FABP6_HUMAN
ID FABP6_HUMAN Reviewed; 128 AA.
AC P51161; Q07DR7; Q8TBI3; Q9UGI7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Gastrotropin;
DE Short=GT;
DE AltName: Full=Fatty acid-binding protein 6;
DE AltName: Full=Ileal lipid-binding protein;
DE Short=ILBP;
DE AltName: Full=Intestinal 15 kDa protein;
DE Short=I-15P;
DE AltName: Full=Intestinal bile acid-binding protein;
DE Short=I-BABP;
GN Name=FABP6; Synonyms=ILBP, ILLBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Ileum;
RX PubMed=7619861; DOI=10.1016/0005-2760(95)00098-w;
RA Oelkers P., Dawson P.A.;
RT "Cloning and chromosomal localization of the human ileal lipid-binding
RT protein.";
RL Biochim. Biophys. Acta 1257:199-202(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BILE ACID-BINDING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Ileum;
RX PubMed=7588781; DOI=10.1111/j.1432-1033.1995.406_2.x;
RA Fujita M., Fujii H., Kanda T., Sato E., Hatakeyama K., Ono T.;
RT "Molecular cloning, expression, and characterization of a human intestinal
RT 15-kDa protein.";
RL Eur. J. Biochem. 233:406-413(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), ALTERNATIVE
RP PROMOTER USAGE, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=17909007; DOI=10.1158/0008-5472.can-06-3690;
RA Fang C., Dean J., Smith J.W.;
RT "A novel variant of ileal bile acid binding protein is up-regulated through
RT nuclear factor-kappaB activation in colorectal adenocarcinoma.";
RL Cancer Res. 67:9039-9046(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS
RP HIS-33 AND TYR-55.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19 (ISOFORM 1).
RA Barley N.F., Shaw-Smith C.J., Chakravarty P., Howard A., Legon S.,
RA Walters J.R.;
RT "The human ileal bile acid binding protein gene: promoter sequence and
RT effects of CDX2 on expression.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP BILE ACID-BINDING.
RX PubMed=11461829; DOI=10.1016/s1357-2725(01)00070-x;
RA Zimmerman A.W., van Moerkerk H.T., Veerkamp J.H.;
RT "Ligand specificity and conformational stability of human fatty acid-
RT binding proteins.";
RL Int. J. Biochem. Cell Biol. 33:865-876(2001).
RN [8]
RP STRUCTURE BY NMR IN COMPLEX WITH TAUROCHOLATE, AND DOMAIN.
RX PubMed=12486725; DOI=10.1002/prot.10289;
RA Kurz M., Brachvogel V., Matter H., Stengelin S., Thuering H., Kramer W.;
RT "Insights into the bile acid transportation system: the human ileal lipid-
RT binding protein-cholyltaurine complex and its comparison with homologous
RT structures.";
RL Proteins 50:312-328(2003).
RN [9]
RP STRUCTURE BY NMR IN COMPLEX WITH GLYCOCHOLATE AND GLYCOCHENODEOXYCHOLATE,
RP AND DOMAIN.
RX PubMed=26613247; DOI=10.1111/febs.13610;
RA Horvath G., Bencsura A., Simon A., Tochtrop G.P., DeKoster G.T.,
RA Covey D.F., Cistola D.P., Toke O.;
RT "Structural determinants of ligand binding in the ternary complex of human
RT ileal bile acid binding protein with glycocholate and
RT glycochenodeoxycholate obtained from solution NMR.";
RL FEBS J. 283:541-555(2016).
RN [10]
RP VARIANT MET-79.
RX PubMed=19744871; DOI=10.1016/j.ymgme.2009.08.001;
RA Fisher E., Grallert H., Klapper M., Pfaefflin A., Schrezenmeir J.,
RA Illig T., Boeing H., Doering F.;
RT "Evidence for the Thr79Met polymorphism of the ileal fatty acid binding
RT protein (FABP6) to be associated with type 2 diabetes in obese
RT individuals.";
RL Mol. Genet. Metab. 98:400-405(2009).
CC -!- FUNCTION: Binds to bile acids and is involved in enterohepatic bile
CC acid metabolism. Required for efficient apical to basolateral transport
CC of conjugated bile acids in ileal enterocytes (By similarity). In vitro
CC binds to bile acids in the order: deoxycholic acid > cholic acid >
CC chenodeoxycholic acid and respective BA conjugation modifies affinities
CC in the order taurine-conjugated > glycine-conjugated > unconjugated
CC bile acids. Stimulates gastric acid and pepsinogen secretion (By
CC similarity). {ECO:0000250|UniProtKB:P10289,
CC ECO:0000250|UniProtKB:P51162, ECO:0000269|PubMed:12486725,
CC ECO:0000269|PubMed:7588781}.
CC -!- FUNCTION: [Isoform 2]: Essential for the survival of colon cancer cells
CC to bile acid-induced apoptosis. {ECO:0000269|PubMed:17909007}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000250|UniProtKB:P80020}. Membrane; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P50119}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P50119}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:17909007}. Note=Localized close to nucleus on the
CC apical side of both normal and neoplastic cells.
CC {ECO:0000269|PubMed:17909007}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1;
CC IsoId=P51161-1; Sequence=Displayed;
CC Name=2; Synonyms=IBABP-L;
CC IsoId=P51161-2; Sequence=VSP_038039;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in the jejunum, ileum, cecum
CC and ascending colon intestine. Isoform 2 is xpressed in the
CC gallbladder, duodenum, jejunum, ileum, cecum, ascending, transverse and
CC descending colon, sigmoid colon and rectum. Isoform 2 is expressed in
CC colorectal adenocarcinomas and their adjacent normal mucosa (at protein
CC level). {ECO:0000269|PubMed:17909007, ECO:0000269|PubMed:7588781,
CC ECO:0000269|PubMed:7619861}.
CC -!- INDUCTION: Isoform 1 is up-regulated by chenodeoxycholic acid (CDCA)
CC via the FXR transcription pathway. Isoform 2 is up-regulated by NF-
CC kappa-B and in all stages of colorectal adenocarcinoma. Isoform 1 is
CC not up-regulated in all stages of colorectal adenocarcinoma.
CC {ECO:0000269|PubMed:17909007}.
CC -!- DOMAIN: Forms a beta-barrel structure that accommodates the hydrophobic
CC ligand in its interior. Can bind at least two ligands per molecule,
CC however, the stoichiometry is debated. {ECO:0000305|PubMed:12486725,
CC ECO:0000305|PubMed:26613247}.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Fatty-acid binding
CC protein (FABP) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22489.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U19869; AAB82751.1; -; mRNA.
DR EMBL; X90908; CAA62415.1; -; mRNA.
DR EMBL; DQ132786; ABA12611.1; -; mRNA.
DR EMBL; AC008609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022489; AAH22489.1; ALT_INIT; mRNA.
DR EMBL; AJ250902; CAB65728.1; -; Genomic_DNA.
DR CCDS; CCDS43393.1; -. [P51161-2]
DR CCDS; CCDS4349.1; -. [P51161-1]
DR PIR; S63983; S63983.
DR RefSeq; NP_001035532.1; NM_001040442.1. [P51161-2]
DR RefSeq; NP_001124430.1; NM_001130958.1. [P51161-2]
DR RefSeq; NP_001436.1; NM_001445.2. [P51161-1]
DR PDB; 1O1U; NMR; -; A=2-128.
DR PDB; 1O1V; NMR; -; A=2-128.
DR PDB; 2MM3; NMR; -; A=2-128.
DR PDB; 5L8I; X-ray; 1.88 A; A/B/C=1-128.
DR PDB; 5L8N; X-ray; 2.12 A; A/B/C=1-128.
DR PDB; 5L8O; X-ray; 2.39 A; A/B/C=1-128.
DR PDBsum; 1O1U; -.
DR PDBsum; 1O1V; -.
DR PDBsum; 2MM3; -.
DR PDBsum; 5L8I; -.
DR PDBsum; 5L8N; -.
DR PDBsum; 5L8O; -.
DR AlphaFoldDB; P51161; -.
DR BMRB; P51161; -.
DR SMR; P51161; -.
DR BioGRID; 108470; 5.
DR STRING; 9606.ENSP00000377549; -.
DR BindingDB; P51161; -.
DR ChEMBL; CHEMBL4523235; -.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB02691; Glycocholic acid.
DR DrugBank; DB04348; Taurocholic acid.
DR SwissLipids; SLP:000001518; -.
DR iPTMnet; P51161; -.
DR PhosphoSitePlus; P51161; -.
DR BioMuta; FABP6; -.
DR DMDM; 1708457; -.
DR EPD; P51161; -.
DR jPOST; P51161; -.
DR MassIVE; P51161; -.
DR MaxQB; P51161; -.
DR PaxDb; P51161; -.
DR PeptideAtlas; P51161; -.
DR PRIDE; P51161; -.
DR ProteomicsDB; 56292; -. [P51161-1]
DR ProteomicsDB; 56293; -. [P51161-2]
DR Antibodypedia; 1989; 246 antibodies from 30 providers.
DR DNASU; 2172; -.
DR Ensembl; ENST00000393980.8; ENSP00000377549.4; ENSG00000170231.16. [P51161-2]
DR Ensembl; ENST00000402432.4; ENSP00000385433.4; ENSG00000170231.16. [P51161-1]
DR GeneID; 2172; -.
DR KEGG; hsa:2172; -.
DR MANE-Select; ENST00000402432.4; ENSP00000385433.4; NM_001445.3; NP_001436.1.
DR UCSC; uc003lxx.2; human. [P51161-1]
DR CTD; 2172; -.
DR DisGeNET; 2172; -.
DR GeneCards; FABP6; -.
DR HGNC; HGNC:3561; FABP6.
DR HPA; ENSG00000170231; Tissue enriched (intestine).
DR MIM; 600422; gene.
DR neXtProt; NX_P51161; -.
DR OpenTargets; ENSG00000170231; -.
DR PharmGKB; PA27962; -.
DR VEuPathDB; HostDB:ENSG00000170231; -.
DR eggNOG; KOG4015; Eukaryota.
DR GeneTree; ENSGT00940000157139; -.
DR HOGENOM; CLU_113772_4_0_1; -.
DR InParanoid; P51161; -.
DR OrthoDB; 1440574at2759; -.
DR PhylomeDB; P51161; -.
DR TreeFam; TF330348; -.
DR PathwayCommons; P51161; -.
DR Reactome; R-HSA-159418; Recycling of bile acids and salts.
DR Reactome; R-HSA-163560; Triglyceride catabolism.
DR Reactome; R-HSA-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR SIGNOR; P51161; -.
DR BioGRID-ORCS; 2172; 6 hits in 1069 CRISPR screens.
DR ChiTaRS; FABP6; human.
DR EvolutionaryTrace; P51161; -.
DR GeneWiki; FABP6; -.
DR GenomeRNAi; 2172; -.
DR Pharos; P51161; Tbio.
DR PRO; PR:P51161; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P51161; protein.
DR Bgee; ENSG00000170231; Expressed in ileal mucosa and 135 other tissues.
DR ExpressionAtlas; P51161; baseline and differential.
DR Genevisible; P51161; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005504; F:fatty acid binding; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; TAS:ProtInc.
DR GO; GO:0015908; P:fatty acid transport; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR000463; Fatty_acid-bd.
DR InterPro; IPR031259; ILBP.
DR PANTHER; PTHR11955; PTHR11955; 1.
DR PRINTS; PR00178; FATTYACIDBP.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00214; FABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage; Cytoplasm;
KW Lipid transport; Lipid-binding; Membrane; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P10289"
FT CHAIN 2..128
FT /note="Gastrotropin"
FT /id="PRO_0000067380"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P10289"
FT VAR_SEQ 1
FT /note="M -> MKTVTMMMVVEMQALTQVLRAVLSACTWVSRKGDLQRMKQTHKGKPP
FT SSM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17909007"
FT /id="VSP_038039"
FT VARIANT 33
FT /note="R -> H (in dbSNP:rs17856662)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039578"
FT VARIANT 55
FT /note="S -> Y (in dbSNP:rs17852045)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_039579"
FT VARIANT 79
FT /note="T -> M (may be associated with type 2 diabetes obese
FT individuals; dbSNP:rs1130435)"
FT /evidence="ECO:0000269|PubMed:19744871"
FT /id="VAR_039580"
FT STRAND 5..14
FT /evidence="ECO:0007829|PDB:5L8I"
FT HELIX 15..22
FT /evidence="ECO:0007829|PDB:5L8I"
FT HELIX 26..33
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:5L8I"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:5L8O"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:5L8N"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 106..115
FT /evidence="ECO:0007829|PDB:5L8I"
FT STRAND 118..127
FT /evidence="ECO:0007829|PDB:5L8I"
SQ SEQUENCE 128 AA; 14371 MW; 173CBC5DBEDADDE1 CRC64;
MAFTGKFEME SEKNYDEFMK LLGISSDVIE KARNFKIVTE VQQDGQDFTW SQHYSGGHTM
TNKFTVGKES NIQTMGGKTF KATVQMEGGK LVVNFPNYHQ TSEIVGDKLV EVSTIGGVTY
ERVSKRLA
