Reviewed, UniProtKB/Swiss-Prot Q13510 (ASAH1_HUMAN)

Names and origin

Protein names

Recommended name:
    Acid ceramidase
      Short name=AC
    EC=3.5.1.23
Alternative name(s):
    Acylsphingosine deacylase
    N-acylsphingosine amidohydrolase
    Putative 32 kDa heart protein
      Short name=PHP32
Cleaved into the following 2 chains:
    1- Recommended name:
            Acid ceramidase subunit alpha
    2- Recommended name:
            Acid ceramidase subunit beta

Gene names

Name:	ASAH1
Synonyms:	ASAH
ORF Names:	HSD33, HSD-33

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	395 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in ASAH1 are the cause of Farber disease (FD) [MIM:228000]; also known as Farber lipogranulomatosis. This sphingolipid disease is 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. Ref.1 Ref.5 Ref.6 Ref.15 Ref.16 Ref.17
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.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	ceramide metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ceramidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 142	121	Acid ceramidase subunit alpha		PRO_0000002312
	Chain	143 – 395	253	Acid ceramidase subunit beta		PRO_0000002313
Amino acid modifications
	Glycosylation	173	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
	Glycosylation	259	1	N-linked (GlcNAc...) Ref.10 Ref.11 Ref.12
	Glycosylation	286	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 26	26	MPGRS…QHAPP → MNCCIGLGEKARGSHRASYP SLSALFTEASILGFGSFAVK AQ in isoform 2.		VSP_037504
	Natural variant	22	1	Q → H in FD. Ref.5		VAR_038166
	Natural variant	23	1	H → D in FD. Ref.5		VAR_038167
	Natural variant	36	1	Y → C in FD. Ref.15		VAR_021579
	Natural variant	70	1	A → V: dbSNP rs10103355.		VAR_057979
	Natural variant	72	1	V → M: dbSNP rs1071645.		VAR_008860
	Natural variant	88	1	V → M: dbSNP rs1071645.		VAR_057980
	Natural variant	93	1	I → V: dbSNP rs1049874.		VAR_008861
	Natural variant	96	1	Missing in FD. Ref.16		VAR_021580
	Natural variant	97	1	V → E in FD. Ref.16		VAR_021581
	Natural variant	124	1	D → E: dbSNP rs2472205.		VAR_038168
	Natural variant	138	1	E → V in FD. Ref.5 Ref.6		VAR_021582
	Natural variant	182	1	L → V in FD. Ref.17		VAR_038169
	Natural variant	222	1	T → K in FD. Ref.1 Ref.5		VAR_008862
	Natural variant	235	1	G → R in FD. Ref.16		VAR_021583
	Natural variant	246	1	V → A: dbSNP rs10103355.		VAR_038170
	Natural variant	254	1	R → G in FD. Ref.6		VAR_021584
	Natural variant	320	1	N → D in FD. Ref.5 Ref.15		VAR_021585
	Natural variant	362	1	P → R in FD. Ref.6		VAR_021586
	Natural variant	369	1	V → I: dbSNP rs17636067. Ref.16		VAR_021587
Experimental info
	Sequence conflict	122	1	V → A in AAQ75550. Ref.4
	Sequence conflict	155	1	L → P in AAQ75550. Ref.4
	Sequence conflict	233	1	Y → N in AAQ75550. Ref.4
	Sequence conflict	364	1	L → P in AAQ75550. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 16, 2009. Version 5. Checksum: 83467DBE8917DB6D	FASTA	395	44,660
	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
	Isoform 2. Checksum: 09D3BF40743119CF	FASTA	411	46,504
	10 20 30 40 50 60 MNCCIGLGEK ARGSHRASYP SLSALFTEAS ILGFGSFAVK AQWTEDCRKS TYPPSGPTYR 70 80 90 100 110 120 GAVPWYTINL DLPPYKRWHE LMLDKAPVLK VIVNSLKNMI NTFVPSGKIM QVVDEKLPGL 130 140 150 160 170 180 LGNFPGPFEE EMKGIAAVTD IPLGEIISFN IFYELFTICT SIVAEDKKGH LIHGRNMDFG 190 200 210 220 230 240 VFLGWNINND TWVITEQLKP LTVNLDFQRN NKTVFKASSF AGYVGMLTGF KPGLFSLTLN 250 260 270 280 290 300 ERFSINGGYL GILEWILGKK DVMWIGFLTR TVLENSTSYE EAKNLLTKTK ILAPAYFILG 310 320 330 340 350 360 GNQSGEGCVI TRDRKESLDV YELDAKQGRW YVVQTNYDRW KHPFFLDDRR TPAKMCLNRT 370 380 390 400 410 SQENISFETM YDVLSTKPVL NKLTVYTTLI DVTKGQFETY LRDCPDPCIG W

References

	« Hide 'large scale' referencesShow '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: 8955159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT FD 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: 10993717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS FD 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: 10610716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS FD 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. , 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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS MET-72; VAL-93 AND ALA-246. Tissue: 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: 7744740] [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: 12754519] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259, MASS SPECTROMETRY. 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: 16263699] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259, MASS SPECTROMETRY. Tissue: Platelet.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-259 AND ASN-286, MASS SPECTROMETRY. Tissue: Liver.
[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: 11241842] [Abstract] Cited for: VARIANTS FD 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: 12638942] [Abstract] Cited for: VARIANTS FD 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: 16951918] [Abstract] Cited for: VARIANT FD VAL-182.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00013698. IPI00418446.
UniGene	Hs.527412 Hs.633993
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13510. 2 interactions.
Protein family/group databases
MEROPS	C89.001.
Proteomic databases
PRIDE	Q13510.
Genome annotation databases
Ensembl	ENSG00000104763. Homo sapiens. [Contig view]
Organism-specific databases
GeneCards	GC08M017958.
HGNC	HGNC:735. ASAH1.
HPA	HPA005468.
MIM	228000. gene+phenotype.
Orphanet	333. Farber lipogranulomatosis.
PharmGKB	PA35025.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q13510.
Enzyme and pathway databases
BRENDA	3.5.1.23. 247.
Pathway_Interaction_DB	ceramidepathway. Ceramide signaling pathway.
Gene expression databases
ArrayExpress	Q13510.
Bgee	Q13510. Q6W898.
CleanEx	HS_ASAH1.
GermOnline	ENSG00000104763. Homo sapiens.
Family and domain databases
InterPro	IPR016699. Acid_ceramidase-like. IPR003199. Chologlycine_hydro. [Graphical view]
Pfam	PF02275. CBAH. 1 hit. [Graphical view]
PIRSF	PIRSF017632. Acid_ceramidase-like. 1 hit.
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

ASAH1_HUMAN

Accession

Primary (citable) accession number: Q13510
Secondary accession number(s): Q6W898

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 16, 2009
Last modified:	June 16, 2009
This is version 94 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)