FRMD8_HUMAN
ID FRMD8_HUMAN Reviewed; 464 AA.
AC Q9BZ67; B4E2P1; Q86V56; Q8NCB5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=FERM domain-containing protein 8;
DE AltName: Full=Band4.1 inhibitor LRP interactor {ECO:0000303|PubMed:19572019};
DE Short=Bili {ECO:0000303|PubMed:19572019};
DE AltName: Full=iRhom tail-associated protein {ECO:0000303|PubMed:29897333};
DE Short=iTAP {ECO:0000303|PubMed:29897333};
GN Name=FRMD8; ORFNames=FKSG44;
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).
RA Wang Y.-G., Gong L.;
RT "Identification of FKSG44, a novel gene located on human chromosome
RT 11q13.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Testis;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, INTERACTION WITH LRP6, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19572019; DOI=10.1371/journal.pone.0006129;
RA Kategaya L.S., Changkakoty B., Biechele T., Conrad W.H., Kaykas A.,
RA Dasgupta R., Moon R.T.;
RT "Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of
RT axin to LRP6.";
RL PLoS ONE 4:E6129-E6129(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439 AND SER-446, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383; SER-387 AND SER-408, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP FUNCTION, INTERACTION WITH RHBDF1 AND RHBDF2, AND SUBCELLULAR LOCATION.
RX PubMed=29897333; DOI=10.7554/elife.35032;
RA Oikonomidi I., Burbridge E., Cavadas M., Sullivan G., Collis B.,
RA Naegele H., Clancy D., Brezinova J., Hu T., Bileck A., Gerner C.,
RA Bolado A., von Kriegsheim A., Martin S.J., Steinberg F., Strisovsky K.,
RA Adrain C.;
RT "iTAP, a novel iRhom interactor, controls TNF secretion by policing the
RT stability of iRhom/TACE.";
RL Elife 7:0-0(2018).
RN [12]
RP FUNCTION, AND INTERACTION WITH ADAM17; RHBDF1 AND RHBDF2.
RX PubMed=29897336; DOI=10.7554/elife.35012;
RA Kuenzel U., Grieve A.G., Meng Y., Sieber B., Cowley S.A., Freeman M.;
RT "FRMD8 promotes inflammatory and growth factor signalling by stabilising
RT the iRhom/ADAM17 sheddase complex.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Promotes the cell surface stability of iRhom1/RHBDF1 and
CC iRhom2/RHBDF2 and prevents their degradation via the endolysosomal
CC pathway. By acting on iRhoms, involved in ADAM17-mediated shedding of
CC TNF, amphiregulin/AREG, HBEGF and TGFA from the cell surface
CC (PubMed:29897333, PubMed:29897336). Negatively regulates Wnt signaling,
CC possibly by antagonizing the recruitment of AXIN1 to LRP6
CC (PubMed:19572019). {ECO:0000269|PubMed:19572019,
CC ECO:0000269|PubMed:29897333, ECO:0000269|PubMed:29897336}.
CC -!- SUBUNIT: Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2 (via
CC cytoplasmic N-termini); this interaction leads to mutual protein
CC stabilization (PubMed:29897333). Interacts with ADAM17; this
CC interaction is indirect and mediated by iRhom proteins
CC (PubMed:29897333, PubMed:29897336). Interacts with LRP6; this
CC interaction affects LRP6-binding to AXIN1 (PubMed:19572019).
CC {ECO:0000269|PubMed:19572019, ECO:0000269|PubMed:29897333,
CC ECO:0000269|PubMed:29897336}.
CC -!- INTERACTION:
CC Q9BZ67; Q969F0: FATE1; NbExp=3; IntAct=EBI-5773072, EBI-743099;
CC Q9BZ67; Q96HH9: GRAMD2B; NbExp=6; IntAct=EBI-5773072, EBI-2832937;
CC Q9BZ67; Q12809-2: KCNH2; NbExp=3; IntAct=EBI-5773072, EBI-12966028;
CC Q9BZ67; Q9H400: LIME1; NbExp=3; IntAct=EBI-5773072, EBI-2830566;
CC Q9BZ67; Q9H8W4: PLEKHF2; NbExp=8; IntAct=EBI-5773072, EBI-742388;
CC Q9BZ67; Q9NWS9-2: ZNF446; NbExp=3; IntAct=EBI-5773072, EBI-740232;
CC Q9BZ67; Q6S9Z5: ZNF474; NbExp=3; IntAct=EBI-5773072, EBI-17269964;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19572019,
CC ECO:0000269|PubMed:29897333}. Cell membrane
CC {ECO:0000269|PubMed:19572019, ECO:0000269|PubMed:29897333}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9BZ67-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZ67-2; Sequence=VSP_027085;
CC Name=3;
CC IsoId=Q9BZ67-3; Sequence=VSP_056059;
CC -!- TISSUE SPECIFICITY: Widely expressed, with high expression in heart and
CC spleen. {ECO:0000269|PubMed:19572019}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF334946; AAG50295.1; -; mRNA.
DR EMBL; AK074850; BAC11244.1; -; mRNA.
DR EMBL; AK304363; BAG65203.1; -; mRNA.
DR EMBL; AP000944; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044658; AAH44658.1; -; mRNA.
DR EMBL; BC051695; AAH51695.1; -; mRNA.
DR CCDS; CCDS73320.1; -. [Q9BZ67-3]
DR CCDS; CCDS76432.1; -. [Q9BZ67-2]
DR CCDS; CCDS8102.1; -. [Q9BZ67-1]
DR RefSeq; NP_001287761.1; NM_001300832.2. [Q9BZ67-2]
DR RefSeq; NP_001287762.1; NM_001300833.2. [Q9BZ67-3]
DR RefSeq; NP_114110.1; NM_031904.4. [Q9BZ67-1]
DR AlphaFoldDB; Q9BZ67; -.
DR SMR; Q9BZ67; -.
DR BioGRID; 123761; 15.
DR IntAct; Q9BZ67; 11.
DR MINT; Q9BZ67; -.
DR STRING; 9606.ENSP00000319726; -.
DR iPTMnet; Q9BZ67; -.
DR PhosphoSitePlus; Q9BZ67; -.
DR BioMuta; FRMD8; -.
DR DMDM; 74733481; -.
DR EPD; Q9BZ67; -.
DR jPOST; Q9BZ67; -.
DR MassIVE; Q9BZ67; -.
DR MaxQB; Q9BZ67; -.
DR PaxDb; Q9BZ67; -.
DR PeptideAtlas; Q9BZ67; -.
DR PRIDE; Q9BZ67; -.
DR ProteomicsDB; 5840; -.
DR ProteomicsDB; 79768; -. [Q9BZ67-1]
DR ProteomicsDB; 79769; -. [Q9BZ67-2]
DR Antibodypedia; 1109; 125 antibodies from 19 providers.
DR DNASU; 83786; -.
DR Ensembl; ENST00000317568.10; ENSP00000319726.4; ENSG00000126391.14. [Q9BZ67-1]
DR Ensembl; ENST00000355991.9; ENSP00000348270.5; ENSG00000126391.14. [Q9BZ67-2]
DR Ensembl; ENST00000416776.6; ENSP00000392111.2; ENSG00000126391.14. [Q9BZ67-3]
DR GeneID; 83786; -.
DR KEGG; hsa:83786; -.
DR MANE-Select; ENST00000317568.10; ENSP00000319726.4; NM_031904.5; NP_114110.1.
DR UCSC; uc001odu.5; human. [Q9BZ67-1]
DR CTD; 83786; -.
DR DisGeNET; 83786; -.
DR GeneCards; FRMD8; -.
DR HGNC; HGNC:25462; FRMD8.
DR HPA; ENSG00000126391; Low tissue specificity.
DR MIM; 618337; gene.
DR neXtProt; NX_Q9BZ67; -.
DR OpenTargets; ENSG00000126391; -.
DR PharmGKB; PA162388963; -.
DR VEuPathDB; HostDB:ENSG00000126391; -.
DR eggNOG; KOG4335; Eukaryota.
DR GeneTree; ENSGT00530000063721; -.
DR HOGENOM; CLU_032351_0_0_1; -.
DR InParanoid; Q9BZ67; -.
DR OMA; GSHYRAY; -.
DR PhylomeDB; Q9BZ67; -.
DR TreeFam; TF317921; -.
DR PathwayCommons; Q9BZ67; -.
DR SignaLink; Q9BZ67; -.
DR BioGRID-ORCS; 83786; 10 hits in 1080 CRISPR screens.
DR ChiTaRS; FRMD8; human.
DR GenomeRNAi; 83786; -.
DR Pharos; Q9BZ67; Tdark.
DR PRO; PR:Q9BZ67; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BZ67; protein.
DR Bgee; ENSG00000126391; Expressed in pancreatic ductal cell and 168 other tissues.
DR ExpressionAtlas; Q9BZ67; baseline and differential.
DR Genevisible; Q9BZ67; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR CDD; cd14473; FERM_B-lobe; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR Pfam; PF00373; FERM_M; 1.
DR SMART; SM00295; B41; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..464
FT /note="FERM domain-containing protein 8"
FT /id="PRO_0000295778"
FT DOMAIN 30..376
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2R3"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 419
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q3UFK8"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 29..84
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_027085"
FT VAR_SEQ 85..118
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056059"
FT CONFLICT 198
FT /note="D -> N (in Ref. 4; AAH51695)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 51218 MW; 1F880DFCA5C12D7A CRC64;
MDGTEGSAGQ PGPAERSHRS SVSSVGARAA DVLVYLADDT VVPLAVENLP SLSAHELHRA
VREVLQLPDI ALDVFALWLV SPLLEVQLKP KHQPYKLGRQ WPELLLRFTS APDDDVAMDE
PFLQFRRNVF FPKRRELQIH DEEVLRLLYE EAKGNVLAAR YPCDVEDCEA LGALVCRVQL
GPYQPGRPAA CDLREKLDSF LPAHLCKRGQ SLFAALRGRG ARAGPGEQGL LNAYRQVQEV
SSDGGCEAAL GTHYRAYLLK CHELPFYGCA FFHGEVDKPA QGFLHRGGRK PVSVAISLEG
VHVIDSREKH VLLGLRFQEL SWDHTSPEEE EPILWLEFDG DSEGTPVNKL LKIYSKQAEL
MSSLIEYCIE LSQAAEPAGP QDSATGSPSD PSSSLAPVQR PKLRRQGSVV SSRIQHLSTI
DYVEDGKGIR RVKPKRTTSF FSRQLSLGQG SYTVVQPGDS LEQG
