Reviewed, UniProtKB/Swiss-Prot Q13510 (ASAH1_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	ASAH1
Synonyms:	ASAH

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 + H(2)O = 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.
Sequence similarities	Belongs to the acid ceramidase family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	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
Molecular function	catalytic activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 142	121	Acid ceramidase subunit alpha
	Chain	143 – 395	253	Acid ceramidase subunit beta
Amino acid modifications
	Glycosylation	173	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
	Glycosylation	259	1	N-linked (GlcNAc...)
	Glycosylation	286	1	N-linked (GlcNAc...)
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	22	1	Q → H in FD.
	Natural variant	23	1	H → D in FD.
	Natural variant	36	1	Y → C in FD.
	Natural variant	72	1	M → V: dbSNP rs1071645.
	Natural variant	93	1	V → I: dbSNP rs1049874.
	Natural variant	96	1	Missing in FD.
	Natural variant	97	1	V → E in FD.
	Natural variant	124	1	D → E: dbSNP rs2472205.
	Natural variant	138	1	E → V in FD.
	Natural variant	182	1	L → V in FD.
	Natural variant	222	1	T → K in FD.
	Natural variant	235	1	G → R in FD.
	Natural variant	246	1	A → V: dbSNP rs10103355.
	Natural variant	254	1	R → G in FD.
	Natural variant	320	1	N → D in FD.
	Natural variant	362	1	P → R in FD.
	Natural variant	369	1	V → I: dbSNP rs17636067.
Experimental info
	Sequence conflict	16 – 21	6	VSCAVA → SAVPS in AAC73009. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q13510-1 [UniParc]. Last modified May 30, 2000. Version 4. Checksum: 789F3B936791C128	FASTA	395	44,650
	10 20 30 40 50 60 MPGRSCVALV LLAAAVSCAV AQHAPPWTED CRKSTYPPSG PTYRGAVPWY TINLDLPPYK 70 80 90 100 110 120 RWHELMLDKA PMLKVIVNSL KNMINTFVPS GKVMQVVDEK 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 LGKKDAMWIG FLTRTVLENS TSYEEAKNLL TKTKILAPAY FILGGNQSGE GCVITRDRKE 310 320 330 340 350 360 SLDVYELDAK QGRWYVVQTN YDRWKHPFFL DDRRTPAKMC LNRTSQENIS FETMYDVLST 370 380 390 KPVLNKLTVY TTLIDVTKGQ FETYLRDCPD PCIGW

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], PARTIAL PROTEIN SEQUENCE, VARIANT FD LYS-222, VARIANTS VAL-72 AND ILE-93. 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].
[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]	"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-72; ILE-93; VAL-138; LYS-222 AND ASP-320.
[5]	"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.
[6]	"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], VARIANT VAL-246.
[7]	"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]. Tissue: Skin.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U70063 mRNA. Translation: AAC50907.1. U47674 mRNA. Translation: AAC73009.1. AF220175, AF220172, AF220173 Genomic DNA. Translation: AAF91230.1. AC124242 Genomic DNA. No translation available. BC016481 mRNA. Translation: AAH16481.1.
UniGene	Hs.527412 Hs.633993
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	C89.001.
Genome annotation databases
Ensembl	ENSG00000104763. Homo sapiens. [Contig view]
Organism-specific databases
HGNC	HGNC:735. ASAH1.
HPA	HPA005468.
MIM	228000. gene+phenotype.
Orphanet	333. Farber lipogranulomatosis.
PharmGKB	PA35025.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOVERGEN	Q13510.
Gene expression databases
ArrayExpress	Q13510.
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.
ProDom	Q13510. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ASAH1_HUMAN

Accession

Primary (citable) accession number: Q13510

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 30, 2000
Last modified:	July 22, 2008
This is version 85 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)