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FLASH GENE
Symbol FABP4 contributors: mct/npt - updated : 17-06-2016
HGNC name fatty acid binding protein 4, adipocyte
HGNC id 3559
Location 8q21.13      Physical location : 82.390.731 - 82.395.473
Synonym name
  • adipocyte protein 2
  • adipocyte fatty acid-binding protein
  • Synonym symbol(s) A-FABP, AP2, AFABP, ALBP, HEL-S-104, aP2
    DNA
    TYPE functioning gene
    STRUCTURE 4.74 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure binding site for CEBPA, involved in transcriptional activation of promoter
    MAPPING cloned Y linked   status provisional
    Map cen - D8S1436E - D8S1736 - FABP4 - D8S275 - D8S435 - qter
    Physical map
    PKIA 8q13-q21.3 protein kinase (cAMP-dependent, catalytic) inhibitor alpha CGI-62 8q21.11 CGI-62 protein IL7 8q12-q13 interleukin 7 STMN2 8p13.2 stathmin-like 2 HEY1 8q21 hairy/enhancer-of-split related with YRPW motif 1 MRPS28 8q21.1-q21.2 mitochondrial ribosomal protein S28 TPD52 8q21 tumor protein D52 LOC389671 8 LOC389671 LOC392236 8 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein LOC340443 8q21.12 similar to ribosomal protein S5; 40S ribosomal protein S5 RINZF LOC389672 8 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC392237 8 similar to mitochondrial carrier triple repeat 1 CKS1A 8q21 CDC28 protein kinase regulatory subunit 1A PAG 8q21.13 CDC28 protein kinase regulatory subunit 1A LOC392238 8 LOC392238 LOC392239 FABP5 15q12-q24.3 fatty acid binding protein 5 (psoriasis-associated) PMP2 8q21.3-q22.1 peripheral myelin protein 2 FABP4 8q21 fatty acid binding protein 4, adipocyte LOC389673 8 similar to Myelin P2 protein LOC392240 8 similar to hypothetical protein MGC5466 IMPA1 8q21.2-q21.3 inositol(myo)-1(or 4)-monophosphatase 1 FLJ14007 8q21.13 hypothetical protein FLJ14007 Shax3 8q21.13 Snf7 homologue associated with Alix 3 SNX16 8q21.13 sorting nexin 16 LOC389674 8 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) LOC392241 8 similar to tropomyosin 3, gamma LOC138046 8q21.13 hypothetical protein LOC138046 KIAA1764 8q21.13-q21.2 KIAA1764 protein E2F5 8q21.13 E2F transcription factor 5, p130-binding MGC59868 CA1 8q13-q22.1 carbonic anhydrase I
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 838 15 132 - Cabre (2008)
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Endocrineparathyroid   highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Muscularstriatumcardiacmyocardium  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage Homo sapiens
    Muscularmyocyte Homo sapiens
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • repeated structure with topology beta barrel and remarkable structural signature
  • a consensus alignment for the binding site as F-Acidic-Acidic-YMKX2GVG (Smith 2008)
  • an helix-turn-helix domain being a site for homodimerization
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • lipocalin, calycin family
  • cytoplasmic fatty acid-binding protein (FABP) multigene family
  • CATEGORY adaptor , regulatory , transport carrier
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • fatty acid-binding protein 4, involved in lipid transport protein in adipocytes
  • with hormone-sensitive lipase (LIPE), form a physical complex that affects basal and hormone-stimulated adipocyte fatty acid efflux ((Smith 2008)
  • having a role as a fatty acid sensor affecting cellular metabolism via protein-protein interactions (Thompson 2009)
  • fatty acid carrier solubilizing and enabling diffusion of fatty acids throughout the aqueous cellular environment (Thompson 2009)
  • mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
  • is an adipokine linking adipocytes to hepatic glucose production
  • FABP4/5 is potentially novel targets for the modulation of energy homeostasis
  • cytoplasmic fatty acid chaperone expressed primarily in adipocytes and myeloid cells and implicated in the development of insulin resistance and atherosclerosis
  • might promote human prostate cancer cell progression by binding with fatty acids
  • is functionally expressed in endometrial epithelium and is necessary for maintaining the cell function of epithelial cells of endometrium
  • mediates apoptosis via endoplasmic reticulum stress in mesangial cells of diabetic nephropathy
  • adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation
  • plays an important role in regulating heart function under pressure overload
  • FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds both long chain fatty acid and retinoic acid
  • two lipogenic genes encoding DGAT2 and FABP4 were induced in ELOVL2-overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FASN) gene
  • interaction with LIPE (hormone-sensitive lipase) requires that a fatty acid be bound to FABP4 and the association is considered to be regulatory, serving as a potential negative feedback loop regulating lipid hydrolysis (Smith 2008)
  • interacts with JAK2 in a fatty acid-dependent manner, through the helix-turn-helix domain (Thompson 2009)
  • suppression of PPARG by FABP4 in visceral fat may explain the reported role of FABP4 in the development of obesity-related morbidities, including insulin resistance, diabetes, and atherosclerosis
  • FABP4 induction by VEGFA was reduced by blockade of DLL4 binding to NOTCH1 or inhibition of NOTCH1 signal transduction
  • exogenous FABP4 interacts with plasma membrane proteins, specifically KRT1
  • PATZ1 acted as a potent transcriptional corepressor of FABP4, an essential convergence point for angiogenic and metabolic signaling pathways in endothelial cells (ECs)
  • cell & other
    REGULATION
    induced by NOTCH1 (is directly induced by NOTCH1 and stimulation of NOTCH1 signaling with human recombinant DLL4 led to FABP4 induction, independently of VEGFA)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    elevation of circulating FABP4 may contribute to left ventricular (LV) diastolic dysfunction
    tumoral     --over  
    in bone metastasis samples from prostate cancer patients
    constitutional     --over  
    before the clinical onset of preeclampsia, and this increase occurs independently of maternal body mass index
    Susceptibility to type 2 diabetes, hypertriglyceridemia, and cardiovascular disease
    Variant & Polymorphism other T-87C polymorphism having lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes
    Candidate gene clinical biomarker for atherogenic dyslipidemia, independent of obesity and insulin resistance, in type 2 diabetic subjects
    Marker
  • significantly associated with ischemic stroke and may serve as a useful prognostic indicator for early mortality
  • may potentially serve as a novel biomarker for the prediction of gestational diabetes mellitus
  • FABP4 in leucocytes is a potential and easy accessible biomarker of atherosclerosis which could be of future clinical relevance
  • Therapy target
    SystemTypeDisorderPubmed
    diabete  
    neutralizing secreted FABP4 may represent an effective therapeutic strategy against diabetes
    ANIMAL & CELL MODELS
  • mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of fatty acid (FA) with compensatory up-regulation of glucose consumption in these tissues during fasting