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P09960

- LKHA4_HUMAN

UniProt

P09960 - LKHA4_HUMAN

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Protein

Leukotriene A-4 hydrolase

Gene
LTA4H, LTA4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.7 Publications

Catalytic activityi

(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (6Z,8E,10E,14Z)-(5S,12R)-5,12-dihydroxyicosa-6,8,10,14-tetraenoate.6 Publications

Cofactori

Binds 1 zinc ion per subunit.3 Publications

Enzyme regulationi

Inhibited by bestatin. Subject to suicide inhibition by leukotriene A4, due to the formation of a covalent adduct at Tyr-379.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi296 – 2961Zinc; catalytic
Active sitei297 – 2971Proton acceptor Inferred
Metal bindingi300 – 3001Zinc; catalytic
Metal bindingi319 – 3191Zinc; catalytic
Sitei376 – 3761Essential for epoxide hydrolase activity, but not for aminopeptidase activity
Sitei379 – 3791Covalently modified during suicide inhibition by leukotrienes
Active sitei384 – 3841Proton donor Inferred

GO - Molecular functioni

  1. aminopeptidase activity Source: UniProtKB
  2. epoxide hydrolase activity Source: UniProtKB
  3. leukotriene-A4 hydrolase activity Source: UniProtKB
  4. metallopeptidase activity Source: UniProtKB-KW
  5. peptidase activity Source: ProtInc
  6. poly(A) RNA binding Source: UniProtKB
  7. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. arachidonic acid metabolic process Source: Reactome
  2. inflammatory response Source: ProtInc
  3. leukotriene biosynthetic process Source: UniProtKB
  4. leukotriene metabolic process Source: Reactome
  5. peptide catabolic process Source: UniProtKB
  6. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Leukotriene biosynthesis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS03372-MONOMER.
BRENDAi3.3.2.6. 2681.
ReactomeiREACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
UniPathwayiUPA00878.

Protein family/group databases

MEROPSiM01.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukotriene A-4 hydrolase (EC:3.3.2.6)
Short name:
LTA-4 hydrolase
Alternative name(s):
Leukotriene A(4) hydrolase
Gene namesi
Name:LTA4H
Synonyms:LTA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:6710. LTA4H.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. extracellular vesicular exosome Source: UniProt
  4. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi135 – 1351Q → A or L: Srongly increased epoxide hydrolase activity. 2 Publications
Mutagenesisi135 – 1351Q → A: Strongly reduced aminopeptidase activity. Strongly decreased affinity for leukotriene. Abolishes epoxide hydrolase activity. 2 Publications
Mutagenesisi137 – 1371Q → A: No loss of activity. 2 Publications
Mutagenesisi137 – 1371Q → L: Aminopeptidase activity strongly impaired, but keeps LTA4 activity. 2 Publications
Mutagenesisi137 – 1371Q → N: Aminopeptidase activity almost absent, but keeps LTA4 activity. 2 Publications
Mutagenesisi140 – 1401H → Q: Aminopeptidase activity almost absent, but keeps LTA4 activity. 2 Publications
Mutagenesisi269 – 2691G → A: No loss of activity. 1 Publication
Mutagenesisi270 – 2701G → A: No loss of activity. 2 Publications
Mutagenesisi271 – 2711M → L: No loss of activity. 2 Publications
Mutagenesisi272 – 2721E → A or D: Complete loss of activity. 2 Publications
Mutagenesisi272 – 2721E → Q: Loss of LTA4 activity, and aminopeptidase activity strongly impaired. 2 Publications
Mutagenesisi273 – 2731N → A: No loss of activity. 2 Publications
Mutagenesisi296 – 2961H → Y: Complete loss of activity. 1 Publication
Mutagenesisi297 – 2971E → A: Loss of both activities. 4 Publications
Mutagenesisi297 – 2971E → K: Loss of both activities. 4 Publications
Mutagenesisi297 – 2971E → Q: Loss of aminopeptidase activity, but keeps LTA4 activity. 4 Publications
Mutagenesisi300 – 3001H → L: Complete loss of activity. 1 Publication
Mutagenesisi319 – 3191E → A: Complete loss of activity. 1 Publication
Mutagenesisi372 – 3721D → N: No loss of activity. 2 Publications
Mutagenesisi374 – 3741D → N: No loss of activity. 2 Publications
Mutagenesisi376 – 3761D → A: Strongly reduced hydrolysis of peptides starting with Arg. Small effect on hydrolysis of peptides starting with Ala. Strongly reduced epoxide hydrolase activity. 3 Publications
Mutagenesisi376 – 3761D → E: Strongly reduced aminopeptidase activity. Abolishes epoxide hydrolase activity. 3 Publications
Mutagenesisi376 – 3761D → N: Abolishes aminopeptidase and epoxide hydrolase activity. 3 Publications
Mutagenesisi385 – 3851E → Q: Reduced aminopeptidase activity. Minor effect on epoxide hydrolase activity. 2 Publications
Mutagenesisi564 – 5641R → A, K or M: Abolishes epoxide hydrolase activity. Reduced aminopeptidase activity. 2 Publications
Mutagenesisi566 – 5661K → A or M: Strongly reduced affinity for peptide substrates. Reduced epoxide hydrolase and aminopeptidase activity. 2 Publications
Mutagenesisi566 – 5661K → R: No effect on epoxide hydrolase and aminopeptidase activity. 2 Publications

Organism-specific databases

PharmGKBiPA24345.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 611610Leukotriene A-4 hydrolasePRO_0000095124Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei73 – 731N6-acetyllysine1 Publication
Modified residuei337 – 3371N6-acetyllysine1 Publication
Modified residuei414 – 4141N6-acetyllysine1 Publication
Modified residuei416 – 4161Phosphoserine1 Publication
Modified residuei573 – 5731N6-acetyllysine1 Publication

Post-translational modificationi

Phosphorylation at Ser-416 inhibits enzymatic activity.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP09960.
PaxDbiP09960.
PRIDEiP09960.

2D gel databases

REPRODUCTION-2DPAGEIPI00219077.

PTM databases

PhosphoSiteiP09960.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.

Gene expression databases

ArrayExpressiP09960.
BgeeiP09960.
CleanExiHS_LTA4H.
GenevestigatoriP09960.

Organism-specific databases

HPAiCAB015221.
HPA008399.
HPA017017.

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi110226. 12 interactions.
IntActiP09960. 5 interactions.
MINTiMINT-1388946.
STRINGi9606.ENSP00000228740.

Structurei

Secondary structure

1
611
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni14 – 163
Beta strandi17 – 2913
Turni30 – 334
Beta strandi34 – 4512
Beta strandi50 – 5910
Beta strandi61 – 677
Beta strandi74 – 763
Helixi81 – 833
Beta strandi85 – 9511
Beta strandi100 – 1089
Beta strandi116 – 1194
Helixi121 – 1233
Beta strandi124 – 1296
Beta strandi131 – 1344
Turni137 – 1404
Helixi141 – 1433
Beta strandi155 – 16410
Beta strandi167 – 18014
Beta strandi182 – 1843
Beta strandi187 – 19812
Helixi200 – 2023
Beta strandi205 – 2095
Beta strandi211 – 2166
Beta strandi219 – 2235
Helixi225 – 2273
Helixi228 – 2347
Turni235 – 2373
Helixi238 – 24912
Beta strandi258 – 2614
Beta strandi267 – 2715
Beta strandi276 – 2794
Helixi281 – 2833
Beta strandi286 – 2883
Turni289 – 2913
Helixi292 – 2998
Turni300 – 3023
Turni304 – 3063
Beta strandi307 – 3115
Helixi312 – 3143
Helixi315 – 33420
Helixi336 – 35722
Helixi362 – 3643
Beta strandi365 – 3673
Helixi375 – 3784
Helixi382 – 39817
Helixi401 – 41515
Beta strandi418 – 4203
Helixi422 – 43211
Helixi434 – 4363
Helixi437 – 4415
Helixi445 – 4506
Turni464 – 4663
Helixi467 – 47812
Helixi481 – 4866
Helixi489 – 4924
Helixi497 – 50812
Helixi515 – 52511
Helixi527 – 5293
Helixi533 – 54513
Helixi551 – 56111
Helixi565 – 57713
Helixi579 – 59214
Helixi593 – 5953
Helixi598 – 60811

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1GW6X-ray2.20A2-611[»]
1H19X-ray2.10A2-611[»]
1HS6X-ray1.95A1-611[»]
1SQMX-ray2.30A2-611[»]
2R59X-ray1.89A2-611[»]
2VJ8X-ray1.80A1-611[»]
3B7RX-ray1.81L2-611[»]
3B7SX-ray1.47A2-611[»]
3B7TX-ray2.30A2-611[»]
3B7UX-ray1.90X2-611[»]
3CHOX-ray1.80A2-611[»]
3CHPX-ray2.10A2-611[»]
3CHQX-ray2.09A2-611[»]
3CHRX-ray2.20A2-611[»]
3CHSX-ray2.55A2-611[»]
3FH5X-ray1.63A1-611[»]
3FH7X-ray2.05A1-611[»]
3FH8X-ray1.67A1-611[»]
3FHEX-ray2.16A1-611[»]
3FTSX-ray2.33A1-611[»]
3FTUX-ray1.90A1-611[»]
3FTVX-ray1.70A1-611[»]
3FTWX-ray1.85A1-611[»]
3FTXX-ray1.96A1-611[»]
3FTYX-ray2.15A1-611[»]
3FTZX-ray2.00A1-611[»]
3FU0X-ray1.80A1-611[»]
3FU3X-ray2.00A1-611[»]
3FU5X-ray2.30A1-611[»]
3FU6X-ray2.05A1-611[»]
3FUDX-ray2.20A1-611[»]
3FUEX-ray2.38A1-611[»]
3FUFX-ray2.60A1-611[»]
3FUHX-ray1.80A1-611[»]
3FUIX-ray2.20A1-611[»]
3FUJX-ray1.90A1-611[»]
3FUKX-ray1.95A1-611[»]
3FULX-ray2.39A1-611[»]
3FUMX-ray2.15A1-611[»]
3FUNX-ray1.58A1-611[»]
3U9WX-ray1.25A4-611[»]
4DPRX-ray2.02A1-611[»]
4L2LX-ray1.65A1-611[»]
4MKTX-ray1.62A1-611[»]
4MS6X-ray1.72A1-611[»]
ProteinModelPortaliP09960.
SMRiP09960. Positions 4-611.

Miscellaneous databases

EvolutionaryTraceiP09960.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni135 – 1373Substrate binding
Regioni267 – 2726Substrate binding
Regioni564 – 5663Substrate binding

Sequence similaritiesi

Belongs to the peptidase M1 family.

Phylogenomic databases

eggNOGiCOG0308.
HOGENOMiHOG000293296.
HOVERGENiHBG001274.
InParanoidiP09960.
KOiK01254.
OMAiSPASVCQ.
OrthoDBiEOG7SJD42.
PhylomeDBiP09960.
TreeFamiTF300758.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
SUPFAMiSSF48371. SSF48371. 1 hit.
TIGRFAMsiTIGR02411. leuko_A4_hydro. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P09960-1) [UniParc]FASTAAdd to Basket

Also known as: L-LTA4

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

MPEIVDTCSL ASPASVCRTK HLHLRCSVDF TRRTLTGTAA LTVQSQEDNL    50
RSLVLDTKDL TIEKVVINGQ EVKYALGERQ SYKGSPMEIS LPIALSKNQE 100
IVIEISFETS PKSSALQWLT PEQTSGKEHP YLFSQCQAIH CRAILPCQDT 150
PSVKLTYTAE VSVPKELVAL MSAIRDGETP DPEDPSRKIY KFIQKVPIPC 200
YLIALVVGAL ESRQIGPRTL VWSEKEQVEK SAYEFSETES MLKIAEDLGG 250
PYVWGQYDLL VLPPSFPYGG MENPCLTFVT PTLLAGDKSL SNVIAHEISH 300
SWTGNLVTNK TWDHFWLNEG HTVYLERHIC GRLFGEKFRH FNALGGWGEL 350
QNSVKTFGET HPFTKLVVDL TDIDPDVAYS SVPYEKGFAL LFYLEQLLGG 400
PEIFLGFLKA YVEKFSYKSI TTDDWKDFLY SYFKDKVDVL NQVDWNAWLY 450
SPGLPPIKPN YDMTLTNACI ALSQRWITAK EDDLNSFNAT DLKDLSSHQL 500
NEFLAQTLQR APLPLGHIKR MQEVYNFNAI NNSEIRFRWL RLCIQSKWED 550
AIPLALKMAT EQGRMKFTRP LFKDLAAFDK SHDQAVRTYQ EHKASMHPVT 600
AMLVGKDLKV D 611
Length:611
Mass (Da):69,285
Last modified:January 23, 2007 - v2
Checksum:i329BF6D04D4A06E1
GO
Isoform 2 (identifier: P09960-2) [UniParc]FASTAAdd to Basket

Also known as: S-LTA4

The sequence of this isoform differs from the canonical sequence as follows:
     511-532: APLPLGHIKRMQEVYNFNAINN → MAAALHSIQVGGRNSFGAKDGN
     533-611: Missing.

Show »
Length:532
Mass (Da):59,733
Checksum:i474891F08B0215A8
GO
Isoform 3 (identifier: P09960-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MPEIVDTCSL...QSQEDNLRSL → MLPQRNLSKRQVPTMHIPVKTRRLLAALK
     511-532: APLPLGHIKRMQEVYNFNAINN → MAAALHSIQVGGRNSFGAKDGN
     533-611: Missing.

Show »
Length:508
Mass (Da):57,300
Checksum:iA1CDA72AF83A875C
GO
Isoform 4 (identifier: P09960-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-53: MPEIVDTCSL...QSQEDNLRSL → MLPQRNLSKRQVPTMHIPVKTRRLLAALK

Note: No experimental confirmation available.

Show »
Length:587
Mass (Da):66,852
Checksum:iA70BF2792A0427C7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311Y → H.
Corresponds to variant rs45630737 [ dbSNP | Ensembl ].
VAR_051570

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5353MPEIV…NLRSL → MLPQRNLSKRQVPTMHIPVK TRRLLAALK in isoform 3 and isoform 4. VSP_041107Add
BLAST
Alternative sequencei511 – 53222APLPL…NAINN → MAAALHSIQVGGRNSFGAKD GN in isoform 2 and isoform 3. VSP_041108Add
BLAST
Alternative sequencei533 – 61179Missing in isoform 2 and isoform 3. VSP_041109Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti115 – 1151A → T in BX647158. 1 Publication
Sequence conflicti123 – 1231Q → R in BX647158. 1 Publication
Sequence conflicti297 – 2971E → G in BAG60321. 1 Publication
Sequence conflicti309 – 3091N → S in BX647158. 1 Publication
Sequence conflicti378 – 3781A → V in BX647158. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J03459 mRNA. Translation: AAA36176.1.
J02959 mRNA. Translation: AAA36177.1.
U27293
, U27275, U27276, U27277, U27278, U27279, U27280, U27281, U27282, U27283, U27284, U27285, U27286, U27287, U27288, U27289, U27290, U27291, U27292 Genomic DNA. Translation: AAA89077.1.
AK298017 mRNA. Translation: BAG60321.1.
CR457068 mRNA. Translation: CAG33349.1.
BX647158 mRNA. No translation available.
AC007298 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97559.1.
BC032528 mRNA. Translation: AAH32528.1.
U43410 Genomic DNA. No translation available.
U43411 Genomic DNA. No translation available.
CCDSiCCDS58266.1. [P09960-3]
CCDS58267.1. [P09960-4]
CCDS9059.1. [P09960-1]
PIRiS65947.
RefSeqiNP_000886.1. NM_000895.2. [P09960-1]
NP_001243572.1. NM_001256643.1. [P09960-4]
NP_001243573.1. NM_001256644.1. [P09960-3]
XP_005268928.1. XM_005268871.1. [P09960-2]
UniGeneiHs.524648.

Genome annotation databases

EnsembliENST00000228740; ENSP00000228740; ENSG00000111144. [P09960-1]
ENST00000413268; ENSP00000395051; ENSG00000111144. [P09960-3]
ENST00000552789; ENSP00000449958; ENSG00000111144. [P09960-4]
GeneIDi4048.
KEGGihsa:4048.
UCSCiuc001ten.2. human. [P09960-1]
uc010suz.2. human. [P09960-3]

Polymorphism databases

DMDMi126353.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J03459 mRNA. Translation: AAA36176.1 .
J02959 mRNA. Translation: AAA36177.1 .
U27293
, U27275 , U27276 , U27277 , U27278 , U27279 , U27280 , U27281 , U27282 , U27283 , U27284 , U27285 , U27286 , U27287 , U27288 , U27289 , U27290 , U27291 , U27292 Genomic DNA. Translation: AAA89077.1 .
AK298017 mRNA. Translation: BAG60321.1 .
CR457068 mRNA. Translation: CAG33349.1 .
BX647158 mRNA. No translation available.
AC007298 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97559.1 .
BC032528 mRNA. Translation: AAH32528.1 .
U43410 Genomic DNA. No translation available.
U43411 Genomic DNA. No translation available.
CCDSi CCDS58266.1. [P09960-3 ]
CCDS58267.1. [P09960-4 ]
CCDS9059.1. [P09960-1 ]
PIRi S65947.
RefSeqi NP_000886.1. NM_000895.2. [P09960-1 ]
NP_001243572.1. NM_001256643.1. [P09960-4 ]
NP_001243573.1. NM_001256644.1. [P09960-3 ]
XP_005268928.1. XM_005268871.1. [P09960-2 ]
UniGenei Hs.524648.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1GW6 X-ray 2.20 A 2-611 [» ]
1H19 X-ray 2.10 A 2-611 [» ]
1HS6 X-ray 1.95 A 1-611 [» ]
1SQM X-ray 2.30 A 2-611 [» ]
2R59 X-ray 1.89 A 2-611 [» ]
2VJ8 X-ray 1.80 A 1-611 [» ]
3B7R X-ray 1.81 L 2-611 [» ]
3B7S X-ray 1.47 A 2-611 [» ]
3B7T X-ray 2.30 A 2-611 [» ]
3B7U X-ray 1.90 X 2-611 [» ]
3CHO X-ray 1.80 A 2-611 [» ]
3CHP X-ray 2.10 A 2-611 [» ]
3CHQ X-ray 2.09 A 2-611 [» ]
3CHR X-ray 2.20 A 2-611 [» ]
3CHS X-ray 2.55 A 2-611 [» ]
3FH5 X-ray 1.63 A 1-611 [» ]
3FH7 X-ray 2.05 A 1-611 [» ]
3FH8 X-ray 1.67 A 1-611 [» ]
3FHE X-ray 2.16 A 1-611 [» ]
3FTS X-ray 2.33 A 1-611 [» ]
3FTU X-ray 1.90 A 1-611 [» ]
3FTV X-ray 1.70 A 1-611 [» ]
3FTW X-ray 1.85 A 1-611 [» ]
3FTX X-ray 1.96 A 1-611 [» ]
3FTY X-ray 2.15 A 1-611 [» ]
3FTZ X-ray 2.00 A 1-611 [» ]
3FU0 X-ray 1.80 A 1-611 [» ]
3FU3 X-ray 2.00 A 1-611 [» ]
3FU5 X-ray 2.30 A 1-611 [» ]
3FU6 X-ray 2.05 A 1-611 [» ]
3FUD X-ray 2.20 A 1-611 [» ]
3FUE X-ray 2.38 A 1-611 [» ]
3FUF X-ray 2.60 A 1-611 [» ]
3FUH X-ray 1.80 A 1-611 [» ]
3FUI X-ray 2.20 A 1-611 [» ]
3FUJ X-ray 1.90 A 1-611 [» ]
3FUK X-ray 1.95 A 1-611 [» ]
3FUL X-ray 2.39 A 1-611 [» ]
3FUM X-ray 2.15 A 1-611 [» ]
3FUN X-ray 1.58 A 1-611 [» ]
3U9W X-ray 1.25 A 4-611 [» ]
4DPR X-ray 2.02 A 1-611 [» ]
4L2L X-ray 1.65 A 1-611 [» ]
4MKT X-ray 1.62 A 1-611 [» ]
4MS6 X-ray 1.72 A 1-611 [» ]
ProteinModelPortali P09960.
SMRi P09960. Positions 4-611.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110226. 12 interactions.
IntActi P09960. 5 interactions.
MINTi MINT-1388946.
STRINGi 9606.ENSP00000228740.

Chemistry

BindingDBi P09960.
ChEMBLi CHEMBL4618.
GuidetoPHARMACOLOGYi 1395.

Protein family/group databases

MEROPSi M01.004.

PTM databases

PhosphoSitei P09960.

Polymorphism databases

DMDMi 126353.

2D gel databases

REPRODUCTION-2DPAGE IPI00219077.

Proteomic databases

MaxQBi P09960.
PaxDbi P09960.
PRIDEi P09960.

Protocols and materials databases

DNASUi 4048.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000228740 ; ENSP00000228740 ; ENSG00000111144 . [P09960-1 ]
ENST00000413268 ; ENSP00000395051 ; ENSG00000111144 . [P09960-3 ]
ENST00000552789 ; ENSP00000449958 ; ENSG00000111144 . [P09960-4 ]
GeneIDi 4048.
KEGGi hsa:4048.
UCSCi uc001ten.2. human. [P09960-1 ]
uc010suz.2. human. [P09960-3 ]

Organism-specific databases

CTDi 4048.
GeneCardsi GC12M096394.
HGNCi HGNC:6710. LTA4H.
HPAi CAB015221.
HPA008399.
HPA017017.
MIMi 151570. gene.
neXtProti NX_P09960.
PharmGKBi PA24345.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0308.
HOGENOMi HOG000293296.
HOVERGENi HBG001274.
InParanoidi P09960.
KOi K01254.
OMAi SPASVCQ.
OrthoDBi EOG7SJD42.
PhylomeDBi P09960.
TreeFami TF300758.

Enzyme and pathway databases

UniPathwayi UPA00878 .
BioCyci MetaCyc:HS03372-MONOMER.
BRENDAi 3.3.2.6. 2681.
Reactomei REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).

Miscellaneous databases

ChiTaRSi LTA4H. human.
EvolutionaryTracei P09960.
GenomeRNAii 4048.
NextBioi 15856.
PROi P09960.
SOURCEi Search...

Gene expression databases

ArrayExpressi P09960.
Bgeei P09960.
CleanExi HS_LTA4H.
Genevestigatori P09960.

Family and domain databases

InterProi IPR016024. ARM-type_fold.
IPR012777. Leukotriene_A4_hydrolase.
IPR001930. Peptidase_M1.
IPR015211. Peptidase_M1_C.
IPR014782. Peptidase_M1_N.
[Graphical view ]
PANTHERi PTHR11533. PTHR11533. 1 hit.
Pfami PF09127. Leuk-A4-hydro_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view ]
PRINTSi PR00756. ALADIPTASE.
SUPFAMi SSF48371. SSF48371. 1 hit.
TIGRFAMsi TIGR02411. leuko_A4_hydro. 1 hit.
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis."
    Minami M., Ohno S., Kawasaki H., Raedmark O., Samuelsson B., Joernvall H., Shimizu T., Seyama Y., Suzuki K.
    J. Biol. Chem. 262:13873-13876(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
  3. "Cloning and characterization of the human leukotriene A4 hydrolase gene."
    Mancini J.A., Evans J.F.
    Eur. J. Biochem. 231:65-71(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Lung.
  5. "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).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
    Tissue: Esophageal carcinoma.
  7. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Eye.
  10. "Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme."
    Odlander B., Claesson H.E., Bergman T., Radmark O., Joernvall H., Haeggstrom J.Z.
    Arch. Biochem. Biophys. 287:167-174(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-22, FUNCTION, CATALYTIC ACTIVITY.
    Tissue: B-cell.
  11. "Leukotriene A4 hydrolase in human leukocytes. Purification and properties."
    Radmark O., Shimizu T., Joernvall H., Samuelsson B.
    J. Biol. Chem. 259:12339-12345(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-16.
  12. "Leukotriene A4 hydrolase: mapping of a henicosapeptide involved in mechanism-based inactivation."
    Mueller M.J., Wetterholm A., Blomster M., Jornvall H., Samuelsson B., Haeggstrom J.Z.
    Proc. Natl. Acad. Sci. U.S.A. 92:8383-8387(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 366-386, ENZYME REGULATION, COVALENT MODIFICATION AT TYR-379, CATALYTIC ACTIVITY.
  13. "The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms."
    Jendraschak E., Kaminski W.E., Kiefl R., von Schacky C.
    Biochem. J. 314:733-737(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 511-611, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
  14. "Molecular evolution and zinc ion binding motif of leukotriene A4 hydrolase."
    Toh H., Minami M., Shimizu T.
    Biochem. Biophys. Res. Commun. 171:216-221(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: ZINC-BINDING, FUNCTION AS A PEPTIDASE, SIMILARITY TO ZINC PROTEASES.
  15. Cited for: ZINC-BINDING, FUNCTION AS A PEPTIDASE.
  16. "Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site-directed mutagenesis and zinc analysis."
    Medina J.F., Wetterholm A., Raadmark O., Shapiro R., Haeggstroem J.Z., Vallee B.L., Samuelsson B.
    Proc. Natl. Acad. Sci. U.S.A. 88:7620-7624(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ZINC LIGANDS.
  17. "Leukotriene A4 hydrolase, a bifunctional enzyme. Distinction of leukotriene A4 hydrolase and aminopeptidase activities by site-directed mutagenesis at Glu-297."
    Minami M., Bito H., Ohishi N., Tsuge H., Miyano M., Mori M., Wada H., Mutoh H., Shimada S., Izumi T., Abe K., Shimuzu T.
    FEBS Lett. 309:353-357(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-297.
  18. "Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of glutamic acid-296."
    Wetterholm A., Medina J.F., Raadmark O., Shapiro R., Haeggstroem J.Z., Vallee B.L., Samuelsson B.
    Proc. Natl. Acad. Sci. U.S.A. 89:9141-9145(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-297.
  19. "Regulation of leukotriene A4 hydrolase activity in endothelial cells by phosphorylation."
    Rybina I.V., Liu H., Gor Y., Feinmark S.J.
    J. Biol. Chem. 272:31865-31871(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-416.
  20. "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(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-337; LYS-414 AND LYS-573, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation."
    Thunnissen M.M.G.M., Nordlund P., Haeggstroem J.Z.
    Nat. Struct. Biol. 8:131-135(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
  24. "Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors."
    Thunnissen M.M., Andersson B., Samuelsson B., Wong C.H., Haeggstrom J.Z.
    FASEB J. 16:1648-1650(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH CAPTOPRIL AND ZINC IONS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, ACTIVE SITE.
  25. "Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms."
    Rudberg P.C., Tholander F., Thunnissen M.M.G.M., Haeggstroem J.Z.
    J. Biol. Chem. 277:1398-1404(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT GLN-272, MUTAGENESIS OF GLN-137; GLY-270; MET-271; GLU-272 AND ASN-273.
  26. "Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375."
    Rudberg P.C., Tholander F., Thunnissen M.M., Samuelsson B., Haeggstrom J.Z.
    Proc. Natl. Acad. Sci. U.S.A. 99:4215-4220(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ASN-376 IN COMPLEX WITH BESTATIN AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLN-135; HIS-140; ASP-372; ASP-374; ASP-376 AND GLU-385.
  27. "Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates."
    Rudberg P.C., Tholander F., Andberg M., Thunnissen M.M., Haeggstrom J.Z.
    J. Biol. Chem. 279:27376-27382(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ALA-564 IN COMPLEX WITH ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, MUTAGENESIS OF ARG-564 AND LYS-566.
  28. "Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design."
    Tholander F., Muroya A., Roques B.P., Fournie-Zaluski M.C., Thunnissen M.M., Haeggstrom J.Z.
    Chem. Biol. 15:920-929(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF MUTANT GLN-297 IN COMPLEXES WITH SUBSTRATE TRIPEPTIDES AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, MUTAGENESIS OF GLU-297 AND ASP-376.
  29. Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) IN COMPLEXES WITH INHIBITORS AND ZINC IONS.

Entry informationi

Entry nameiLKHA4_HUMAN
AccessioniPrimary (citable) accession number: P09960
Secondary accession number(s): B4DNQ9
, F8VV40, Q6IAT6, Q9UCT7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 179 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Peptidase families
    Classification of peptidase families and list of entries
  8. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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