ID   FAN_HUMAN               Reviewed;         917 AA.
AC   Q92636; B4DFB0; E9PCH0; Q8IW26;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2008, sequence version 2.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Protein FAN;
DE   AltName: Full=Factor associated with neutral sphingomyelinase activation;
DE            Short=Factor associated with N-SMase activation;
GN   Name=NSMAF; Synonyms=FAN;
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], AND VARIANT THR-850 (ISOFORM 1).
RC   TISSUE=Muscle;
RX   PubMed=8808629; DOI=10.1016/s0092-8674(00)80169-5;
RA   Adam-Klages S., Adam D., Wiegmann K., Struve S., Kolanus W.,
RA   Schneider-Mergener J., Kroenke M.;
RT   "FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral
RT   sphingomyelinase.";
RL   Cell 86:937-947(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Cerebellum;
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=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA   Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA   Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA   Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA   Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA   Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA   Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA   O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA   Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA   Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA   Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA   Platzer M., Shimizu N., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Uterus;
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: Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral
CC       sphingomyelinase (N-SMASE). Specifically binds to the N-smase
CC       activation domain of TNF-R55. May regulate ceramide production by N-
CC       SMASE.
CC   -!- INTERACTION:
CC       Q92636; P60709: ACTB; NbExp=2; IntAct=EBI-2947053, EBI-353944;
CC       Q92636; Q9NPI6: DCP1A; NbExp=2; IntAct=EBI-2947053, EBI-374238;
CC       Q92636; Q8IZD4: DCP1B; NbExp=2; IntAct=EBI-2947053, EBI-521595;
CC       Q92636; O95166: GABARAP; NbExp=2; IntAct=EBI-2947053, EBI-712001;
CC       Q92636; Q9H0R8: GABARAPL1; NbExp=7; IntAct=EBI-2947053, EBI-746969;
CC       Q92636; P50552: VASP; NbExp=2; IntAct=EBI-2947053, EBI-748201;
CC       Q92636; Q9SJF3: At1g08370; Xeno; NbExp=2; IntAct=EBI-2947053, EBI-7786643;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q92636-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q92636-2; Sequence=VSP_042036;
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
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DR   EMBL; X96586; CAA65405.1; -; mRNA.
DR   EMBL; AK294009; BAG57371.1; -; mRNA.
DR   EMBL; AC068522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC092700; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471068; EAW86817.1; -; Genomic_DNA.
DR   EMBL; BC041124; AAH41124.1; -; mRNA.
DR   CCDS; CCDS47864.1; -. [Q92636-2]
DR   CCDS; CCDS6173.1; -. [Q92636-1]
DR   RefSeq; NP_001138244.1; NM_001144772.1. [Q92636-2]
DR   RefSeq; NP_003571.2; NM_003580.3. [Q92636-1]
DR   AlphaFoldDB; Q92636; -.
DR   SMR; Q92636; -.
DR   BioGRID; 114019; 43.
DR   DIP; DIP-44106N; -.
DR   IntAct; Q92636; 39.
DR   MINT; Q92636; -.
DR   STRING; 9606.ENSP00000411012; -.
DR   GlyGen; Q92636; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q92636; -.
DR   PhosphoSitePlus; Q92636; -.
DR   BioMuta; NSMAF; -.
DR   DMDM; 209572614; -.
DR   EPD; Q92636; -.
DR   jPOST; Q92636; -.
DR   MassIVE; Q92636; -.
DR   MaxQB; Q92636; -.
DR   PaxDb; 9606-ENSP00000411012; -.
DR   PeptideAtlas; Q92636; -.
DR   ProteomicsDB; 75390; -. [Q92636-1]
DR   ProteomicsDB; 75391; -. [Q92636-2]
DR   Pumba; Q92636; -.
DR   Antibodypedia; 11802; 149 antibodies from 25 providers.
DR   DNASU; 8439; -.
DR   Ensembl; ENST00000038176.8; ENSP00000038176.3; ENSG00000035681.9. [Q92636-1]
DR   Ensembl; ENST00000427130.6; ENSP00000411012.2; ENSG00000035681.9. [Q92636-2]
DR   GeneID; 8439; -.
DR   KEGG; hsa:8439; -.
DR   MANE-Select; ENST00000038176.8; ENSP00000038176.3; NM_003580.4; NP_003571.2.
DR   UCSC; uc003xtt.4; human. [Q92636-1]
DR   AGR; HGNC:8017; -.
DR   CTD; 8439; -.
DR   DisGeNET; 8439; -.
DR   GeneCards; NSMAF; -.
DR   HGNC; HGNC:8017; NSMAF.
DR   HPA; ENSG00000035681; Low tissue specificity.
DR   MIM; 603043; gene.
DR   neXtProt; NX_Q92636; -.
DR   OpenTargets; ENSG00000035681; -.
DR   PharmGKB; PA31795; -.
DR   VEuPathDB; HostDB:ENSG00000035681; -.
DR   eggNOG; KOG1786; Eukaryota.
DR   GeneTree; ENSGT00940000155059; -.
DR   HOGENOM; CLU_000218_5_2_1; -.
DR   InParanoid; Q92636; -.
DR   OMA; LLKFPGC; -.
DR   OrthoDB; 47483at2759; -.
DR   PhylomeDB; Q92636; -.
DR   TreeFam; TF324912; -.
DR   PathwayCommons; Q92636; -.
DR   Reactome; R-HSA-5626978; TNFR1-mediated ceramide production.
DR   SignaLink; Q92636; -.
DR   BioGRID-ORCS; 8439; 7 hits in 1148 CRISPR screens.
DR   ChiTaRS; NSMAF; human.
DR   GenomeRNAi; 8439; -.
DR   Pharos; Q92636; Tbio.
DR   PRO; PR:Q92636; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q92636; Protein.
DR   Bgee; ENSG00000035681; Expressed in gingival epithelium and 202 other cell types or tissues.
DR   ExpressionAtlas; Q92636; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016230; F:sphingomyelin phosphodiesterase activator activity; IEA:Ensembl.
DR   GO; GO:0006672; P:ceramide metabolic process; TAS:ProtInc.
DR   GO; GO:0034250; P:positive regulation of amide metabolic process; IEA:Ensembl.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0045834; P:positive regulation of lipid metabolic process; IEA:Ensembl.
DR   GO; GO:1905038; P:regulation of membrane lipid metabolic process; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR   CDD; cd06071; Beach; 1.
DR   CDD; cd00200; WD40; 1.
DR   Gene3D; 1.10.1540.10; BEACH domain; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 3.
DR   InterPro; IPR000409; BEACH_dom.
DR   InterPro; IPR036372; BEACH_dom_sf.
DR   InterPro; IPR004182; GRAM.
DR   InterPro; IPR023362; PH-BEACH_dom.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   InterPro; IPR001680; WD40_rpt.
DR   PANTHER; PTHR13743; BEIGE/BEACH-RELATED; 1.
DR   PANTHER; PTHR13743:SF162; PROTEIN FAN; 1.
DR   Pfam; PF02138; Beach; 1.
DR   Pfam; PF02893; GRAM; 1.
DR   Pfam; PF00400; WD40; 5.
DR   SMART; SM01026; Beach; 1.
DR   SMART; SM00568; GRAM; 1.
DR   SMART; SM00320; WD40; 7.
DR   SUPFAM; SSF81837; BEACH domain; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF50978; WD40 repeat-like; 1.
DR   PROSITE; PS50197; BEACH; 1.
DR   PROSITE; PS51783; PH_BEACH; 1.
DR   PROSITE; PS50082; WD_REPEATS_2; 4.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
DR   Genevisible; Q92636; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Reference proteome; Repeat; WD repeat.
FT   CHAIN           1..917
FT                   /note="Protein FAN"
FT                   /id="PRO_0000050975"
FT   DOMAIN          176..247
FT                   /note="GRAM"
FT   DOMAIN          189..286
FT                   /note="BEACH-type PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01119"
FT   DOMAIN          290..575
FT                   /note="BEACH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00026"
FT   REPEAT          628..658
FT                   /note="WD 1"
FT   REPEAT          670..700
FT                   /note="WD 2"
FT   REPEAT          712..740
FT                   /note="WD 3"
FT   REPEAT          761..791
FT                   /note="WD 4"
FT   REPEAT          803..833
FT                   /note="WD 5"
FT   REPEAT          884..914
FT                   /note="WD 6"
FT   VAR_SEQ         1..20
FT                   /note="MAFIRKKQQEQQLQLYSKER -> MTGQARFHRGAEACRAIRQCRSRRPRAA
FT                   HPEGRAGSGRGSRHASPGVRRGG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_042036"
FT   VARIANT         626
FT                   /note="Y -> C (in dbSNP:rs2228505)"
FT                   /id="VAR_047023"
FT   CONFLICT        218
FT                   /note="T -> A (in Ref. 2; BAG57371)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   917 AA;  104372 MW;  36498B5A1378E49C CRC64;
     MAFIRKKQQE QQLQLYSKER FSLLLLNLEE YYFEQHRANH ILHKGSHHER KIRGSLKICS
     KSVIFEPDSI SQPIIKIPLR DCIKIGKHGE NGANRHFTKA KSGGISLIFS QVYFIKEHNV
     VAPYKIERGK MEYVFELDVP GKVEDVVETL LQLHRASCLD KLGDQTAMIT AILQSRLART
     SFDKNRFQNI SEKLHMECKA EMVTPLVTNP GHVCITDTNL YFQPLNGYPK PVVQITLQDV
     RRIYKRRHGL MPLGLEVFCT EDDLCSDIYL KFYEPQDRDD LYFYIATYLE HHVAEHTAES
     YMLQWQRGHL SNYQYLLHLN NLADRSCNDL SQYPVFPWII HDYSSSELDL SNPGTFRDLS
     KPVGALNKER LERLLTRYQE MPEPKFMYGS HYSSPGYVLF YLVRIAPEYM LCLQNGRFDN
     ADRMFNSIAE TWKNCLDGAT DFKELIPEFY GDDVSFLVNS LKLDLGKRQG GQMVDDVELP
     PWASSPEDFL QKSKDALESN YVSEHLHEWI DLIFGYKQKG SDAVGAHNVF HPLTYEGGVD
     LNSIQDPDEK VAMLTQILEF GQTPKQLFVT PHPRRITPKF KSLSQTSSYN ASMADSPGEE
     SFEDLTEESK TLAWNNITKL QLHEHYKIHK EAVTGITVSR NGSSVFTTSQ DSTLKMFSKE
     SKMLQRSISF SNMALSSCLL LPGDATVITS SWDNNVYFYS IAFGRRQDTL MGHDDAVSKI
     CWHDNRLYSA SWDSTVKVWS GVPAEMPGTK RHHFDLLAEL EHDVSVDTIS LNAASTLLVS
     GTKEGTVNIW DLTTATLMHQ IPCHSGIVCD TAFSPDSRHV LSTGTDGCLN VIDVQTGMLI
     SSMTSDEPQR CFVWDGNSVL SGSQSGELLV WDLLGAKISE RIQGHTGAVT CIWMNEQCSS
     IITGGEDRQI IFWKLQY
//