Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Sphingomyelin phosphodiesterase 4

Gene

SMPD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606). May sensitize cells to DNA damage-induced apoptosis (PubMed:18505924).2 Publications

Catalytic activityi

Sphingomyelin + H2O = N-acylsphingosine + phosphocholine.1 Publication

Cofactori

Mg2+1 Publication

Activity regulationi

Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin.1 Publication

pH dependencei

Optimum pH is 7.0.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.4.12 2681
ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingomyelin phosphodiesterase 4Curated (EC:3.1.4.121 Publication)
Alternative name(s):
Neutral sphingomyelinase 31 Publication
Short name:
nSMase-31 Publication
Short name:
nSMase31 Publication
Neutral sphingomyelinase III
Gene namesi
Name:SMPD4Imported
Synonyms:KIAA1418, SKNY
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000136699.19
HGNCiHGNC:32949 SMPD4
MIMi610457 gene
neXtProtiNX_Q9NXE4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei822 – 842HelicalSequence analysis1 PublicationAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi862 – 865KLHQ → AAAA: No effect on endoplasmic reticulum location. 1 Publication4

Organism-specific databases

OpenTargetsiENSG00000136699
PharmGKBiPA145148067

Chemistry databases

DrugBankiDB00144 Phosphatidyl serine

Polymorphism and mutation databases

BioMutaiSMPD4
DMDMi124015179

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002731631 – 866Sphingomyelin phosphodiesterase 4Add BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei169PhosphoserineCombined sources1
Modified residuei285PhosphoserineBy similarity1
Modified residuei708PhosphothreonineCombined sources1
Modified residuei792PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NXE4
MaxQBiQ9NXE4
PaxDbiQ9NXE4
PeptideAtlasiQ9NXE4
PRIDEiQ9NXE4
ProteomicsDBi83079
83080 [Q9NXE4-2]
83081 [Q9NXE4-3]
83082 [Q9NXE4-4]
83083 [Q9NXE4-5]

PTM databases

iPTMnetiQ9NXE4
PhosphoSitePlusiQ9NXE4

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart and skeletal muscle.2 Publications

Inductioni

Expression is induced by DNA-damage and TNF.1 Publication

Gene expression databases

BgeeiENSG00000136699 Expressed in 90 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_SMPD4
ExpressionAtlasiQ9NXE4 baseline and differential
GenevisibleiQ9NXE4 HS

Organism-specific databases

HPAiHPA046279
HPA049426

Interactioni

Protein-protein interaction databases

BioGridi120766, 34 interactors
IntActiQ9NXE4, 25 interactors
MINTiQ9NXE4
STRINGi9606.ENSP00000386531

Structurei

3D structure databases

ProteinModelPortaliQ9NXE4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi242 – 264Pro-richPROSITE-ProRule annotation1 PublicationAdd BLAST23

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4396 Eukaryota
ENOG410YYEJ LUCA
GeneTreeiENSGT00390000006044
HOGENOMiHOG000026800
HOVERGENiHBG082060
InParanoidiQ9NXE4
KOiK12353
OMAiLNPHQMS
OrthoDBiEOG091G052W
PhylomeDBiQ9NXE4
TreeFamiTF324409

Family and domain databases

InterProiView protein in InterPro
IPR024129 Sphingomy_SMPD4
PANTHERiPTHR12988 PTHR12988, 1 hit
PfamiView protein in Pfam
PF14724 mit_SMPDase, 1 hit

Sequences (10+)i

Sequence statusi: Complete.

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 10 described isoforms and 11 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9NXE4-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MTTFGAVAEW RLPSLRRATL WIPQWFAKKA IFNSPLEAAM AFPHLQQPSF
60 70 80 90 100
LLASLKADSI NKPFAQQCQD LVKVIEDFPA KELHTIFPWL VESIFGSLDG
110 120 130 140 150
VLVGWNLRCL QGRVNPVEYS IVMEFLDPGG PMMKLVYKLQ AEDYKFDFPV
160 170 180 190 200
SYLPGPVKAS IQECILPDSP LYHNKVQFTP TGGLGLNLAL NPFEYYIFFF
210 220 230 240 250
ALSLITQKPL PVSLHVRTSD CAYFILVDRY LSWFLPTEGS VPPPLSSSPG
260 270 280 290 300
GTSPSPPPRT PAIPFASYGL HHTSLLKRHI SHQTSVNADP ASHEIWRSET
310 320 330 340 350
LLQVFVEMWL HHYSLEMYQK MQSPHAKLEV LHYRLSVSSA LYSPAQPSLQ
360 370 380 390 400
ALHAYQESFT PTEEHVLVVR LLLKHLHAFA NSLKPEQASP SAHSHATSPL
410 420 430 440 450
EEFKRAAVPR FVQQKLYLFL QHCFGHWPLD ASFRAVLEMW LSYLQPWRYA
460 470 480 490 500
PDKQAPGSDS QPRCVSEKWA PFVQENLLMY TKLFVGFLNR ALRTDLVSPK
510 520 530 540 550
HALMVFRVAK VFAQPNLAEM IQKGEQLFLE PELVIPHRQH RLFTAPTFTG
560 570 580 590 600
SFLSPWPPAV TDASFKVKSH VYSLEGQDCK YTPMFGPEAR TLVLRLAQLI
610 620 630 640 650
TQAKHTAKSI SDQCAESPAG HSFLSWLGFS SMDTNGSYTA NDLDEMGQDS
660 670 680 690 700
VRKTDEYLEK ALEYLRQIFR LSEAQLRQFT LALGTTQDEN GKKQLPDCIV
710 720 730 740 750
GEDGLILTPL GRYQIINGLR RFEIEYQGDP ELQPIRSYEI ASLVRTLFRL
760 770 780 790 800
SSAINHRFAG QMAALCSRDD FLGSFCRYHL TEPGLASRHL LSPVGRRQVA
810 820 830 840 850
GHTRGPRLSL RFLGSYRTLV SLLLAFFVAS LFCVGPLPCT LLLTLGYVLY
860
ASAMTLLTER GKLHQP
Length:866
Mass (Da):97,810
Last modified:March 28, 2018 - v3
Checksum:i3D7C615AAF733865
GO
Isoform 2 (identifier: Q9NXE4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     328-356: Missing.

Show »
Length:837
Mass (Da):94,585
Checksum:iEC3FF50A2AB89CCE
GO
Isoform 3 (identifier: Q9NXE4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: Missing.

Note: No experimental confirmation available.
Show »
Length:735
Mass (Da):83,071
Checksum:iD8AB07DB58C4FC79
GO
Isoform 4 (identifier: Q9NXE4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     404-404: K → KRMGLNLPEVPSALPRRSQPSLMGALGSSVSRASLLGKQQVTLPIPC

Note: No experimental confirmation available.
Show »
Length:912
Mass (Da):102,607
Checksum:i67A75EB57719A97D
GO
Isoform 5 (identifier: Q9NXE4-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     40-468: Missing.
     469-523: WAPFVQENLL...QPNLAEMIQK → MSATYCVGDA...VGARFVSCLL

Note: No experimental confirmation available.
Show »
Length:437
Mass (Da):48,681
Checksum:iEA400159F52BE3B0
GO
Isoform 6 (identifier: Q9NXE4-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     82-154: Missing.
     328-356: Missing.

Show »
Length:764
Mass (Da):86,193
Checksum:iB9110FD449F73E04
GO
Isoform 7 (identifier: Q9NXE4-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: MTTFGAVAEW...LDPGGPMMKL → MQTPPPTRSG...FSSGCVQDEE
     136-355: Missing.

Note: No experimental confirmation available.
Show »
Length:607
Mass (Da):68,254
Checksum:i34101AA98A60F6BE
GO
Isoform 8 (identifier: Q9NXE4-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     82-154: Missing.
     155-303: Missing.
     328-356: Missing.

Note: No experimental confirmation available.
Show »
Length:615
Mass (Da):69,804
Checksum:i0C84F51DDCC86612
GO
Isoform 9 (identifier: Q9NXE4-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: MTTFGAVAEW...DLVKVIEDFP → MQTPPPTRSG...CIKKCSPLMP
     80-404: Missing.

Note: No experimental confirmation available.
Show »
Length:502
Mass (Da):56,805
Checksum:iC9DC3697BFF9243D
GO
Isoform 10 (identifier: Q9NXE4-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-307: Missing.
     328-356: Missing.

Note: No experimental confirmation available.
Show »
Length:530
Mass (Da):60,173
Checksum:iE9572BAAA322C832
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BXF4H7BXF4_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
837Annotation score:
H7C1Q6H7C1Q6_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
741Annotation score:
C9J647C9J647_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
135Annotation score:
H7C235H7C235_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
211Annotation score:
H7C2J2H7C2J2_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
274Annotation score:
H7C2E2H7C2E2_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
265Annotation score:
F8WF03F8WF03_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
50Annotation score:
H7C0W5H7C0W5_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
313Annotation score:
F8WEQ5F8WEQ5_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
88Annotation score:
F2Z2W5F2Z2W5_HUMAN
Sphingomyelin phosphodiesterase 4
SMPD4
57Annotation score:
There is more potential isoformShow all

Sequence cautioni

The sequence AAY14883 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA91070 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA91368 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA91567 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA92656 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti203S → G in BAG61230 (PubMed:14702039).Curated1
Sequence conflicti579C → R in BAA91567 (PubMed:14702039).Curated1
Sequence conflicti731E → K in BAA91368 (PubMed:14702039).Curated1
Sequence conflicti732L → Q in BAA91567 (PubMed:14702039).Curated1
Sequence conflicti742S → G in BAC86751 (PubMed:14702039).Curated1
Sequence conflicti862K → E in BAG61230 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0553431 – 307Missing in isoform 10. 1 PublicationAdd BLAST307
Alternative sequenceiVSP_0543821 – 135MTTFG…PMMKL → MQTPPPTRSGGQKLCSRFLL KCGFITIPWRCIKKCSPLMP SWRFCTTDSVSPAPSTAPPN PASRPSTPTKSLGNRGSDAR GFYWAEFSSGCVQDEE in isoform 7. 1 PublicationAdd BLAST135
Alternative sequenceiVSP_0224801 – 131Missing in isoform 3. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_0543831 – 79MTTFG…IEDFP → MQTPPPTRSGGQKLCSRFLL KCGFITIPWRCIKKCSPLMP in isoform 9. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_02247940 – 468Missing in isoform 5. 1 PublicationAdd BLAST429
Alternative sequenceiVSP_05438480 – 404Missing in isoform 9. 1 PublicationAdd BLAST325
Alternative sequenceiVSP_04449582 – 154Missing in isoform 6 and isoform 8. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_054385136 – 355Missing in isoform 7. 1 PublicationAdd BLAST220
Alternative sequenceiVSP_054386155 – 303Missing in isoform 8. 1 PublicationAdd BLAST149
Alternative sequenceiVSP_022481328 – 356Missing in isoform 2, isoform 6, isoform 8 and isoform 10. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_022482404K → KRMGLNLPEVPSALPRRSQP SLMGALGSSVSRASLLGKQQ VTLPIPC in isoform 4. 1 Publication1
Alternative sequenceiVSP_022483469 – 523WAPFV…EMIQK → MSATYCVGDAARQGLRRTPL GHGSPDTSETPQNPKGSSRV LCLREVGARFVSCLL in isoform 5. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU367941 mRNA Translation: ACA48221.1
AB037839 mRNA Translation: BAA92656.1 Different initiation.
AK000304 mRNA Translation: BAA91070.1 Different initiation.
AK000763 mRNA Translation: BAA91368.1 Different initiation.
AK001227 mRNA Translation: BAA91567.1 Different initiation.
AK126920 mRNA Translation: BAC86751.1
AK297257 mRNA Translation: BAG59735.1
AK298609 mRNA Translation: BAG60793.1
AK299185 mRNA Translation: BAG61230.1
AK303427 mRNA Translation: BAG64478.1
AK301576 mRNA Translation: BAG63069.1
AC018804 Genomic DNA Translation: AAY14883.1 Different initiation.
CH471263 Genomic DNA Translation: EAW55600.1
BC064947 mRNA Translation: AAH64947.1
AL136737 mRNA Translation: CAB66671.2
CR533550 mRNA Translation: CAG38581.1
CCDSiCCDS2156.2 [Q9NXE4-2]
CCDS42751.1 [Q9NXE4-1]
CCDS54398.1 [Q9NXE4-6]
RefSeqiNP_001164554.1, NM_001171083.2 [Q9NXE4-6]
NP_060221.2, NM_017751.4 [Q9NXE4-2]
NP_060421.2, NM_017951.4 [Q9NXE4-1]
XP_011509747.1, XM_011511445.2 [Q9NXE4-3]
XP_016859937.1, XM_017004448.1 [Q9NXE4-7]
XP_016859938.1, XM_017004449.1
UniGeneiHs.516450

Genome annotation databases

EnsembliENST00000351288; ENSP00000259217; ENSG00000136699 [Q9NXE4-2]
ENST00000409031; ENSP00000386531; ENSG00000136699 [Q9NXE4-1]
ENST00000431183; ENSP00000405187; ENSG00000136699 [Q9NXE4-6]
GeneIDi55627
KEGGihsa:55627
UCSCiuc002tqq.3 human
uc010zab.3 human [Q9NXE4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNSMA3_HUMAN
AccessioniPrimary (citable) accession number: Q9NXE4
Secondary accession number(s): B1PBA3
, B4DM23, B4DQ31, B4DRB8, B4DWK7, B4E0L6, E7ESA2, E9PCE6, Q6FI76, Q6P1P7, Q6ZT43, Q9H0M2, Q9NW20, Q9NWL2, Q9P2C9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: March 28, 2018
Last modified: September 12, 2018
This is version 122 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again