P28838 (AMPL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytosol aminopeptidase
EC=3.4.11.1

Alternative name(s):
Leucine aminopeptidase 3
Short name=LAP-3
Leucyl aminopeptidase
Peptidase S
Proline aminopeptidase
EC=3.4.11.5
Prolyl aminopeptidase

Gene names

Name:	LAP3
Synonyms:	LAPEP, PEPS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.
Catalytic activity	Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low. Release of N-terminal proline from a peptide.
Cofactor	Binds 2 zinc ions per subunit. One zinc ion is tightly bound and essential for enzyme activity, while the second metal coordination site can be occupied by zinc, magnesium or manganese to give enzymes of different activities By similarity.
Subunit structure	Homohexamer.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase M17 family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative initiation
Ligand	Magnesium Manganese Metal-binding Zinc
Molecular function	Aminopeptidase Hydrolase Protease
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	proteolysis Non-traceable author statement Ref.5. Source: UniProtKB
Cellular component	nucleus Inferred from direct assay. Source: HPA
Molecular function	aminopeptidase activity Non-traceable author statement Ref.5. Source: UniProtKB magnesium ion binding Non-traceable author statement. Source: UniProtKB manganese ion binding Non-traceable author statement. Source: UniProtKB metalloexopeptidase activity Non-traceable author statement Ref.5. Source: UniProtKB zinc ion binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: P28838-1)

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: P28838-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Note: Met-1 is removed.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 519	519	Cytosol aminopeptidase		PRO_0000165825
Sites
	Active site	294	1	By similarity
	Active site	368	1	By similarity
	Metal binding	282	1	Zinc 2 By similarity
	Metal binding	287	1	Zinc 1 By similarity
	Metal binding	287	1	Zinc 2 By similarity
	Metal binding	305	1	Zinc 2 By similarity
	Metal binding	364	1	Zinc 1 By similarity
	Metal binding	366	1	Zinc 1 By similarity
	Metal binding	366	1	Zinc 2 By similarity
Amino acid modifications
	Modified residue	33	1	N-acetylthreonine By similarity
	Modified residue	221	1	N6-acetyllysine Ref.6
Natural variations
	Alternative sequence	1 – 31	31	Missing in isoform 2.		VSP_022631
Experimental info
	Sequence conflict	20	1	R → V in AAD17527. Ref.1
	Sequence conflict	22	1	F → S in AAD17527. Ref.1
	Sequence conflict	29	1	T → A in CAG33409. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: D960F8F5B9024585	FASTA	519	56,166
	10 20 30 40 50 60 MFLLPLPAAG RVVVRRLAVR RFGSRSLSTA DMTKGLVLGI YSKEKEDDVP QFTSAGENFD 70 80 90 100 110 120 KLLAGKLRET LNISGPPLKA GKTRTFYGLH QDFPSVVLVG LGKKAAGIDE QENWHEGKEN 130 140 150 160 170 180 IRAAVAAGCR QIQDLELSSV EVDPCGDAQA AAEGAVLGLY EYDDLKQKKK MAVSAKLYGS 190 200 210 220 230 240 GDQEAWQKGV LFASGQNLAR QLMETPANEM TPTRFAEIIE KNLKSASSKT EVHIRPKSWI 250 260 270 280 290 300 EEQAMGSFLS VAKGSDEPPV FLEIHYKGSP NANEPPLVFV GKGITFDSGG ISIKASANMD 310 320 330 340 350 360 LMRADMGGAA TICSAIVSAA KLNLPINIIG LAPLCENMPS GKANKPGDVV RAKNGKTIQV 370 380 390 400 410 420 DNTDAEGRLI LADALCYAHT FNPKVILNAA TLTGAMDVAL GSGATGVFTN SSWLWNKLFE 430 440 450 460 470 480 ASIETGDRVW RMPLFEHYTR QVVDCQLADV NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL 490 500 510 DIAGVMTNKD EVPYLRKGMT GRPTRTLIEF LLRFSQDNA
	Isoform 2 [UniParc]. Checksum: 0CADB3E07FD10B8B	FASTA	488	52,771
	10 20 30 40 50 60 MTKGLVLGIY SKEKEDDVPQ FTSAGENFDK LLAGKLRETL NISGPPLKAG KTRTFYGLHQ 70 80 90 100 110 120 DFPSVVLVGL GKKAAGIDEQ ENWHEGKENI RAAVAAGCRQ IQDLELSSVE VDPCGDAQAA 130 140 150 160 170 180 AEGAVLGLYE YDDLKQKKKM AVSAKLYGSG DQEAWQKGVL FASGQNLARQ LMETPANEMT 190 200 210 220 230 240 PTRFAEIIEK NLKSASSKTE VHIRPKSWIE EQAMGSFLSV AKGSDEPPVF LEIHYKGSPN 250 260 270 280 290 300 ANEPPLVFVG KGITFDSGGI SIKASANMDL MRADMGGAAT ICSAIVSAAK LNLPINIIGL 310 320 330 340 350 360 APLCENMPSG KANKPGDVVR AKNGKTIQVD NTDAEGRLIL ADALCYAHTF NPKVILNAAT 370 380 390 400 410 420 LTGAMDVALG SGATGVFTNS SWLWNKLFEA SIETGDRVWR MPLFEHYTRQ VVDCQLADVN 430 440 450 460 470 480 NIGKYRSAGA CTAAAFLKEF VTHPKWAHLD IAGVMTNKDE VPYLRKGMTG RPTRTLIEFL LRFSQDNA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Mao M., Liu T., Zhang J., Wu J., Zhang Q., Fu G., Shen Y., Zhou J., Yu Y., Wang Z., Chen S., Chen Z. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"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 2). Tissue: Embryo.
[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 1). Tissue: Eye and Lung.
[5]	"Structural and immunological evidence for the identity of prolyl aminopeptidase with leucyl aminopeptidase." Matsushima M., Takahashi T., Ichinose M., Miki K., Kurokawa K., Takahashi K. Biochem. Biophys. Res. Commun. 178:1459-1464(1991) [PubMed: 1908238] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-54. Tissue: Liver.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-221, MASS SPECTROMETRY.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF061738 mRNA. Translation: AAD17527.1. CR457128 mRNA. Translation: CAG33409.1. AK022055 mRNA. Translation: BAG51065.1. AK298613 mRNA. Translation: BAG60795.1. BC065564 mRNA. Translation: AAH65564.1. BC006199 mRNA. Translation: AAH06199.3.
IPI	IPI00419237. IPI00789806.
PIR	PT0431.
RefSeq	NP_056991.2. NM_015907.2.
UniGene	Hs.570791.
3D structure databases
ProteinModelPortal	P28838.
SMR	P28838. Positions 33-516.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28838. 3 interactions.
STRING	P28838.
Protein family/group databases
MEROPS	M17.001.
PTM databases
PhosphoSite	P28838.
Polymorphism databases
DMDM	124028615.
2D gel databases
REPRODUCTION-2DPAGE	IPI00789806. P28838.
UCD-2DPAGE	P28838.
Proteomic databases
PRIDE	P28838.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000226299; ENSP00000226299; ENSG00000002549.
GeneID	51056.
KEGG	hsa:51056.
UCSC	uc003gph.1. human.
Organism-specific databases
CTD	51056.
GeneCards	GC04P017578.
H-InvDB	HIX0004121.
HGNC	HGNC:18449. LAP3.
HPA	HPA029606. HPA029607.
MIM	170250. gene.
neXtProt	NX_P28838.
PharmGKB	PA38537.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18219.
GeneTree	ENSGT00530000063255.
HOGENOM	HBG742580.
HOVERGEN	HBG003320.
InParanoid	P28838.
OMA	NSGLMST.
OrthoDB	EOG4P2Q21.
PhylomeDB	P28838.
Gene expression databases
ArrayExpress	P28838.
Bgee	P28838.
CleanEx	HS_LAP3.
Genevestigator	P28838.
GermOnline	ENSG00000002549. Homo sapiens.
Family and domain databases
InterPro	IPR011356. Peptidase_M17. IPR000819. Peptidase_M17_C. IPR023042. Peptidase_M17_cytosol_amino. IPR008283. Peptidase_M17_N. [Graphical view]
KO	K11142.
Pfam	PF00883. Peptidase_M17. 1 hit. PF02789. Peptidase_M17_N. 1 hit. [Graphical view]
PRINTS	PR00481. LAMNOPPTDASE.
PROSITE	PS00631. CYTOSOL_AP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	53624.
SOURCE	Search...

Entry information

Entry name

AMPL_HUMAN

Accession

Primary (citable) accession number: P28838
Secondary accession number(s): B3KMQ3 , Q6IAM6, Q6P0L6, Q9UQE3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.