Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SMPD3

contributors: mct/npt - updated : 06-05-2019

HGNC name	sphingomyelin phosphodiesterase 3, neutral membrane (neutral sphingomyelinase II)
HGNC id	14240

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_018667 9 - 5269 NP_061137 - 655 - 2018 29337691

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Lymphoid/Immune thymus       highly Nervous brain basal nuclei striatum   highly Homo sapiens Respiratory lung       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Homo sapiens Connective cartilage       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive odontoblast Homo sapiens Nervous neuron Homo sapiens not specific chondrocyte Homo sapiens Skeleton osteoblast Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two putative N-terminal hydrophobic membrane-anchoring domains
	a collagen-like linker region
	a C-terminal catalytic domain

HOMOLOGY

Homologene

FAMILY

neutral sphingomyelinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus

basic FUNCTION	catalyzing the hydrolysis of sphingomyelin to form ceramide and phosphocholine
	may be acting as a regulator of postnatal development
	and participating in bone and dentin mineralization
	acting as a bona fide SMPD2 in cells, and is implicated in the regulation of cell growth and cell signaling (Marchesini 2003)
	membrane-bound enzyme that cleaves sphingomyelin to generate several bioactive metabolites
	its expression in odontoblasts is required for tooth mineralization
	critical role of ceramide generated by SMPD3 in stem cell ciliogenesis and differentiation
	is the major sphingomyelinase activated in response to pro-inflammatory cytokines and during oxidative stress
	is a redox-sensitive enzyme, whose basal activity is influenced by thioredoxin-mediated changes in its oligomeric state
	key regulator of skeletal development
	SMPD3 expression in both chondrocytes and osteoblasts is required for normal endochondral bone development
	key enzyme for ceramide generation that is involved in regulating cellular stress responses and exosome-mediated intercellular communication
	important function of SMPD3 in the striatum
	plays a significant role in extracellular matrix (ECM) mineralization and chondrocyte apoptosis during fracture healing
	SMPD3 controls homeostasis of the sphingomyelin cycle in the Golgi compartment, essential for membrane remodeling, initiating multiform vesicle formation and transport in the Golgi secretory pathway

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with EED (with EED are recruited to the TNFRSF1A•NSMAF•RACK1-complex in a timeframe concurrent with activation of SMPD3 (Philipp 2010)
	binds to EED through its C-terminal catalytic domain, but not through its N terminus (Philipp 2010)
	IL1B regulates FOXO1 activity through a novel SMPD3-dependent pathway

cell & other

REGULATION

activated by

exclusively by the 55-kDa receptor TNF receptor 1 (TNFRSF1A) (Philipp 2009)

Other

regulated by PRKCD (PRKCD is a regulator of SMPD3 and a point of cross-talk between the PKC and sphingolipid pathways) (Clarke 2008)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function responsible for developmental defects of bone (Kim 2008) tumoral somatic mutation       implicate the ceramide pathway in human leukemias (Kim 2008) constitutional     --over   may increase cellular ceramide levels, leading to enhanced cell death and arrested cell proliferation (Zhu 2010) constitutional       loss of function perturbs neuronal proteostasis and causes progressive cognitive impairment tumoral       loss of function plays a role in the survival or proliferation ofiver cancer stem-like cells (CSCs), leading to spontaneous tumors, which is associated with tumor-specific effects on lipid homeostasis constitutional       gain of function is required for the development of infection-induced diaphragm calpain activation and muscle weakness

Susceptibility

Variant & Polymorphism

Candidate gene	SMPD3 deficiency is the pathogenetic basis of a novel form of chondrodysplasia
Marker
Therapy target
	System Type Disorder Pubmed immunology infectious   therapies that inhibit SMPD3 in patients may prevent infection-induced skeletal muscle dysfunction

ANIMAL & CELL MODELS

Smpd3 deficiency in the neutral sphingomyelinase (Smpd3-/-) mouse results in a novel form of juvenile dwarfism