ID   AZIN2_RAT               Reviewed;         457 AA.
AC   D4A693;
DT   01-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 2.
DT   03-AUG-2022, entry version 77.
DE   RecName: Full=Antizyme inhibitor 2;
DE            Short=AzI2;
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=19718454; DOI=10.1371/journal.pone.0006858;
RA   Kanerva K., Lappalainen J., Makitie L.T., Virolainen S., Kovanen P.T.,
RA   Andersson L.C.;
RT   "Expression of antizyme inhibitor 2 in mast cells and role of polyamines as
RT   selective regulators of serotonin secretion.";
RL   PLoS ONE 4:E6858-E6858(2009).
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. Inhibits antizyme-dependent ODC
CC       degradation and releases ODC monomers from their inactive complex with
CC       antizymes, leading to formation of the catalytically active ODC
CC       homodimer and restoring polyamine production. Participates in the
CC       morphological integrity of the trans-Golgi network (TGN) and functions
CC       as a regulator of intracellular secretory vesicle trafficking.
CC       {ECO:0000250|UniProtKB:Q8BVM4, ECO:0000250|UniProtKB:Q96A70}.
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:0000250|UniProtKB:Q8BVM4,
CC       ECO:0000250|UniProtKB:Q96A70}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19718454}. Cytoplasm
CC       {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Membrane
CC       {ECO:0000250}. Cytoplasmic vesicle {ECO:0000250}. Endoplasmic
CC       reticulum-Golgi intermediate compartment {ECO:0000250}. Golgi
CC       apparatus, cis-Golgi network {ECO:0000250}. Golgi apparatus, trans-
CC       Golgi network {ECO:0000250}. Cytoplasmic granule
CC       {ECO:0000269|PubMed:19718454}. Cell projection, axon {ECO:0000250}.
CC       Cell projection, dendrite {ECO:0000250}. Perikaryon {ECO:0000250}.
CC       Note=Colocalizes with KDEL receptors in ER-Golgi intermediate
CC       compartment (ERGIC). Translocates from the ERGIC structure to the
CC       cytoplasm in a antizyme-dependent manner. Localizes with vesicle-
CC       associated membrane protein VAMP8 in the vicinity of the plasma
CC       membrane within serotonin-containing secretory granules. Detected as
CC       vesicle-like pattern in neurite outgrowths. Localizes to the vesicular
CC       compartments of the secretory pathway, predominantly in the trans-Golgi
CC       network (TGN) (By similarity). Localizes with vesicle-associated
CC       membrane protein VAMP8 in the vicinity of the plasma membrane within
CC       serotonin-containing secretory granules. {ECO:0000250}.
CC   -!- INDUCTION: Up-regulated in activated mast cells (MC) (at protein
CC       level). {ECO:0000269|PubMed:19718454}.
CC   -!- DOMAIN: The N-terminus domain is necessary for its localization to the
CC       ER-Golgi intermediate compartment (ERGIC). {ECO:0000250}.
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       (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: Arg-68 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: Human ortholog was initially reported to have ornithine
CC       decarboxylase or arginine decarboxylase activities, but it was later
CC       found that the mouse ortholog does not possess neither of them.
CC       {ECO:0000305}.
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DR   EMBL; AABR06040008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR06040009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR06040010; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR06040011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; D4A693; -.
DR   SMR; D4A693; -.
DR   STRING; 10116.ENSRNOP00000059346; -.
DR   PaxDb; D4A693; -.
DR   PRIDE; D4A693; -.
DR   RGD; 1564776; Azin2.
DR   eggNOG; KOG0622; Eukaryota.
DR   InParanoid; D4A693; -.
DR   Reactome; R-RNO-351143; Agmatine biosynthesis.
DR   PRO; PR:D4A693; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; ISS:UniProtKB.
DR   GO; GO:1990005; C:granular vesicle; IDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; IDA: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; ISS:UniProtKB.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0006591; P:ornithine metabolic process; ISO:RGD.
DR   GO; GO:0043085; P:positive regulation of catalytic activity; ISS:UniProtKB.
DR   GO; GO:1902269; P:positive regulation of polyamine transmembrane transport; ISS: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; Reference proteome; Transport; Ubl conjugation.
FT   CHAIN           1..457
FT                   /note="Antizyme inhibitor 2"
FT                   /id="PRO_0000430358"
FT   REGION          115..138
FT                   /note="Necessary for polyamine uptake stimulation"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   457 AA;  49420 MW;  B39AEF9E437F7830 CRC64;
     MAGYLSESDF VMVEEGFSTR DLLEELTLGA SQATTGKVAA FFVADAVVRK HFCFLKYLPR
     VRPFYAVRCN SSLGVLKVLA ELGLGFSCAS KAEMELVQHI GVPASKIICA NPCKQVAQIK
     YAAKHGVRLL SFDNEVELAK VVKSHPSAKS WGEVLTLDAL GLHHTHRRVG CSLMFQASVI
     ASVAQGYLEL VCQPFHIGSG CPDPQAYAQS IADARLVFQM GAELGHTMNI LDLGGGFPGL
     EGAKVRFEEV TSVIGKNIPF YTPPPCHVPL RTHATKKMTS SDFCCRVHVT AKEKPLFSPF
     LTEQTGAAPK SIVYHLDEGV YGVFNSVLFD NTCPTPALQK KPSADQPLYS SSLWGPAVDG
     CDCVAEGLWL PQLQVGDWLV FDNMGAYTVD TKSLLGGTQA CRVTYAMSRL AWEALQGQLL
     PAEEDQDAEG VCKPLSCGWE ITDSLCVGPV FTPASIM