UniProtKB - Q8R4X1 (ACER1_MOUSE)
Alkaline ceramidase 1
Acer1
Functioni
Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline pH (PubMed:12783875).
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:12783875).
Exhibits a strong substrate specificity towards the natural stereoisomer of ceramides with D-erythro-sphingosine as a backbone and has a higher activity towards very long-chain unsaturated fatty acids like the C24:1-ceramide (PubMed:12783875).
May also hydrolyze dihydroceramides to produce dihydrosphingosine (By similarity).
ACER1 is a skin-specific ceramidase that regulates the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes and more generally plays an important role in skin homeostasis (PubMed:27126290, PubMed:29056331).
1 PublicationBy similarity3 PublicationsCatalytic activityi
- EC:3.5.1.232 PublicationsThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
pH dependencei
: sphingolipid metabolism Pathwayi
This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.2 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 | 22 | CalciumBy similarity | 1 | |
Metal bindingi | 23 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 25 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 27 | CalciumBy similarity | 1 | |
Metal bindingi | 36 | CalciumBy similarity | 1 | |
Metal bindingi | 86 | Zinc; catalyticBy similarity | 1 | |
Metal bindingi | 215 | Zinc; catalyticBy similarity | 1 | |
Metal bindingi | 219 | Zinc; catalyticBy similarity | 1 |
GO - Molecular functioni
- ceramidase activity Source: UniProtKB-EC
- dihydroceramidase activity Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- N-acylsphingosine amidohydrolase activity Source: UniProtKB
GO - Biological processi
- cell differentiation Source: MGI
- cellular response to calcium ion Source: MGI
- ceramide catabolic process Source: MGI
- keratinocyte differentiation Source: Ensembl
- regulation of lipid metabolic process Source: MGI
- regulation of water loss via skin Source: UniProtKB
- response to alkaline pH Source: MGI
- sebaceous gland development Source: UniProtKB
- sphingolipid biosynthetic process Source: MGI
- sphingolipid metabolic process Source: MGI
- 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, 3474 |
Reactomei | R-MMU-1660661, Sphingolipid de novo biosynthesis |
UniPathwayi | UPA00222 |
Chemistry databases
SwissLipidsi | SLP:000000676 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2181962, Acer1 |
VEuPathDBi | HostDB:ENSMUSG00000045019 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 36 | LumenalSequence analysisAdd BLAST | 36 | |
Transmembranei | 37 – 57 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 58 – 72 | CytoplasmicSequence analysisAdd BLAST | 15 | |
Transmembranei | 73 – 93 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 94 – 114 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 115 – 126 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 127 – 147 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 148 – 149 | LumenalSequence analysis | 2 | |
Transmembranei | 150 – 167 | HelicalSequence analysisAdd BLAST | 18 | |
Topological domaini | 168 – 177 | CytoplasmicSequence analysis | 10 | |
Transmembranei | 178 – 198 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 199 – 215 | LumenalSequence analysisAdd BLAST | 17 | |
Transmembranei | 216 – 236 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 237 – 273 | CytoplasmicSequence analysisAdd BLAST | 37 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000247746 | 1 – 273 | Alkaline ceramidase 1Add BLAST | 273 |
Proteomic databases
PaxDbi | Q8R4X1 |
PRIDEi | Q8R4X1 |
ProteomicsDBi | 285537 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000045019, Expressed in ear and 66 other tissues |
Genevisiblei | Q8R4X1, MM |
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000062037 |
Miscellaneous databases
RNActi | Q8R4X1, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2329, Eukaryota |
GeneTreei | ENSGT00730000110920 |
HOGENOMi | CLU_088280_1_0_1 |
InParanoidi | Q8R4X1 |
OMAi | HSEHVVE |
OrthoDBi | 969354at2759 |
PhylomeDBi | Q8R4X1 |
TreeFami | TF313019 |
Family and domain databases
InterProi | View protein in InterPro IPR008901, ACER |
PANTHERi | PTHR46139, PTHR46139, 1 hit |
Pfami | View protein in Pfam PF05875, Ceramidase, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MHVPGTRAKM SSIFAYQSSE VDWCESNFQH SELVAEFYNT FSNVFFLIFG
60 70 80 90 100
PLMMFLMHPY AQKRTRCFYG VSVLFMLIGL FSMYFHMTLS FLGQLLDEIS
110 120 130 140 150
ILWLLASGYS VWLPRCYFPK FVKGNRFYFS CLVTITTIIS TFLTFVKPTV
160 170 180 190 200
NAYALNSIAI HILYIVRTEY KKIRDDDLRH LIAVSVVLWA AALTSWISDR
210 220 230 240 250
VLCSFWQRIH FYYLHSIWHV LISITFPYGI VTMALVDAKY EMPDKTLKVH
260 270
YWPRDSWVIG LPYVEIQEND KNC
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF347023 mRNA Translation: AAL83821.1 AK028901 mRNA Translation: BAC26186.1 AK075884 mRNA Translation: BAC36029.1 BC130254 mRNA Translation: AAI30255.1 |
CCDSi | CCDS28919.1 |
RefSeqi | NP_783858.1, NM_175731.4 |
Genome annotation databases
Ensembli | ENSMUST00000056113; ENSMUSP00000062037; ENSMUSG00000045019 |
GeneIDi | 171168 |
KEGGi | mmu:171168 |
UCSCi | uc008ddl.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF347023 mRNA Translation: AAL83821.1 AK028901 mRNA Translation: BAC26186.1 AK075884 mRNA Translation: BAC36029.1 BC130254 mRNA Translation: AAI30255.1 |
CCDSi | CCDS28919.1 |
RefSeqi | NP_783858.1, NM_175731.4 |
3D structure databases
SMRi | Q8R4X1 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000062037 |
Chemistry databases
SwissLipidsi | SLP:000000676 |
Proteomic databases
PaxDbi | Q8R4X1 |
PRIDEi | Q8R4X1 |
ProteomicsDBi | 285537 |
Protocols and materials databases
Antibodypediai | 49939, 144 antibodies from 24 providers |
DNASUi | 171168 |
Genome annotation databases
Ensembli | ENSMUST00000056113; ENSMUSP00000062037; ENSMUSG00000045019 |
GeneIDi | 171168 |
KEGGi | mmu:171168 |
UCSCi | uc008ddl.1, mouse |
Organism-specific databases
CTDi | 125981 |
MGIi | MGI:2181962, Acer1 |
VEuPathDBi | HostDB:ENSMUSG00000045019 |
Phylogenomic databases
eggNOGi | KOG2329, Eukaryota |
GeneTreei | ENSGT00730000110920 |
HOGENOMi | CLU_088280_1_0_1 |
InParanoidi | Q8R4X1 |
OMAi | HSEHVVE |
OrthoDBi | 969354at2759 |
PhylomeDBi | Q8R4X1 |
TreeFami | TF313019 |
Enzyme and pathway databases
UniPathwayi | UPA00222 |
BRENDAi | 3.5.1.23, 3474 |
Reactomei | R-MMU-1660661, Sphingolipid de novo biosynthesis |
Miscellaneous databases
BioGRID-ORCSi | 171168, 1 hit in 66 CRISPR screens |
ChiTaRSi | Acer1, mouse |
PROi | PR:Q8R4X1 |
RNActi | Q8R4X1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000045019, Expressed in ear and 66 other tissues |
Genevisiblei | Q8R4X1, MM |
Family and domain databases
InterProi | View protein in InterPro IPR008901, ACER |
PANTHERi | PTHR46139, PTHR46139, 1 hit |
Pfami | View protein in Pfam PF05875, Ceramidase, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ACER1_MOUSE | |
Accessioni | Q8R4X1Primary (citable) accession number: Q8R4X1 Secondary accession number(s): A1L3S2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 25, 2006 |
Last sequence update: | June 1, 2002 | |
Last modified: | February 23, 2022 | |
This is version 123 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families