ID FAIM3_HUMAN Reviewed; 390 AA. AC O60667; A8K7J2; B7Z6Z0; D9MWM3; DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 13-FEB-2019, entry version 149. DE RecName: Full=Fas apoptotic inhibitory molecule 3 {ECO:0000305}; DE AltName: Full=IgM Fc fragment receptor {ECO:0000312|HGNC:HGNC:14315}; DE AltName: Full=Regulator of Fas-induced apoptosis Toso {ECO:0000303|PubMed:9586636}; DE Flags: Precursor; GN Name=FCMR {ECO:0000312|HGNC:HGNC:14315}; Synonyms=FAIM3, TOSO; 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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, RP AND INDUCTION. RX PubMed=9586636; DOI=10.1016/S1074-7613(00)80551-8; RA Hitoshi Y., Lorens J., Kitada S., Fisher J., LaBarge M., Ring H.Z., RA Francke U., Reed J.C., Kinoshita S., Nolan G.P.; RT "Toso, a cell surface, specific regulator of Fas-induced apoptosis in RT T cells."; RL Immunity 8:461-471(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), IDENTIFICATION BY MASS RP SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=21908424; DOI=10.1182/blood-2011-04-350793; RA Li F.J., Kubagawa Y., McCollum M.K., Wilson L., Motohashi T., RA Bertoli L.F., Barton J.C., Barnes S., Davis R.S., Kubagawa H.; RT "Enhanced levels of both the membrane-bound and soluble forms of IgM RT Fc receptor (Fc?R) in patients with chronic lymphocytic leukemia."; RL Blood 118:4902-4909(2011). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Spleen; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=B-cell; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: May play a role in the immune system processes. Protects CC cells from FAS-, TNF alpha- and FADD-induced apoptosis without CC increasing expression of the inhibitors of apoptosis BCL2 and CC BCLXL. Seems to activate an inhibitory pathway that prevents CASP8 CC activation following FAS stimulation, rather than blocking CC apoptotic signals downstream. May inhibit FAS-induced apoptosis by CC preventing CASP8 processing through CFLAR up-regulation. CC {ECO:0000269|PubMed:9586636}. CC -!- SUBCELLULAR LOCATION: Isoform 1: Membrane CC {ECO:0000269|PubMed:21908424}; Single-pass membrane protein CC {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: Isoform 3: Secreted CC {ECO:0000269|PubMed:21908424}. Note=Detected in the serum. CC {ECO:0000269|PubMed:21908424}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O60667-1; Sequence=Displayed; CC Name=2; CC IsoId=O60667-2; Sequence=VSP_042947; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=O60667-3; Sequence=VSP_045188, VSP_045189; CC -!- TISSUE SPECIFICITY: Expressed in lymph nodes, peripheral blood CC leukocytes, lung, thymus and kidneys. Very weak expression CC detected in spleen, liver, heart, and salivary gland. Expressed in CC lymphoid cell lines such as Jurkat, CEM-T4, MOLT-4, HB11;19 and CC Reh. No expression detected in nonhematopoietic cell lines CC including Hep-G2, HEK293 and HeLa. Detected at high levels in CC chronic lymphocytic leukemia cells. {ECO:0000269|PubMed:21908424, CC ECO:0000269|PubMed:9586636}. CC -!- INDUCTION: By T-cell activation. {ECO:0000269|PubMed:9586636}. CC -!- DOMAIN: The Ig-like domain is required for the anti-apoptotic CC ability. CC -!- MISCELLANEOUS: 'Toso' is a Japanese liquor drunk on New Year's day CC to celebrate long life and eternal youth. 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; AF057557; AAC18830.1; -; mRNA. DR EMBL; HM480394; ADK11426.1; -; mRNA. DR EMBL; BT006797; AAP35443.1; -; mRNA. DR EMBL; AK292007; BAF84696.1; -; mRNA. DR EMBL; AK301187; BAH13426.1; -; mRNA. DR EMBL; AK316336; BAH14707.1; -; mRNA. DR EMBL; AC098935; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471100; EAW93517.1; -; Genomic_DNA. DR EMBL; BC006401; AAH06401.1; -; mRNA. DR CCDS; CCDS1473.1; -. [O60667-1] DR CCDS; CCDS44304.1; -. [O60667-2] DR CCDS; CCDS53467.1; -. [O60667-3] DR RefSeq; NP_001135945.1; NM_001142473.1. [O60667-2] DR RefSeq; NP_001180267.1; NM_001193338.1. [O60667-3] DR RefSeq; NP_005440.1; NM_005449.4. [O60667-1] DR UniGene; Hs.58831; -. DR UniGene; Hs.744273; -. DR ProteinModelPortal; O60667; -. DR SMR; O60667; -. DR BioGrid; 114648; 3. DR IntAct; O60667; 1. DR STRING; 9606.ENSP00000356058; -. DR iPTMnet; O60667; -. DR PhosphoSitePlus; O60667; -. DR BioMuta; FCMR; -. DR PaxDb; O60667; -. DR PeptideAtlas; O60667; -. DR PRIDE; O60667; -. DR ProteomicsDB; 49511; -. DR ProteomicsDB; 49512; -. [O60667-2] DR DNASU; 9214; -. DR Ensembl; ENST00000367091; ENSP00000356058; ENSG00000162894. [O60667-1] DR Ensembl; ENST00000442471; ENSP00000404136; ENSG00000162894. [O60667-2] DR Ensembl; ENST00000628511; ENSP00000485739; ENSG00000162894. [O60667-3] DR GeneID; 9214; -. DR KEGG; hsa:9214; -. DR UCSC; uc001hey.4; human. [O60667-1] DR CTD; 9214; -. DR DisGeNET; 9214; -. DR EuPathDB; HostDB:ENSG00000162894.11; -. DR GeneCards; FCMR; -. DR HGNC; HGNC:14315; FCMR. DR HPA; HPA003910; -. DR MIM; 606015; gene. DR neXtProt; NX_O60667; -. DR OpenTargets; ENSG00000162894; -. DR PharmGKB; PA142671899; -. DR eggNOG; ENOG410IJ2J; Eukaryota. DR eggNOG; ENOG41113GQ; LUCA. DR GeneTree; ENSGT00940000162282; -. DR HOGENOM; HOG000013142; -. DR HOVERGEN; HBG107910; -. DR InParanoid; O60667; -. DR OMA; TIECPLP; -. DR OrthoDB; 1378301at2759; -. DR PhylomeDB; O60667; -. DR TreeFam; TF338713; -. DR ChiTaRS; FCMR; human. DR GenomeRNAi; 9214; -. DR PRO; PR:O60667; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000162894; Expressed in 153 organ(s), highest expression level in blood. DR ExpressionAtlas; O60667; baseline and differential. DR Genevisible; O60667; HS. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc. DR Gene3D; 2.60.40.10; -; 1. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR013106; Ig_V-set. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 1. DR SUPFAM; SSF48726; SSF48726; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Disulfide bond; Immunity; KW Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome; KW Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 390 Fas apoptotic inhibitory molecule 3. FT /FTId=PRO_0000284421. FT TOPO_DOM 18 251 Extracellular. {ECO:0000255}. FT TRANSMEM 252 272 Helical. {ECO:0000255}. FT TOPO_DOM 273 390 Cytoplasmic. {ECO:0000255}. FT DOMAIN 33 105 Ig-like. FT COMPBIAS 274 323 Arg-rich. FT MOD_RES 92 92 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q5M871}. FT DISULFID 37 104 {ECO:0000250}. FT VAR_SEQ 13 124 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_042947. FT VAR_SEQ 237 245 RALDYGSQS -> SPLQAGPPT (in isoform 3). FT {ECO:0000303|PubMed:21908424}. FT /FTId=VSP_045188. FT VAR_SEQ 249 390 GQGFHILIPTILGLFLLALLGLVVKRAVERRKALSRRARRL FT AVRMRALESSQRPRGSPRPRSQNNIYSACPRRARGADAAGT FT GEAPVPGPGAPLPPAPLQVSESPWLHAPSLKTSCEYVSLYH FT QPAAMMEDSDSDDYINVPA -> DARPGELPEAPRVAATAL FT PKQHLQRLPAARSWSGRCRHRGGPRSRPRSAVAPRPAAGV FT (in isoform 3). FT {ECO:0000303|PubMed:21908424}. FT /FTId=VSP_045189. SQ SEQUENCE 390 AA; 43146 MW; FE91D217EECA99C6 CRC64; MDFWLWPLYF LPVSGALRIL PEVKVEGELG GSVTIKCPLP EMHVRIYLCR EMAGSGTCGT VVSTTNFIKA EYKGRVTLKQ YPRKNLFLVE VTQLTESDSG VYACGAGMNT DRGKTQKVTL NVHSEYEPSW EEQPMPETPK WFHLPYLFQM PAYASSSKFV TRVTTPAQRG KVPPVHHSSP TTQITHRPRV SRASSVAGDK PRTFLPSTTA SKISALEGLL KPQTPSYNHH TRLHRQRALD YGSQSGREGQ GFHILIPTIL GLFLLALLGL VVKRAVERRK ALSRRARRLA VRMRALESSQ RPRGSPRPRS QNNIYSACPR RARGADAAGT GEAPVPGPGA PLPPAPLQVS ESPWLHAPSL KTSCEYVSLY HQPAAMMEDS DSDDYINVPA //