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Q13510 (ASAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Acid ceramidase

Short name=AC
Short name=ACDase
Short name=Acid CDase
EC=3.5.1.23
Alternative name(s):
Acylsphingosine deacylase
N-acylsphingosine amidohydrolase
Putative 32 kDa heart protein
Short name=PHP32
Gene names
Name:ASAH1
Synonyms:ASAH
ORF Names:HSD-33, HSD33
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid.

Catalytic activity

N-acylsphingosine + H2O = a carboxylate + sphingosine.

Subunit structure

Heterodimer of one alpha and one beta subunit.

Subcellular location

Lysosome.

Tissue specificity

Broadly expressed with highest expression in heart.

Involvement in disease

Farber lipogranulomatosis (FL) [MIM:228000]: Sphingolipid disease characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, marked accumulation of ceramide in lysosomes, and death by three years of age.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.6 Ref.15 Ref.16 Ref.17

Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) [MIM:159950]: An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18

Sequence similarities

Belongs to the acid ceramidase family.

Sequence caution

The sequence AAC73009.1 differs from that shown. Reason: Frameshift at positions 15 and 21.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13510-1)

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: Q13510-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MPGRSCVALVLLAAAVSCAVAQHAPP → MNCCIGLGEKARGSHRASYPSLSALFTEASILGFGSFAVKAQ
Isoform 3 (identifier: Q13510-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: MPGRSCVALVLLAAAVSCAVAQHAPP → MNCCIGLGEKARGSHRASYPSLSALFTEASILGFGSFAVKAQ
     42-42: T → TVFPAVIR
     73-101: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 142121Acid ceramidase subunit alpha
PRO_0000002312
Chain143 – 395253Acid ceramidase subunit beta
PRO_0000002313

Amino acid modifications

Glycosylation1731N-linked (GlcNAc...) Potential
Glycosylation1951N-linked (GlcNAc...) Potential
Glycosylation2591N-linked (GlcNAc...) Ref.10 Ref.11 Ref.12 Ref.13
Glycosylation2861N-linked (GlcNAc...) Ref.10 Ref.13
Glycosylation3421N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2626MPGRS…QHAPP → MNCCIGLGEKARGSHRASYP SLSALFTEASILGFGSFAVK AQ in isoform 2 and isoform 3.
VSP_037504
Alternative sequence421T → TVFPAVIR in isoform 3.
VSP_046284
Alternative sequence73 – 10129Missing in isoform 3.
VSP_046285
Natural variant221Q → H in FL. Ref.5
VAR_038166
Natural variant231H → D in FL. Ref.5
VAR_038167
Natural variant361Y → C in FL. Ref.15
VAR_021579
Natural variant421T → M in SMAPME; results in reduced activity. Ref.18
VAR_068722
Natural variant701A → V.
Corresponds to variant rs10103355 [ dbSNP | Ensembl ].
VAR_057979
Natural variant721V → M. Ref.1 Ref.2 Ref.5 Ref.8
Corresponds to variant rs1071645 [ dbSNP | Ensembl ].
VAR_008860
Natural variant881V → M.
Corresponds to variant rs1071645 [ dbSNP | Ensembl ].
VAR_057980
Natural variant931I → V. Ref.1 Ref.2 Ref.5 Ref.8
Corresponds to variant rs1049874 [ dbSNP | Ensembl ].
VAR_008861
Natural variant961Missing in FL. Ref.16
VAR_021580
Natural variant971V → E in FL. Ref.16
VAR_021581
Natural variant1241D → E.
Corresponds to variant rs2472205 [ dbSNP | Ensembl ].
VAR_038168
Natural variant1381E → V in FL. Ref.5 Ref.6
Corresponds to variant rs28934273 [ dbSNP | Ensembl ].
VAR_021582
Natural variant1821L → V in FL. Ref.17
VAR_038169
Natural variant2221T → K in FL. Ref.1 Ref.5
VAR_008862
Natural variant2351G → R in FL. Ref.16
VAR_021583
Natural variant2461V → A. Ref.1 Ref.2 Ref.5 Ref.8
Corresponds to variant rs10103355 [ dbSNP | Ensembl ].
VAR_038170
Natural variant2541R → G in FL. Ref.6
VAR_021584
Natural variant3201N → D in FL. Ref.5 Ref.15
VAR_021585
Natural variant3621P → R in FL. Ref.6
VAR_021586
Natural variant3691V → I. Ref.16
Corresponds to variant rs17636067 [ dbSNP | Ensembl ].
VAR_021587

Experimental info

Sequence conflict1221V → A in AAQ75550. Ref.4
Sequence conflict1421I → V in AAH16828. Ref.8
Sequence conflict1551L → P in AAQ75550. Ref.4
Sequence conflict2331Y → N in AAQ75550. Ref.4
Sequence conflict3641L → P in AAQ75550. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 16, 2009. Version 5.
Checksum: 83467DBE8917DB6D

FASTA39544,660
        10         20         30         40         50         60 
MPGRSCVALV LLAAAVSCAV AQHAPPWTED CRKSTYPPSG PTYRGAVPWY TINLDLPPYK 

        70         80         90        100        110        120 
RWHELMLDKA PVLKVIVNSL KNMINTFVPS GKIMQVVDEK LPGLLGNFPG PFEEEMKGIA 

       130        140        150        160        170        180 
AVTDIPLGEI ISFNIFYELF TICTSIVAED KKGHLIHGRN MDFGVFLGWN INNDTWVITE 

       190        200        210        220        230        240 
QLKPLTVNLD FQRNNKTVFK ASSFAGYVGM LTGFKPGLFS LTLNERFSIN GGYLGILEWI 

       250        260        270        280        290        300 
LGKKDVMWIG FLTRTVLENS TSYEEAKNLL TKTKILAPAY FILGGNQSGE GCVITRDRKE 

       310        320        330        340        350        360 
SLDVYELDAK QGRWYVVQTN YDRWKHPFFL DDRRTPAKMC LNRTSQENIS FETMYDVLST 

       370        380        390 
KPVLNKLTVY TTLIDVTKGQ FETYLRDCPD PCIGW 

« Hide

Isoform 2 [UniParc].

Checksum: 09D3BF40743119CF
Show »

FASTA41146,504
Isoform 3 [UniParc].

Checksum: 56A2FF8FB1911AD5
Show »

FASTA38944,046

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification of the first molecular lesion causing Farber disease."
Koch J., Gaertner S., Li C.M., Quintern L.E., Bernardo K., Levran O., Schnabel D., Desnick R.J., Schuchman E.H., Sandhoff K.
J. Biol. Chem. 271:33110-33115(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT FL LYS-222, VARIANTS MET-72; VAL-93 AND ALA-246.
Tissue: Fibroblast, Pituitary and Urine.
[2]"A new gene family predicted by a novel human heart cDNA."
Churchill J.R., Wieland S.J., Hoffman S., Gallin E.K., Murphy P.M.
Mol. Biol. Cell 6:418-418(1995)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MET-72; VAL-93 AND ALA-246.
[3]Wieland S.J., Hoffman S., Churchill J.R., Gallin E.K., Murphy P.M.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[4]"A new spermatogenesis related gene."
Fan M.M., Miao S.Y., Zhang X.D., Qiao Y., Liang G., Wang L.F.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[5]"Human acid ceramidase gene: novel mutations in Farber disease."
Zhang Z., Mandal A.K., Mital A., Popescu N., Zimonjic D., Moser A., Moser H., Mukherjee A.B.
Mol. Genet. Metab. 70:301-309(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS FL HIS-22; ASP-23; VAL-138; LYS-222 AND ASP-320, VARIANTS MET-72; VAL-93 AND ALA-246.
[6]"The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression."
Li C.M., Park J.H., He X., Levy B., Chen F., Arai K., Adler D.A., Disteche C.M., Koch J., Sandhoff K., Schuchman E.H.
Genomics 62:223-231(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS FL VAL-138; GLY-254 AND ARG-362.
[7]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS MET-72; VAL-93 AND ALA-246.
Tissue: Bone marrow and Skin.
[9]"Purification, characterization, and biosynthesis of human acid ceramidase."
Bernardo K., Hurwitz R., Zenk T., Desnick R.J., Ferlinz K., Schuchman E.H., Sandhoff K.
J. Biol. Chem. 270:11098-11102(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[10]"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
Zhang H., Li X.-J., Martin D.B., Aebersold R.
Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-259 AND ASN-286.
[11]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259.
Tissue: Plasma.
[12]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259.
Tissue: Platelet.
[13]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259 AND ASN-286.
Tissue: Liver.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Molecular analysis of acid ceramidase deficiency in patients with Farber disease."
Bar J., Linke T., Ferlinz K., Neumann U., Schuchman E.H., Sandhoff K.
Hum. Mutat. 17:199-209(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FL CYS-36 AND ASP-320.
[16]"Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease."
Muramatsu T., Sakai N., Yanagihara L., Yamada M., Nishigaki T., Kokubu C., Tsukamoto H., Ito M., Inui K.
J. Inherit. Metab. Dis. 25:585-592(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FL VAL-96 DEL; GLU-97 AND ARG-235, VARIANT ILE-369.
[17]"Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family."
Devi A.R.R., Gopikrishna M., Ratheesh R., Savithri G., Swarnalata G., Bashyam M.
J. Hum. Genet. 51:811-814(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FL VAL-182.
[18]"Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1."
Zhou J., Tawk M., Tiziano F.D., Veillet J., Bayes M., Nolent F., Garcia V., Servidei S., Bertini E., Castro-Giner F., Renda Y., Carpentier S., Andrieu-Abadie N., Gut I., Levade T., Topaloglu H., Melki J.
Am. J. Hum. Genet. 91:5-14(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SMAPME MET-42, CHARACTERIZATION OF VARIANT SMAPME MET-42.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U70063 mRNA. Translation: AAC50907.1.
U47674 mRNA. Translation: AAC73009.1. Frameshift.
AY305384 mRNA. Translation: AAQ75550.1.
AF220175, AF220172, AF220173 Genomic DNA. Translation: AAF91230.1.
AC124242 Genomic DNA. No translation available.
BC016481 mRNA. Translation: AAH16481.1.
BC016828 mRNA. Translation: AAH16828.1.
CCDSCCDS47813.1. [Q13510-3]
CCDS6005.1. [Q13510-2]
CCDS6006.1. [Q13510-1]
RefSeqNP_001120977.1. NM_001127505.1. [Q13510-3]
NP_004306.3. NM_004315.4. [Q13510-2]
NP_808592.2. NM_177924.3. [Q13510-1]
UniGeneHs.527412.
Hs.633993.

3D structure databases

ProteinModelPortalQ13510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106920. 8 interactions.
IntActQ13510. 7 interactions.
MINTMINT-1368026.
STRING9606.ENSP00000371152.

Chemistry

ChEMBLCHEMBL5463.

Protein family/group databases

MEROPSC89.001.

PTM databases

PhosphoSiteQ13510.

Polymorphism databases

DMDM239938949.

Proteomic databases

MaxQBQ13510.
PaxDbQ13510.
PRIDEQ13510.

Protocols and materials databases

DNASU427.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262097; ENSP00000262097; ENSG00000104763. [Q13510-1]
ENST00000314146; ENSP00000326970; ENSG00000104763. [Q13510-3]
ENST00000381733; ENSP00000371152; ENSG00000104763. [Q13510-2]
GeneID427.
KEGGhsa:427.
UCSCuc003wyl.2. human. [Q13510-1]
uc003wyn.2. human. [Q13510-2]

Organism-specific databases

CTD427.
GeneCardsGC08M017958.
HGNCHGNC:735. ASAH1.
HPAHPA005468.
MIM159950. phenotype.
228000. phenotype.
613468. gene.
neXtProtNX_Q13510.
Orphanet333. Farber lipogranulomatosis.
2590. Hereditary myoclonus - progressive distal muscular atrophy.
PharmGKBPA35025.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84249.
HOVERGENHBG050586.
KOK12348.
OMAYTINLDL.
OrthoDBEOG7TTQ7P.
PhylomeDBQ13510.
TreeFamTF313219.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKQ13510.

Gene expression databases

ArrayExpressQ13510.
BgeeQ13510.
CleanExHS_ASAH1.
GenevestigatorQ13510.

Family and domain databases

Gene3D3.60.60.10. 1 hit.
InterProIPR016699. Acid_ceramidase-like.
IPR029130. Acid_ceramidase_N.
IPR029132. CBAH/NAAA_C.
IPR003199. Chologlycine_hydro.
[Graphical view]
PfamPF02275. CBAH. 1 hit.
PF15508. NAAA-beta. 1 hit.
[Graphical view]
PIRSFPIRSF017632. Acid_ceramidase-like. 1 hit.
ProtoNetSearch...

Other

ChiTaRSASAH1. human.
GeneWikiASAH1.
GenomeRNAi427.
NextBio1787.
PROQ13510.
SOURCESearch...

Entry information

Entry nameASAH1_HUMAN
AccessionPrimary (citable) accession number: Q13510
Secondary accession number(s): E9PDS0, Q6W898, Q96AS2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: July 9, 2014
This is version 146 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM