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Protein

Cytosol aminopeptidase

Gene

LAP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Presumably involved in the processing and regular turnover of intracellular proteins. Catalyzes the removal of unsubstituted N-terminal amino acids from various peptides.

Catalytic activityi

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.

Cofactori

Note: 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi282 – 2821Zinc 2By similarity
Metal bindingi287 – 2871Zinc 1By similarity
Metal bindingi287 – 2871Zinc 2By similarity
Active sitei294 – 2941By similarity
Metal bindingi305 – 3051Zinc 2By similarity
Metal bindingi364 – 3641Zinc 1By similarity
Metal bindingi366 – 3661Zinc 1By similarity
Metal bindingi366 – 3661Zinc 2By similarity
Active sitei368 – 3681By similarity

GO - Molecular functioni

  1. aminopeptidase activity Source: UniProtKB
  2. manganese ion binding Source: InterPro
  3. metalloexopeptidase activity Source: UniProtKB

GO - Biological processi

  1. proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Protease

Keywords - Ligandi

Magnesium, Manganese, Metal-binding, Zinc

Protein family/group databases

MEROPSiM17.001.

Names & Taxonomyi

Protein namesi
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 namesi
Name:LAP3
Synonyms:LAPEP, PEPS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:18449. LAP3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. extracellular vesicular exosome Source: UniProtKB
  3. focal adhesion Source: UniProtKB
  4. mitochondrion Source: Ensembl
  5. nucleoplasm Source: HPA
  6. nucleus Source: UniProtKB
  7. trans-Golgi network Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38537.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 519519Cytosol aminopeptidasePRO_0000165825Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei45 – 451N6-succinyllysineBy similarity
Modified residuei61 – 611N6-succinyllysineBy similarity
Modified residuei103 – 1031N6-succinyllysineBy similarity
Modified residuei180 – 1801PhosphoserineBy similarity
Modified residuei194 – 1941Phosphoserine1 Publication
Modified residuei221 – 2211N6-acetyllysine; alternate1 Publication
Modified residuei221 – 2211N6-succinyllysine; alternateBy similarity
Modified residuei238 – 2381Phosphoserine1 Publication
Modified residuei455 – 4551N6-acetyllysine; alternateBy similarity
Modified residuei455 – 4551N6-succinyllysine; alternateBy similarity
Modified residuei476 – 4761N6-succinyllysineBy similarity
Modified residuei489 – 4891N6-acetyllysine; alternateBy similarity
Modified residuei489 – 4891N6-succinyllysine; alternateBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP28838.
PaxDbiP28838.
PRIDEiP28838.

2D gel databases

REPRODUCTION-2DPAGEIPI00789806.
P28838.
UCD-2DPAGEP28838.

PTM databases

PhosphoSiteiP28838.

Expressioni

Gene expression databases

BgeeiP28838.
CleanExiHS_LAP3.
ExpressionAtlasiP28838. baseline and differential.
GenevestigatoriP28838.

Organism-specific databases

HPAiHPA029606.
HPA029607.

Interactioni

Subunit structurei

Homohexamer.

Protein-protein interaction databases

BioGridi119248. 19 interactions.
IntActiP28838. 7 interactions.
MINTiMINT-2802173.
STRINGi9606.ENSP00000226299.

Structurei

3D structure databases

ProteinModelPortaliP28838.
SMRiP28838. Positions 33-516.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M17 family.Curated

Phylogenomic databases

eggNOGiCOG0260.
GeneTreeiENSGT00530000063255.
HOGENOMiHOG000243129.
HOVERGENiHBG003320.
InParanoidiP28838.
KOiK11142.
OMAiGMDAMRA.
OrthoDBiEOG7F24SG.
PhylomeDBiP28838.
TreeFamiTF314954.

Family and domain databases

HAMAPiMF_00181. Cytosol_peptidase_M17.
InterProiIPR011356. Leucine_aapep/pepB.
IPR000819. Peptidase_M17_C.
IPR023042. Peptidase_M17_leu_NH2_pept.
IPR008283. Peptidase_M17_N.
[Graphical view]
PfamiPF00883. Peptidase_M17. 1 hit.
PF02789. Peptidase_M17_N. 1 hit.
[Graphical view]
PRINTSiPR00481. LAMNOPPTDASE.
PROSITEiPS00631. CYTOSOL_AP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P28838-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MFLLPLPAAG RVVVRRLAVR RFGSRSLSTA DMTKGLVLGI YSKEKEDDVP
60 70 80 90 100
QFTSAGENFD KLLAGKLRET LNISGPPLKA GKTRTFYGLH QDFPSVVLVG
110 120 130 140 150
LGKKAAGIDE QENWHEGKEN IRAAVAAGCR QIQDLELSSV EVDPCGDAQA
160 170 180 190 200
AAEGAVLGLY EYDDLKQKKK MAVSAKLYGS GDQEAWQKGV LFASGQNLAR
210 220 230 240 250
QLMETPANEM TPTRFAEIIE KNLKSASSKT EVHIRPKSWI EEQAMGSFLS
260 270 280 290 300
VAKGSDEPPV FLEIHYKGSP NANEPPLVFV GKGITFDSGG ISIKASANMD
310 320 330 340 350
LMRADMGGAA TICSAIVSAA KLNLPINIIG LAPLCENMPS GKANKPGDVV
360 370 380 390 400
RAKNGKTIQV DNTDAEGRLI LADALCYAHT FNPKVILNAA TLTGAMDVAL
410 420 430 440 450
GSGATGVFTN SSWLWNKLFE ASIETGDRVW RMPLFEHYTR QVVDCQLADV
460 470 480 490 500
NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL DIAGVMTNKD EVPYLRKGMT
510
GRPTRTLIEF LLRFSQDNA
Length:519
Mass (Da):56,166
Last modified:January 23, 2007 - v3
Checksum:iD960F8F5B9024585
GO
Isoform 2 (identifier: P28838-2) [UniParc]FASTAAdd to basket

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

Note: Initiator Met-1 is removed.

Show »
Length:488
Mass (Da):52,771
Checksum:i0CADB3E07FD10B8B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti20 – 201R → V in AAD17527 (Ref. 1) Curated
Sequence conflicti22 – 221F → S in AAD17527 (Ref. 1) Curated
Sequence conflicti29 – 291T → A in CAG33409 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3131Missing in isoform 2. 1 PublicationVSP_022631Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3422.1. [P28838-1]
PIRiPT0431.
RefSeqiNP_056991.2. NM_015907.2. [P28838-1]
UniGeneiHs.570791.

Genome annotation databases

EnsembliENST00000226299; ENSP00000226299; ENSG00000002549. [P28838-1]
ENST00000606142; ENSP00000476028; ENSG00000002549. [P28838-2]
ENST00000618908; ENSP00000481000; ENSG00000002549. [P28838-1]
GeneIDi51056.
KEGGihsa:51056.
UCSCiuc003gph.1. human. [P28838-1]

Polymorphism databases

DMDMi124028615.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3422.1. [P28838-1]
PIRiPT0431.
RefSeqiNP_056991.2. NM_015907.2. [P28838-1]
UniGeneiHs.570791.

3D structure databases

ProteinModelPortaliP28838.
SMRiP28838. Positions 33-516.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119248. 19 interactions.
IntActiP28838. 7 interactions.
MINTiMINT-2802173.
STRINGi9606.ENSP00000226299.

Chemistry

BindingDBiP28838.
ChEMBLiCHEMBL3965.

Protein family/group databases

MEROPSiM17.001.

PTM databases

PhosphoSiteiP28838.

Polymorphism databases

DMDMi124028615.

2D gel databases

REPRODUCTION-2DPAGEIPI00789806.
P28838.
UCD-2DPAGEP28838.

Proteomic databases

MaxQBiP28838.
PaxDbiP28838.
PRIDEiP28838.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226299; ENSP00000226299; ENSG00000002549. [P28838-1]
ENST00000606142; ENSP00000476028; ENSG00000002549. [P28838-2]
ENST00000618908; ENSP00000481000; ENSG00000002549. [P28838-1]
GeneIDi51056.
KEGGihsa:51056.
UCSCiuc003gph.1. human. [P28838-1]

Organism-specific databases

CTDi51056.
GeneCardsiGC04P017578.
H-InvDBHIX0004121.
HGNCiHGNC:18449. LAP3.
HPAiHPA029606.
HPA029607.
MIMi170250. gene.
neXtProtiNX_P28838.
PharmGKBiPA38537.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0260.
GeneTreeiENSGT00530000063255.
HOGENOMiHOG000243129.
HOVERGENiHBG003320.
InParanoidiP28838.
KOiK11142.
OMAiGMDAMRA.
OrthoDBiEOG7F24SG.
PhylomeDBiP28838.
TreeFamiTF314954.

Miscellaneous databases

ChiTaRSiLAP3. human.
GenomeRNAii51056.
NextBioi53624.
PROiP28838.
SOURCEiSearch...

Gene expression databases

BgeeiP28838.
CleanExiHS_LAP3.
ExpressionAtlasiP28838. baseline and differential.
GenevestigatoriP28838.

Family and domain databases

HAMAPiMF_00181. Cytosol_peptidase_M17.
InterProiIPR011356. Leucine_aapep/pepB.
IPR000819. Peptidase_M17_C.
IPR023042. Peptidase_M17_leu_NH2_pept.
IPR008283. Peptidase_M17_N.
[Graphical view]
PfamiPF00883. Peptidase_M17. 1 hit.
PF02789. Peptidase_M17_N. 1 hit.
[Graphical view]
PRINTSiPR00481. LAMNOPPTDASE.
PROSITEiPS00631. CYTOSOL_AP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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 (MAR-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 (MAY-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(2003) [PubMed] [Europe PMC] [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(2003) [PubMed] [Europe PMC] [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(1990) [PubMed] [Europe PMC] [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.C., Olsen J.V., Mann M.
    Science 325:834-840(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-221, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiAMPL_HUMAN
AccessioniPrimary (citable) accession number: P28838
Secondary accession number(s): B3KMQ3
, Q6IAM6, Q6P0L6, Q9UQE3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: January 23, 2007
Last modified: March 4, 2015
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.