Reviewed, UniProtKB/Swiss-Prot Q8N6M6 (AMPO_HUMAN)

Names and origin

Protein names

Recommended name:
    Aminopeptidase O
      Short name=AP-O
    EC=3.4.11.-

Gene names

Name:	AOPEP
Synonyms:	C9orf3, ONPEP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	819 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Aminopeptidases catalyze the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates. Able to cleave angiotensin III to generate angiotensin IV, a bioactive peptide of the renin-angiotensin pathway. Not able to cleave angiotensin I and angiotensin II. May play a role in the proteolytic processing of bioactive peptides in tissues such as testis and heart. Ref.1
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Strongly inhibited by ophenanthroline, a metalloprotease inhibitor. Inhibited by arphamenine A, a potent inhibitor of aminopeptidases. Not affected by AEBSF and E-64, which are common inhibitors of serine- and cysteine-proteases, respectively. Ref.1
Subcellular location	Cytoplasm Potential.
Tissue specificity	Predominantly expressed in pancreas, placenta, liver, testis and heart. Expressed at lower level in brain, lung and kidney. Ref.1
Sequence similarities	Belongs to the peptidase M1 family.
Biophysicochemical properties	Kinetic parameters: KM=6 µM for Asn-AMC

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Aminopeptidase Hydrolase Metalloprotease Protease
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	leukotriene biosynthetic process Inferred from electronic annotation. Source: InterPro proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aminopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB metallopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N6M6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8N6M6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     455-553: Missing.

Isoform 3 (identifier: Q8N6M6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     555-565: PSKDKTGHTSD → FPHVGGCSGSF
     566-819: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q8N6M6-4)

The sequence of this isoform differs from the canonical sequence as follows:
     455-553: Missing.
     774-784: AMGVYLYGELM → VGVIFQQMGIL
     785-819: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 819	819	Aminopeptidase O		PRO_0000095091
Sites
	Active site	480	1	By similarity
	Active site	586	1	Proton donor By similarity
	Metal binding	479	1	Zinc; catalytic By similarity
	Metal binding	483	1	Zinc; catalytic By similarity
	Metal binding	502	1	Zinc; catalytic By similarity
Natural variations
	Alternative sequence	455 – 553	99	Missing in isoform 2 and isoform 4.		VSP_013161
	Alternative sequence	555 – 565	11	PSKDKTGHTSD → FPHVGGCSGSF in isoform 3.		VSP_013162
	Alternative sequence	566 – 819	254	Missing in isoform 3.		VSP_013163
	Alternative sequence	774 – 784	11	AMGVYLYGELM → VGVIFQQMGIL in isoform 4.		VSP_013164
	Alternative sequence	785 – 819	35	Missing in isoform 4.		VSP_013165
	Natural variant	179	1	V → A: dbSNP rs16911679.		VAR_021511
	Natural variant	179	1	V → I: dbSNP rs16911679.		VAR_057053
	Natural variant	255	1	R → Q: dbSNP rs16911681.		VAR_057054
	Natural variant	386	1	R → C: dbSNP rs34557833.		VAR_057055

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 9EB4F19295B92674	FASTA	819	93,572
	10 20 30 40 50 60 MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG NRFKKQNSSI 70 80 90 100 110 120 EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA ICSKGEKDTS DKDGNHDNQE 130 140 150 160 170 180 HASGISSSKY CCDTGNHGSE DFLLVLDCCD LSVLKVEEVD VAAVPGLEKF TRSPELTVVS 190 200 210 220 230 240 EEFRNQIVRE LVTLPANRWR EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF 250 260 270 280 290 300 PHAIRIWYKT KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA 310 320 330 340 350 360 AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK METWSSNDLA 370 380 390 400 410 420 TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH RVFAPVCLTG ACQETLLRLI 430 440 450 460 470 480 PPCLSAAHSV LGAHPFSRLD VLIVPANFPS LGMASPHIMF LSQSILTGGN HLCGTRLCHE 490 500 510 520 530 540 IAHAWFGLAI GARDWTEEWL SEGFATHLED VFWATAQQLA PYEAREQQEL RACLRWRRLQ 550 560 570 580 590 600 DEMQCSPEEM QVLRPSKDKT GHTSDSGASV IKHGLNPEKI FMQVHYLKGY FLLRFLAKRL 610 620 630 640 650 660 GDETYFSFLR KFVHTFHGQL ILSQDFLQML LENIPEEKRL ELSVENIYQD WLESSGIPKP 670 680 690 700 710 720 LQRERRAGAE CGLARQVRAE VTKWIGVNRR PRKRKRREKE EVFEKLLPDQ LVLLLEHLLE 730 740 750 760 770 780 QKTLSPRTLQ SLQRTYHLQD QDAEVRHRWC ELIVKHKFTK AYKSVERFLQ EDQAMGVYLY 790 800 810 GELMVSEDAR QQQLARRCFE RTKEQMDRSS AQVVAEMLF
	Isoform 2. Checksum: 12A6A6169C56A627	FASTA	720	82,105
	10 20 30 40 50 60 MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG NRFKKQNSSI 70 80 90 100 110 120 EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA ICSKGEKDTS DKDGNHDNQE 130 140 150 160 170 180 HASGISSSKY CCDTGNHGSE DFLLVLDCCD LSVLKVEEVD VAAVPGLEKF TRSPELTVVS 190 200 210 220 230 240 EEFRNQIVRE LVTLPANRWR EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF 250 260 270 280 290 300 PHAIRIWYKT KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA 310 320 330 340 350 360 AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK METWSSNDLA 370 380 390 400 410 420 TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH RVFAPVCLTG ACQETLLRLI 430 440 450 460 470 480 PPCLSAAHSV LGAHPFSRLD VLIVPANFPS LGMARPSKDK TGHTSDSGAS VIKHGLNPEK 490 500 510 520 530 540 IFMQVHYLKG YFLLRFLAKR LGDETYFSFL RKFVHTFHGQ LILSQDFLQM LLENIPEEKR 550 560 570 580 590 600 LELSVENIYQ DWLESSGIPK PLQRERRAGA ECGLARQVRA EVTKWIGVNR RPRKRKRREK 610 620 630 640 650 660 EEVFEKLLPD QLVLLLEHLL EQKTLSPRTL QSLQRTYHLQ DQDAEVRHRW CELIVKHKFT 670 680 690 700 710 720 KAYKSVERFL QEDQAMGVYL YGELMVSEDA RQQQLARRCF ERTKEQMDRS SAQVVAEMLF
	Isoform 3. Checksum: BD4D00E45C2A467D	FASTA	565	63,275
	10 20 30 40 50 60 MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG NRFKKQNSSI 70 80 90 100 110 120 EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA ICSKGEKDTS DKDGNHDNQE 130 140 150 160 170 180 HASGISSSKY CCDTGNHGSE DFLLVLDCCD LSVLKVEEVD VAAVPGLEKF TRSPELTVVS 190 200 210 220 230 240 EEFRNQIVRE LVTLPANRWR EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF 250 260 270 280 290 300 PHAIRIWYKT KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA 310 320 330 340 350 360 AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK METWSSNDLA 370 380 390 400 410 420 TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH RVFAPVCLTG ACQETLLRLI 430 440 450 460 470 480 PPCLSAAHSV LGAHPFSRLD VLIVPANFPS LGMASPHIMF LSQSILTGGN HLCGTRLCHE 490 500 510 520 530 540 IAHAWFGLAI GARDWTEEWL SEGFATHLED VFWATAQQLA PYEAREQQEL RACLRWRRLQ 550 560 DEMQCSPEEM QVLRFPHVGG CSGSF
	Isoform 4. Checksum: 57667BB61D258FD2	FASTA	685	77,937
	10 20 30 40 50 60 MDIQLDPARD DLPLMANTSH ILVKHYVLDL DVDFESQVIE GTIVLFLEDG NRFKKQNSSI 70 80 90 100 110 120 EEACQSESNK ACKFGMPEPC HIPVTNARTF SSEMEYNDFA ICSKGEKDTS DKDGNHDNQE 130 140 150 160 170 180 HASGISSSKY CCDTGNHGSE DFLLVLDCCD LSVLKVEEVD VAAVPGLEKF TRSPELTVVS 190 200 210 220 230 240 EEFRNQIVRE LVTLPANRWR EQLDYYARCS QAPGCGELLF DTDTWSLQIR KTGAQTATDF 250 260 270 280 290 300 PHAIRIWYKT KPEGRSVTWT SDQSGRPCVY TVGSPINNRA LFPCQEPPVA MSTWQATVRA 310 320 330 340 350 360 AASFVVLMSG ENSAKPTQLW EECSSWYYYV TMPMPASTFT IAVGCWTEMK METWSSNDLA 370 380 390 400 410 420 TERPFSPSEA NFRHVGVCSH MEYPCRFQNA SATTQEIIPH RVFAPVCLTG ACQETLLRLI 430 440 450 460 470 480 PPCLSAAHSV LGAHPFSRLD VLIVPANFPS LGMARPSKDK TGHTSDSGAS VIKHGLNPEK 490 500 510 520 530 540 IFMQVHYLKG YFLLRFLAKR LGDETYFSFL RKFVHTFHGQ LILSQDFLQM LLENIPEEKR 550 560 570 580 590 600 LELSVENIYQ DWLESSGIPK PLQRERRAGA ECGLARQVRA EVTKWIGVNR RPRKRKRREK 610 620 630 640 650 660 EEVFEKLLPD QLVLLLEHLL EQKTLSPRTL QSLQRTYHLQ DQDAEVRHRW CELIVKHKFT 670 680 KAYKSVERFL QEDQVGVIFQ QMGIL

References

[1]	"Identification of human aminopeptidase O, a novel metalloprotease with structural similarity to aminopeptidase B and leukotriene A4 hydrolase." Diaz-Perales A., Quesada V., Sanchez L.M., Ugalde A.P., Suarez M.F., Fueyo A., Lopez-Otin C. J. Biol. Chem. 280:14310-14317(2005) [PubMed: 15687497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME ACTIVITY, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"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(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 178-819 (ISOFORM 4). Tissue: Teratocarcinoma and Testis.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-819 (ISOFORM 1). Tissue: Lung and Muscle.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ560639 mRNA. Translation: CAD90259.1. AK027581 mRNA. Translation: BAB55210.1. Different initiation. AK057450 mRNA. Translation: BAB71491.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13040.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41125.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41325.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13039.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41126.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41326.1. AL157936, AL353768 Genomic DNA. Translation: CAI13037.1. AL353768, AL157936 Genomic DNA. Translation: CAI41124.1. AL157936, AL353768, AL354893 Genomic DNA. Translation: CAI13041.1. AL353768, AL157936, AL354893 Genomic DNA. Translation: CAI41127.1. AL354893, AL157936, AL353768 Genomic DNA. Translation: CAI41327.1. AL157936 Genomic DNA. Translation: CAI13038.1. BC020194 mRNA. Translation: AAH20194.1. Different initiation. BC029616 mRNA. Translation: AAH29616.1.
IPI	IPI00163493. IPI00171144. IPI00187032. IPI00554492.
RefSeq	NP_116212.3.
UniGene	Hs.434253
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8N6M6.
Protein family/group databases
MEROPS	M01.028.
PTM databases
PhosphoSite	Q8N6M6.
Proteomic databases
PRIDE	Q8N6M6.
Genome annotation databases
Ensembl	ENST00000375315; ENSP00000364464; ENSG00000148120; Homo sapiens. [Genome view]
GeneID	84909.
KEGG	hsa:84909.
UCSC	uc004aux.1. human. uc004auy.1. human. uc004auz.1. human. uc004ava.1. human.
Organism-specific databases
CTD	84909.
GeneCards	GC09P096528.
H-InvDB	HIX0008192.
HGNC	HGNC:1361. C9orf3.
HPA	HPA004633.
PharmGKB	PA25978.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8N6M6.
OMA	FESQVIE
Gene expression databases
ArrayExpress	Q8N6M6.
Bgee	Q8N6M6.
CleanEx	HS_C9orf3.
Genevestigator	Q8N6M6.
GermOnline	ENSG00000148120. Homo sapiens.
Family and domain databases
InterPro	IPR016024. ARM-type_fold. IPR001930. Peptidase_M1. IPR015211. Peptidase_M1_C. IPR014782. Peptidase_M1_N. [Graphical view]
PANTHER	PTHR11533. Peptidase_M1. 1 hit.
Pfam	PF09127. Leuk-A4-hydro_C. 1 hit. PF01433. Peptidase_M1. 1 hit. [Graphical view]
PROSITE	PS00142. ZINC_PROTEASE. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	75288.

Entry information

Entry name

AMPO_HUMAN

Accession

Primary (citable) accession number: Q8N6M6
Secondary accession number(s): Q5T9B1 , Q5T9B3, Q5T9B4, Q8WUL6, Q96M23, Q96SS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	November 24, 2009
This is version 63 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.