Q9NXE4 (NSMA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 76.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Sphingomyelin phosphodiesterase 4 EC=3.1.4.12 Alternative name(s): Neutral sphingomyelinase 3 Short name=nSMase-3 Short name=nSMase3 Neutral sphingomyelinase III | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 827 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. Ref.7 |
| Catalytic activity | Sphingomyelin + H2O = N-acylsphingosine + phosphocholine. |
| Cofactor | Magnesium. Ref.7 |
| Enzyme regulation | Activated by phosphatidylserine and tumor necrosis factor (TNF). Inhibited by scyphostatin. Ref.7 |
| Subcellular location | Endoplasmic reticulum membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein Ref.7. |
| Tissue specificity | Widely expressed, with highest levels in heart and skeletal muscle. Ref.7 |
| Biophysicochemical properties | pH dependence: Optimum pH is 7.0. Ref.7 |
| Sequence caution | The sequence BAA91368.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA91567.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA92656.1 differs from that shown. Reason: Erroneous initiation. |
Ontologies
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9NXE4-1) 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: Q9NXE4-2) The sequence of this isoform differs from the canonical sequence as follows: 289-317: Missing. | ||||||
| Isoform 3 (identifier: Q9NXE4-3) The sequence of this isoform differs from the canonical sequence as follows: 1-92: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q9NXE4-4) The sequence of this isoform differs from the canonical sequence as follows: 365-365: K → KRMGLNLPEVPSALPRRSQPSLMGALGSSVSRASLLGKQQVTLPIPC | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 5 (identifier: Q9NXE4-5) The sequence of this isoform differs from the canonical sequence as follows: 1-429: Missing. 430-484: WAPFVQENLL...QPNLAEMIQK → MSATYCVGDA...VGARFVSCLL | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 6 (identifier: Q9NXE4-6) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MTTFGAVAEWRLPSLRRATLWIPQWFAKKAIFNSPLEAAM 43-115: Missing. 289-317: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 827 | 827 | Sphingomyelin phosphodiesterase 4 | PRO_0000273163 | |||||
Regions | |||||||||
| Transmembrane | 783 – 803 | 21 | Helical; Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 130 | 1 | Phosphoserine Ref.8 Ref.9 | ||||||
| Modified residue | 669 | 1 | Phosphothreonine Ref.8 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 429 | 429 | Missing in isoform 5. | VSP_022479 | |||||
| Alternative sequence | 1 – 92 | 92 | Missing in isoform 3. | VSP_022480 | |||||
| Alternative sequence | 1 | 1 | M → MTTFGAVAEWRLPSLRRATL WIPQWFAKKAIFNSPLEAAM in isoform 6. | VSP_044494 | |||||
| Alternative sequence | 43 – 115 | 73 | Missing in isoform 6. | VSP_044495 | |||||
| Alternative sequence | 289 – 317 | 29 | Missing in isoform 2 and isoform 6. | VSP_022481 | |||||
| Alternative sequence | 365 | 1 | K → KRMGLNLPEVPSALPRRSQP SLMGALGSSVSRASLLGKQQ VTLPIPC in isoform 4. | VSP_022482 | |||||
| Alternative sequence | 430 – 484 | 55 | WAPFV…EMIQK → MSATYCVGDAARQGLRRTPL GHGSPDTSETPQNPKGSSRV LCLREVGARFVSCLL in isoform 5. | VSP_022483 | |||||
Experimental info | |||||||||
| Sequence conflict | 164 | 1 | S → G in BAG61230. Ref.2 | ||||||
| Sequence conflict | 540 | 1 | C → R in BAA91567. Ref.2 | ||||||
| Sequence conflict | 692 | 1 | E → K in BAA91368. Ref.2 | ||||||
| Sequence conflict | 693 | 1 | L → Q in BAA91567. Ref.2 | ||||||
| Sequence conflict | 703 | 1 | S → G in BAC86751. Ref.2 | ||||||
| Sequence conflict | 823 | 1 | K → E in BAG61230. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 5 AND 6), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 134-827 (ISOFORM 4). |
| [3] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [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 3). Tissue: Lung. |
| [5] | "Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. Poustka A.Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 397-827. Tissue: Testis. |
| [6] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 400-827. |
| [7] | "Novel tumor necrosis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein." Krut O., Wiegmann K., Kashkar H., Yazdanpanah B., Kroenke M. J. Biol. Chem. 281:13784-13793(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [8] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 AND THR-669, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [9] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [10] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [11] | "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB037839 mRNA. Translation: BAA92656.1. Different initiation. AK000304 mRNA. Translation: BAA91070.1. AK000763 mRNA. Translation: BAA91368.1. Different initiation. AK001227 mRNA. Translation: BAA91567.1. Different initiation. AK126920 mRNA. Translation: BAC86751.1. AK299185 mRNA. Translation: BAG61230.1. AC018804 Genomic DNA. Translation: AAY14883.1. BC064947 mRNA. Translation: AAH64947.1. AL136737 mRNA. Translation: CAB66671.2. CR533550 mRNA. Translation: CAG38581.1. |
| IPI | IPI00793691. IPI00827746. IPI00828125. IPI00828176. IPI00903175. IPI00910464. |
| RefSeq | NP_001164554.1. NM_001171083.2. NP_060221.2. NM_017751.4. |
| UniGene | Hs.516450. |
3D structure databases | |
| ProteinModelPortal | Q9NXE4. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9NXE4. 1 interaction. |
| STRING | 9606.ENSP00000376704. |
PTM databases | |
| PhosphoSite | Q9NXE4. |
Polymorphism databases | |
| DMDM | 124015179. |
Proteomic databases | |
| PaxDb | Q9NXE4. |
| PRIDE | Q9NXE4. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000431183; ENSP00000405187; ENSG00000136699. |
| GeneID | 55627. |
| KEGG | hsa:55627. |
| UCSC | uc002tqo.2. human. uc002tqp.2. human. uc002tqr.2. human. uc002tqs.2. human. |
Organism-specific databases | |
| CTD | 55627. |
| GeneCards | GC02M130908. |
| HGNC | HGNC:32949. SMPD4. |
| MIM | 610457. gene. |
| neXtProt | NX_Q9NXE4. |
| PharmGKB | PA145148067. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG240539. |
| HOVERGEN | HBG082060. |
| InParanoid | Q9NXE4. |
| KO | K12353. |
Enzyme and pathway databases | |
| Reactome | REACT_111217. Metabolism. |
Gene expression databases | |
| ArrayExpress | Q9NXE4. |
| Bgee | Q9NXE4. |
| CleanEx | HS_SMPD4. |
| Genevestigator | Q9NXE4. |
Family and domain databases | |
| InterPro | IPR024129. Sphingomy_SMPD4. [Graphical view] |
| PANTHER | PTHR12988. PTHR12988. 1 hit. |
| ProtoNet | Search... |
Other | |
| ChiTaRS | SMPD4. human. |
| DrugBank | DB00144. Phosphatidylserine. |
| GenomeRNAi | 55627. |
| NextBio | 60251. |
| SOURCE | Search... |
Entry information
| Entry name | NSMA3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9NXE4 Secondary accession number(s): B4DRB8 Q9P2C9 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |

Clusters with
