OAZ1_HUMAN
ID OAZ1_HUMAN Reviewed; 228 AA.
AC P54368; O43382; Q14989; Q92595; Q9UPL9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Ornithine decarboxylase antizyme 1;
DE Short=AZ1;
DE Short=ODC-Az;
GN Name=OAZ1; Synonyms=OAZ;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=7811704; DOI=10.1016/0167-4838(94)90199-6;
RA Tewari D.S., Qian Y., Thornton R.D., Pieringer J., Taub R., Mochan E.,
RA Tewari M.;
RT "Molecular cloning and sequencing of a human cDNA encoding ornithine
RT decarboxylase antizyme.";
RL Biochim. Biophys. Acta 1209:293-295(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Hideyama T., Nisiyama M., Hayashi S.;
RT "Molecular cloning of human antizyme from brain library.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphoma;
RX PubMed=9132164;
RA Yang D., Takii T., Hayashi H., Itoh S., Hayashi M., Onozaki K.;
RT "Molecular cloning of human antizyme cDNA.";
RL Biochem. Mol. Biol. Int. 38:957-964(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9426243; DOI=10.1016/s0378-1119(97)00504-0;
RA Hayashi T., Matsufuji S., Hayashi S.;
RT "Characterization of the human antizyme gene.";
RL Gene 203:131-139(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-32; ASP-44; PHE-50;
RP PHE-53 AND VAL-147.
RG NIEHS SNPs program;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP IDENTIFICATION IN A COMPLEX WITH PSMB4 AND SMAD1, AND FUNCTION.
RX PubMed=12097147; DOI=10.1186/1471-2121-3-15;
RA Lin Y., Martin J., Gruendler C., Farley J., Meng X., Li B.-Y.,
RA Lechleider R., Huff C., Kim R.H., Grasser W.A., Paralkar V., Wang T.;
RT "A novel link between the proteasome pathway and the signal transduction
RT pathway of the bone morphogenetic proteins (BMPs).";
RL BMC Cell Biol. 3:15-15(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH AZIN2.
RX PubMed=17900240; DOI=10.1042/bj20071004;
RA Kanerva K., Makitie L.T., Pelander A., Heiskala M., Andersson L.C.;
RT "Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor
RT but not an arginine decarboxylase.";
RL Biochem. J. 409:187-192(2008).
RN [9]
RP INTERACTION WITH FAM171A1.
RX PubMed=30312582; DOI=10.1016/j.ajpath.2018.09.006;
RA Rasila T., Saavalainen O., Attalla H., Lankila P., Haglund C., Hoelttae E.,
RA Andersson L.C.;
RT "Astroprincin (FAM171A1, C10orf38): A Regulator of Human Cell Shape and
RT Invasive Growth.";
RL Am. J. Pathol. 189:177-189(2019).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) OF 95-219 IN COMPLEXES WITH ODC1 AND
RP AZIN1.
RX PubMed=26305948; DOI=10.1073/pnas.1508187112;
RA Wu H.Y., Chen S.F., Hsieh J.Y., Chou F., Wang Y.H., Lin W.T., Lee P.Y.,
RA Yu Y.J., Lin L.Y., Lin T.S., Lin C.L., Liu G.Y., Tzeng S.R., Hung H.C.,
RA Chan N.L.;
RT "Structural basis of antizyme-mediated regulation of polyamine
RT homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11229-11234(2015).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 69-228 IN COMPLEX WITH ODC1.
RX PubMed=26443277; DOI=10.1038/srep14738;
RA Wu D., Kaan H.Y., Zheng X., Tang X., He Y., Vanessa Tan Q., Zhang N.,
RA Song H.;
RT "Structural basis of ornithine decarboxylase inactivation and accelerated
RT degradation by polyamine sensor antizyme1.";
RL Sci. Rep. 5:14738-14738(2015).
CC -!- FUNCTION: Ornithine decarboxylase (ODC) antizyme protein that
CC negatively regulates ODC activity and intracellular polyamine
CC biosynthesis and uptake in response to increased intracellular
CC polyamine levels. Binds to ODC monomers, inhibiting the assembly of the
CC functional ODC homodimer, and targets the monomers for ubiquitin-
CC independent proteolytic destruction by the 26S proteasome
CC (PubMed:17900240, PubMed:26305948, PubMed:26443277). Triggers ODC
CC degradation by inducing the exposure of a cryptic proteasome-
CC interacting surface of ODC (PubMed:26305948). Stabilizes AZIN2 by
CC interfering with its ubiquitination (PubMed:17900240). Also inhibits
CC cellular uptake of polyamines by inactivating the polyamine uptake
CC transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the
CC CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZIN2
CC from ER-Golgi intermediate compartment (ERGIC) to the cytosol
CC (PubMed:12097147). {ECO:0000269|PubMed:12097147,
CC ECO:0000269|PubMed:17900240, ECO:0000269|PubMed:26305948,
CC ECO:0000269|PubMed:26443277}.
CC -!- SUBUNIT: Interacts with ODC1 and thereby sterically blocks ODC
CC homodimerization (PubMed:26305948, PubMed:26443277). Forms a ternary
CC complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S
CC proteasome (PubMed:12097147). Interacts with AZIN2; this interaction
CC disrupts the interaction between the antizyme and ODC1
CC (PubMed:17900240). Interacts with FAM171A1 (PubMed:30312582).
CC {ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:17900240,
CC ECO:0000269|PubMed:26305948, ECO:0000269|PubMed:26443277,
CC ECO:0000269|PubMed:30312582}.
CC -!- INTERACTION:
CC P54368; P30556: AGTR1; NbExp=2; IntAct=EBI-948441, EBI-6623016;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=1;
CC Comment=A ribosomal frameshift occurs between the codons for Ser-68
CC and Asp-69. An autoregulatory mechanism enables modulation of
CC frameshifting according to the cellular concentration of polyamines.
CC {ECO:0000250|UniProtKB:P54370};
CC Name=1;
CC IsoId=P54368-1; Sequence=Displayed;
CC -!- INDUCTION: Induced by a ribosomal frameshifting mechanism in response
CC to increased levels of intracellular polyamines.
CC {ECO:0000250|UniProtKB:P54370}.
CC -!- SIMILARITY: Belongs to the ODC antizyme family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA11374.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/oaz1/";
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DR EMBL; U09202; AAA82155.1; ALT_SEQ; mRNA.
DR EMBL; U09202; AAA82154.1; ALT_SEQ; mRNA.
DR EMBL; D87914; BAA13497.1; -; mRNA.
DR EMBL; D78361; BAA11373.1; -; mRNA.
DR EMBL; D78361; BAA11374.1; ALT_INIT; mRNA.
DR EMBL; D89870; BAA23101.1; -; Genomic_DNA.
DR EMBL; AY865622; AAW56074.1; -; Genomic_DNA.
DR EMBL; AC004152; AAC02802.1; -; Genomic_DNA.
DR EMBL; AC004152; AAC02803.1; -; Genomic_DNA.
DR CCDS; CCDS58639.1; -. [P54368-1]
DR PIR; I38591; I38591.
DR RefSeq; NP_004143.1; NM_004152.3. [P54368-1]
DR PDB; 4ZGY; X-ray; 2.63 A; B=95-219.
DR PDB; 4ZGZ; X-ray; 5.81 A; B/D=110-228.
DR PDB; 5BWA; X-ray; 3.20 A; B=69-228.
DR PDBsum; 4ZGY; -.
DR PDBsum; 4ZGZ; -.
DR PDBsum; 5BWA; -.
DR AlphaFoldDB; P54368; -.
DR SMR; P54368; -.
DR BioGRID; 111000; 36.
DR CORUM; P54368; -.
DR IntAct; P54368; 22.
DR MINT; P54368; -.
DR STRING; 9606.ENSP00000473381; -.
DR ChEMBL; CHEMBL4523241; -.
DR DrugBank; DB00129; Ornithine.
DR iPTMnet; P54368; -.
DR PhosphoSitePlus; P54368; -.
DR BioMuta; OAZ1; -.
DR DMDM; 1709427; -.
DR MassIVE; P54368; -.
DR PaxDb; P54368; -.
DR PeptideAtlas; P54368; -.
DR PRIDE; P54368; -.
DR ProteomicsDB; 56685; -. [P54368-1]
DR Antibodypedia; 1951; 118 antibodies from 25 providers.
DR DNASU; 4946; -.
DR Ensembl; ENST00000602676.6; ENSP00000473381.1; ENSG00000104904.12. [P54368-1]
DR GeneID; 4946; -.
DR KEGG; hsa:4946; -.
DR UCSC; uc002lvk.4; human. [P54368-1]
DR CTD; 4946; -.
DR DisGeNET; 4946; -.
DR GeneCards; OAZ1; -.
DR HGNC; HGNC:8095; OAZ1.
DR HPA; ENSG00000104904; Low tissue specificity.
DR MIM; 601579; gene.
DR neXtProt; NX_P54368; -.
DR OpenTargets; ENSG00000104904; -.
DR PharmGKB; PA31884; -.
DR VEuPathDB; HostDB:ENSG00000104904; -.
DR eggNOG; KOG4387; Eukaryota.
DR GeneTree; ENSGT00940000159808; -.
DR InParanoid; P54368; -.
DR OMA; TRIFNVQ; -.
DR OrthoDB; 1403675at2759; -.
DR PhylomeDB; P54368; -.
DR TreeFam; TF314741; -.
DR PathwayCommons; P54368; -.
DR Reactome; R-HSA-350562; Regulation of ornithine decarboxylase (ODC).
DR SignaLink; P54368; -.
DR BioGRID-ORCS; 4946; 46 hits in 1078 CRISPR screens.
DR ChiTaRS; OAZ1; human.
DR GeneWiki; OAZ1; -.
DR GenomeRNAi; 4946; -.
DR Pharos; P54368; Tbio.
DR PRO; PR:P54368; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P54368; protein.
DR Bgee; ENSG00000104904; Expressed in pons and 211 other tissues.
DR ExpressionAtlas; P54368; baseline and differential.
DR Genevisible; P54368; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0008073; F:ornithine decarboxylase inhibitor activity; IDA:UniProtKB.
DR GO; GO:1902268; P:negative regulation of polyamine transmembrane transport; IEA:Ensembl.
DR GO; GO:0006596; P:polyamine biosynthetic process; TAS:ProtInc.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.630.60; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR029914; ODC-AZ_1.
DR InterPro; IPR002993; ODC_AZ.
DR InterPro; IPR038581; ODC_AZ_sf.
DR PANTHER; PTHR10279; PTHR10279; 1.
DR PANTHER; PTHR10279:SF8; PTHR10279:SF8; 1.
DR Pfam; PF02100; ODC_AZ; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS01337; ODC_AZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Polyamine biosynthesis; Reference proteome;
KW Ribosomal frameshifting; Transport.
FT CHAIN 1..228
FT /note="Ornithine decarboxylase antizyme 1"
FT /id="PRO_0000220849"
FT REGION 17..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 32
FT /note="R -> L (in dbSNP:rs4667)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022215"
FT VARIANT 44
FT /note="G -> D (in dbSNP:rs28359762)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022216"
FT VARIANT 50
FT /note="S -> F (in dbSNP:rs28384673)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022217"
FT VARIANT 53
FT /note="S -> F (in dbSNP:rs2230749)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022218"
FT VARIANT 147
FT /note="A -> V (in dbSNP:rs28384677)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022219"
FT CONFLICT 69
FT /note="D -> C (in Ref. 2; BAA13497)"
FT /evidence="ECO:0000305"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 111..120
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 128..135
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:5BWA"
FT HELIX 152..165
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 170..179
FT /evidence="ECO:0007829|PDB:4ZGY"
FT HELIX 183..193
FT /evidence="ECO:0007829|PDB:4ZGY"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:5BWA"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:4ZGY"
SQ SEQUENCE 228 AA; 25406 MW; DA43B74DF030BD9D CRC64;
MVKSSLQRIL NSHCFAREKE GDKPSATIHA SRTMPLLSLH SRGGSSSESS RVSLHCCSNP
GPGPRWCSDA PHPPLKIPGG RGNSQRDHNL SANLFYSDDR LNVTEELTSN DKTRILNVQS
RLTDAKRINW RTVLSGGSLY IEIPGGALPE GSKDSFAVLL EFAEEQLRAD HVFICFHKNR
EDRAALLRTF SFLGFEIVRP GHPLVPKRPD ACFMAYTFER ESSGEEEE
