYAMS RLAWEALRGQ
LLPAEEDQDA EGVCKPLSCG WEITDTLCVG PVFTPASIM
