Full text data of FAT1
FAT1
(CDHF7, FAT)
[Confidence: low (only semi-automatic identification from reviews)]
Protocadherin Fat 1 (Cadherin family member 7; Cadherin-related tumor suppressor homolog; Protein fat homolog; Protocadherin Fat 1, nuclear form; Flags: Precursor)
Protocadherin Fat 1 (Cadherin family member 7; Cadherin-related tumor suppressor homolog; Protein fat homolog; Protocadherin Fat 1, nuclear form; Flags: Precursor)
UniProt
Q14517
ID FAT1_HUMAN Reviewed; 4588 AA.
AC Q14517;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-MAY-2011, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Protocadherin Fat 1;
DE AltName: Full=Cadherin family member 7;
DE AltName: Full=Cadherin-related tumor suppressor homolog;
DE AltName: Full=Protein fat homolog;
DE Contains:
DE RecName: Full=Protocadherin Fat 1, nuclear form;
DE Flags: Precursor;
GN Name=FAT1; Synonyms=CDHF7, FAT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=8586420; DOI=10.1006/geno.1995.9884;
RA Dunne J., Hanby A.M., Poulsom R., Jones T.A., Sheer D., Chin W.G.,
RA Da S.M., Zhao Q., Beverley P.C.L., Owen M.J.;
RT "Molecular cloning and tissue expression of FAT, the human homologue
RT of the Drosophila fat gene that is located on chromosome 4q34-q35 and
RT encodes a putative adhesion molecule.";
RL Genomics 30:207-223(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [3]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15922730; DOI=10.1016/j.yexcr.2005.03.006;
RA Magg T., Schreiner D., Solis G.P., Bade E.G., Hofer H.W.;
RT "Processing of the human protocadherin Fat1 and translocation of its
RT cytoplasmic domain to the nucleus.";
RL Exp. Cell Res. 307:100-108(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [5]
RP INTERACTION WITH ATN1 AND RERE.
RX PubMed=19131340; DOI=10.1074/jbc.M809333200;
RA Hou R., Sibinga N.E.;
RT "Atrophin proteins interact with the Fat1 cadherin and regulate
RT migration and orientation in vascular smooth muscle cells.";
RL J. Biol. Chem. 284:6955-6965(2009).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-3415; ASN-3422 AND
RP ASN-3716, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-3716, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Plays an essential role for cellular polarization,
CC directed cell migration and modulating cell-cell contact (By
CC similarity).
CC -!- SUBUNIT: Interacts (via the C-terminus 4300-4400 AA) with ATN1.
CC Interacts with RERE. Interacts (via EVH1 domains) with ENAH (By
CC similarity). Interacts (via cytoplasmic domain) with CTNNB1 (By
CC similarity).
CC -!- INTERACTION:
CC Q8N8S7:ENAH; NbExp=2; IntAct=EBI-1171918, EBI-2834410;
CC Q9NSC5:HOMER3; NbExp=4; IntAct=EBI-1171918, EBI-748420;
CC Q99JP6:Homer3 (xeno); NbExp=2; IntAct=EBI-1171918, EBI-6272061;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Nucleus. Cytoplasm, perinuclear region.
CC -!- TISSUE SPECIFICITY: Expressed in many epithelial and some
CC endothelial and smooth muscle cells.
CC -!- DOMAIN: A PTB-like motif (DNXYH sequence) is required for the
CC targeting to the leading edge. This motif represents a minimal
CC protein-protein interaction core motif that is not regulated by
CC tyrosine phosphorylation (By similarity).
CC -!- PTM: Undergoes proteolytic cleavage. The extracellular domain is
CC cleaved off and the cytoplasmic domain (about 400 AA) shuttles to
CC the nucleus.
CC -!- SIMILARITY: Contains 33 cadherin domains.
CC -!- SIMILARITY: Contains 5 EGF-like domains.
CC -!- SIMILARITY: Contains 1 laminin G-like domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FAT1ID40533ch4q35.html";
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DR EMBL; X87241; CAA60685.1; -; mRNA.
DR EMBL; AC107050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_005236.2; NM_005245.3.
DR UniGene; Hs.481371; -.
DR ProteinModelPortal; Q14517; -.
DR IntAct; Q14517; 10.
DR MINT; MINT-2806731; -.
DR STRING; 9606.ENSP00000406229; -.
DR PhosphoSite; Q14517; -.
DR DMDM; 8928104; -.
DR PaxDb; Q14517; -.
DR PRIDE; Q14517; -.
DR Ensembl; ENST00000441802; ENSP00000406229; ENSG00000083857.
DR GeneID; 2195; -.
DR KEGG; hsa:2195; -.
DR UCSC; uc003izf.3; human.
DR CTD; 2195; -.
DR GeneCards; GC04M187508; -.
DR HGNC; HGNC:3595; FAT1.
DR HPA; HPA001869; -.
DR HPA; HPA023882; -.
DR MIM; 600976; gene.
DR neXtProt; NX_Q14517; -.
DR PharmGKB; PA164719952; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000046499; -.
DR HOVERGEN; HBG005641; -.
DR InParanoid; Q14517; -.
DR KO; K16506; -.
DR OMA; PYEAFIV; -.
DR OrthoDB; EOG7WMCHJ; -.
DR ChiTaRS; FAT1; human.
DR GeneWiki; FAT_(gene); -.
DR GenomeRNAi; 2195; -.
DR NextBio; 8873; -.
DR PRO; PR:Q14517; -.
DR ArrayExpress; Q14517; -.
DR Bgee; Q14517; -.
DR CleanEx; HS_FAT1; -.
DR Genevestigator; Q14517; -.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0016337; P:cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; ISS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion; IEA:InterPro.
DR Gene3D; 2.60.120.200; -; 2.
DR Gene3D; 2.60.40.60; -; 33.
DR InterPro; IPR002126; Cadherin.
DR InterPro; IPR015919; Cadherin-like.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
DR InterPro; IPR000742; EG-like_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR001791; Laminin_G.
DR Pfam; PF00028; Cadherin; 29.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF02210; Laminin_G_2; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 34.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00282; LamG; 1.
DR SUPFAM; SSF49313; SSF49313; 33.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00232; CADHERIN_1; 17.
DR PROSITE; PS50268; CADHERIN_2; 33.
DR PROSITE; PS00022; EGF_1; 4.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 5.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50025; LAM_G_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Complete proteome; Cytoplasm;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Nucleus;
KW Polymorphism; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 21 Potential.
FT CHAIN 22 4588 Protocadherin Fat 1.
FT /FTId=PRO_0000004017.
FT CHAIN ? 4588 Protocadherin Fat 1, nuclear form.
FT /FTId=PRO_0000408559.
FT TOPO_DOM 22 4181 Extracellular (Potential).
FT TRANSMEM 4182 4202 Helical; (Potential).
FT TOPO_DOM 4203 4588 Cytoplasmic (Potential).
FT DOMAIN 35 149 Cadherin 1.
FT DOMAIN 150 257 Cadherin 2.
FT DOMAIN 368 463 Cadherin 3.
FT DOMAIN 464 569 Cadherin 4.
FT DOMAIN 570 673 Cadherin 5.
FT DOMAIN 718 822 Cadherin 6.
FT DOMAIN 823 927 Cadherin 7.
FT DOMAIN 928 1034 Cadherin 8.
FT DOMAIN 1035 1139 Cadherin 9.
FT DOMAIN 1140 1245 Cadherin 10.
FT DOMAIN 1246 1357 Cadherin 11.
FT DOMAIN 1359 1456 Cadherin 12.
FT DOMAIN 1457 1562 Cadherin 13.
FT DOMAIN 1563 1667 Cadherin 14.
FT DOMAIN 1668 1765 Cadherin 15.
FT DOMAIN 1766 1879 Cadherin 16.
FT DOMAIN 1880 1979 Cadherin 17.
FT DOMAIN 1980 2081 Cadherin 18.
FT DOMAIN 2082 2182 Cadherin 19.
FT DOMAIN 2183 2283 Cadherin 20.
FT DOMAIN 2284 2390 Cadherin 21.
FT DOMAIN 2391 2492 Cadherin 22.
FT DOMAIN 2493 2596 Cadherin 23.
FT DOMAIN 2597 2703 Cadherin 24.
FT DOMAIN 2704 2809 Cadherin 25.
FT DOMAIN 2810 2918 Cadherin 26.
FT DOMAIN 2919 3023 Cadherin 27.
FT DOMAIN 3024 3125 Cadherin 28.
FT DOMAIN 3126 3230 Cadherin 29.
FT DOMAIN 3231 3335 Cadherin 30.
FT DOMAIN 3336 3440 Cadherin 31.
FT DOMAIN 3441 3545 Cadherin 32.
FT DOMAIN 3546 3647 Cadherin 33.
FT DOMAIN 3790 3827 EGF-like 1.
FT DOMAIN 3829 4009 Laminin G-like.
FT DOMAIN 4013 4050 EGF-like 2.
FT DOMAIN 4052 4088 EGF-like 3.
FT DOMAIN 4089 4125 EGF-like 4.
FT DOMAIN 4127 4163 EGF-like 5; calcium-binding (Potential).
FT MOTIF 4204 4214 Nuclear localization signal (Potential).
FT MOTIF 4378 4382 PTB-like motif (By similarity).
FT CARBOHYD 40 40 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 333 333 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 660 660 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 740 740 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 791 791 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 998 998 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1426 1426 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1551 1551 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1748 1748 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1864 1864 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1902 1902 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1940 1940 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1991 1991 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 2325 2325 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 2464 2464 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3324 3324 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3415 3415 N-linked (GlcNAc...).
FT CARBOHYD 3422 3422 N-linked (GlcNAc...).
FT CARBOHYD 3444 3444 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3613 3613 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3640 3640 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3716 3716 N-linked (GlcNAc...).
FT CARBOHYD 4152 4152 N-linked (GlcNAc...) (Potential).
FT DISULFID 3794 3805 By similarity.
FT DISULFID 3799 3816 By similarity.
FT DISULFID 3818 3826 By similarity.
FT DISULFID 3976 4009 By similarity.
FT DISULFID 4017 4028 By similarity.
FT DISULFID 4022 4038 By similarity.
FT DISULFID 4040 4049 By similarity.
FT DISULFID 4056 4067 By similarity.
FT DISULFID 4061 4076 By similarity.
FT DISULFID 4078 4087 By similarity.
FT DISULFID 4093 4104 By similarity.
FT DISULFID 4098 4113 By similarity.
FT DISULFID 4115 4124 By similarity.
FT DISULFID 4131 4142 By similarity.
FT DISULFID 4136 4151 By similarity.
FT DISULFID 4153 4162 By similarity.
FT VARIANT 131 131 A -> V (in dbSNP:rs3733415).
FT /FTId=VAR_055590.
FT VARIANT 1330 1330 N -> S (in dbSNP:rs874111).
FT /FTId=VAR_055591.
FT VARIANT 1564 1564 A -> T (in dbSNP:rs2304867).
FT /FTId=VAR_055592.
FT VARIANT 1605 1605 N -> D (in dbSNP:rs6836935).
FT /FTId=VAR_055593.
FT VARIANT 3800 3800 P -> H (in dbSNP:rs11731738).
FT /FTId=VAR_055594.
FT CONFLICT 322 322 G -> D (in Ref. 1; CAA60685).
FT CONFLICT 404 404 S -> R (in Ref. 1; CAA60685).
FT CONFLICT 482 482 V -> I (in Ref. 1; CAA60685).
FT CONFLICT 614 614 F -> L (in Ref. 1; CAA60685).
FT CONFLICT 862 862 V -> L (in Ref. 1; CAA60685).
FT CONFLICT 1064 1064 R -> G (in Ref. 1; CAA60685).
FT CONFLICT 1273 1273 H -> R (in Ref. 1; CAA60685).
FT CONFLICT 1351 1351 P -> Q (in Ref. 1; CAA60685).
FT CONFLICT 1526 1529 HQHT -> SPAH (in Ref. 1; CAA60685).
FT CONFLICT 1604 1604 G -> GNIG (in Ref. 1; CAA60685).
FT CONFLICT 2006 2006 N -> S (in Ref. 1; CAA60685).
FT CONFLICT 2054 2054 T -> I (in Ref. 1; CAA60685).
FT CONFLICT 2385 2385 D -> G (in Ref. 1; CAA60685).
FT CONFLICT 2618 2619 VL -> S (in Ref. 1; CAA60685).
FT CONFLICT 2718 2718 I -> V (in Ref. 1; CAA60685).
FT CONFLICT 3113 3113 L -> V (in Ref. 1; CAA60685).
FT CONFLICT 4059 4059 K -> N (in Ref. 1; CAA60685).
SQ SEQUENCE 4588 AA; 506273 MW; 1896223E46E3B892 CRC64;
MGRHLALLLL LLLLFQHFGD SDGSQRLEQT PLQFTHLEYN VTVQENSAAK TYVGHPVKMG
VYITHPAWEV RYKIVSGDSE NLFKAEEYIL GDFCFLRIRT KGGNTAILNR EVKDHYTLIV
KALEKNTNVE ARTKVRVQVL DTNDLRPLFS PTSYSVSLPE NTAIRTSIAR VSATDADIGT
NGEFYYSFKD RTDMFAIHPT SGVIVLTGRL DYLETKLYEM EILAADRGMK LYGSSGISSM
AKLTVHIEQA NECAPVITAV TLSPSELDRD PAYAIVTVDD CDQGANGDIA SLSIVAGDLL
QQFRTVRSFP GSKEYKVKAI GGIDWDSHPF GYNLTLQAKD KGTPPQFSSV KVIHVTSPQF
KAGPVKFEKD VYRAEISEFA PPNTPVVMVK AIPAYSHLRY VFKSTPGKAK FSLNYNTGLI
SILEPVKRQQ AAHFELEVTT SDRKASTKVL VKVLGANSNP PEFTQTAYKA AFDENVPIGT
TVMSLSAVDP DEGENGYVTY SIANLNHVPF AIDHFTGAVS TSENLDYELM PRVYTLRIRA
SDWGLPYRRE VEVLATITLN NLNDNTPLFE KINCEGTIPR DLGVGEQITT VSAIDADELQ
LVQYQIEAGN ELDFFSLNPN SGVLSLKRSL MDGLGAKVSF HSLRITATDG ENFATPLYIN
ITVAASHKLV NLQCEETGVA KMLAEKLLQA NKLHNQGEVE DIFFDSHSVN AHIPQFRSTL
PTGIQVKENQ PVGSSVIFMN STDLDTGFNG KLVYAVSGGN EDSCFMIDME TGMLKILSPL
DRETTDKYTL NITVYDLGIP QKAAWRLLHV VVVDANDNPP EFLQESYFVE VSEDKEVHSE
IIQVEATDKD LGPNGHVTYS IVTDTDTFSI DSVTGVVNIA RPLDRELQHE HSLKIEARDQ
AREEPQLFST VVVKVSLEDV NDNPPTFIPP NYRVKVREDL PEGTVIMWLE AHDPDLGQSG
QVRYSLLDHG EGNFDVDKLS GAVRIVQQLD FEKKQVYNLT VRAKDKGKPV SLSSTCYVEV
EVVDVNENLH PPVFSSFVEK GTVKEDAPVG SLVMTVSAHD EDARRDGEIR YSIRDGSGVG
VFKIGEETGV IETSDRLDRE STSHYWLTVF ATDQGVVPLS SFIEIYIEVE DVNDNAPQTS
EPVYYPEIME NSPKDVSVVQ IEAFDPDSSS NDKLMYKITS GNPQGFFSIH PKTGLITTTS
RKLDREQQDE HILEVTVTDN GSPPKSTIAR VIVKILDEND NKPQFLQKFY KIRLPEREKP
DRERNARREP LYHVIATDKD EGPNAEISYS IEDGNEHGKF FIEPKTGVVS SKRFSAAGEY
DILSIKAVDN GRPQKSSTTR LHIEWISKPK PSLEPISFEE SFFTFTVMES DPVAHMIGVI
SVEPPGIPLW FDITGGNYDS HFDVDKGTGT IIVAKPLDAE QKSNYNLTVE ATDGTTTILT
QVFIKVIDTN DHRPQFSTSK YEVVIPEDTA PETEILQISA VDQDEKNKLI YTLQSSRDPL
SLKKFRLDPA TGSLYTSEKL DHEAVHQHTL TVMVRDQDVP VKRNFARIVV NVSDTNDHAP
WFTASSYKGR VYESAAVGSV VLQVTALDKD KGKNAEVLYS IESGNIGNSF MIDPVLGSIK
TAKELDRSNQ AEYDLMVKAT DKGSPPMSEI TSVRIFVTIA DNASPKFTSK EYSVELSETV
SIGSFVGMVT AHSQSSVVYE IKDGNTGDAF DINPHSGTII TQKALDFETL PIYTLIIQGT
NMAGLSTNTT VLVHLQDEND NAPVFMQAEY TGLISESASI NSVVLTDRNV PLVIRAADAD
KDSNALLVYH IVEPSVHTYF AIDSSTGAIH TVLSLDYEET SIFHFTVQVH DMGTPRLFAE
YAANVTVHVI DINDCPPVFA KPLYEASLLL PTYKGVKVIT VNATDADSSA FSQLIYSITE
GNIGEKFSMD YKTGALTVQN TTQLRSRYEL TVRASDGRFA GLTSVKINVK ESKESHLKFT
QDVYSAVVKE NSTEAETLAV ITAIGNPINE PLFYHILNPD RRFKISRTSG VLSTTGTPFD
REQQEAFDVV VEVTEEHKPS AVAHVVVKVI VEDQNDNAPV FVNLPYYAVV KVDTEVGHVI
RYVTAVDRDS GRNGEVHYYL KEHHEHFQIG PLGEISLKKQ FELDTLNKEY LVTVVAKDGG
NPAFSAEVIV PITVMNKAMP VFEKPFYSAE IAESIQVHSP VVHVQANSPE GLKVFYSITD
GDPFSQFTIN FNTGVINVIA PLDFEAHPAY KLSIRATDSL TGAHAEVFVD IIVDDINDNP
PVFAQQSYAV TLSEASVIGT SVVQVRATDS DSEPNRGISY QMFGNHSKSH DHFHVDSSTG
LISLLRTLDY EQSRQHTIFV RAVDGGMPTL SSDVIVTVDV TDLNDNPPLF EQQIYEARIS
EHAPHGHFVT CVKAYDADSS DIDKLQYSIL SGNDHKHFVI DSATGIITLS NLHRHALKPF
YSLNLSVSDG VFRSSTQVHV TVIGGNLHSP AFLQNEYEVE LAENAPLHTL VMEVKTTDGD
SGIYGHVTYH IVNDFAKDRF YINERGQIFT LEKLDRETPA EKVISVRLMA KDAGGKVAFC
TVNVILTDDN DNAPQFRATK YEVNIGSSAA KGTSVVKVLA SDADEGSNAD ITYAIEADSE
SVKENLEINK LSGVITTKES LIGLENEFFT FFVRAVDNGS PSKESVVLVY VKILPPEMQL
PKFSEPFYTF TVSEDVPIGT EIDLIRAEHS GTVLYSLVKG NTPESNRDES FVIDRQSGRL
KLEKSLDHET TKWYQFSILA RCTQDDHEMV ASVDVSIQVK DANDNSPVFE SSPYEAFIVE
NLPGGSRVIQ IRASDADSGT NGQVMYSLDQ SQSVEVIESF AINMETGWIT TLKELDHEKR
DNYQIKVVAS DHGEKIQLSS TAIVDVTVTD VNDSPPRFTA EIYKGTVSED DPQGGVIAIL
STTDADSEEI NRQVTYFITG GDPLGQFAVE TIQNEWKVYV KKPLDREKRD NYLLTITATD
GTFSSKAIVE VKVLDANDNS PVCEKTLYSD TIPEDVLPGK LIMQISATDA DIRSNAEITY
TLLGSGAEKF KLNPDTGELK TSTPLDREEQ AVYHLLVRAT DGGGRFCQAS IVLTLEDVND
NAPEFSADPY AITVFENTEP GTLLTRVQAT DADAGLNRKI LYSLIDSADG QFSINELSGI
IQLEKPLDRE LQAVYTLSLK AVDQGLPRRL TATGTVIVSV LDINDNPPVF EYREYGATVS
EDILVGTEVL QVYAASRDIE ANAEITYSII SGNEHGKFSI DSKTGAVFII ENLDYESSHE
YYLTVEATDG GTPSLSDVAT VNVNVTDIND NTPVFSQDTY TTVISEDAVL EQSVITVMAD
DADGPSNSHI HYSIIDGNQG SSFTIDPVRG EVKVTKLLDR ETISGYTLTV QASDNGSPPR
VNTTTVNIDV SDVNDNAPVF SRGNYSVIIQ ENKPVGFSVL QLVVTDEDSS HNGPPFFFTI
VTGNDEKAFE VNPQGVLLTS SAIKRKEKDH YLLQVKVADN GKPQLSSLTY IDIRVIEESI
YPPAILPLEI FITSSGEEYS GGVIGKIHAT DQDVYDTLTY SLDPQMDNLF SVSSTGGKLI
AHKKLDIGQY LLNVSVTDGK FTTVADITVH IRQVTQEMLN HTIAIRFANL TPEEFVGDYW
RNFQRALRNI LGVRRNDIQI VSLQSSEPHP HLDVLLFVEK PGSAQISTKQ LLHKINSSVT
DIEEIIGVRI LNVFQKLCAG LDCPWKFCDE KVSVDESVMS THSTARLSFV TPRHHRAAVC
LCKEGRCPPV HHGCEDDPCP EGSECVSDPW EEKHTCVCPS GRFGQCPGSS SMTLTGNSYV
KYRLTENENK LEMKLTMRLR TYSTHAVVMY ARGTDYSILE IHHGRLQYKF DCGSGPGIVS
VQSIQVNDGQ WHAVALEVNG NYARLVLDQV HTASGTAPGT LKTLNLDNYV FFGGHIRQQG
TRHGRSPQVG NGFRGCMDSI YLNGQELPLN SKPRSYAHIE ESVDVSPGCF LTATEDCASN
PCQNGGVCNP SPAGGYYCKC SALYIGTHCE ISVNPCSSKP CLYGGTCVVD NGGFVCQCRG
LYTGQRCQLS PYCKDEPCKN GGTCFDSLDG AVCQCDSGFR GERCQSDIDE CSGNPCLHGA
LCENTHGSYH CNCSHEYRGR HCEDAAPNQY VSTPWNIGLA EGIGIVVFVA GIFLLVVVFV
LCRKMISRKK KHQAEPKDKH LGPATAFLQR PYFDSKLNKN IYSDIPPQVP VRPISYTPSI
PSDSRNNLDR NSFEGSAIPE HPEFSTFNPE SVHGHRKAVA VCSVAPNLPP PPPSNSPSDS
DSIQKPSWDF DYDTKVVDLD PCLSKKPLEE KPSQPYSARE SLSEVQSLSS FQSESCDDNG
YHWDTSDWMP SVPLPDIQEF PNYEVIDEQT PLYSADPNAI DTDYYPGGYD IESDFPPPPE
DFPAADELPP LPPEFSNQFE SIHPPRDMPA AGSLGSSSRN RQRFNLNQYL PNFYPLDMSE
PQTKGTGENS TCREPHAPYP PGYQRHFEAP AVESMPMSVY ASTASCSDVS ACCEVESEVM
MSDYESGDDG HFEEVTIPPL DSQQHTEV
//
ID FAT1_HUMAN Reviewed; 4588 AA.
AC Q14517;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-MAY-2011, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Protocadherin Fat 1;
DE AltName: Full=Cadherin family member 7;
DE AltName: Full=Cadherin-related tumor suppressor homolog;
DE AltName: Full=Protein fat homolog;
DE Contains:
DE RecName: Full=Protocadherin Fat 1, nuclear form;
DE Flags: Precursor;
GN Name=FAT1; Synonyms=CDHF7, FAT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=8586420; DOI=10.1006/geno.1995.9884;
RA Dunne J., Hanby A.M., Poulsom R., Jones T.A., Sheer D., Chin W.G.,
RA Da S.M., Zhao Q., Beverley P.C.L., Owen M.J.;
RT "Molecular cloning and tissue expression of FAT, the human homologue
RT of the Drosophila fat gene that is located on chromosome 4q34-q35 and
RT encodes a putative adhesion molecule.";
RL Genomics 30:207-223(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [3]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15922730; DOI=10.1016/j.yexcr.2005.03.006;
RA Magg T., Schreiner D., Solis G.P., Bade E.G., Hofer H.W.;
RT "Processing of the human protocadherin Fat1 and translocation of its
RT cytoplasmic domain to the nucleus.";
RL Exp. Cell Res. 307:100-108(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [5]
RP INTERACTION WITH ATN1 AND RERE.
RX PubMed=19131340; DOI=10.1074/jbc.M809333200;
RA Hou R., Sibinga N.E.;
RT "Atrophin proteins interact with the Fat1 cadherin and regulate
RT migration and orientation in vascular smooth muscle cells.";
RL J. Biol. Chem. 284:6955-6965(2009).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-3415; ASN-3422 AND
RP ASN-3716, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-3716, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Plays an essential role for cellular polarization,
CC directed cell migration and modulating cell-cell contact (By
CC similarity).
CC -!- SUBUNIT: Interacts (via the C-terminus 4300-4400 AA) with ATN1.
CC Interacts with RERE. Interacts (via EVH1 domains) with ENAH (By
CC similarity). Interacts (via cytoplasmic domain) with CTNNB1 (By
CC similarity).
CC -!- INTERACTION:
CC Q8N8S7:ENAH; NbExp=2; IntAct=EBI-1171918, EBI-2834410;
CC Q9NSC5:HOMER3; NbExp=4; IntAct=EBI-1171918, EBI-748420;
CC Q99JP6:Homer3 (xeno); NbExp=2; IntAct=EBI-1171918, EBI-6272061;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Nucleus. Cytoplasm, perinuclear region.
CC -!- TISSUE SPECIFICITY: Expressed in many epithelial and some
CC endothelial and smooth muscle cells.
CC -!- DOMAIN: A PTB-like motif (DNXYH sequence) is required for the
CC targeting to the leading edge. This motif represents a minimal
CC protein-protein interaction core motif that is not regulated by
CC tyrosine phosphorylation (By similarity).
CC -!- PTM: Undergoes proteolytic cleavage. The extracellular domain is
CC cleaved off and the cytoplasmic domain (about 400 AA) shuttles to
CC the nucleus.
CC -!- SIMILARITY: Contains 33 cadherin domains.
CC -!- SIMILARITY: Contains 5 EGF-like domains.
CC -!- SIMILARITY: Contains 1 laminin G-like domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FAT1ID40533ch4q35.html";
CC -----------------------------------------------------------------------
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DR EMBL; X87241; CAA60685.1; -; mRNA.
DR EMBL; AC107050; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_005236.2; NM_005245.3.
DR UniGene; Hs.481371; -.
DR ProteinModelPortal; Q14517; -.
DR IntAct; Q14517; 10.
DR MINT; MINT-2806731; -.
DR STRING; 9606.ENSP00000406229; -.
DR PhosphoSite; Q14517; -.
DR DMDM; 8928104; -.
DR PaxDb; Q14517; -.
DR PRIDE; Q14517; -.
DR Ensembl; ENST00000441802; ENSP00000406229; ENSG00000083857.
DR GeneID; 2195; -.
DR KEGG; hsa:2195; -.
DR UCSC; uc003izf.3; human.
DR CTD; 2195; -.
DR GeneCards; GC04M187508; -.
DR HGNC; HGNC:3595; FAT1.
DR HPA; HPA001869; -.
DR HPA; HPA023882; -.
DR MIM; 600976; gene.
DR neXtProt; NX_Q14517; -.
DR PharmGKB; PA164719952; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000046499; -.
DR HOVERGEN; HBG005641; -.
DR InParanoid; Q14517; -.
DR KO; K16506; -.
DR OMA; PYEAFIV; -.
DR OrthoDB; EOG7WMCHJ; -.
DR ChiTaRS; FAT1; human.
DR GeneWiki; FAT_(gene); -.
DR GenomeRNAi; 2195; -.
DR NextBio; 8873; -.
DR PRO; PR:Q14517; -.
DR ArrayExpress; Q14517; -.
DR Bgee; Q14517; -.
DR CleanEx; HS_FAT1; -.
DR Genevestigator; Q14517; -.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0016337; P:cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; ISS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion; IEA:InterPro.
DR Gene3D; 2.60.120.200; -; 2.
DR Gene3D; 2.60.40.60; -; 33.
DR InterPro; IPR002126; Cadherin.
DR InterPro; IPR015919; Cadherin-like.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR008985; ConA-like_lec_gl_sf.
DR InterPro; IPR013320; ConA-like_subgrp.
DR InterPro; IPR000742; EG-like_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR001791; Laminin_G.
DR Pfam; PF00028; Cadherin; 29.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF02210; Laminin_G_2; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 34.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00282; LamG; 1.
DR SUPFAM; SSF49313; SSF49313; 33.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00232; CADHERIN_1; 17.
DR PROSITE; PS50268; CADHERIN_2; 33.
DR PROSITE; PS00022; EGF_1; 4.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 5.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50025; LAM_G_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Complete proteome; Cytoplasm;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Nucleus;
KW Polymorphism; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 21 Potential.
FT CHAIN 22 4588 Protocadherin Fat 1.
FT /FTId=PRO_0000004017.
FT CHAIN ? 4588 Protocadherin Fat 1, nuclear form.
FT /FTId=PRO_0000408559.
FT TOPO_DOM 22 4181 Extracellular (Potential).
FT TRANSMEM 4182 4202 Helical; (Potential).
FT TOPO_DOM 4203 4588 Cytoplasmic (Potential).
FT DOMAIN 35 149 Cadherin 1.
FT DOMAIN 150 257 Cadherin 2.
FT DOMAIN 368 463 Cadherin 3.
FT DOMAIN 464 569 Cadherin 4.
FT DOMAIN 570 673 Cadherin 5.
FT DOMAIN 718 822 Cadherin 6.
FT DOMAIN 823 927 Cadherin 7.
FT DOMAIN 928 1034 Cadherin 8.
FT DOMAIN 1035 1139 Cadherin 9.
FT DOMAIN 1140 1245 Cadherin 10.
FT DOMAIN 1246 1357 Cadherin 11.
FT DOMAIN 1359 1456 Cadherin 12.
FT DOMAIN 1457 1562 Cadherin 13.
FT DOMAIN 1563 1667 Cadherin 14.
FT DOMAIN 1668 1765 Cadherin 15.
FT DOMAIN 1766 1879 Cadherin 16.
FT DOMAIN 1880 1979 Cadherin 17.
FT DOMAIN 1980 2081 Cadherin 18.
FT DOMAIN 2082 2182 Cadherin 19.
FT DOMAIN 2183 2283 Cadherin 20.
FT DOMAIN 2284 2390 Cadherin 21.
FT DOMAIN 2391 2492 Cadherin 22.
FT DOMAIN 2493 2596 Cadherin 23.
FT DOMAIN 2597 2703 Cadherin 24.
FT DOMAIN 2704 2809 Cadherin 25.
FT DOMAIN 2810 2918 Cadherin 26.
FT DOMAIN 2919 3023 Cadherin 27.
FT DOMAIN 3024 3125 Cadherin 28.
FT DOMAIN 3126 3230 Cadherin 29.
FT DOMAIN 3231 3335 Cadherin 30.
FT DOMAIN 3336 3440 Cadherin 31.
FT DOMAIN 3441 3545 Cadherin 32.
FT DOMAIN 3546 3647 Cadherin 33.
FT DOMAIN 3790 3827 EGF-like 1.
FT DOMAIN 3829 4009 Laminin G-like.
FT DOMAIN 4013 4050 EGF-like 2.
FT DOMAIN 4052 4088 EGF-like 3.
FT DOMAIN 4089 4125 EGF-like 4.
FT DOMAIN 4127 4163 EGF-like 5; calcium-binding (Potential).
FT MOTIF 4204 4214 Nuclear localization signal (Potential).
FT MOTIF 4378 4382 PTB-like motif (By similarity).
FT CARBOHYD 40 40 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 333 333 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 660 660 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 740 740 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 791 791 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 998 998 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1426 1426 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1551 1551 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1748 1748 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1864 1864 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1902 1902 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1940 1940 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1991 1991 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 2325 2325 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 2464 2464 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3324 3324 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3415 3415 N-linked (GlcNAc...).
FT CARBOHYD 3422 3422 N-linked (GlcNAc...).
FT CARBOHYD 3444 3444 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3613 3613 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3640 3640 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 3716 3716 N-linked (GlcNAc...).
FT CARBOHYD 4152 4152 N-linked (GlcNAc...) (Potential).
FT DISULFID 3794 3805 By similarity.
FT DISULFID 3799 3816 By similarity.
FT DISULFID 3818 3826 By similarity.
FT DISULFID 3976 4009 By similarity.
FT DISULFID 4017 4028 By similarity.
FT DISULFID 4022 4038 By similarity.
FT DISULFID 4040 4049 By similarity.
FT DISULFID 4056 4067 By similarity.
FT DISULFID 4061 4076 By similarity.
FT DISULFID 4078 4087 By similarity.
FT DISULFID 4093 4104 By similarity.
FT DISULFID 4098 4113 By similarity.
FT DISULFID 4115 4124 By similarity.
FT DISULFID 4131 4142 By similarity.
FT DISULFID 4136 4151 By similarity.
FT DISULFID 4153 4162 By similarity.
FT VARIANT 131 131 A -> V (in dbSNP:rs3733415).
FT /FTId=VAR_055590.
FT VARIANT 1330 1330 N -> S (in dbSNP:rs874111).
FT /FTId=VAR_055591.
FT VARIANT 1564 1564 A -> T (in dbSNP:rs2304867).
FT /FTId=VAR_055592.
FT VARIANT 1605 1605 N -> D (in dbSNP:rs6836935).
FT /FTId=VAR_055593.
FT VARIANT 3800 3800 P -> H (in dbSNP:rs11731738).
FT /FTId=VAR_055594.
FT CONFLICT 322 322 G -> D (in Ref. 1; CAA60685).
FT CONFLICT 404 404 S -> R (in Ref. 1; CAA60685).
FT CONFLICT 482 482 V -> I (in Ref. 1; CAA60685).
FT CONFLICT 614 614 F -> L (in Ref. 1; CAA60685).
FT CONFLICT 862 862 V -> L (in Ref. 1; CAA60685).
FT CONFLICT 1064 1064 R -> G (in Ref. 1; CAA60685).
FT CONFLICT 1273 1273 H -> R (in Ref. 1; CAA60685).
FT CONFLICT 1351 1351 P -> Q (in Ref. 1; CAA60685).
FT CONFLICT 1526 1529 HQHT -> SPAH (in Ref. 1; CAA60685).
FT CONFLICT 1604 1604 G -> GNIG (in Ref. 1; CAA60685).
FT CONFLICT 2006 2006 N -> S (in Ref. 1; CAA60685).
FT CONFLICT 2054 2054 T -> I (in Ref. 1; CAA60685).
FT CONFLICT 2385 2385 D -> G (in Ref. 1; CAA60685).
FT CONFLICT 2618 2619 VL -> S (in Ref. 1; CAA60685).
FT CONFLICT 2718 2718 I -> V (in Ref. 1; CAA60685).
FT CONFLICT 3113 3113 L -> V (in Ref. 1; CAA60685).
FT CONFLICT 4059 4059 K -> N (in Ref. 1; CAA60685).
SQ SEQUENCE 4588 AA; 506273 MW; 1896223E46E3B892 CRC64;
MGRHLALLLL LLLLFQHFGD SDGSQRLEQT PLQFTHLEYN VTVQENSAAK TYVGHPVKMG
VYITHPAWEV RYKIVSGDSE NLFKAEEYIL GDFCFLRIRT KGGNTAILNR EVKDHYTLIV
KALEKNTNVE ARTKVRVQVL DTNDLRPLFS PTSYSVSLPE NTAIRTSIAR VSATDADIGT
NGEFYYSFKD RTDMFAIHPT SGVIVLTGRL DYLETKLYEM EILAADRGMK LYGSSGISSM
AKLTVHIEQA NECAPVITAV TLSPSELDRD PAYAIVTVDD CDQGANGDIA SLSIVAGDLL
QQFRTVRSFP GSKEYKVKAI GGIDWDSHPF GYNLTLQAKD KGTPPQFSSV KVIHVTSPQF
KAGPVKFEKD VYRAEISEFA PPNTPVVMVK AIPAYSHLRY VFKSTPGKAK FSLNYNTGLI
SILEPVKRQQ AAHFELEVTT SDRKASTKVL VKVLGANSNP PEFTQTAYKA AFDENVPIGT
TVMSLSAVDP DEGENGYVTY SIANLNHVPF AIDHFTGAVS TSENLDYELM PRVYTLRIRA
SDWGLPYRRE VEVLATITLN NLNDNTPLFE KINCEGTIPR DLGVGEQITT VSAIDADELQ
LVQYQIEAGN ELDFFSLNPN SGVLSLKRSL MDGLGAKVSF HSLRITATDG ENFATPLYIN
ITVAASHKLV NLQCEETGVA KMLAEKLLQA NKLHNQGEVE DIFFDSHSVN AHIPQFRSTL
PTGIQVKENQ PVGSSVIFMN STDLDTGFNG KLVYAVSGGN EDSCFMIDME TGMLKILSPL
DRETTDKYTL NITVYDLGIP QKAAWRLLHV VVVDANDNPP EFLQESYFVE VSEDKEVHSE
IIQVEATDKD LGPNGHVTYS IVTDTDTFSI DSVTGVVNIA RPLDRELQHE HSLKIEARDQ
AREEPQLFST VVVKVSLEDV NDNPPTFIPP NYRVKVREDL PEGTVIMWLE AHDPDLGQSG
QVRYSLLDHG EGNFDVDKLS GAVRIVQQLD FEKKQVYNLT VRAKDKGKPV SLSSTCYVEV
EVVDVNENLH PPVFSSFVEK GTVKEDAPVG SLVMTVSAHD EDARRDGEIR YSIRDGSGVG
VFKIGEETGV IETSDRLDRE STSHYWLTVF ATDQGVVPLS SFIEIYIEVE DVNDNAPQTS
EPVYYPEIME NSPKDVSVVQ IEAFDPDSSS NDKLMYKITS GNPQGFFSIH PKTGLITTTS
RKLDREQQDE HILEVTVTDN GSPPKSTIAR VIVKILDEND NKPQFLQKFY KIRLPEREKP
DRERNARREP LYHVIATDKD EGPNAEISYS IEDGNEHGKF FIEPKTGVVS SKRFSAAGEY
DILSIKAVDN GRPQKSSTTR LHIEWISKPK PSLEPISFEE SFFTFTVMES DPVAHMIGVI
SVEPPGIPLW FDITGGNYDS HFDVDKGTGT IIVAKPLDAE QKSNYNLTVE ATDGTTTILT
QVFIKVIDTN DHRPQFSTSK YEVVIPEDTA PETEILQISA VDQDEKNKLI YTLQSSRDPL
SLKKFRLDPA TGSLYTSEKL DHEAVHQHTL TVMVRDQDVP VKRNFARIVV NVSDTNDHAP
WFTASSYKGR VYESAAVGSV VLQVTALDKD KGKNAEVLYS IESGNIGNSF MIDPVLGSIK
TAKELDRSNQ AEYDLMVKAT DKGSPPMSEI TSVRIFVTIA DNASPKFTSK EYSVELSETV
SIGSFVGMVT AHSQSSVVYE IKDGNTGDAF DINPHSGTII TQKALDFETL PIYTLIIQGT
NMAGLSTNTT VLVHLQDEND NAPVFMQAEY TGLISESASI NSVVLTDRNV PLVIRAADAD
KDSNALLVYH IVEPSVHTYF AIDSSTGAIH TVLSLDYEET SIFHFTVQVH DMGTPRLFAE
YAANVTVHVI DINDCPPVFA KPLYEASLLL PTYKGVKVIT VNATDADSSA FSQLIYSITE
GNIGEKFSMD YKTGALTVQN TTQLRSRYEL TVRASDGRFA GLTSVKINVK ESKESHLKFT
QDVYSAVVKE NSTEAETLAV ITAIGNPINE PLFYHILNPD RRFKISRTSG VLSTTGTPFD
REQQEAFDVV VEVTEEHKPS AVAHVVVKVI VEDQNDNAPV FVNLPYYAVV KVDTEVGHVI
RYVTAVDRDS GRNGEVHYYL KEHHEHFQIG PLGEISLKKQ FELDTLNKEY LVTVVAKDGG
NPAFSAEVIV PITVMNKAMP VFEKPFYSAE IAESIQVHSP VVHVQANSPE GLKVFYSITD
GDPFSQFTIN FNTGVINVIA PLDFEAHPAY KLSIRATDSL TGAHAEVFVD IIVDDINDNP
PVFAQQSYAV TLSEASVIGT SVVQVRATDS DSEPNRGISY QMFGNHSKSH DHFHVDSSTG
LISLLRTLDY EQSRQHTIFV RAVDGGMPTL SSDVIVTVDV TDLNDNPPLF EQQIYEARIS
EHAPHGHFVT CVKAYDADSS DIDKLQYSIL SGNDHKHFVI DSATGIITLS NLHRHALKPF
YSLNLSVSDG VFRSSTQVHV TVIGGNLHSP AFLQNEYEVE LAENAPLHTL VMEVKTTDGD
SGIYGHVTYH IVNDFAKDRF YINERGQIFT LEKLDRETPA EKVISVRLMA KDAGGKVAFC
TVNVILTDDN DNAPQFRATK YEVNIGSSAA KGTSVVKVLA SDADEGSNAD ITYAIEADSE
SVKENLEINK LSGVITTKES LIGLENEFFT FFVRAVDNGS PSKESVVLVY VKILPPEMQL
PKFSEPFYTF TVSEDVPIGT EIDLIRAEHS GTVLYSLVKG NTPESNRDES FVIDRQSGRL
KLEKSLDHET TKWYQFSILA RCTQDDHEMV ASVDVSIQVK DANDNSPVFE SSPYEAFIVE
NLPGGSRVIQ IRASDADSGT NGQVMYSLDQ SQSVEVIESF AINMETGWIT TLKELDHEKR
DNYQIKVVAS DHGEKIQLSS TAIVDVTVTD VNDSPPRFTA EIYKGTVSED DPQGGVIAIL
STTDADSEEI NRQVTYFITG GDPLGQFAVE TIQNEWKVYV KKPLDREKRD NYLLTITATD
GTFSSKAIVE VKVLDANDNS PVCEKTLYSD TIPEDVLPGK LIMQISATDA DIRSNAEITY
TLLGSGAEKF KLNPDTGELK TSTPLDREEQ AVYHLLVRAT DGGGRFCQAS IVLTLEDVND
NAPEFSADPY AITVFENTEP GTLLTRVQAT DADAGLNRKI LYSLIDSADG QFSINELSGI
IQLEKPLDRE LQAVYTLSLK AVDQGLPRRL TATGTVIVSV LDINDNPPVF EYREYGATVS
EDILVGTEVL QVYAASRDIE ANAEITYSII SGNEHGKFSI DSKTGAVFII ENLDYESSHE
YYLTVEATDG GTPSLSDVAT VNVNVTDIND NTPVFSQDTY TTVISEDAVL EQSVITVMAD
DADGPSNSHI HYSIIDGNQG SSFTIDPVRG EVKVTKLLDR ETISGYTLTV QASDNGSPPR
VNTTTVNIDV SDVNDNAPVF SRGNYSVIIQ ENKPVGFSVL QLVVTDEDSS HNGPPFFFTI
VTGNDEKAFE VNPQGVLLTS SAIKRKEKDH YLLQVKVADN GKPQLSSLTY IDIRVIEESI
YPPAILPLEI FITSSGEEYS GGVIGKIHAT DQDVYDTLTY SLDPQMDNLF SVSSTGGKLI
AHKKLDIGQY LLNVSVTDGK FTTVADITVH IRQVTQEMLN HTIAIRFANL TPEEFVGDYW
RNFQRALRNI LGVRRNDIQI VSLQSSEPHP HLDVLLFVEK PGSAQISTKQ LLHKINSSVT
DIEEIIGVRI LNVFQKLCAG LDCPWKFCDE KVSVDESVMS THSTARLSFV TPRHHRAAVC
LCKEGRCPPV HHGCEDDPCP EGSECVSDPW EEKHTCVCPS GRFGQCPGSS SMTLTGNSYV
KYRLTENENK LEMKLTMRLR TYSTHAVVMY ARGTDYSILE IHHGRLQYKF DCGSGPGIVS
VQSIQVNDGQ WHAVALEVNG NYARLVLDQV HTASGTAPGT LKTLNLDNYV FFGGHIRQQG
TRHGRSPQVG NGFRGCMDSI YLNGQELPLN SKPRSYAHIE ESVDVSPGCF LTATEDCASN
PCQNGGVCNP SPAGGYYCKC SALYIGTHCE ISVNPCSSKP CLYGGTCVVD NGGFVCQCRG
LYTGQRCQLS PYCKDEPCKN GGTCFDSLDG AVCQCDSGFR GERCQSDIDE CSGNPCLHGA
LCENTHGSYH CNCSHEYRGR HCEDAAPNQY VSTPWNIGLA EGIGIVVFVA GIFLLVVVFV
LCRKMISRKK KHQAEPKDKH LGPATAFLQR PYFDSKLNKN IYSDIPPQVP VRPISYTPSI
PSDSRNNLDR NSFEGSAIPE HPEFSTFNPE SVHGHRKAVA VCSVAPNLPP PPPSNSPSDS
DSIQKPSWDF DYDTKVVDLD PCLSKKPLEE KPSQPYSARE SLSEVQSLSS FQSESCDDNG
YHWDTSDWMP SVPLPDIQEF PNYEVIDEQT PLYSADPNAI DTDYYPGGYD IESDFPPPPE
DFPAADELPP LPPEFSNQFE SIHPPRDMPA AGSLGSSSRN RQRFNLNQYL PNFYPLDMSE
PQTKGTGENS TCREPHAPYP PGYQRHFEAP AVESMPMSVY ASTASCSDVS ACCEVESEVM
MSDYESGDDG HFEEVTIPPL DSQQHTEV
//
MIM
600976
*RECORD*
*FIELD* NO
600976
*FIELD* TI
*600976 FAT TUMOR SUPPRESSOR, DROSOPHILA, HOMOLOG OF, 1; FAT1
*FIELD* TX
CLONING
read moreThe Drosophila 'fat' gene does not belong to the classical cadherin gene
family (see CDH1; 1921910) yet encodes a transmembrane protein
containing 34 cadherin repeats in association with a number of other
motifs Mahoney et al. (1991). The Drosophila 'fat' locus encodes a tumor
suppressor gene, and recessive (loss-of-function) mutations lead to
hyperplastic overgrowth of the imaginal discs, indicating that
contact-dependent cell interactions may play an important role in
regulating growth (Bryant et al., 1988). This excessive cell
proliferation occurs while maintaining normal epithelial organization
and differentiation potential. Dunne et al. (1995) reported the sequence
of a cDNA that was serendipitously obtained during a screen of a human
T-lymphocyte cDNA library. The full-length cDNA had the potential to
encode a large protein that most resembled the Drosophila 'fat' protein
in its possession of 34 cadherin repeats and other characteristics.
Therefore, they named the gene and the gene product FAT. Analysis of the
expression of FAT in fetal and adult tissues revealed that FAT mRNA is
present in many epithelial and some endothelial and smooth muscle cells.
The authors commented that the molecule is probably important in
mammalian developmental processes and cell communication. The large FAT
protein was predicted to contain nearly 4600 residues.
Katoh and Katoh (2006) determined that full-length FAT1 has 33 cadherin
repeats, a laminin G (see LAMC1; 150290) domain, and 2 EGF (131530)
domains in its extracellular region, followed by a transmembrane region
and a C-terminal cytoplasmic domain containing a PDZ-binding motif. In
silico analysis identified FAT1 mRNAs in embryonic stem cells, neural
tissues, and a variety of tumors.
GENE FAMILY
Cell-cell interactions that involve adhesion molecules are important in
many developmental processes. Dunne et al. (1995) stated that many
adhesion molecules have been found to be conserved between Drosophila
and vertebrates, indicating that the adhesion molecules involved in
tissue morphogenesis evolved long before the divergence of the
arthropods and chordates Hortsch and Goodman, 1991). Adhesion molecules
have been classified into 4 major families: the immunoglobulin
superfamily, the integrin superfamily, the selectin family, and the
cadherin superfamily. Cadherins mediate homophilic, calcium-dependent
cell-cell adhesion in a wide variety of tissues and are important
regulators of morphogenesis, and loss of function may be involved in the
invasion and metastasis of malignant tumors. The original or classical
adherins have a highly conserved domain structure typically including 5
extracellular, conserved repeated amino acid sequences (cadherin
repeats).
GENE FUNCTION
The atypical cadherin Fat acts as a receptor for a signaling pathway
that regulates growth, gene expression, and planar cell polarity.
Genetic studies in Drosophila identified the 'four-jointed' (Fj) gene
(612206) as a regulator of Fat signaling. Ishikawa et al. (2008) showed
that Four-jointed encodes a protein kinase that phosphorylates serine or
threonine residues within extracellular cadherin domains of Fat and its
transmembrane ligand, Dachsous (see 603057). Four-jointed functions in
the Golgi and was the first molecularly defined kinase that
phosphorylates protein domains destined to be extracellular. An acidic
sequence motif (Asp-Asn-Glu) within Four-jointed was essential for its
kinase activity in vitro and for its biologic activity in vivo. Ishikawa
et al. (2008) concluded that Four-jointed regulates Fat signaling by
phosphorylating cadherin domains of Fat and Dachsous as they transit
through the Golgi.
GENE STRUCTURE
Katoh and Katoh (2006) identified a TCF/LEF (see LEF1; 153245)-binding
site within the 5-prime promoter region of the FAT1 gene.
MAPPING
Dunne et al. (1995) localized the FAT1 gene to chromosome 4q34-q35 by
isotopic in situ hybridization.
By genomic sequence analysis, Katoh and Katoh (2006) mapped the FAT1
gene to chromosome 4q35.2, where it is linked with the MTNR1A gene
(600665). The FAT1-MTNR1A locus on chromosome 4 is paralogous to the
FAT3 (612483)-MTNR1B (600804) locus on chromosome 11.
Morris et al. (2013) reported recurrent somatic mutations in FAT1 in
glioblastoma ( 8 of 39; 20.5%), colorectal cancer (3 of 39; 7.7%), and
head and neck cancer (4 of 60; 6.7%). FAT1 encodes a cadherin-like
protein, which was able to potently suppress cancer cell growth in vitro
and in vivo by binding beta-catenin (116806) and antagonizing its
nuclear localization. Inactivation of FAT1 via mutation therefore
promotes Wnt signaling and tumorigenesis and affects patient survival.
Morris et al. (2013) concluded that the data strongly point to FAT1 as a
tumor suppressor gene driving loss of chromosome 4q35, a prevalent
region of deletion in cancer. Loss of FAT1 function is a frequent event
during oncogenesis.
*FIELD* RF
1. Bryant, P. J.; Huettner, B.; Held, L. I., Jr.; Ryerse, J.; Szidonya,
J.: Mutations at the fat locus interfere with cell proliferation
control and epithelial morphogenesis in Drosophila. Dev. Biol. 129:
541-554, 1988.
2. Dunne, J.; Hanby, A. M.; Poulsom, R.; Jones, T. A.; Sheer, D.;
Chin, W. G.; Da, S. M.; Zhao, Q.; Beverley, P. C. L.; Owen, M. J.
: Molecular cloning and tissue expression of FAT, the human homologue
of the Drosophila fat gene that is located on chromosome 4q34-q35
and encodes a putative adhesion molecule. Genomics 30: 207-223,
1995.
3. Hortsch, M.; Goodman, C. S.: Cell and substrate adhesion molecules
in Drosophila. Ann. Rev. Cell. Biol. 7: 505-557, 1991.
4. Ishikawa, H. O.; Takeuchi, H.; Haltiwanger, R. S.; Irvine, K. D.
: Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin
domains. Science 321: 401-404, 2008.
5. Katoh, Y.; Katoh, M.: Comparative integromics on FAT1, FAT2, FAT3
and FAT4. Int. J. Molec. Med. 18: 523-528, 2006.
6. Mahoney, P. A.; Weber, U.; Onofrechuk, P.; Biessmann, H.; Bryant,
P. J.; Goodman, C. S.: The fat tumor suppressor gene in Drosophila
encodes a novel member of the cadherin gene superfamily. Cell 67:
853-868, 1991.
7. Morris, L. G. T.; Kaufman, A. M.; Gong, Y.; Ramaswami, D.; Walsh,
L. A.; Turcan, S.; Eng, S.; Kannan, K.; Zou, Y.; Peng, L.; Banuchi,
V. E.; Paty, P.; and 10 others: Recurrent somatic mutation of FAT1
in multiple human cancers leads to aberrant Wnt activation. Nature
Genet. 45: 253-261, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/29/2014
Patricia A. Hartz - updated: 12/9/2008
Ada Hamosh - updated: 8/13/2008
*FIELD* CD
Victor A. McKusick: 1/11/1996
*FIELD* ED
alopez: 01/29/2014
mgross: 12/16/2008
terry: 12/9/2008
alopez: 11/17/2008
alopez: 8/18/2008
terry: 8/13/2008
psherman: 10/28/1999
terry: 2/6/1996
mark: 1/15/1996
*RECORD*
*FIELD* NO
600976
*FIELD* TI
*600976 FAT TUMOR SUPPRESSOR, DROSOPHILA, HOMOLOG OF, 1; FAT1
*FIELD* TX
CLONING
read moreThe Drosophila 'fat' gene does not belong to the classical cadherin gene
family (see CDH1; 1921910) yet encodes a transmembrane protein
containing 34 cadherin repeats in association with a number of other
motifs Mahoney et al. (1991). The Drosophila 'fat' locus encodes a tumor
suppressor gene, and recessive (loss-of-function) mutations lead to
hyperplastic overgrowth of the imaginal discs, indicating that
contact-dependent cell interactions may play an important role in
regulating growth (Bryant et al., 1988). This excessive cell
proliferation occurs while maintaining normal epithelial organization
and differentiation potential. Dunne et al. (1995) reported the sequence
of a cDNA that was serendipitously obtained during a screen of a human
T-lymphocyte cDNA library. The full-length cDNA had the potential to
encode a large protein that most resembled the Drosophila 'fat' protein
in its possession of 34 cadherin repeats and other characteristics.
Therefore, they named the gene and the gene product FAT. Analysis of the
expression of FAT in fetal and adult tissues revealed that FAT mRNA is
present in many epithelial and some endothelial and smooth muscle cells.
The authors commented that the molecule is probably important in
mammalian developmental processes and cell communication. The large FAT
protein was predicted to contain nearly 4600 residues.
Katoh and Katoh (2006) determined that full-length FAT1 has 33 cadherin
repeats, a laminin G (see LAMC1; 150290) domain, and 2 EGF (131530)
domains in its extracellular region, followed by a transmembrane region
and a C-terminal cytoplasmic domain containing a PDZ-binding motif. In
silico analysis identified FAT1 mRNAs in embryonic stem cells, neural
tissues, and a variety of tumors.
GENE FAMILY
Cell-cell interactions that involve adhesion molecules are important in
many developmental processes. Dunne et al. (1995) stated that many
adhesion molecules have been found to be conserved between Drosophila
and vertebrates, indicating that the adhesion molecules involved in
tissue morphogenesis evolved long before the divergence of the
arthropods and chordates Hortsch and Goodman, 1991). Adhesion molecules
have been classified into 4 major families: the immunoglobulin
superfamily, the integrin superfamily, the selectin family, and the
cadherin superfamily. Cadherins mediate homophilic, calcium-dependent
cell-cell adhesion in a wide variety of tissues and are important
regulators of morphogenesis, and loss of function may be involved in the
invasion and metastasis of malignant tumors. The original or classical
adherins have a highly conserved domain structure typically including 5
extracellular, conserved repeated amino acid sequences (cadherin
repeats).
GENE FUNCTION
The atypical cadherin Fat acts as a receptor for a signaling pathway
that regulates growth, gene expression, and planar cell polarity.
Genetic studies in Drosophila identified the 'four-jointed' (Fj) gene
(612206) as a regulator of Fat signaling. Ishikawa et al. (2008) showed
that Four-jointed encodes a protein kinase that phosphorylates serine or
threonine residues within extracellular cadherin domains of Fat and its
transmembrane ligand, Dachsous (see 603057). Four-jointed functions in
the Golgi and was the first molecularly defined kinase that
phosphorylates protein domains destined to be extracellular. An acidic
sequence motif (Asp-Asn-Glu) within Four-jointed was essential for its
kinase activity in vitro and for its biologic activity in vivo. Ishikawa
et al. (2008) concluded that Four-jointed regulates Fat signaling by
phosphorylating cadherin domains of Fat and Dachsous as they transit
through the Golgi.
GENE STRUCTURE
Katoh and Katoh (2006) identified a TCF/LEF (see LEF1; 153245)-binding
site within the 5-prime promoter region of the FAT1 gene.
MAPPING
Dunne et al. (1995) localized the FAT1 gene to chromosome 4q34-q35 by
isotopic in situ hybridization.
By genomic sequence analysis, Katoh and Katoh (2006) mapped the FAT1
gene to chromosome 4q35.2, where it is linked with the MTNR1A gene
(600665). The FAT1-MTNR1A locus on chromosome 4 is paralogous to the
FAT3 (612483)-MTNR1B (600804) locus on chromosome 11.
Morris et al. (2013) reported recurrent somatic mutations in FAT1 in
glioblastoma ( 8 of 39; 20.5%), colorectal cancer (3 of 39; 7.7%), and
head and neck cancer (4 of 60; 6.7%). FAT1 encodes a cadherin-like
protein, which was able to potently suppress cancer cell growth in vitro
and in vivo by binding beta-catenin (116806) and antagonizing its
nuclear localization. Inactivation of FAT1 via mutation therefore
promotes Wnt signaling and tumorigenesis and affects patient survival.
Morris et al. (2013) concluded that the data strongly point to FAT1 as a
tumor suppressor gene driving loss of chromosome 4q35, a prevalent
region of deletion in cancer. Loss of FAT1 function is a frequent event
during oncogenesis.
*FIELD* RF
1. Bryant, P. J.; Huettner, B.; Held, L. I., Jr.; Ryerse, J.; Szidonya,
J.: Mutations at the fat locus interfere with cell proliferation
control and epithelial morphogenesis in Drosophila. Dev. Biol. 129:
541-554, 1988.
2. Dunne, J.; Hanby, A. M.; Poulsom, R.; Jones, T. A.; Sheer, D.;
Chin, W. G.; Da, S. M.; Zhao, Q.; Beverley, P. C. L.; Owen, M. J.
: Molecular cloning and tissue expression of FAT, the human homologue
of the Drosophila fat gene that is located on chromosome 4q34-q35
and encodes a putative adhesion molecule. Genomics 30: 207-223,
1995.
3. Hortsch, M.; Goodman, C. S.: Cell and substrate adhesion molecules
in Drosophila. Ann. Rev. Cell. Biol. 7: 505-557, 1991.
4. Ishikawa, H. O.; Takeuchi, H.; Haltiwanger, R. S.; Irvine, K. D.
: Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin
domains. Science 321: 401-404, 2008.
5. Katoh, Y.; Katoh, M.: Comparative integromics on FAT1, FAT2, FAT3
and FAT4. Int. J. Molec. Med. 18: 523-528, 2006.
6. Mahoney, P. A.; Weber, U.; Onofrechuk, P.; Biessmann, H.; Bryant,
P. J.; Goodman, C. S.: The fat tumor suppressor gene in Drosophila
encodes a novel member of the cadherin gene superfamily. Cell 67:
853-868, 1991.
7. Morris, L. G. T.; Kaufman, A. M.; Gong, Y.; Ramaswami, D.; Walsh,
L. A.; Turcan, S.; Eng, S.; Kannan, K.; Zou, Y.; Peng, L.; Banuchi,
V. E.; Paty, P.; and 10 others: Recurrent somatic mutation of FAT1
in multiple human cancers leads to aberrant Wnt activation. Nature
Genet. 45: 253-261, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/29/2014
Patricia A. Hartz - updated: 12/9/2008
Ada Hamosh - updated: 8/13/2008
*FIELD* CD
Victor A. McKusick: 1/11/1996
*FIELD* ED
alopez: 01/29/2014
mgross: 12/16/2008
terry: 12/9/2008
alopez: 11/17/2008
alopez: 8/18/2008
terry: 8/13/2008
psherman: 10/28/1999
terry: 2/6/1996
mark: 1/15/1996