FAN_HUMAN
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 03-AUG-2022, entry version 180.
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.
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; 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 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; Q92636; -.
DR PeptideAtlas; Q92636; -.
DR PRIDE; Q92636; -.
DR ProteomicsDB; 75390; -. [Q92636-1]
DR ProteomicsDB; 75391; -. [Q92636-2]
DR Antibodypedia; 11802; 126 antibodies from 24 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 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; QVYKRRY; -.
DR OrthoDB; 101142at2759; -.
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 1072 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 200 other tissues.
DR ExpressionAtlas; Q92636; baseline and differential.
DR Genevisible; Q92636; HS.
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:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd06071; Beach; 1.
DR Gene3D; 1.10.1540.10; -; 1.
DR Gene3D; 2.130.10.10; -; 3.
DR Gene3D; 2.30.29.30; -; 1.
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; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF02138; Beach; 1.
DR Pfam; PF02893; GRAM; 1.
DR Pfam; PF00400; WD40; 3.
DR SMART; SM01026; Beach; 1.
DR SMART; SM00568; GRAM; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81837; SSF81837; 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.
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
