AMPO_HUMAN
ID AMPO_HUMAN Reviewed; 819 AA.
AC Q8N6M6; Q5T9B1; Q5T9B3; Q5T9B4; Q8WUL6; Q96M23; Q96SS1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Aminopeptidase O {ECO:0000305};
DE Short=AP-O;
DE EC=3.4.11.- {ECO:0000250|UniProtKB:P15144};
GN Name=AOPEP {ECO:0000312|HGNC:HGNC:1361}; Synonyms=C9orf3, ONPEP;
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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 178-819 (ISOFORM 4).
RC TISSUE=Teratocarcinoma, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 219-819 (ISOFORM 1).
RC TISSUE=Lung, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP RETRACTED PAPER.
RC TISSUE=Brain;
RX PubMed=15687497; DOI=10.1074/jbc.m413222200;
RA Diaz-Perales A., Quesada V., Sanchez L.M., Ugalde A.P., Suarez M.F.,
RA Fueyo A., Lopez-Otin C.;
RT "Identification of human aminopeptidase O, a novel metalloprotease with
RT structural similarity to aminopeptidase B and leukotriene A4 hydrolase.";
RL J. Biol. Chem. 280:14310-14317(2005).
RN [5]
RP RETRACTION NOTICE OF PUBMED:15687497.
RX PubMed=30808004; DOI=10.1074/jbc.w118.007327;
RA Diaz-Perales A., Quesada V., Sanchez L.M., Ugalde A.P., Suarez M.F.,
RA Fueyo A., Lopez-Otin C.;
RL J. Biol. Chem. 294:1433-1433(2019).
RN [6]
RP VARIANTS DYT31 255-ARG--PHE-819 DEL; 259-TRP--PHE-819 DEL AND
RP 493-ARG--PHE-819 DEL, AND INVOLVEMENT IN DYT31.
RX PubMed=34596301; DOI=10.1002/mds.28804;
RA Zech M., Kumar K.R., Reining S., Reunert J., Tchan M., Riley L.G.,
RA Drew A.P., Adam R.J., Berutti R., Biskup S., Derive N., Bakhtiari S.,
RA Jin S.C., Kruer M.C., Bardakjian T., Gonzalez-Alegre P.,
RA Keller Sarmiento I.J., Mencacci N.E., Lubbe S.J., Kurian M.A., Clot F.,
RA Meneret A., de Sainte Agathe J.M., Fung V.S.C., Vidailhet M., Baumann M.,
RA Marquardt T., Winkelmann J., Boesch S.;
RT "Biallelic AOPEP loss-of-function variants cause progressive dystonia with
RT prominent limb involvement.";
RL Mov. Disord. 37:137-147(2022).
CC -!- FUNCTION: Aminopeptidase which catalyzes the hydrolysis of amino acid
CC residues from the N-terminus of peptide or protein substrates.
CC {ECO:0000250|UniProtKB:P15144}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P15144};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15144};
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q8BXQ6}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q8BXQ6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8N6M6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N6M6-2; Sequence=VSP_013161;
CC Name=3;
CC IsoId=Q8N6M6-3; Sequence=VSP_013162, VSP_013163;
CC Name=4;
CC IsoId=Q8N6M6-4; Sequence=VSP_013161, VSP_013164, VSP_013165;
CC -!- DISEASE: Dystonia 31 (DYT31) [MIM:619565]: A form of dystonia, a
CC disorder defined by the presence of sustained involuntary muscle
CC contraction, often leading to abnormal postures. DYT31 is an autosomal
CC recessive, progressive form with onset from childhood to young
CC adulthood. Involuntary muscle twisting movements and postural
CC abnormalities affect the upper and lower limbs, neck, face, and trunk.
CC Some patients may have orofacial dyskinesia resulting in articulation
CC and swallowing difficulties. {ECO:0000269|PubMed:34596301}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- CAUTION: A paper describing the function, enzyme activity and
CC expression patterns of this protein has been retracted due to concerns
CC of image manipulation. {ECO:0000305|PubMed:15687497,
CC ECO:0000305|PubMed:30808004}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20194.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55210.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ560639; CAD90259.1; -; mRNA.
DR EMBL; AK027581; BAB55210.1; ALT_INIT; mRNA.
DR EMBL; AK057450; BAB71491.1; -; mRNA.
DR EMBL; AL157936; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354893; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020194; AAH20194.1; ALT_INIT; mRNA.
DR EMBL; BC029616; AAH29616.1; -; mRNA.
DR CCDS; CCDS55327.1; -. [Q8N6M6-3]
DR CCDS; CCDS55328.1; -. [Q8N6M6-1]
DR CCDS; CCDS6713.1; -. [Q8N6M6-2]
DR RefSeq; NP_001180258.1; NM_001193329.1. [Q8N6M6-1]
DR RefSeq; NP_001180260.1; NM_001193331.2. [Q8N6M6-3]
DR RefSeq; NP_116212.3; NM_032823.5. [Q8N6M6-2]
DR RefSeq; XP_006717369.1; XM_006717306.1. [Q8N6M6-1]
DR RefSeq; XP_016870719.1; XM_017015230.1. [Q8N6M6-1]
DR RefSeq; XP_016870720.1; XM_017015231.1. [Q8N6M6-2]
DR AlphaFoldDB; Q8N6M6; -.
DR SMR; Q8N6M6; -.
DR BioGRID; 124346; 73.
DR IntAct; Q8N6M6; 16.
DR MINT; Q8N6M6; -.
DR STRING; 9606.ENSP00000364464; -.
DR ChEMBL; CHEMBL3831223; -.
DR MEROPS; M01.028; -.
DR iPTMnet; Q8N6M6; -.
DR PhosphoSitePlus; Q8N6M6; -.
DR BioMuta; C9orf3; -.
DR DMDM; 61211648; -.
DR EPD; Q8N6M6; -.
DR MassIVE; Q8N6M6; -.
DR PaxDb; Q8N6M6; -.
DR PeptideAtlas; Q8N6M6; -.
DR PRIDE; Q8N6M6; -.
DR ProteomicsDB; 72195; -. [Q8N6M6-1]
DR ProteomicsDB; 72196; -. [Q8N6M6-2]
DR ProteomicsDB; 72197; -. [Q8N6M6-3]
DR ProteomicsDB; 72198; -. [Q8N6M6-4]
DR Antibodypedia; 985; 87 antibodies from 19 providers.
DR DNASU; 84909; -.
DR Ensembl; ENST00000277198.6; ENSP00000277198.2; ENSG00000148120.18. [Q8N6M6-3]
DR Ensembl; ENST00000297979.9; ENSP00000297979.5; ENSG00000148120.18. [Q8N6M6-2]
DR Ensembl; ENST00000375315.8; ENSP00000364464.2; ENSG00000148120.18. [Q8N6M6-1]
DR GeneID; 84909; -.
DR KEGG; hsa:84909; -.
DR MANE-Select; ENST00000375315.8; ENSP00000364464.2; NM_001193329.3; NP_001180258.1.
DR UCSC; uc004aux.3; human. [Q8N6M6-1]
DR CTD; 84909; -.
DR DisGeNET; 84909; -.
DR GeneCards; AOPEP; -.
DR HGNC; HGNC:1361; AOPEP.
DR HPA; ENSG00000148120; Low tissue specificity.
DR MalaCards; AOPEP; -.
DR MIM; 619565; phenotype.
DR MIM; 619600; gene.
DR neXtProt; NX_Q8N6M6; -.
DR OpenTargets; ENSG00000148120; -.
DR PharmGKB; PA25978; -.
DR VEuPathDB; HostDB:ENSG00000148120; -.
DR eggNOG; KOG1047; Eukaryota.
DR GeneTree; ENSGT00940000155211; -.
DR InParanoid; Q8N6M6; -.
DR OMA; YERSAVW; -.
DR OrthoDB; 775595at2759; -.
DR PhylomeDB; Q8N6M6; -.
DR TreeFam; TF332004; -.
DR PathwayCommons; Q8N6M6; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SABIO-RK; Q8N6M6; -.
DR SignaLink; Q8N6M6; -.
DR BioGRID-ORCS; 84909; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; C9orf3; human.
DR GenomeRNAi; 84909; -.
DR Pharos; Q8N6M6; Tbio.
DR PRO; PR:Q8N6M6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8N6M6; protein.
DR Bgee; ENSG00000148120; Expressed in apex of heart and 149 other tissues.
DR ExpressionAtlas; Q8N6M6; baseline and differential.
DR Genevisible; Q8N6M6; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 1.25.40.320; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR033577; AOPep.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR038502; M1_LTA-4_hydro/amino_C_sf.
DR InterPro; IPR015211; Peptidase_M1_C.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR PANTHER; PTHR46627; PTHR46627; 1.
DR Pfam; PF09127; Leuk-A4-hydro_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR SMART; SM01263; Leuk-A4-hydro_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF63737; SSF63737; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aminopeptidase; Cytoplasm; Disease variant; Dystonia;
KW Hydrolase; Metal-binding; Metalloprotease; Nucleus; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..819
FT /note="Aminopeptidase O"
FT /id="PRO_0000095091"
FT MOTIF 689..699
FT /note="Nucleolar localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q8BXQ6"
FT ACT_SITE 480
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P15144,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 483
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 502
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT SITE 586
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT VAR_SEQ 455..553
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013161"
FT VAR_SEQ 555..565
FT /note="PSKDKTGHTSD -> FPHVGGCSGSFS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013162"
FT VAR_SEQ 566..819
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013163"
FT VAR_SEQ 774..784
FT /note="AMGVYLYGELM -> VGVIFQQMGIL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013164"
FT VAR_SEQ 785..819
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013165"
FT VARIANT 179
FT /note="V -> A (in dbSNP:rs16911679)"
FT /id="VAR_021511"
FT VARIANT 179
FT /note="V -> I (in dbSNP:rs16911679)"
FT /id="VAR_057053"
FT VARIANT 255..819
FT /note="Missing (in DYT31)"
FT /evidence="ECO:0000269|PubMed:34596301"
FT /id="VAR_086438"
FT VARIANT 255
FT /note="R -> Q (in dbSNP:rs16911681)"
FT /id="VAR_057054"
FT VARIANT 259..819
FT /note="Missing (in DYT31)"
FT /evidence="ECO:0000269|PubMed:34596301"
FT /id="VAR_086439"
FT VARIANT 386
FT /note="R -> C (in dbSNP:rs34557833)"
FT /id="VAR_057055"
FT VARIANT 493..819
FT /note="Missing (in DYT31)"
FT /evidence="ECO:0000269|PubMed:34596301"
FT /id="VAR_086440"
SQ SEQUENCE 819 AA; 93572 MW; 9EB4F19295B92674 CRC64;
MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG NRFKKQNSSI
EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA ICSKGEKDTS DKDGNHDNQE
HASGISSSKY CCDTGNHGSE DFLLVLDCCD LSVLKVEEVD VAAVPGLEKF TRSPELTVVS
EEFRNQIVRE LVTLPANRWR EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF
PHAIRIWYKT KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA
AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK METWSSNDLA
TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH RVFAPVCLTG ACQETLLRLI
PPCLSAAHSV LGAHPFSRLD VLIVPANFPS LGMASPHIMF LSQSILTGGN HLCGTRLCHE
IAHAWFGLAI GARDWTEEWL SEGFATHLED VFWATAQQLA PYEAREQQEL RACLRWRRLQ
DEMQCSPEEM QVLRPSKDKT GHTSDSGASV IKHGLNPEKI FMQVHYLKGY FLLRFLAKRL
GDETYFSFLR KFVHTFHGQL ILSQDFLQML LENIPEEKRL ELSVENIYQD WLESSGIPKP
LQRERRAGAE CGLARQVRAE VTKWIGVNRR PRKRKRREKE EVFEKLLPDQ LVLLLEHLLE
QKTLSPRTLQ SLQRTYHLQD QDAEVRHRWC ELIVKHKFTK AYKSVERFLQ EDQAMGVYLY
GELMVSEDAR QQQLARRCFE RTKEQMDRSS AQVVAEMLF
