| IED ID | IndEnz0002005952 |
| Enzyme Type ID | protease005952 |
| Protein Name |
Leucyl-cystinyl aminopeptidase Cystinyl aminopeptidase EC 3.4.11.3 Insulin-regulated membrane aminopeptidase Insulin-responsive aminopeptidase IRAP Oxytocinase OTase Placental leucine aminopeptidase P-LAP Cleaved into: Leucyl-cystinyl aminopeptidase, pregnancy serum form |
| Gene Name | LNPEP OTASE |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MEPFTNDRLQLPRNMIENSMFEEEPDVVDLAKEPCLHPLEPDEVEYEPRGSRLLVRGLGEHEMEEDEEDYESSAKLLGMSFMNRSSGLRNSATGYRQSPDGACSVPSARTMVVCAFVIVVAVSVIMVIYLLPRCTFTKEGCHKKNQSIGLIQPFATNGKLFPWAQIRLPTAVVPLRYELSLHPNLTSMTFRGSVTISVQALQVTWNIILHSTGHNISRVTFMSAVSSQEKQAEILEYAYHGQIAIVAPEALLAGHNYTLKIEYSANISSSYYGFYGFSYTDESNEKKYFAATQFEPLAARSAFPCFDEPAFKATFIIKIIRDEQYTALSNMPKKSSVVLDDGLVQDEFSESVKMSTYLVAFIVGEMKNLSQDVNGTLVSIYAVPEKIGQVHYALETTVKLLEFFQNYFEIQYPLKKLDLVAIPDFEAGAMENWGLLTFREETLLYDSNTSSMADRKLVTKIIAHELAHQWFGNLVTMKWWNDLWLNEGFATFMEYFSLEKIFKELSSYEDFLDARFKTMKKDSLNSSHPISSSVQSSEQIEEMFDSLSYFKGSSLLLMLKTYLSEDVFQHAVVLYLHNHSYASIQSDDLWDSFNEVTNQTLDVKRMMKTWTLQKGFPLVTVQKKGKELFIQQERFFLNMKPEIQPSDTSYLWHIPLSYVTEGRNYSKYQSVSLLDKKSGVINLTEEVLWVKVNINMNGYYIVHYADDDWEALIHQLKINPYVLSDKDRANLINNIFELAGLGKVPLKRAFDLINYLGNENHTAPITEALFQTDLIYNLLEKLGYMDLASRLVTRVFKLLQNQIQQQTWTDEGTPSMRELRSALLEFACTHNLGNCSTTAMKLFDDWMASNGTQSLPTDVMTTVFKVGAKTDKGWSFLLGKYISIGSEAEKNKILEALASSEDVRKLYWLMKSSLNGDNFRTQKLSFIIRTVGRHFPGHLLAWDFVKENWNKLVQKFPLGSYTIQNIVAGSTYLFSTKTHLSEVQAFFENQSEATFRLRCVQEALEVIQLNIQWMEKNLKSLTWWL |
| Enzyme Length | 1025 |
| Uniprot Accession Number | Q9UIQ6 |
| Absorption | |
| Active Site | ACT_SITE 465; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Activity Regulation | |
| Binding Site | BINDING 295; /note=Substrate; /evidence=ECO:0000250 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Release of an N-terminal amino acid, Cys-|-Xaa-, in which the half-cystine residue is involved in a disulfide loop, notably in oxytocin or vasopressin. Hydrolysis rates on a range of aminoacyl arylamides exceed that for the cystinyl derivative, however.; EC=3.4.11.3; Evidence={ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:1731608}; |
| DNA Binding | |
| EC Number | 3.4.11.3 |
| Enzyme Function | FUNCTION: Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. {ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:11707427, ECO:0000269|PubMed:1731608}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (2); Beta strand (39); Binding site (1); Chain (2); Erroneous initiation (1); Frameshift (1); Glycosylation (17); Helix (38); Metal binding (3); Modified residue (4); Motif (2); Natural variant (5); Region (2); Sequence conflict (9); Site (2); Topological domain (2); Transmembrane (1); Turn (8) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Aminopeptidase;Cell membrane;Direct protein sequencing;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome;Secreted;Signal-anchor;Transmembrane;Transmembrane helix;Zinc |
| Interact With | Q969F0; Q04864; P15884; Q13520; P07307-3; Q99675; P78358; Q96KR6; Q969F0; Q9UJ14; O15529; Q8TED1; Q8NBQ5; P80188; Q8TAF8; Q8N4V1; Q9H6H4; Q7Z769; Q9NUM3; Q8WWF3; P27105; P59542; Q96MV1; Q53FP2; Q9UMX0; Q86WB7-2 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11389728}; Single-pass type II membrane protein {ECO:0000269|PubMed:11389728}. Note=In brain only the membrane-bound form is found. The protein resides in intracellular vesicles together with GLUT4 and can then translocate to the cell surface in response to insulin and/or oxytocin. Localization may be determined by dileucine internalization motifs, and/or by interaction with tankyrases.; SUBCELLULAR LOCATION: [Leucyl-cystinyl aminopeptidase, pregnancy serum form]: Secreted. Note=During pregnancy serum levels are low in the first trimester, rise progressively during the second and third trimester and decrease rapidly after parturition. |
| Modified Residue | MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0007744|PubMed:22814378"; MOD_RES 70; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q8C129"; MOD_RES 80; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 91; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" |
| Post Translational Modification | PTM: The pregnancy serum form is derived from the membrane-bound form by proteolytic processing.; PTM: N-glycosylated. {ECO:0000269|PubMed:19349973}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (6) |
| Cross Reference PDB | 4P8Q; 4PJ6; 4Z7I; 5C97; 5JHQ; 5MJ6; |
| Mapped Pubmed ID | 10523666; 11062501; 11994271; 12080061; 12569180; 12700100; 12734182; 12808134; 12871575; 14522993; 14527672; 15187412; 15224091; 15224092; 15894523; 15919790; 15971998; 16054015; 16113565; 16136012; 16762977; 16849449; 16855591; 16880201; 17059388; 17369524; 17373876; 17391061; 17692401; 17999179; 18396141; 18398343; 18502721; 18669636; 18996364; 19013499; 19071192; 19252894; 19372382; 19498108; 19578876; 19897488; 19918052; 20150869; 20217867; 20304486; 20711500; 21314638; 21330387; 21348480; 21454690; 21656680; 22153077; 23500679; 23889750; 23897274; 25408552; 25416956; 26259583; 26311161; 26366890; 26496610; 26638075; 27501164; 27594684; 27834335; 28035472; 28079283; 28328206; 30581499; 32619880; 9668046; |
| Motif | MOTIF 53..54; /note=Dileucine internalization motif; /evidence=ECO:0000255; MOTIF 76..77; /note=Dileucine internalization motif; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 117,349 |
| Kinetics | |
| Metal Binding | METAL 464; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 468; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095; METAL 487; /note=Zinc; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU10095 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.11.3; |