FAIM3_HUMAN
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 03-AUG-2022, entry version 166.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP 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 T
RT 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., Bertoli L.F.,
RA Barton J.C., Barnes S., Davis R.S., Kubagawa H.;
RT "Enhanced levels of both the membrane-bound and soluble forms of IgM Fc
RT 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 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., 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 [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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 BCLXL.
CC Seems to activate an inhibitory pathway that prevents CASP8 activation
CC following FAS stimulation, rather than blocking apoptotic signals
CC downstream. May inhibit FAS-induced apoptosis by preventing CASP8
CC processing through CFLAR up-regulation. {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 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 detected in
CC spleen, liver, heart, and salivary gland. Expressed in lymphoid cell
CC lines such as Jurkat, CEM-T4, MOLT-4, HB11;19 and Reh. No expression
CC detected in nonhematopoietic cell lines including Hep-G2, HEK293 and
CC HeLa. Detected at high levels in chronic lymphocytic leukemia cells.
CC {ECO:0000269|PubMed:21908424, 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 ability.
CC -!- MISCELLANEOUS: 'Toso' is a Japanese liquor drunk on New Year's day to
CC celebrate long life and eternal youth.
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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 AlphaFoldDB; O60667; -.
DR SMR; O60667; -.
DR BioGRID; 114648; 3.
DR IntAct; O60667; 4.
DR STRING; 9606.ENSP00000356058; -.
DR GlyGen; O60667; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60667; -.
DR PhosphoSitePlus; O60667; -.
DR BioMuta; FCMR; -.
DR MassIVE; O60667; -.
DR PaxDb; O60667; -.
DR PeptideAtlas; O60667; -.
DR PRIDE; O60667; -.
DR ProteomicsDB; 49511; -. [O60667-1]
DR ProteomicsDB; 49512; -. [O60667-2]
DR Antibodypedia; 1164; 315 antibodies from 33 providers.
DR DNASU; 9214; -.
DR Ensembl; ENST00000367091.8; ENSP00000356058.3; ENSG00000162894.12. [O60667-1]
DR Ensembl; ENST00000442471.4; ENSP00000404136.2; ENSG00000162894.12. [O60667-2]
DR Ensembl; ENST00000628511.2; ENSP00000485739.1; ENSG00000162894.12. [O60667-3]
DR GeneID; 9214; -.
DR KEGG; hsa:9214; -.
DR MANE-Select; ENST00000367091.8; ENSP00000356058.3; NM_005449.5; NP_005440.1.
DR UCSC; uc001hey.4; human. [O60667-1]
DR CTD; 9214; -.
DR DisGeNET; 9214; -.
DR GeneCards; FCMR; -.
DR HGNC; HGNC:14315; FCMR.
DR HPA; ENSG00000162894; Group enriched (intestine, lymphoid tissue).
DR MIM; 606015; gene.
DR neXtProt; NX_O60667; -.
DR OpenTargets; ENSG00000162894; -.
DR PharmGKB; PA142671899; -.
DR VEuPathDB; HostDB:ENSG00000162894; -.
DR eggNOG; ENOG502S6XH; Eukaryota.
DR GeneTree; ENSGT00940000162282; -.
DR HOGENOM; CLU_059565_0_0_1; -.
DR InParanoid; O60667; -.
DR OMA; RMYLCRQ; -.
DR OrthoDB; 1378301at2759; -.
DR PhylomeDB; O60667; -.
DR TreeFam; TF338713; -.
DR PathwayCommons; O60667; -.
DR SignaLink; O60667; -.
DR BioGRID-ORCS; 9214; 6 hits in 1070 CRISPR screens.
DR ChiTaRS; FCMR; human.
DR GenomeRNAi; 9214; -.
DR Pharos; O60667; Tbio.
DR PRO; PR:O60667; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O60667; protein.
DR Bgee; ENSG00000162894; Expressed in spleen and 148 other tissues.
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:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
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; Disulfide bond; Immunity; Immunoglobulin domain;
KW Membrane; Phosphoprotein; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..390
FT /note="Fas apoptotic inhibitory molecule 3"
FT /id="PRO_0000284421"
FT TOPO_DOM 18..251
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 33..105
FT /note="Ig-like"
FT REGION 166..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..317
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 92
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5M871"
FT DISULFID 37..104
FT /evidence="ECO:0000250"
FT VAR_SEQ 13..124
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042947"
FT VAR_SEQ 237..245
FT /note="RALDYGSQS -> SPLQAGPPT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21908424"
FT /id="VSP_045188"
FT VAR_SEQ 249..390
FT /note="GQGFHILIPTILGLFLLALLGLVVKRAVERRKALSRRARRLAVRMRALESSQ
FT RPRGSPRPRSQNNIYSACPRRARGADAAGTGEAPVPGPGAPLPPAPLQVSESPWLHAPS
FT LKTSCEYVSLYHQPAAMMEDSDSDDYINVPA -> DARPGELPEAPRVAATALPKQHLQ
FT RLPAARSWSGRCRHRGGPRSRPRSAVAPRPAAGV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21908424"
FT /id="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
