ASM3B_HUMAN
ID ASM3B_HUMAN Reviewed; 455 AA.
AC Q92485; B7ZB35; Q5T0Z0; Q96CB7;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Acid sphingomyelinase-like phosphodiesterase 3b;
DE Short=ASM-like phosphodiesterase 3b;
DE EC=3.1.4.- {ECO:0000269|PubMed:26095358};
DE Flags: Precursor;
GN Name=SMPDL3B; Synonyms=ASML3B, ASMLPD;
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).
RA Hofmann K.;
RT "Acid sphingomyelinase is a member of a multi-gene family and shares motifs
RT with a large family of metallo-phosphoesterases.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
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=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 [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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).
RN [6]
RP PHOSPHODIESTERASE ACTIVITY, MUTAGENESIS OF HIS-135, GLYCOSYLATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006;
RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G.,
RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P.,
RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T.,
RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R.,
RA Superti-Furga G.;
RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity.";
RL Cell Rep. 11:1919-1928(2015).
CC -!- FUNCTION: Lipid-modulating phosphodiesterase (PubMed:26095358). Active
CC on the surface of macrophages and dendritic cells and strongly
CC influences macrophage lipid composition and membrane fluidity. Acts as
CC a negative regulator of Toll-like receptor signaling (By similarity).
CC Has in vitro phosphodiesterase activity, but the physiological
CC substrate is unknown (PubMed:26095358). Lacks activity with
CC phosphocholine-containing lipids, but can cleave CDP-choline, and can
CC release phosphate from ATP and ADP (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P58242, ECO:0000269|PubMed:26095358}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P58242};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P58242};
CC -!- SUBUNIT: Interacts with TLR4, TLR7, TLR8 and TLR9.
CC {ECO:0000250|UniProtKB:P58242}.
CC -!- INTERACTION:
CC Q92485-2; P06213-1: INSR; NbExp=2; IntAct=EBI-21501656, EBI-15558981;
CC Q92485-2; P06213-2: INSR; NbExp=2; IntAct=EBI-21501656, EBI-9984921;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cell membrane
CC {ECO:0000250|UniProtKB:P58242}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P58242}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92485-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92485-2; Sequence=VSP_013478, VSP_013479;
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26095358}.
CC -!- SIMILARITY: Belongs to the acid sphingomyelinase family. {ECO:0000305}.
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DR EMBL; Y08134; CAA69328.1; -; mRNA.
DR EMBL; AK316500; BAH14871.1; -; mRNA.
DR EMBL; AL512288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07721.1; -; Genomic_DNA.
DR EMBL; BC014444; AAH14444.1; -; mRNA.
DR CCDS; CCDS30655.1; -. [Q92485-1]
DR CCDS; CCDS30656.1; -. [Q92485-2]
DR RefSeq; NP_001009568.1; NM_001009568.2. [Q92485-2]
DR RefSeq; NP_055289.2; NM_014474.3. [Q92485-1]
DR AlphaFoldDB; Q92485; -.
DR SMR; Q92485; -.
DR BioGRID; 118117; 77.
DR IntAct; Q92485; 9.
DR MINT; Q92485; -.
DR STRING; 9606.ENSP00000363001; -.
DR GlyGen; Q92485; 3 sites.
DR iPTMnet; Q92485; -.
DR PhosphoSitePlus; Q92485; -.
DR BioMuta; SMPDL3B; -.
DR DMDM; 62906890; -.
DR EPD; Q92485; -.
DR jPOST; Q92485; -.
DR MassIVE; Q92485; -.
DR MaxQB; Q92485; -.
DR PaxDb; Q92485; -.
DR PeptideAtlas; Q92485; -.
DR PRIDE; Q92485; -.
DR ProteomicsDB; 75266; -. [Q92485-1]
DR ProteomicsDB; 75267; -. [Q92485-2]
DR Antibodypedia; 30880; 96 antibodies from 20 providers.
DR DNASU; 27293; -.
DR Ensembl; ENST00000373888.8; ENSP00000362995.4; ENSG00000130768.15. [Q92485-2]
DR Ensembl; ENST00000373894.8; ENSP00000363001.3; ENSG00000130768.15. [Q92485-1]
DR GeneID; 27293; -.
DR KEGG; hsa:27293; -.
DR MANE-Select; ENST00000373894.8; ENSP00000363001.3; NM_014474.4; NP_055289.2.
DR UCSC; uc001bpf.4; human. [Q92485-1]
DR CTD; 27293; -.
DR DisGeNET; 27293; -.
DR GeneCards; SMPDL3B; -.
DR HGNC; HGNC:21416; SMPDL3B.
DR HPA; ENSG00000130768; Tissue enhanced (intestine, pancreas).
DR MIM; 617737; gene.
DR neXtProt; NX_Q92485; -.
DR OpenTargets; ENSG00000130768; -.
DR PharmGKB; PA134889099; -.
DR VEuPathDB; HostDB:ENSG00000130768; -.
DR eggNOG; KOG3770; Eukaryota.
DR GeneTree; ENSGT00950000183182; -.
DR HOGENOM; CLU_014743_0_2_1; -.
DR InParanoid; Q92485; -.
DR OMA; DSPWHLI; -.
DR OrthoDB; 1116351at2759; -.
DR PhylomeDB; Q92485; -.
DR TreeFam; TF313674; -.
DR PathwayCommons; Q92485; -.
DR SignaLink; Q92485; -.
DR BioGRID-ORCS; 27293; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; SMPDL3B; human.
DR GenomeRNAi; 27293; -.
DR Pharos; Q92485; Tbio.
DR PRO; PR:Q92485; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q92485; protein.
DR Bgee; ENSG00000130768; Expressed in mucosa of transverse colon and 110 other tissues.
DR ExpressionAtlas; Q92485; baseline and differential.
DR Genevisible; Q92485; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IMP:UniProtKB.
DR GO; GO:0004767; F:sphingomyelin phosphodiesterase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0046466; P:membrane lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IEA:InterPro.
DR CDD; cd00842; MPP_ASMase; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR017064; ASM-like_Pdiesterase_prd.
DR InterPro; IPR045473; ASM_C.
DR InterPro; IPR041805; ASMase/PPN1_MPP.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR Pfam; PF19272; ASMase_C; 1.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF036767; ASM-like_PDE; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Glycosidase; GPI-anchor; Hydrolase; Immunity; Inflammatory response;
KW Innate immunity; Lipid degradation; Lipid metabolism; Lipoprotein;
KW Membrane; Metal-binding; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..455
FT /note="Acid sphingomyelinase-like phosphodiesterase 3b"
FT /id="PRO_0000002331"
FT BINDING 28
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 277
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT BINDING 279
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..64
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT DISULFID 405..409
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT DISULFID 415..428
FT /evidence="ECO:0000250|UniProtKB:P58242"
FT VAR_SEQ 336..373
FT /note="DMVTYFMNLSQANAQGTPRWELEYQLTEAYGVPDASAH -> VRSPAEARGG
FT GWEGLKCITTFPHSQLIHLPLTTEPQEG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013478"
FT VAR_SEQ 374..455
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013479"
FT VARIANT 381
FT /note="R -> H (in dbSNP:rs34560878)"
FT /id="VAR_048340"
FT MUTAGEN 135
FT /note="H->A: Reduced phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:26095358"
FT CONFLICT 375..376
FT /note="MH -> ID (in Ref. 1; CAA69328)"
FT /evidence="ECO:0000305"
FT CONFLICT 453..455
FT /note="LVL -> TRAVTCQAHHSSW (in Ref. 1; CAA69328)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 50814 MW; E947E49C3A8449BA CRC64;
MRLLAWLIFL ANWGGARAEP GKFWHIADLH LDPDYKVSKD PFQVCPSAGS QPVPDAGPWG
DYLCDSPWAL INSSIYAMKE IEPEPDFILW TGDDTPHVPD EKLGEAAVLE IVERLTKLIR
EVFPDTKVYA ALGNHDFHPK NQFPAGSNNI YNQIAELWKP WLSNESIALF KKGAFYCEKL
PGPSGAGRIV VLNTNLYYTS NALTADMADP GQQFQWLEDV LTDASKAGDM VYIVGHVPPG
FFEKTQNKAW FREGFNEKYL KVVRKHHRVI AGQFFGHHHT DSFRMLYDDA GVPISAMFIT
PGVTPWKTTL PGVVNGANNP AIRVFEYDRA TLSLKDMVTY FMNLSQANAQ GTPRWELEYQ
LTEAYGVPDA SAHSMHTVLD RIAGDQSTLQ RYYVYNSVSY SAGVCDEACS MQHVCAMRQV
DIDAYTTCLY ASGTTPVPQL PLLLMALLGL CTLVL
