Q92636 (FAN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein FAN

Alternative name(s):
Factor associated with neutral sphingomyelinase activation
Short name=Factor associated with N-SMase activation

Gene names

Name:	NSMAF
Synonyms:	FAN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	917 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral sphingomyelinase (N-SMASE). Specifically binds to the N-smase activation domain of TNF-R55. May regulate ceramide production by N-SMASE.
Tissue specificity	Ubiquitous.
Sequence similarities	Contains 1 BEACH domain. Contains 1 GRAM domain. Contains 6 WD repeats.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ceramide metabolic process Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc soluble fraction Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct receptor signaling protein activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAP	O95166	2	EBI-2947053,EBI-712001
GABARAPL1	Q9H0R8	6	EBI-2947053,EBI-746969

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92636-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92636-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: MAFIRKKQQEQQLQLYSKER → MTGQARFHRGAEACRAIRQCRSRRPRAAHPEGRAGSGRGSRHASPGVRRGG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 917	917	Protein FAN		PRO_0000050975
Regions
	Domain	176 – 247	72	GRAM
	Domain	290 – 575	286	BEACH
	Repeat	628 – 658	31	WD 1
	Repeat	670 – 700	31	WD 2
	Repeat	712 – 740	29	WD 3
	Repeat	761 – 791	31	WD 4
	Repeat	803 – 833	31	WD 5
	Repeat	884 – 914	31	WD 6
	Compositional bias	23 – 28	6	Poly-Leu
Natural variations
	Alternative sequence	1 – 20	20	MAFIR…YSKER → MTGQARFHRGAEACRAIRQC RSRRPRAAHPEGRAGSGRGS RHASPGVRRGG in isoform 2.		VSP_042036
	Natural variant	626	1	Y → C. Corresponds to variant rs2228505 [ dbSNP | Ensembl ].		VAR_047023
	Natural variant	850	1	R → T. Ref.1 Corresponds to variant rs1131173 [ dbSNP | Ensembl ].		VAR_047024
Experimental info
	Sequence conflict	218	1	T → A in BAG57371. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 36498B5A1378E49C	FASTA	917	104,372
	10 20 30 40 50 60 MAFIRKKQQE QQLQLYSKER FSLLLLNLEE YYFEQHRANH ILHKGSHHER KIRGSLKICS 70 80 90 100 110 120 KSVIFEPDSI SQPIIKIPLR DCIKIGKHGE NGANRHFTKA KSGGISLIFS QVYFIKEHNV 130 140 150 160 170 180 VAPYKIERGK MEYVFELDVP GKVEDVVETL LQLHRASCLD KLGDQTAMIT AILQSRLART 190 200 210 220 230 240 SFDKNRFQNI SEKLHMECKA EMVTPLVTNP GHVCITDTNL YFQPLNGYPK PVVQITLQDV 250 260 270 280 290 300 RRIYKRRHGL MPLGLEVFCT EDDLCSDIYL KFYEPQDRDD LYFYIATYLE HHVAEHTAES 310 320 330 340 350 360 YMLQWQRGHL SNYQYLLHLN NLADRSCNDL SQYPVFPWII HDYSSSELDL SNPGTFRDLS 370 380 390 400 410 420 KPVGALNKER LERLLTRYQE MPEPKFMYGS HYSSPGYVLF YLVRIAPEYM LCLQNGRFDN 430 440 450 460 470 480 ADRMFNSIAE TWKNCLDGAT DFKELIPEFY GDDVSFLVNS LKLDLGKRQG GQMVDDVELP 490 500 510 520 530 540 PWASSPEDFL QKSKDALESN YVSEHLHEWI DLIFGYKQKG SDAVGAHNVF HPLTYEGGVD 550 560 570 580 590 600 LNSIQDPDEK VAMLTQILEF GQTPKQLFVT PHPRRITPKF KSLSQTSSYN ASMADSPGEE 610 620 630 640 650 660 SFEDLTEESK TLAWNNITKL QLHEHYKIHK EAVTGITVSR NGSSVFTTSQ DSTLKMFSKE 670 680 690 700 710 720 SKMLQRSISF SNMALSSCLL LPGDATVITS SWDNNVYFYS IAFGRRQDTL MGHDDAVSKI 730 740 750 760 770 780 CWHDNRLYSA SWDSTVKVWS GVPAEMPGTK RHHFDLLAEL EHDVSVDTIS LNAASTLLVS 790 800 810 820 830 840 GTKEGTVNIW DLTTATLMHQ IPCHSGIVCD TAFSPDSRHV LSTGTDGCLN VIDVQTGMLI 850 860 870 880 890 900 SSMTSDEPQR CFVWDGNSVL SGSQSGELLV WDLLGAKISE RIQGHTGAVT CIWMNEQCSS 910 IITGGEDRQI IFWKLQY
	Isoform 2 [UniParc]. Checksum: 2682F63DEBDE1765	FASTA	948	107,314
	10 20 30 40 50 60 MTGQARFHRG AEACRAIRQC RSRRPRAAHP EGRAGSGRGS RHASPGVRRG GFSLLLLNLE 70 80 90 100 110 120 EYYFEQHRAN HILHKGSHHE RKIRGSLKIC SKSVIFEPDS ISQPIIKIPL RDCIKIGKHG 130 140 150 160 170 180 ENGANRHFTK AKSGGISLIF SQVYFIKEHN VVAPYKIERG KMEYVFELDV PGKVEDVVET 190 200 210 220 230 240 LLQLHRASCL DKLGDQTAMI TAILQSRLAR TSFDKNRFQN ISEKLHMECK AEMVTPLVTN 250 260 270 280 290 300 PGHVCITDTN LYFQPLNGYP KPVVQITLQD VRRIYKRRHG LMPLGLEVFC TEDDLCSDIY 310 320 330 340 350 360 LKFYEPQDRD DLYFYIATYL EHHVAEHTAE SYMLQWQRGH LSNYQYLLHL NNLADRSCND 370 380 390 400 410 420 LSQYPVFPWI IHDYSSSELD LSNPGTFRDL SKPVGALNKE RLERLLTRYQ EMPEPKFMYG 430 440 450 460 470 480 SHYSSPGYVL FYLVRIAPEY MLCLQNGRFD NADRMFNSIA ETWKNCLDGA TDFKELIPEF 490 500 510 520 530 540 YGDDVSFLVN SLKLDLGKRQ GGQMVDDVEL PPWASSPEDF LQKSKDALES NYVSEHLHEW 550 560 570 580 590 600 IDLIFGYKQK GSDAVGAHNV FHPLTYEGGV DLNSIQDPDE KVAMLTQILE FGQTPKQLFV 610 620 630 640 650 660 TPHPRRITPK FKSLSQTSSY NASMADSPGE ESFEDLTEES KTLAWNNITK LQLHEHYKIH 670 680 690 700 710 720 KEAVTGITVS RNGSSVFTTS QDSTLKMFSK ESKMLQRSIS FSNMALSSCL LLPGDATVIT 730 740 750 760 770 780 SSWDNNVYFY SIAFGRRQDT LMGHDDAVSK ICWHDNRLYS ASWDSTVKVW SGVPAEMPGT 790 800 810 820 830 840 KRHHFDLLAE LEHDVSVDTI SLNAASTLLV SGTKEGTVNI WDLTTATLMH QIPCHSGIVC 850 860 870 880 890 900 DTAFSPDSRH VLSTGTDGCL NVIDVQTGML ISSMTSDEPQ RCFVWDGNSV LSGSQSGELL 910 920 930 940 VWDLLGAKIS ERIQGHTGAV TCIWMNEQCS SIITGGEDRQ IIFWKLQY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase." Adam-Klages S., Adam D., Wiegmann K., Struve S., Kolanus W., Schneider-Mergener J., Kroenke M. Cell 86:937-947(1996) [PubMed: 8808629] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-850 (ISOFORM 1). Tissue: Muscle.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Cerebellum.
[3]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X96586 mRNA. Translation: CAA65405.1. AK294009 mRNA. Translation: BAG57371.1. AC068522 Genomic DNA. No translation available. AC092700 Genomic DNA. No translation available. CH471068 Genomic DNA. Translation: EAW86817.1. BC041124 mRNA. Translation: AAH41124.1.
IPI	IPI00328260.
RefSeq	NP_001138244.1. NM_001144772.1. NP_003571.2. NM_003580.3.
UniGene	Hs.372000.
3D structure databases
ProteinModelPortal	Q92636.
SMR	Q92636. Positions 192-575, 622-916.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92636. 12 interactions.
MINT	MINT-2813141.
STRING	Q92636.
PTM databases
PhosphoSite	Q92636.
Polymorphism databases
DMDM	209572614.
Proteomic databases
PRIDE	Q92636.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000038176; ENSP00000038176; ENSG00000035681.
GeneID	8439.
KEGG	hsa:8439.
Organism-specific databases
CTD	8439.
GeneCards	GC08M059496.
H-InvDB	HIX0007527.
HGNC	HGNC:8017. NSMAF.
HPA	HPA023067. HPA023148. HPA023151.
MIM	603043. gene.
neXtProt	NX_Q92636.
PharmGKB	PA31795.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12377.
GeneTree	ENSGT00600000084290.
HOVERGEN	HBG005639.
InParanoid	Q92636.
OrthoDB	EOG4M91QQ.
PhylomeDB	Q92636.
Enzyme and pathway databases
Pathway_Interaction_DB	tnfpathway. TNF receptor signaling pathway.
Gene expression databases
ArrayExpress	Q92636.
Bgee	Q92636.
CleanEx	HS_NSMAF.
Genevestigator	Q92636.
GermOnline	ENSG00000035681. Homo sapiens.
Family and domain databases
InterPro	IPR000409. BEACH_dom. IPR004182. GRAM. IPR023362. PH-BEACH_dom. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR011046. WD40_repeat-like_dom. IPR017986. WD40_repeat_dom. [Graphical view]
Gene3D	G3DSA:1.10.1540.10. Beige_BEACH. 1 hit. G3DSA:2.30.29.40. G3DSA:2.30.29.40. 1 hit. G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
Pfam	PF02138. Beach. 1 hit. PF02893. GRAM. 1 hit. PF00400. WD40. 5 hits. [Graphical view]
SMART	SM01026. Beach. 1 hit. SM00568. GRAM. 1 hit. SM00320. WD40. 7 hits. [Graphical view]
SUPFAM	SSF81837. Beige_BEACH. 1 hit. SSF50978. WD40_like. 1 hit.
PROSITE	PS50197. BEACH. 1 hit. PS00678. WD_REPEATS_1. False negative. PS50082. WD_REPEATS_2. 4 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

FAN_HUMAN

Accession

Primary (citable) accession number: Q92636
Secondary accession number(s): B4DFB0, E9PCH0, Q8IW26

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 14, 2008
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.