Q5QJU3 (ACER2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alkaline ceramidase 2
Short name=AlkCDase 2
Short name=Alkaline CDase 2
Short name=haCER2
EC=3.5.1.23

Alternative name(s):
Acylsphingosine deacylase 3-like
N-acylsphingosine amidohydrolase 3-like

Gene names

Name:	ACER2
Synonyms:	ASAH3L
ORF Names:	PP11646

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	275 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid. Unsaturated long-chain ceramides are the best substrates, saturated long-chain ceramides and unsaturated very long-chain ceramides are good substrates, whereas saturated very long-chain ceramides and short-chain ceramides were poor substrates. The substrate preference is D-erythro-C(18:1)-, C(20:1)-, C(20:4)-ceramide > D-erythro-C(16:0)-, C(18:0), C(20:0)-ceramide > D-erythro-C(24:1)-ceramide > D-erythro-C(12:0)-ceramide, D-erythro-C(14:0)-ceramides > D-erythro-C(24:0)-ceramide > D-erythro-C(6:0)-ceramide. Inhibits the maturation of protein glycosylation in the Golgi complex, including that of integrin beta-1 (ITGB1) and of LAMP1, by increasing the levels of sphingosine. Inhibits cell adhesion by reducing the level of ITGB1 in the cell surface. May have a role in cell proliferation and apoptosis that seems to depend on the balance between sphingosine and sphingosine-1-phosphate. Ref.1 Ref.5 Ref.6
Catalytic activity	N-acylsphingosine + H2O = a carboxylate + sphingosine.
Enzyme regulation	Specifically activated by lumenal, but not cytosolic Ca2+. Inhibited by Zn2+ or Cu2+. Mg2+ or Mn2+ have no effect on ceramidase activity. Ref.6
Subcellular location	Golgi apparatus membrane; Multi-pass membrane protein Ref.1 Ref.6.
Tissue specificity	Highly expressed in placenta. Ref.1
Sequence similarities	Belongs to the alkaline ceramidase family.
Biophysicochemical properties	Kinetic parameters: KM=81 µM for D-erythro-C(24:1)-ceramide (at 37 degrees Celsius and pH 9.0) Ref.6 Vmax=27 pmol/min/mg enzyme with D-erythro-C(24:1)-ceramide as substrate pH dependence: Optimum pH is 7.5-9.0.

Ontologies

Keywords
Biological process	Lipid metabolism
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 20628055. Source: BHF-UCL cellular response to drug Inferred from expression pattern PubMed 20628055. Source: BHF-UCL ceramide metabolic process Inferred from electronic annotation. Source: InterPro negative regulation of cell adhesion mediated by integrin Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of cell-matrix adhesion Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of protein glycosylation in Golgi Inferred from mutant phenotype Ref.6. Source: UniProtKB phospholipid metabolic process Traceable author statement. Source: Reactome positive regulation of cell death Inferred from mutant phenotype PubMed 20628055. Source: BHF-UCL positive regulation of cell proliferation Inferred from direct assay Ref.1. Source: UniProtKB response to retinoic acid Inferred from direct assay Ref.5. Source: UniProtKB sphingosine biosynthetic process Inferred from direct assay Ref.1Ref.6. Source: UniProtKB
Cellular_component	integral to Golgi membrane Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	dihydroceramidase activity Inferred from direct assay PubMed 20628055. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5QJU3-1)

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: Q5QJU3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.

Isoform 3 (identifier: Q5QJU3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
     169-189: CDNMRVFKLGLFSGLWWTLAL → HERNQRRRHRKGGQQGGGDKV
     190-275: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 275	275	Alkaline ceramidase 2		PRO_0000247748
Regions
	Topological domain	1 – 32	32	Lumenal Potential
	Transmembrane	33 – 53	21	Helical; Potential
	Topological domain	54 – 62	9	Cytoplasmic Potential
	Transmembrane	63 – 83	21	Helical; Potential
	Topological domain	84 – 86	3	Lumenal Potential
	Transmembrane	87 – 107	21	Helical; Potential
	Topological domain	108 – 124	17	Cytoplasmic Potential
	Transmembrane	125 – 142	18	Helical; Potential
	Topological domain	143	1	Lumenal Potential
	Transmembrane	144 – 164	21	Helical; Potential
	Topological domain	165 – 173	9	Cytoplasmic Potential
	Transmembrane	174 – 194	21	Helical; Potential
	Topological domain	195 – 211	17	Lumenal Potential
	Transmembrane	212 – 232	21	Helical; Potential
	Topological domain	233 – 275	43	Cytoplasmic Potential
	Region	1 – 13	13	Essential for localization in the Golgi apparatus and for activity
Amino acid modifications
	Glycosylation	23	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 49	49	Missing in isoform 2 and isoform 3.		VSP_020033
	Alternative sequence	169 – 189	21	CDNMR…WTLAL → HERNQRRRHRKGGQQGGGDK V in isoform 3.		VSP_020034
	Alternative sequence	190 – 275	86	Missing in isoform 3.		VSP_020035
	Natural variant	134	1	A → V. Corresponds to variant rs10964136 [ dbSNP | Ensembl ].		VAR_027150
Experimental info
	Sequence conflict	274	1	I → T in AAQ85132. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 25, 2006. Version 2. Checksum: 56FD619B53C296B1	FASTA	275	31,309
	10 20 30 40 50 60 MGAPHWWDQL QAGSSEVDWC EDNYTIVPAI AEFYNTISNV LFFILPPICM CLFRQYATCF 70 80 90 100 110 120 NSGIYLIWTL LVVVGIGSVY FHATLSFLGQ MLDELAVLWV LMCALAMWFP RRYLPKIFRN 130 140 150 160 170 180 DRGRFKVVVS VLSAVTTCLA FVKPAINNIS LMTLGVPCTA LLIAELKRCD NMRVFKLGLF 190 200 210 220 230 240 SGLWWTLALF CWISDRAFCE LLSSFNFPYL HCMWHILICL AAYLGCVCFA YFDAASEIPE 250 260 270 QGPVIKFWPN EKWAFIGVPY VSLLCANKKS SVKIT
	Isoform 2 [UniParc]. Checksum: 49441E790CBAD583	FASTA	226	25,724
	10 20 30 40 50 60 MCLFRQYATC FNSGIYLIWT LLVVVGIGSV YFHATLSFLG QMLDELAVLW VLMCALAMWF 70 80 90 100 110 120 PRRYLPKIFR NDRGRFKVVV SVLSAVTTCL AFVKPAINNI SLMTLGVPCT ALLIAELKRC 130 140 150 160 170 180 DNMRVFKLGL FSGLWWTLAL FCWISDRAFC ELLSSFNFPY LHCMWHILIC LAAYLGCVCF 190 200 210 220 AYFDAASEIP EQGPVIKFWP NEKWAFIGVP YVSLLCANKK SSVKIT
	Isoform 3 [UniParc]. Checksum: 7888DB0189A6DF42	FASTA	140	15,864
	10 20 30 40 50 60 MCLFRQYATC FNSGIYLIWT LLVVVGIGSV YFHATLSFLG QMLDELAVLW VLMCALAMWF 70 80 90 100 110 120 PRRYLPKIFR NDRGRFKVVV SVLSAVTTCL AFVKPAINNI SLMTLGVPCT ALLIAELKRH 130 140 ERNQRRRHRK GGQQGGGDKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P." Xu R., Jin J., Hu W., Sun W., Bielawski J., Szulc Z., Taha T., Obeid L.M., Mao C. FASEB J. 20:1813-1825(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 2). Tissue: Placenta.
[5]	"Alkaline ceramidase 2 regulates beta1 integrin maturation and cell adhesion." Sun W., Hu W., Xu R., Jin J., Szulc Z.M., Zhang G., Galadari S.H., Obeid L.M., Mao C. FASEB J. 23:656-666(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2)." Sun W., Jin J., Xu R., Hu W., Szulc Z.M., Bielawski J., Obeid L.M., Mao C. J. Biol. Chem. 285:8995-9007(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TOPOLOGY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY312516 mRNA. Translation: AAQ85132.1. AF370405 mRNA. Translation: AAQ15241.1. AL158206, AL391834 Genomic DNA. Translation: CAH73022.1. AL391834, AL158206 Genomic DNA. Translation: CAM21146.1. BC092487 mRNA. Translation: AAH92487.1.
IPI	IPI00420054. IPI00479560. IPI00783055.
RefSeq	NP_001010887.2. NM_001010887.2.
UniGene	Hs.41379.
3D structure databases
ProteinModelPortal	Q5QJU3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000342609.
Polymorphism databases
DMDM	110832756.
Proteomic databases
PaxDb	Q5QJU3.
PRIDE	Q5QJU3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340967; ENSP00000342609; ENSG00000177076. ENST00000380376; ENSP00000369735; ENSG00000177076.
GeneID	340485.
KEGG	hsa:340485.
UCSC	uc003zny.1. human.
Organism-specific databases
CTD	340485.
GeneCards	GC09P019400.
H-InvDB	HIX0025758.
HGNC	HGNC:23675. ACER2.
HPA	HPA014092.
MIM	613492. gene.
neXtProt	NX_Q5QJU3.
PharmGKB	PA164714853.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG323012.
HOGENOM	HOG000220878.
InParanoid	Q5QJU3.
KO	K01441.
OMA	KRCDNVR.
OrthoDB	EOG41G34Q.
Enzyme and pathway databases
BRENDA	3.5.1.23. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
Bgee	Q5QJU3.
CleanEx	HS_ACER2.
Genevestigator	Q5QJU3.
Family and domain databases
InterPro	IPR008901. Ceramidase. [Graphical view]
Pfam	PF05875. Ceramidase. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	340485.
NextBio	97878.
SOURCE	Search...

Entry information

Entry name

ACER2_HUMAN

Accession

Primary (citable) accession number: Q5QJU3
Secondary accession number(s): A2A3R8 , Q569G5, Q5VZR7, Q71RD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	July 25, 2006
Last modified:	April 3, 2013
This is version 65 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.