Reviewed, UniProtKB/Swiss-Prot P00727 (AMPL_BOVIN)

Names and origin

Protein names

Recommended name:
    Cytosol aminopeptidase
    EC=3.4.11.1
Alternative name(s):
    Leucine aminopeptidase
    Leucyl aminopeptidase
    Leucine aminopeptidase 3
      Short name=LAP
    Proline aminopeptidase
    EC=3.4.11.5
    Prolyl aminopeptidase
    Peptidase S

Gene names

Name:

LAP3

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Enzyme regulation	Inhibited by bestatin.
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	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrion Inferred from sequence or structural similarity. Source: AgBase
Molecular function	aminopeptidase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: InterPro metalloexopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P00727-1)

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.

Notes: No experimental confirmation available.

Isoform 2 (identifier: P00727-2)

The sequence of this isoform differs from the canonical sequence as follows:
     11-31: Missing.

Notes: The initiator methionine is removed.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 519

519

Cytosol aminopeptidase

PRO_0000165824

Sites

Active site

294

1

Active site

368

1

Metal binding

282

1

Zinc 2

Metal binding

287

1

Zinc 1

Metal binding

287

1

Zinc 2

Metal binding

305

1

Zinc 2

Metal binding

364

1

Zinc 1

Metal binding

366

1

Zinc 1

Metal binding

366

1

Zinc 2

Amino acid modifications

Modified residue

33

1

N-acetylthreonine

Natural variations

Alternative sequence

11 – 31

21

Missing in isoform 2.

VSP_022634

Experimental info

Sequence conflict

77

1

P → S in AAB28170. Ref.2

Sequence conflict

414 – 415

2

LW → M Ref.4 Ref.5

Sequence conflict

506 – 513

8

Missing Ref.4 Ref.5

Secondary structure

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519

Helix Strand Turn

Details...

Beta strand

34 – 40

7

Helix

54 – 62

9

Turn

63 – 65

3

Helix

66 – 73

8

Beta strand

83 – 90

8

Beta strand

93 – 100

8

Turn

110 – 113

4

Helix

116 – 134

19

Beta strand

138 – 142

5

Helix

148 – 159

12

Beta strand

174 – 181

8

Helix

183 – 204

22

Turn

207 – 209

3

Helix

212 – 226

15

Beta strand

228 – 235

8

Helix

237 – 242

6

Helix

246 – 252

7

Beta strand

255 – 257

3

Beta strand

260 – 267

8

Beta strand

269 – 271

3

Beta strand

277 – 281

5

Beta strand

283 – 287

5

Helix

299 – 304

6

Helix

307 – 321

15

Beta strand

325 – 337

13

Beta strand

348 – 351

4

Beta strand

357 – 361

5

Helix

367 – 379

13

Beta strand

384 – 390

7

Helix

394 – 400

7

Beta strand

405 – 410

6

Helix

412 – 425

14

Beta strand

429 – 431

3

Helix

436 – 443

8

Beta strand

446 – 453

8

Beta strand

455 – 457

3

Helix

460 – 469

10

Beta strand

475 – 481

7

Helix

483 – 485

3

Beta strand

486 – 492

7

Beta strand

497 – 499

3

Helix

504 – 515

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: CDA6AED4D937F624	FASTA	519	56,289
	10 20 30 40 50 60 MFLLPLPAAA RVAVRHLSVK RLWAPGPAAA DMTKGLVLGI YSKEKEEDEP QFTSAGENFN 70 80 90 100 110 120 KLVSGKLREI LNISGPPLKA GKTRTFYGLH EDFPSVVVVG LGKKTAGIDE QENWHEGKEN 130 140 150 160 170 180 IRAAVAAGCR QIQDLEIPSV EVDPCGDAQA AAEGAVLGLY EYDDLKQKRK VVVSAKLHGS 190 200 210 220 230 240 EDQEAWQRGV LFASGQNLAR RLMETPANEM TPTKFAEIVE ENLKSASIKT DVFIRPKSWI 250 260 270 280 290 300 EEQEMGSFLS VAKGSEEPPV FLEIHYKGSP NASEPPLVFV GKGITFDSGG ISIKAAANMD 310 320 330 340 350 360 LMRADMGGAA TICSAIVSAA KLDLPINIVG LAPLCENMPS GKANKPGDVV RARNGKTIQV 370 380 390 400 410 420 DNTDAEGRLI LADALCYAHT FNPKVIINAA TLTGAMDIAL GSGATGVFTN SSWLWNKLFE 430 440 450 460 470 480 ASIETGDRVW RMPLFEHYTR QVIDCQLADV NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL 490 500 510 DIAGVMTNKD EVPYLRKGMA GRPTRTLIEF LFRFSQDSA
	Isoform 2 [UniParc]. Checksum: 70766756087AB1FD		498	54,037
	10 20 30 40 50 60 MFLLPLPAAA MTKGLVLGIY SKEKEEDEPQ FTSAGENFNK LVSGKLREIL NISGPPLKAG 70 80 90 100 110 120 KTRTFYGLHE DFPSVVVVGL GKKTAGIDEQ ENWHEGKENI RAAVAAGCRQ IQDLEIPSVE 130 140 150 160 170 180 VDPCGDAQAA AEGAVLGLYE YDDLKQKRKV VVSAKLHGSE DQEAWQRGVL FASGQNLARR 190 200 210 220 230 240 LMETPANEMT PTKFAEIVEE NLKSASIKTD VFIRPKSWIE EQEMGSFLSV AKGSEEPPVF 250 260 270 280 290 300 LEIHYKGSPN ASEPPLVFVG KGITFDSGGI SIKAAANMDL MRADMGGAAT ICSAIVSAAK 310 320 330 340 350 360 LDLPINIVGL APLCENMPSG KANKPGDVVR ARNGKTIQVD NTDAEGRLIL ADALCYAHTF 370 380 390 400 410 420 NPKVIINAAT LTGAMDIALG SGATGVFTNS SWLWNKLFEA SIETGDRVWR MPLFEHYTRQ 430 440 450 460 470 480 VIDCQLADVN NIGKYRSAGA CTAAAFLKEF VTHPKWAHLD IAGVMTNKDE VPYLRKGMAG 490 RPTRTLIEFL FRFSQDSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Bovine sequencing consortium Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Hereford.
[2]	"Isolation of bovine kidney leucine aminopeptidase cDNA: comparison with the lens enzyme and tissue-specific expression of two mRNAs." Wallner B.P., Hession C., Tizard R., Frey A.Z., Zuliani A., Mura C., Jahngen-Hodge J., Taylor A. Biochemistry 32:9296-9301(1993) [PubMed: 8369298] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Kidney.
[3]	NIH - Mammalian Gene Collection (MGC) project Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-519 (ISOFORM 1). Strain: Hereford. Tissue: Hypothalamus.
[4]	"The primary structure of leucine aminopeptidase from bovine eye lens." Cuypers H.T., van Loon-Klaassen L.A.H., Vree Egberts W.T.M., de Jong W.W., Bloemendal H. J. Biol. Chem. 257:7077-7085(1982) [PubMed: 7085616] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-519. Tissue: Lens.
[5]	"Sulfhydryl content of bovine eye lens leucine aminopeptidase. Determination of the reactivity of the sulfhydryl groups of the zinc metalloenzyme, of the enzyme activated by Mg2+, Mn2+, and Co2+, and of the metal-free apoenzyme." Cuypers H.T., van Loon-Klaassen L.A.H., Vree Egberts W.T.M., de Jong W.W., Bloemendal H. J. Biol. Chem. 257:7086-7091(1982) [PubMed: 7085617] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-519.
[6]	Seroussi E. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 431-478. Strain: Holstein.
[7]	"Molecular structure of leucine aminopeptidase at 2.7-A resolution." Burley S.K., David P.R., Taylor A., Lipscomb W.N. Proc. Natl. Acad. Sci. U.S.A. 87:6878-6882(1990) [PubMed: 2395881] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 33-519.
[8]	"Structure determination and refinement of bovine lens leucine aminopeptidase and its complex with bestatin." Burley S.K., David P.R., Sweet R.M., Taylor A., Lipscomb W.N. J. Mol. Biol. 224:113-140(1992) [PubMed: 1548695] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 33-519.
[9]	"Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography." Straeter N., Lipscomb W.N. Biochemistry 34:14792-14800(1995) [PubMed: 7578088] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 33-519.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

S65367 mRNA. Translation: AAB28170.1. Different initiation.
BC105385 mRNA. Translation: AAI05386.1.
AJ871963 Genomic DNA. Translation: CAI44744.1.

PIR

APBOL. A54338.

RefSeq

NP_776523.2.
XP_001787300.1.

UniGene

Bt.56962

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BLL	X-ray	2.40	E	-	[»]
1BPM	X-ray	2.90	A	-	[»]
1BPN	X-ray	2.90	A	-	[»]
1LAM	X-ray	1.60	A	33-516	[»]
1LAN	X-ray	1.90	A	33-516	[»]
1LAP	X-ray	2.70	A	33-519	[»]
1LCP	X-ray	1.65	A/B	33-516	[»]
2EWB	X-ray	1.85	A	33-518	[»]
2J9A	X-ray	1.73	A	33-519	[»]

ModBase

Search...

Protein family/group databases

MEROPS

M17.001.

Genome annotation databases

Ensembl

ENSBTAG00000005989. Bos taurus. [Contig view]