UniProtKB - Q9NUN7 (ACER3_HUMAN)
Protein
Alkaline ceramidase 3
Gene
ACER3
Organism
Homo sapiens (Human)
Status
Functioni
Endoplasmic reticulum and Golgi ceramidase that catalyzes the hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-ceramides, dihydroceramides and phytoceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:20068046, PubMed:26792856, PubMed:20207939, PubMed:11356846, PubMed:30575723). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:20068046). Controls the generation of sphingosine in erythrocytes, and thereby sphingosine-1-phosphate in plasma (PubMed:20207939). Through the regulation of ceramides and sphingosine-1-phosphate homeostasis in the brain may play a role in neurons survival and function (By similarity). By regulating the levels of proinflammatory ceramides in immune cells and tissues, may modulate the inflammatory response (By similarity).1 PublicationBy similarity5 Publications
Catalytic activityi
- This reaction proceeds in the forward1 Publication direction.
- H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphing-4-enine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphing-4-enine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphinganine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + sphinganine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-4-hydroxysphinganine = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 4-hydroxysphinganine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- H2O + N-(11Z-eicosenoyl)-4-hydroxysphinganine = (11Z)-eicosenoate + 4-hydroxysphinganine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- H2O + N-(9Z-octadecenoyl)-4-hydroxysphinganine = (9Z)-octadecenoate + 4-hydroxysphinganine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- EC:3.5.1.233 PublicationsThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Cofactori
Zn2+1 Publication
Activity regulationi
Activated by 5 mM Ca2+ and inhibited by 5 mM Zn2+.1 Publication
pH dependencei
Optimum pH is 9.5.1 Publication
: sphingolipid metabolism Pathwayi
This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.3 PublicationsView all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 19 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 20 | Calcium; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 22 | Calcium; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 24 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 33 | CalciumCombined sources1 Publication | 1 | |
Metal bindingi | 81 | Zinc; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 217 | Zinc; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 221 | Zinc; catalyticCombined sources1 Publication | 1 |
GO - Molecular functioni
- calcium ion binding Source: UniProtKB
- ceramidase activity Source: UniProtKB-EC
- dihydroceramidase activity Source: UniProtKB
- N-acylsphingosine amidohydrolase activity Source: UniProtKB
- phytoceramidase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- ceramide catabolic process Source: UniProtKB
- inflammatory response Source: Ensembl
- myelination Source: UniProtKB
- phytosphingosine biosynthetic process Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- regulation of programmed cell death Source: UniProtKB
- sphingolipid biosynthetic process Source: Reactome
- sphingosine biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid metabolism, Sphingolipid metabolism |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.5.1.23, 2681 |
PathwayCommonsi | Q9NUN7 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
UniPathwayi | UPA00222 |
Chemistry databases
SwissLipidsi | SLP:000000680 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:ACER3 Synonyms:APHC, PHCA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000078124.11 |
HGNCi | HGNC:16066, ACER3 |
MIMi | 617036, gene |
neXtProti | NX_Q9NUN7 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Multi-pass membrane protein 2 Publications
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 2 Publications
Endoplasmic reticulum
- endoplasmic reticulum Source: GO_Central
- endoplasmic reticulum membrane Source: Reactome
- integral component of endoplasmic reticulum membrane Source: UniProtKB
Golgi apparatus
- integral component of Golgi membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 33 | Cytoplasmic1 PublicationAdd BLAST | 33 | |
Transmembranei | 34 – 55 | Helical1 PublicationAdd BLAST | 22 | |
Topological domaini | 56 – 61 | Lumenal1 Publication | 6 | |
Transmembranei | 62 – 82 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 83 – 87 | Cytoplasmic1 Publication | 5 | |
Transmembranei | 88 – 108 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 109 – 118 | Lumenal1 Publication | 10 | |
Transmembranei | 119 – 139 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 140 – 141 | Cytoplasmic1 Publication | 2 | |
Transmembranei | 142 – 162 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 163 – 173 | Lumenal1 PublicationAdd BLAST | 11 | |
Transmembranei | 174 – 194 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 195 – 215 | Cytoplasmic1 PublicationAdd BLAST | 21 | |
Transmembranei | 216 – 236 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 237 – 267 | Lumenal1 PublicationAdd BLAST | 31 |
Keywords - Cellular componenti
Endoplasmic reticulum, Golgi apparatus, MembranePathology & Biotechi
Involvement in diseasei
Leukodystrophy, progressive, early childhood-onset (PLDECO)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of leukodystrophy, a disorder of myelin production or maintenance affecting the central nervous system. PELCO features include neurological regression between 6 and 13 months of age, truncal hypotonia, appendicular spasticity, dystonia, optic disk pallor, peripheral neuropathy and neurogenic bladder. Brain imaging shows progressive diffuse abnormal white matter signals, cerebral atrophy, and thin corpus callosum. Sural nerve biopsy shows decreased myelination. PLDECO inheritance is autosomal recessive.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081205 | 33 | E → G in PLDECO; impaired protein stability; strongly decreased enzyme activity; decreased ceramide catabolic process; in fibroblasts of patients homozygous for the mutation. 2 PublicationsCorresponds to variant dbSNP:rs1554988032EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 19 | D → G: Mildly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 22 | E → G: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 24 | N → G: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 99 | S → A: No effect on enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 149 | Y → A: Decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 228 | S → A: No effect on enzyme activity. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, LeukodystrophyOrganism-specific databases
DisGeNETi | 55331 |
MalaCardsi | ACER3 |
MIMi | 617762, phenotype |
OpenTargetsi | ENSG00000078124 |
Orphaneti | 502444, Alkaline ceramidase 3 deficiency |
PharmGKBi | PA33256 |
Miscellaneous databases
Pharosi | Q9NUN7, Tbio |
Polymorphism and mutation databases
BioMutai | ACER3 |
DMDMi | 296439452 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000212463 | 1 – 267 | Alkaline ceramidase 3Add BLAST | 267 |
Proteomic databases
MassIVEi | Q9NUN7 |
PaxDbi | Q9NUN7 |
PeptideAtlasi | Q9NUN7 |
PRIDEi | Q9NUN7 |
ProteomicsDBi | 82700 [Q9NUN7-1] 82701 [Q9NUN7-2] |
TopDownProteomicsi | Q9NUN7-1 [Q9NUN7-1] |
PTM databases
iPTMneti | Q9NUN7 |
PhosphoSitePlusi | Q9NUN7 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Highly expressed in placenta (PubMed:11356846). Expressed in erythrocytes (PubMed:20207939).2 Publications
Gene expression databases
Bgeei | ENSG00000078124, Expressed in placenta and 219 other tissues |
ExpressionAtlasi | Q9NUN7, baseline and differential |
Genevisiblei | Q9NUN7, HS |
Organism-specific databases
HPAi | ENSG00000078124, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 120612, 3 interactors |
IntActi | Q9NUN7, 1 interactor |
STRINGi | 9606.ENSP00000434480 |
Miscellaneous databases
RNActi | Q9NUN7, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9NUN7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the alkaline ceramidase family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2329, Eukaryota |
GeneTreei | ENSGT00730000110920 |
InParanoidi | Q9NUN7 |
OMAi | IMFEPLR |
OrthoDBi | 969354at2759 |
PhylomeDBi | Q9NUN7 |
TreeFami | TF313019 |
Family and domain databases
InterProi | View protein in InterPro IPR008901, ACER |
PANTHERi | PTHR46187, PTHR46187, 1 hit |
Pfami | View protein in Pfam PF05875, Ceramidase, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9NUN7-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAPAADREGY WGPTTSTLDW CEENYSVTWY IAEFWNTVSN LIMIIPPMFG
60 70 80 90 100
AVQSVRDGLE KRYIASYLAL TVVGMGSWCF HMTLKYEMQL LDELPMIYSC
110 120 130 140 150
CIFVYCMFEC FKIKNSVNYH LLFTLVLFSL IVTTVYLKVK EPIFHQVMYG
160 170 180 190 200
MLVFTLVLRS IYIVTWVYPW LRGLGYTSLG IFLLGFLFWN IDNIFCESLR
210 220 230 240 250
NFRKKVPPII GITTQFHAWW HILTGLGSYL HILFSLYTRT LYLRYRPKVK
260
FLFGIWPVIL FEPLRKH
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB7Z2Q2 | B7Z2Q2_HUMAN | Alkaline ceramidase | ACER3 | 230 | Annotation score: | ||
B7Z2V2 | B7Z2V2_HUMAN | Alkaline ceramidase | ACER3 | 172 | Annotation score: | ||
E9PIN9 | E9PIN9_HUMAN | Alkaline ceramidase | ACER3 | 205 | Annotation score: | ||
E9PL35 | E9PL35_HUMAN | Alkaline ceramidase | ACER3 | 74 | Annotation score: | ||
E9PLZ9 | E9PLZ9_HUMAN | Alkaline ceramidase | ACER3 | 71 | Annotation score: | ||
E9PR08 | E9PR08_HUMAN | Alkaline ceramidase | ACER3 | 80 | Annotation score: | ||
J3KN85 | J3KN85_HUMAN | Alkaline ceramidase | ACER3 | 76 | Annotation score: | ||
E9PKR3 | E9PKR3_HUMAN | Alkaline ceramidase | ACER3 | 51 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 52 | V → I in AAK71923 (PubMed:11356846).Curated | 1 | |
Sequence conflicti | 52 | V → I in AAL56013 (Ref. 2) Curated | 1 | |
Sequence conflicti | 52 | V → I in BAG37496 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 52 | V → I in EAW75010 (Ref. 5) Curated | 1 | |
Sequence conflicti | 52 | V → I in AAH73853 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081205 | 33 | E → G in PLDECO; impaired protein stability; strongly decreased enzyme activity; decreased ceramide catabolic process; in fibroblasts of patients homozygous for the mutation. 2 PublicationsCorresponds to variant dbSNP:rs1554988032EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039162 | 1 – 133 | Missing in isoform 2. 1 PublicationAdd BLAST | 133 | |
Alternative sequenceiVSP_039163 | 134 – 145 | TVYLK…EPIFH → MAQSRLIGTSTS in isoform 2. 1 PublicationAdd BLAST | 12 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF214454 mRNA Translation: AAK71923.1 AF327353 mRNA Translation: AAL56013.1 AK002100 mRNA Translation: BAA92085.1 AK315000 mRNA Translation: BAG37496.1 AP000752 Genomic DNA No translation available. AP002498 Genomic DNA No translation available. AP003119 Genomic DNA No translation available. CH471076 Genomic DNA Translation: EAW75010.1 BC073853 mRNA Translation: AAH73853.1 |
CCDSi | CCDS8247.1 [Q9NUN7-1] |
RefSeqi | NP_060837.3, NM_018367.6 [Q9NUN7-1] |
Genome annotation databases
Ensembli | ENST00000532485; ENSP00000434480; ENSG00000078124 [Q9NUN7-1] |
GeneIDi | 55331 |
KEGGi | hsa:55331 |
UCSCi | uc009yum.2, human [Q9NUN7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF214454 mRNA Translation: AAK71923.1 AF327353 mRNA Translation: AAL56013.1 AK002100 mRNA Translation: BAA92085.1 AK315000 mRNA Translation: BAG37496.1 AP000752 Genomic DNA No translation available. AP002498 Genomic DNA No translation available. AP003119 Genomic DNA No translation available. CH471076 Genomic DNA Translation: EAW75010.1 BC073853 mRNA Translation: AAH73853.1 |
CCDSi | CCDS8247.1 [Q9NUN7-1] |
RefSeqi | NP_060837.3, NM_018367.6 [Q9NUN7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6G7O | X-ray | 2.70 | A | 2-244 | [»] | |
SMRi | Q9NUN7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120612, 3 interactors |
IntActi | Q9NUN7, 1 interactor |
STRINGi | 9606.ENSP00000434480 |
Chemistry databases
SwissLipidsi | SLP:000000680 |
PTM databases
iPTMneti | Q9NUN7 |
PhosphoSitePlusi | Q9NUN7 |
Polymorphism and mutation databases
BioMutai | ACER3 |
DMDMi | 296439452 |
Proteomic databases
MassIVEi | Q9NUN7 |
PaxDbi | Q9NUN7 |
PeptideAtlasi | Q9NUN7 |
PRIDEi | Q9NUN7 |
ProteomicsDBi | 82700 [Q9NUN7-1] 82701 [Q9NUN7-2] |
TopDownProteomicsi | Q9NUN7-1 [Q9NUN7-1] |
Protocols and materials databases
Antibodypediai | 53464, 119 antibodies |
DNASUi | 55331 |
Genome annotation databases
Ensembli | ENST00000532485; ENSP00000434480; ENSG00000078124 [Q9NUN7-1] |
GeneIDi | 55331 |
KEGGi | hsa:55331 |
UCSCi | uc009yum.2, human [Q9NUN7-1] |
Organism-specific databases
CTDi | 55331 |
DisGeNETi | 55331 |
EuPathDBi | HostDB:ENSG00000078124.11 |
GeneCardsi | ACER3 |
HGNCi | HGNC:16066, ACER3 |
HPAi | ENSG00000078124, Low tissue specificity |
MalaCardsi | ACER3 |
MIMi | 617036, gene 617762, phenotype |
neXtProti | NX_Q9NUN7 |
OpenTargetsi | ENSG00000078124 |
Orphaneti | 502444, Alkaline ceramidase 3 deficiency |
PharmGKBi | PA33256 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2329, Eukaryota |
GeneTreei | ENSGT00730000110920 |
InParanoidi | Q9NUN7 |
OMAi | IMFEPLR |
OrthoDBi | 969354at2759 |
PhylomeDBi | Q9NUN7 |
TreeFami | TF313019 |
Enzyme and pathway databases
UniPathwayi | UPA00222 |
BRENDAi | 3.5.1.23, 2681 |
PathwayCommonsi | Q9NUN7 |
Reactomei | R-HSA-1660661, Sphingolipid de novo biosynthesis |
Miscellaneous databases
BioGRID-ORCSi | 55331, 2 hits in 840 CRISPR screens |
ChiTaRSi | ACER3, human |
GeneWikii | ACER3 |
GenomeRNAii | 55331 |
Pharosi | Q9NUN7, Tbio |
PROi | PR:Q9NUN7 |
RNActi | Q9NUN7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000078124, Expressed in placenta and 219 other tissues |
ExpressionAtlasi | Q9NUN7, baseline and differential |
Genevisiblei | Q9NUN7, HS |
Family and domain databases
InterProi | View protein in InterPro IPR008901, ACER |
PANTHERi | PTHR46187, PTHR46187, 1 hit |
Pfami | View protein in Pfam PF05875, Ceramidase, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ACER3_HUMAN | |
Accessioni | Q9NUN7Primary (citable) accession number: Q9NUN7 Secondary accession number(s): B2RC99 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 14, 2001 |
Last sequence update: | May 18, 2010 | |
Last modified: | December 2, 2020 | |
This is version 155 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations