ASAH2_HUMAN
ID ASAH2_HUMAN Reviewed; 780 AA.
AC Q9NR71; Q3KNU1; Q5SNT7; Q5SZP6; Q5SZP7; Q5T1D5; Q71ME6;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Neutral ceramidase {ECO:0000305};
DE Short=N-CDase;
DE Short=NCDase;
DE EC=3.5.1.- {ECO:0000250|UniProtKB:Q9JHE3};
DE EC=3.5.1.23 {ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:11278489, ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:16061940, ECO:0000269|PubMed:19345744, ECO:0000269|PubMed:26190575};
DE AltName: Full=Acylsphingosine deacylase 2;
DE AltName: Full=BCDase;
DE AltName: Full=LCDase;
DE Short=hCD;
DE AltName: Full=N-acylsphingosine amidohydrolase 2;
DE AltName: Full=Non-lysosomal ceramidase;
DE Contains:
DE RecName: Full=Neutral ceramidase soluble form {ECO:0000250|UniProtKB:Q91XT9};
GN Name=ASAH2; Synonyms=HNAC1;
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 [GENOMIC DNA].
RX PubMed=14557071; DOI=10.1016/s0378-1119(03)00721-2;
RA Choi M.S., Anderson M.A., Zhang Z., Zimonjic D.B., Popescu N.,
RA Mukherjee A.B.;
RT "Neutral ceramidase gene: role in regulating ceramide-induced apoptosis.";
RL Gene 315:113-122(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=15946935; DOI=10.1074/jbc.m503002200;
RA Osawa Y., Uchinami H., Bielawski J., Schwabe R.F., Hannun Y.A.,
RA Brenner D.A.;
RT "Roles for C16-ceramide and sphingosine 1-phosphate in regulating
RT hepatocyte apoptosis in response to tumor necrosis factor-alpha.";
RL J. Biol. Chem. 280:27879-27887(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-780 (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10781606; DOI=10.1074/jbc.m002522200;
RA El Bawab S., Roddy P., Qian T., Bielawska A., Lemasters J.J., Hannun Y.A.;
RT "Molecular cloning and characterization of a human mitochondrial
RT ceramidase.";
RL J. Biol. Chem. 275:21508-21513(2000).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11278489; DOI=10.1074/jbc.m009331200;
RA El Bawab S., Birbes H., Roddy P., Szulc Z.M., Bielawska A., Hannun Y.A.;
RT "Biochemical characterization of the reverse activity of rat brain
RT ceramidase. A CoA-independent and fumonisin B1-insensitive ceramide
RT synthase.";
RL J. Biol. Chem. 276:16758-16766(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-780 (ISOFORM 2).
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 [7]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=15845354; DOI=10.1016/j.bbrc.2005.03.134;
RA Hwang Y.H., Tani M., Nakagawa T., Okino N., Ito M.;
RT "Subcellular localization of human neutral ceramidase expressed in HEK293
RT cells.";
RL Biochem. Biophys. Res. Commun. 331:37-42(2005).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16061940; DOI=10.1194/jlr.m500268-jlr200;
RA Tani M., Sano T., Ito M., Igarashi Y.;
RT "Mechanisms of sphingosine and sphingosine 1-phosphate generation in human
RT platelets.";
RL J. Lipid Res. 46:2458-2467(2005).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVE SITE, AND MUTAGENESIS OF SER-258; ASP-352; SER-354;
RP CYS-362; SER-374; SER-396; SER-595 AND SER-729.
RX PubMed=16229686; DOI=10.1042/bj20050682;
RA Galadari S., Wu B.X., Mao C., Roddy P., El Bawab S., Hannun Y.A.;
RT "Identification of a novel amidase motif in neutral ceramidase.";
RL Biochem. J. 393:687-695(2006).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=17475390; DOI=10.1016/j.biochi.2007.03.009;
RA Ohlsson L., Palmberg C., Duan R.D., Olsson M., Bergman T., Nilsson A.;
RT "Purification and characterization of human intestinal neutral
RT ceramidase.";
RL Biochimie 89:950-960(2007).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=17334805; DOI=10.1007/s10048-007-0081-5;
RA Avramopoulos D., Wang R., Valle D., Fallin M.D., Bassett S.S.;
RT "A novel gene derived from a segmental duplication shows perturbed
RT expression in Alzheimer's disease.";
RL Neurogenetics 8:111-120(2007).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INDUCTION BY GEMCITABINE.
RX PubMed=19345744; DOI=10.1016/j.bbalip.2009.03.012;
RA Wu B.X., Zeidan Y.H., Hannun Y.A.;
RT "Downregulation of neutral ceramidase by gemcitabine: Implications for cell
RT cycle regulation.";
RL Biochim. Biophys. Acta 1791:730-739(2009).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24798654; DOI=10.1111/febs.12826;
RA Zhu Q., Kang J., Miao H., Feng Y., Xiao L., Hu Z., Liao D.F., Huang Y.,
RA Jin J., He S.;
RT "Low-dose cytokine-induced neutral ceramidase secretion from INS-1 cells
RT via exosomes and its anti-apoptotic effect.";
RL FEBS J. 281:2861-2870(2014).
RN [14]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=30154232; DOI=10.1194/jlr.m088187;
RA Sakamoto W., Coant N., Canals D., Obeid L.M., Hannun Y.A.;
RT "Functions of neutral ceramidase in the Golgi apparatus.";
RL J. Lipid Res. 59:2116-2125(2018).
RN [15] {ECO:0007744|PDB:4WGK}
RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 99-780 IN COMPLEX WITH CALCIUM;
RP ZINC AND PHOSPHATE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, GLYCOSYLATION
RP AT ASN-151; ASN-217; ASN-308; ASN-440 AND ASN-730, DISULFIDE BONDS, AND
RP MUTAGENESIS OF GLY-124; HIS-194; HIS-196; ALA-211; ARG-257; HIS-303;
RP GLY-465; GLU-540; TYR-579 AND TYR-591.
RX PubMed=26190575; DOI=10.1016/j.str.2015.06.013;
RA Airola M.V., Allen W.J., Pulkoski-Gross M.J., Obeid L.M., Rizzo R.C.,
RA Hannun Y.A.;
RT "Structural Basis for Ceramide Recognition and Hydrolysis by Human Neutral
RT Ceramidase.";
RL Structure 23:1482-1491(2015).
CC -!- FUNCTION: Plasma membrane ceramidase that hydrolyzes sphingolipid
CC ceramides into sphingosine and free fatty acids at neutral pH
CC (PubMed:10781606, PubMed:16229686, PubMed:26190575). Ceramides,
CC sphingosine, and its phosphorylated form sphingosine-1-phosphate are
CC bioactive lipids that mediate cellular signaling pathways regulating
CC several biological processes including cell proliferation, apoptosis
CC and differentiation (PubMed:15946935, PubMed:19345744,
CC PubMed:24798654). Also catalyzes the reverse reaction allowing the
CC synthesis of ceramides from fatty acids and sphingosine
CC (PubMed:11278489, PubMed:17475390). Together with sphingomyelinase,
CC participates in the production of sphingosine and sphingosine-1-
CC phosphate from the degradation of sphingomyelin, a sphingolipid
CC enriched in the plasma membrane of cells (PubMed:16061940). Also
CC participates in the hydrolysis of ceramides from the extracellular
CC milieu allowing the production of sphingosine-1-phosphate inside and
CC outside cells (By similarity). This is the case for instance with the
CC digestion of dietary sphingolipids in the intestinal tract (By
CC similarity). {ECO:0000250|UniProtKB:Q9JHE3,
CC ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:16061940,
CC ECO:0000269|PubMed:16229686, ECO:0000269|PubMed:17475390,
CC ECO:0000269|PubMed:19345744, ECO:0000269|PubMed:24798654,
CC ECO:0000269|PubMed:26190575}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + H2O = a fatty acid + sphing-4-enine;
CC Xref=Rhea:RHEA:20856, ChEBI:CHEBI:15377, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:52639, ChEBI:CHEBI:57756; EC=3.5.1.23;
CC Evidence={ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:11278489,
CC ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:16061940,
CC ECO:0000269|PubMed:19345744, ECO:0000269|PubMed:26190575};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-dodecanoylsphing-4-enine = dodecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41291, ChEBI:CHEBI:15377, ChEBI:CHEBI:18262,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72956;
CC Evidence={ECO:0000269|PubMed:16229686, ECO:0000269|PubMed:30154232};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41292;
CC Evidence={ECO:0000305|PubMed:16229686};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41293;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoylsphing-4-enine = hexadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:38891, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72959;
CC Evidence={ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:17475390};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38892;
CC Evidence={ECO:0000305|PubMed:10781606};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38893;
CC Evidence={ECO:0000305|PubMed:17475390};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octanoylsphing-4-enine = octanoate + sphing-4-enine;
CC Xref=Rhea:RHEA:45092, ChEBI:CHEBI:15377, ChEBI:CHEBI:25646,
CC ChEBI:CHEBI:45815, ChEBI:CHEBI:57756;
CC Evidence={ECO:0000269|PubMed:17475390};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45093;
CC Evidence={ECO:0000305|PubMed:17475390};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(hexanoyl)sphing-4-enine = hexanoate + sphing-4-enine;
CC Xref=Rhea:RHEA:41295, ChEBI:CHEBI:15377, ChEBI:CHEBI:17120,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:63867;
CC Evidence={ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:30154232};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41296;
CC Evidence={ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:30154232};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-octadecanoylsphing-4-enine = octadecanoate + sphing-4-
CC enine; Xref=Rhea:RHEA:41279, ChEBI:CHEBI:15377, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:57756, ChEBI:CHEBI:72961;
CC Evidence={ECO:0000269|PubMed:15946935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41280;
CC Evidence={ECO:0000269|PubMed:15946935};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-tetradecanoylsphing-4-enine = sphing-4-enine +
CC tetradecanoate; Xref=Rhea:RHEA:41287, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57756, ChEBI:CHEBI:72957;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41289;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-sphing-4-enine = (9Z)-octadecenoate
CC + sphing-4-enine; Xref=Rhea:RHEA:41299, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57756, ChEBI:CHEBI:77996;
CC Evidence={ECO:0000269|PubMed:15946935};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41300;
CC Evidence={ECO:0000269|PubMed:15946935};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41301;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(15Z-tetracosenoyl)-sphing-4-enine = (15Z)-
CC tetracosenoate + sphing-4-enine; Xref=Rhea:RHEA:41267,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:32392, ChEBI:CHEBI:57756,
CC ChEBI:CHEBI:74450; Evidence={ECO:0000250|UniProtKB:Q91XT9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:41269;
CC Evidence={ECO:0000250|UniProtKB:Q91XT9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate + sphinganine = H2O + N-hexadecanoylsphinganine;
CC Xref=Rhea:RHEA:43440, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:67042;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:43442;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(octadecanoyl)-sphinganine = octadecanoate +
CC sphinganine; Xref=Rhea:RHEA:45008, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:57817, ChEBI:CHEBI:67033;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45009;
CC Evidence={ECO:0000250|UniProtKB:Q9JHE3};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26190575};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:26190575};
CC -!- ACTIVITY REGULATION: Inhibited by dithiothreitol (DTT) and 2-
CC mercaptoethanol (PubMed:16229686). Activity is mildly stimulated by
CC Ca(2+) and Mg(2+), but is not inhibited by EDTA (PubMed:10781606,
CC PubMed:16229686). Activity is inhibited by millimolar levels of Fe(2+),
CC Zn(2+) and Cu(2+) (PubMed:16229686, PubMed:17475390). Inhibited by
CC cholesterol (PubMed:17475390). {ECO:0000269|PubMed:10781606,
CC ECO:0000269|PubMed:16229686, ECO:0000269|PubMed:17475390}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=60.1 uM for D-erythro-C12-NBD-ceramide (at 37 degrees Celsius and
CC pH 7.5) {ECO:0000269|PubMed:16229686};
CC KM=13 uM for N-octanoylsphing-4-enine (at 37 degrees Celsius and pH
CC 7.0) {ECO:0000269|PubMed:17475390};
CC Vmax=0.68 nmol/min/mg enzyme for the hydrolysis of D-erythro-C12-NBD-
CC ceramide as substrate (at 37 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:16229686};
CC Vmax=0.8 umol/min/mg enzyme for the hydrolysis of N-octanoylsphing-4-
CC enine (at 37 degrees Celsius and pH 7.0)
CC {ECO:0000269|PubMed:17475390};
CC pH dependence:
CC Optimum pH is 7.5-9.5 for N-hexadecanoylsphing-4-enine
CC (PubMed:10781606). Optimum pH is 7.5 for D-erythro-C12-NBD-ceramide
CC (PubMed:16229686). Optimum pH is 7.5 for N-octanoylsphing-4-enine
CC (PubMed:17475390). {ECO:0000269|PubMed:10781606,
CC ECO:0000269|PubMed:16229686, ECO:0000269|PubMed:17475390};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:15946935, ECO:0000269|PubMed:19345744}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase]: Cell membrane
CC {ECO:0000269|PubMed:15845354}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Membrane raft
CC {ECO:0000250|UniProtKB:Q9JHE3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Membrane, caveola
CC {ECO:0000250|UniProtKB:Q9JHE3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:30154232}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q91XT9}. Mitochondrion
CC {ECO:0000269|PubMed:10781606}. Secreted, extracellular exosome
CC {ECO:0000269|PubMed:24798654}. Note=Enriched in exosomes upon
CC stimulation by cytokine (PubMed:24798654). Enriched in caveolae and
CC lipid rafts (By similarity). The localization to the mitochondrion
CC could not be confirmed (PubMed:15845354).
CC {ECO:0000250|UniProtKB:Q9JHE3, ECO:0000269|PubMed:15845354,
CC ECO:0000269|PubMed:24798654}.
CC -!- SUBCELLULAR LOCATION: [Neutral ceramidase soluble form]: Secreted
CC {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NR71-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NR71-2; Sequence=VSP_019928;
CC -!- TISSUE SPECIFICITY: Primarily expressed in intestine (PubMed:17334805).
CC Ubiquitously expressed with higher levels in kidney, skeletal muscle
CC and heart (PubMed:10781606). The ubiquitous expression observed for
CC ASAH2 might be an experimental artifact due to the paralog ASAH2B
CC (PubMed:17334805). {ECO:0000269|PubMed:10781606,
CC ECO:0000269|PubMed:17334805}.
CC -!- INDUCTION: Down-regulated by gemcitabine/GMZ (at protein level)
CC (PubMed:19345744). Down-regulated upon serum starvation
CC (PubMed:19345744). {ECO:0000269|PubMed:19345744}.
CC -!- PTM: Proteolytic cleavage of the N-terminus removes the signal-anchor
CC and produces a soluble form of the protein.
CC {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- PTM: N-glycosylated. Required for enzyme activity.
CC {ECO:0000250|UniProtKB:Q9JHE3}.
CC -!- PTM: O-glycosylated. Required to retain it as a type II membrane
CC protein at the cell surface. {ECO:0000269|PubMed:15845354}.
CC -!- PTM: Phosphorylated. May prevent ubiquitination and subsequent
CC degradation. {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitination is triggered by nitric oxide.
CC {ECO:0000250|UniProtKB:Q91XT9}.
CC -!- SIMILARITY: Belongs to the neutral ceramidase family. {ECO:0000305}.
CC -!- CAUTION: Was proposed to be mitochondrial, based on experiments with an
CC N-terminal GFP-tag (PubMed:10781606). The in vivo localization to the
CC mitochondrion could not be confirmed (PubMed:15845354). However, it has
CC been observed for the mouse (AC Q9JHE3) and rat (AC Q91XT9) orthologs.
CC {ECO:0000269|PubMed:10781606, ECO:0000269|PubMed:15845354,
CC ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL06061.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY049008; AAL06061.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF449759; AAQ04667.2; -; mRNA.
DR EMBL; AL450382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL589794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL954360; CAI17190.1; -; Genomic_DNA.
DR EMBL; AF250847; AAF86240.1; -; mRNA.
DR EMBL; BC107105; AAI07106.1; -; mRNA.
DR CCDS; CCDS44398.1; -. [Q9NR71-2]
DR CCDS; CCDS7239.2; -. [Q9NR71-1]
DR RefSeq; NP_001137446.1; NM_001143974.1. [Q9NR71-2]
DR RefSeq; NP_063946.2; NM_019893.2. [Q9NR71-1]
DR RefSeq; XP_011538272.1; XM_011539970.2.
DR PDB; 4WGK; X-ray; 2.58 A; A/B=99-780.
DR PDBsum; 4WGK; -.
DR AlphaFoldDB; Q9NR71; -.
DR SMR; Q9NR71; -.
DR BioGRID; 121160; 5.
DR STRING; 9606.ENSP00000378897; -.
DR BindingDB; Q9NR71; -.
DR ChEMBL; CHEMBL2021754; -.
DR SwissLipids; SLP:000000163; -.
DR GlyGen; Q9NR71; 23 sites.
DR iPTMnet; Q9NR71; -.
DR PhosphoSitePlus; Q9NR71; -.
DR BioMuta; ASAH2; -.
DR DMDM; 110832757; -.
DR MassIVE; Q9NR71; -.
DR MaxQB; Q9NR71; -.
DR PaxDb; Q9NR71; -.
DR PeptideAtlas; Q9NR71; -.
DR PRIDE; Q9NR71; -.
DR ProteomicsDB; 82290; -. [Q9NR71-1]
DR ProteomicsDB; 82291; -. [Q9NR71-2]
DR Antibodypedia; 27845; 237 antibodies from 31 providers.
DR DNASU; 56624; -.
DR Ensembl; ENST00000395526.9; ENSP00000378897.3; ENSG00000188611.17. [Q9NR71-1]
DR Ensembl; ENST00000682911.1; ENSP00000506746.1; ENSG00000188611.17. [Q9NR71-1]
DR GeneID; 56624; -.
DR KEGG; hsa:56624; -.
DR MANE-Select; ENST00000682911.1; ENSP00000506746.1; NM_019893.4; NP_063946.2.
DR UCSC; uc001jjd.4; human. [Q9NR71-1]
DR CTD; 56624; -.
DR DisGeNET; 56624; -.
DR GeneCards; ASAH2; -.
DR HGNC; HGNC:18860; ASAH2.
DR HPA; ENSG00000188611; Tissue enriched (intestine).
DR MIM; 611202; gene.
DR neXtProt; NX_Q9NR71; -.
DR OpenTargets; ENSG00000188611; -.
DR PharmGKB; PA134977109; -.
DR VEuPathDB; HostDB:ENSG00000188611; -.
DR eggNOG; KOG2232; Eukaryota.
DR GeneTree; ENSGT00390000015792; -.
DR InParanoid; Q9NR71; -.
DR OMA; VWHRTNT; -.
DR OrthoDB; 967085at2759; -.
DR PhylomeDB; Q9NR71; -.
DR TreeFam; TF300786; -.
DR BRENDA; 3.5.1.23; 2681.
DR PathwayCommons; Q9NR71; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SABIO-RK; Q9NR71; -.
DR SignaLink; Q9NR71; -.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 56624; 14 hits in 1068 CRISPR screens.
DR ChiTaRS; ASAH2; human.
DR GeneWiki; ASAH2; -.
DR GenomeRNAi; 56624; -.
DR Pharos; Q9NR71; Tbio.
DR PRO; PR:Q9NR71; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NR71; protein.
DR Bgee; ENSG00000188611; Expressed in duodenum and 101 other tissues.
DR ExpressionAtlas; Q9NR71; baseline and differential.
DR Genevisible; Q9NR71; HS.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0102121; F:ceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0017040; F:N-acylsphingosine amidohydrolase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046514; P:ceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0044241; P:lipid digestion; ISS:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006670; P:sphingosine metabolic process; IDA:UniProtKB.
DR Gene3D; 2.60.40.2300; -; 1.
DR InterPro; IPR006823; Ceramidase_alk.
DR InterPro; IPR038445; NCDase_C_sf.
DR InterPro; IPR031331; NEUT/ALK_ceramidase_C.
DR InterPro; IPR031329; NEUT/ALK_ceramidase_N.
DR PANTHER; PTHR12670; PTHR12670; 1.
DR Pfam; PF04734; Ceramidase_alk; 1.
DR Pfam; PF17048; Ceramidse_alk_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Calcium; Cell membrane;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Lipid metabolism;
KW Membrane; Metal-binding; Mitochondrion; Phosphoprotein; Reference proteome;
KW Secreted; Signal-anchor; Sphingolipid metabolism; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Zinc.
FT CHAIN 1..780
FT /note="Neutral ceramidase"
FT /id="PRO_0000247099"
FT CHAIN 99..780
FT /note="Neutral ceramidase soluble form"
FT /evidence="ECO:0000250|UniProtKB:Q91XT9"
FT /id="PRO_0000247100"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..780
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 47..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 770..780
FT /note="Required for correct folding and localization"
FT /evidence="ECO:0000250|UniProtKB:Q91XT9"
FT ACT_SITE 354
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:16229686"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 579
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 712
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 714
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT BINDING 717
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT SITE 98..99
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q91XT9"
FT CARBOHYD 62
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 67
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 82
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 730
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT CARBOHYD 779
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT DISULFID 362..376
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT DISULFID 369..384
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT DISULFID 448..498
FT /evidence="ECO:0000269|PubMed:26190575,
FT ECO:0007744|PDB:4WGK"
FT VAR_SEQ 410..444
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019928"
FT VARIANT 51
FT /note="T -> A (in dbSNP:rs7067625)"
FT /id="VAR_027064"
FT VARIANT 346
FT /note="A -> S (in dbSNP:rs1052952953)"
FT /id="VAR_027065"
FT MUTAGEN 124
FT /note="G->R: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 194
FT /note="H->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 196
FT /note="H->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 211
FT /note="A->R: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 257
FT /note="R->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 258
FT /note="S->A: Decreased ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 303
FT /note="H->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 352
FT /note="D->S: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 354
FT /note="S->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 362
FT /note="C->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 374
FT /note="S->A: Decreased ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 396
FT /note="S->A: No effect on ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 465
FT /note="G->R: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 540
FT /note="E->A: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 579
FT /note="Y->F: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 591
FT /note="Y->F: Loss of ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:26190575"
FT MUTAGEN 595
FT /note="S->A: Decreased ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT MUTAGEN 729
FT /note="S->A: Decreased ceramide hydrolase activity."
FT /evidence="ECO:0000269|PubMed:16229686"
FT CONFLICT 274
FT /note="S -> P (in Ref. 1; AAL06061 and 4; AAF86240)"
FT /evidence="ECO:0000305"
FT CONFLICT 602
FT /note="T -> A (in Ref. 1; AAL06061 and 4; AAF86240)"
FT /evidence="ECO:0000305"
FT CONFLICT 689
FT /note="T -> N (in Ref. 3; CAI17190)"
FT /evidence="ECO:0000305"
FT STRAND 102..110
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 115..123
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 153..161
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 165..179
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 185..192
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 206..212
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 217..235
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 239..249
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 255..257
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 280..288
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 317..330
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 342..346
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:4WGK"
FT TURN 363..365
FT /evidence="ECO:0007829|PDB:4WGK"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 380..383
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 393..413
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 436..442
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 454..458
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 478..487
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 493..499
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 504..506
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 508..510
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 520..529
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 532..536
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 538..541
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 543..559
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 566..570
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 572..575
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 578..580
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 583..588
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 591..594
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 602..618
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 622..624
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 658..660
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 664..667
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 670..677
FT /evidence="ECO:0007829|PDB:4WGK"
FT HELIX 681..684
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 693..700
FT /evidence="ECO:0007829|PDB:4WGK"
FT TURN 701..704
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 705..711
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 717..723
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 729..736
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 744..756
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 764..771
FT /evidence="ECO:0007829|PDB:4WGK"
FT STRAND 775..779
FT /evidence="ECO:0007829|PDB:4WGK"
SQ SEQUENCE 780 AA; 85516 MW; D2BD7947B022A619 CRC64;
MAKRTFSNLE TFLIFLLVMM SAITVALLSL LFITSGTIEN HKDLGGHFFS TTQSPPATQG
STAAQRSTAT QHSTATQSST ATQTSPVPLT PESPLFQNFS GYHIGVGRAD CTGQVADINL
MGYGKSGQNA QGILTRLYSR AFIMAEPDGS NRTVFVSIDI GMVSQRLRLE VLNRLQSKYG
SLYRRDNVIL SGTHTHSGPA GYFQYTVFVI ASEGFSNQTF QHMVTGILKS IDIAHTNMKP
GKIFINKGNV DGVQINRSPY SYLQNPQSER ARYSSNTDKE MIVLKMVDLN GDDLGLISWF
AIHPVSMNNS NHLVNSDNVG YASYLLEQEK NKGYLPGQGP FVAAFASSNL GDVSPNILGP
RCINTGESCD NANSTCPIGG PSMCIAKGPG QDMFDSTQII GRAMYQRAKE LYASASQEVT
GPLASAHQWV DMTDVTVWLN STHASKTCKP ALGYSFAAGT IDGVGGLNFT QGKTEGDPFW
DTIRDQILGK PSEEIKECHK PKPILLHTGE LSKPHPWHPD IVDVQIITLG SLAITAIPGE
FTTMSGRRLR EAVQAEFASH GMQNMTVVIS GLCNVYTHYI TTYEEYQAQR YEAASTIYGP
HTLSAYIQLF RNLAKAIATD TVANLSRGPE PPFFKQLIVP LIPSIVDRAP KGRTFGDVLQ
PAKPEYRVGE VAEVIFVGAN PKNSVQNQTH QTFLTVEKYE ATSTSWQIVC NDASWETRFY
WHKGLLGLSN ATVEWHIPDT AQPGIYRIRY FGHNRKQDIL KPAVILSFEG TSPAFEVVTI
