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P16301

- LCAT_MOUSE

UniProt

P16301 - LCAT_MOUSE

Protein

Phosphatidylcholine-sterol acyltransferase

Gene

Lcat

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms By similarity. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines.By similarity4 Publications

    Catalytic activityi

    Phosphatidylcholine + a sterol = 1-acylglycerophosphocholine + a sterol ester.PROSITE-ProRule annotation

    Enzyme regulationi

    APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei173 – 1731Determinant for substrate specificity
    Active sitei205 – 2051Charge relay systemPROSITE-ProRule annotation

    GO - Molecular functioni

    1. phosphatidylcholine-sterol O-acyltransferase activity Source: MGI

    GO - Biological processi

    1. cholesterol esterification Source: Ensembl
    2. cholesterol homeostasis Source: Ensembl
    3. cholesterol metabolic process Source: MGI
    4. cholesterol transport Source: MGI
    5. high-density lipoprotein particle remodeling Source: Ensembl
    6. lipoprotein biosynthetic process Source: MGI
    7. phosphatidylcholine biosynthetic process Source: Ensembl
    8. regulation of high-density lipoprotein particle assembly Source: UniProtKB
    9. reverse cholesterol transport Source: Ensembl
    10. very-low-density lipoprotein particle remodeling Source: Ensembl

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

    Enzyme and pathway databases

    ReactomeiREACT_213857. HDL-mediated lipid transport.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylcholine-sterol acyltransferase (EC:2.3.1.43)
    Alternative name(s):
    Lecithin-cholesterol acyltransferase
    Phospholipid-cholesterol acyltransferase
    Gene namesi
    Name:Lcat
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:96755. Lcat.

    Subcellular locationi

    Secreted
    Note: Secreted into blood plasma. Produced in astrocytes and secreted into cerebral spinal fluid (CSF) By similarity.By similarity

    GO - Cellular componenti

    1. extracellular space Source: MGI
    2. high-density lipoprotein particle Source: Ensembl

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Null mice exhibit a 7-fold increase in the cholesteryl ester fatty acid CEFA ratio of APOB lipoprotein CEs. There is also a 3.6 increase in vascular ring O2 production and plasma phospholipid (PL)-bound-F2-isoprostane levels. This effect is paradoxically reversed in the APOE knockout background.3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Add
    BLAST
    Chaini25 – 438414Phosphatidylcholine-sterol acyltransferasePRO_0000017804Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi44 – 441N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi74 ↔ 98By similarity
    Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi337 ↔ 380By similarity
    Glycosylationi397 – 3971N-linked (GlcNAc...)1 Publication
    Glycosylationi408 – 4081N-linked (GlcNAc...)1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP16301.
    PRIDEiP16301.

    PTM databases

    PhosphoSiteiP16301.

    Expressioni

    Tissue specificityi

    Abundantly expressed in liver, brain and testis with highest levels in liver. In the brain, found in cerebellum, cerebral cortex, hippocampus and brain stem. Located to neurons and neuroglia.2 Publications

    Developmental stagei

    In the testis, expressed days 4,8, 14, and 35 of postnatal life with highest levels at day 35. In the brain, expressed in fetal stages and levels begin to rise after day 4 after birth and continue to increase through suckling and weaning reaching a peak at postnatal day 24. In the liver, expressed in fetal life from day 16-21 of gestation with a 3-fold increase in the four final days of gestation.1 Publication

    Gene expression databases

    BgeeiP16301.
    CleanExiMM_LCAT.
    GenevestigatoriP16301.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000038232.

    Structurei

    3D structure databases

    ProteinModelPortaliP16301.
    SMRiP16301. Positions 196-239.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi425 – 43713Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the AB hydrolase superfamily. Lipase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG322613.
    GeneTreeiENSGT00390000004902.
    HOVERGENiHBG017055.
    InParanoidiQ8K139.
    KOiK00650.
    OMAiLRQPQSW.
    OrthoDBiEOG73BVD0.
    TreeFamiTF313258.

    Family and domain databases

    Gene3Di3.40.50.1820. 3 hits.
    InterProiIPR029058. AB_hydrolase.
    IPR003386. LACT/PDAT_acylTrfase.
    [Graphical view]
    PfamiPF02450. LCAT. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 2 hits.
    PROSITEiPS00120. LIPASE_SER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P16301-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGLPGSPWQR VLLLLGLLLP PATPFWLLNV LFPPHTTPKA ELSNHTRPVI    50
    LVPGCLGNRL EAKLDKPDVV NWMCYRKTED FFTIWLDFNL FLPLGVDCWI 100
    DNTRIVYNHS SGRVSNAPGV QIRVPGFGKT ESVEYVDDNK LAGYLHTLVQ 150
    NLVNNGYVRD ETVRAAPYDW RLAPHQQDEY YKKLAGLVEE MYAAYGKPVF 200
    LIGHSLGCLH VLHFLLRQPQ SWKDHFIDGF ISLGAPWGGS IKAMRILASG 250
    DNQGIPILSN IKLKEEQRIT TTSPWMLPAP HVWPEDHVFI STPNFNYTVQ 300
    DFERFFTDLH FEEGWHMFLQ SRDLLERLPA PGVEVYCLYG VGRPTPHTYI 350
    YDHNFPYKDP VAALYEDGDD TVATRSTELC GQWQGRQSQP VHLLPMNETD 400
    HLNMVFSNKT LEHINAILLG AYRTPKSPAA SPSPPPPE 438
    Length:438
    Mass (Da):49,747
    Last modified:July 27, 2011 - v2
    Checksum:i2FDD571853523136
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti411 – 4111L → M in AAA39419. (PubMed:2600083)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05154 mRNA. Translation: AAA39419.1.
    AK149476 mRNA. Translation: BAE28903.1.
    AC159265 Genomic DNA. No translation available.
    BC028861 mRNA. Translation: AAH28861.1.
    X54095 Genomic DNA. Translation: CAA38029.1.
    CCDSiCCDS22622.1.
    PIRiA34158. XXMSN.
    RefSeqiNP_032516.2. NM_008490.2.
    UniGeneiMm.1593.

    Genome annotation databases

    EnsembliENSMUST00000038896; ENSMUSP00000038232; ENSMUSG00000035237.
    GeneIDi16816.
    KEGGimmu:16816.
    UCSCiuc009neq.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05154 mRNA. Translation: AAA39419.1 .
    AK149476 mRNA. Translation: BAE28903.1 .
    AC159265 Genomic DNA. No translation available.
    BC028861 mRNA. Translation: AAH28861.1 .
    X54095 Genomic DNA. Translation: CAA38029.1 .
    CCDSi CCDS22622.1.
    PIRi A34158. XXMSN.
    RefSeqi NP_032516.2. NM_008490.2.
    UniGenei Mm.1593.

    3D structure databases

    ProteinModelPortali P16301.
    SMRi P16301. Positions 196-239.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000038232.

    PTM databases

    PhosphoSitei P16301.

    Proteomic databases

    PaxDbi P16301.
    PRIDEi P16301.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000038896 ; ENSMUSP00000038232 ; ENSMUSG00000035237 .
    GeneIDi 16816.
    KEGGi mmu:16816.
    UCSCi uc009neq.2. mouse.

    Organism-specific databases

    CTDi 3931.
    MGIi MGI:96755. Lcat.

    Phylogenomic databases

    eggNOGi NOG322613.
    GeneTreei ENSGT00390000004902.
    HOVERGENi HBG017055.
    InParanoidi Q8K139.
    KOi K00650.
    OMAi LRQPQSW.
    OrthoDBi EOG73BVD0.
    TreeFami TF313258.

    Enzyme and pathway databases

    Reactomei REACT_213857. HDL-mediated lipid transport.

    Miscellaneous databases

    NextBioi 290700.
    PROi P16301.
    SOURCEi Search...

    Gene expression databases

    Bgeei P16301.
    CleanExi MM_LCAT.
    Genevestigatori P16301.

    Family and domain databases

    Gene3Di 3.40.50.1820. 3 hits.
    InterProi IPR029058. AB_hydrolase.
    IPR003386. LACT/PDAT_acylTrfase.
    [Graphical view ]
    Pfami PF02450. LCAT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53474. SSF53474. 2 hits.
    PROSITEi PS00120. LIPASE_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver."
      Warden C.H., Langner C.A., Gordon J.I., Taylor B.A., McLean J.W., Lusis A.J.
      J. Biol. Chem. 264:21573-21581(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Liver.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Liver.
    5. "Promoter and 5' flanking sequences of the mouse LCAT gene."
      Meroni G., Malgaretti N., Magnaghi P., Taramelli R.
      Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
    6. "Comparative studies on the substrate specificity of lecithin:cholesterol acyltransferase towards the molecular species of phosphatidylcholine in the plasma of 14 vertebrates."
      Subbaiah P.V., Liu M.
      J. Lipid Res. 37:113-122(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBSTRATE SPECIFICITY.
    7. "Oxidative stress is markedly elevated in lecithin:cholesterol acyltransferase-deficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis."
      Ng D.S., Maguire G.F., Wylie J., Ravandi A., Xuan W., Ahmed Z., Eskandarian M., Kuksis A., Connelly P.W.
      J. Biol. Chem. 277:11715-11720(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    8. "In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice."
      Furbee J.W. Jr., Francone O., Parks J.S.
      J. Lipid Res. 43:428-437(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    9. "Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins."
      Zhao Y., Thorngate F.E., Weisgraber K.H., Williams D.L., Parks J.S.
      Biochemistry 44:1013-1025(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION.
    10. "Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
      Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
      J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-397 AND ASN-408.
      Strain: C57BL/6.
      Tissue: Plasma.
    11. "LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins."
      Hirsch-Reinshagen V., Donkin J., Stukas S., Chan J., Wilkinson A., Fan J., Parks J.S., Kuivenhoven J.A., Lutjohann D., Pritchard H., Wellington C.L.
      J. Lipid Res. 50:885-893(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, ENZYME REGULATION, FUNCTION.

    Entry informationi

    Entry nameiLCAT_MOUSE
    AccessioniPrimary (citable) accession number: P16301
    Secondary accession number(s): Q8K139
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 114 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3