FRMD8_MOUSE
ID FRMD8_MOUSE Reviewed; 466 AA.
AC Q3UFK8; Q8C7U3; Q8C7U5; Q99KB3; Q9CSY6; Q9DC30;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=FERM domain-containing protein 8;
DE AltName: Full=iRhom tail-associated protein {ECO:0000303|PubMed:29897333};
DE Short=iTAP {ECO:0000303|PubMed:29897333};
GN Name=Frmd8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Lung, Spinal ganglion, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-420, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [6]
RP FUNCTION, INTERACTION WITH RHBDF2, AND DISRUPTION PHENOTYPE.
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 (PubMed:29897333). By acting on iRhoms, involved in ADAM17-
CC mediated shedding of TNF, amphiregulin/AREG, HBEGF and TGFA from the
CC cell surface (By similarity). Negatively regulates Wnt signaling,
CC possibly by antagonizing the recruitment of AXIN1 to LRP6 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BZ67,
CC ECO:0000269|PubMed:29897333}.
CC -!- SUBUNIT: Interacts with iRhom proteins, including iRhom2/RHBDF2 (via
CC cytoplasmic N-termini); this interaction leads to mutual protein
CC stabilization (PubMed:29897336). Interacts with LRP6; this interaction
CC affects LRP6-binding to AXIN1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9BZ67, ECO:0000269|PubMed:29897336}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9BZ67}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9BZ67}.
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level).
CC {ECO:0000269|PubMed:29897333}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are viable and fertile.
CC {ECO:0000269|PubMed:29897336}.
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DR EMBL; AK011659; BAB27763.1; -; mRNA.
DR EMBL; AK004603; BAB23402.1; -; mRNA.
DR EMBL; AK083902; BAC39054.1; -; mRNA.
DR EMBL; AK088639; BAC40471.1; -; mRNA.
DR EMBL; AK049224; BAC33620.1; -; mRNA.
DR EMBL; AK049233; BAC33626.1; -; mRNA.
DR EMBL; AK148434; BAE28552.1; -; mRNA.
DR EMBL; BC004765; AAH04765.1; -; mRNA.
DR CCDS; CCDS29481.1; -.
DR RefSeq; NP_080445.1; NM_026169.4.
DR RefSeq; XP_006531891.1; XM_006531828.2.
DR AlphaFoldDB; Q3UFK8; -.
DR SMR; Q3UFK8; -.
DR STRING; 10090.ENSMUSP00000025728; -.
DR iPTMnet; Q3UFK8; -.
DR PhosphoSitePlus; Q3UFK8; -.
DR EPD; Q3UFK8; -.
DR jPOST; Q3UFK8; -.
DR MaxQB; Q3UFK8; -.
DR PaxDb; Q3UFK8; -.
DR PeptideAtlas; Q3UFK8; -.
DR PRIDE; Q3UFK8; -.
DR ProteomicsDB; 267629; -.
DR Antibodypedia; 1109; 125 antibodies from 19 providers.
DR DNASU; 67457; -.
DR Ensembl; ENSMUST00000025728; ENSMUSP00000025728; ENSMUSG00000024816.
DR GeneID; 67457; -.
DR KEGG; mmu:67457; -.
DR UCSC; uc008gfn.1; mouse.
DR CTD; 83786; -.
DR MGI; MGI:1914707; Frmd8.
DR VEuPathDB; HostDB:ENSMUSG00000024816; -.
DR eggNOG; KOG4335; Eukaryota.
DR GeneTree; ENSGT00530000063721; -.
DR HOGENOM; CLU_032351_0_0_1; -.
DR InParanoid; Q3UFK8; -.
DR OMA; GSHYRAY; -.
DR OrthoDB; 1068540at2759; -.
DR PhylomeDB; Q3UFK8; -.
DR TreeFam; TF317921; -.
DR BioGRID-ORCS; 67457; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Frmd8; mouse.
DR PRO; PR:Q3UFK8; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q3UFK8; protein.
DR Bgee; ENSMUSG00000024816; Expressed in granulocyte and 249 other tissues.
DR ExpressionAtlas; Q3UFK8; baseline and differential.
DR Genevisible; Q3UFK8; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:MGI.
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; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..466
FT /note="FERM domain-containing protein 8"
FT /id="PRO_0000295779"
FT DOMAIN 30..377
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 379..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ67"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2R3"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ67"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ67"
FT MOD_RES 420
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ67"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZ67"
FT CONFLICT 110
FT /note="N -> D (in Ref. 1; BAE28552 and 2; AAH04765)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="H -> Y (in Ref. 1; BAC33626)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="L -> I (in Ref. 1; BAB27763)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="P -> R (in Ref. 1; BAE28552)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="T -> A (in Ref. 1; BAC33620)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 466 AA; 51828 MW; 8E8F93B96C6C5A4F CRC64;
MEGAEGNAGQ PGPAERSHRS SVSSVGARAA DVLVYLADDT VVPLAVENLS SISAHELHRA
VREVLQLPDV ALEAFALWLV SPLLEVQLKP KHQPYKLGRQ WPELLLRFTN ASDDDVAMDE
PSLQFRRNVF FPRRRELQIH DEEVLRLLYE EAKGNVLTAR YPCDLEDCEV LGGLVCRVQL
GPYQPGQPAA CTLREKLDSF LPAHLCKRGH GLFAAFRGRG AKTGPGEQGL LNAYRQVKEV
TGNNSEREAT LGSHYRAYLL KCHELPFYGC AFFHGEVDKP AQGFLHRGGR KPVTVAISLE
GVHVIDNREK HVLLGLRFQE LSWDHTSPEE EEPVLWLEFD GDSEGTPVNK LLRIYSKQAE
LMSGLIEYCI ELSQAAEPTL SQESASGPHE APSPSPPPTQ RPKLRRQGSV VCSRIQHLST
IDYVEDGKGI KRVKPKRTTS FFSRQLSSSQ GSYTVVQPTD DSLEQS
