Reviewed,
UniProtKB/Swiss-Prot Q96Q15 (SMG1_HUMAN)
Last modified
June 16, 2009.
Version 59.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Serine/threonine-protein kinase SMG1 Short name=SMG-1 Short name=hSMG-1 EC=2.7.11.1 Alternative name(s): Lambda/iota protein kinase C-interacting protein Short name=Lambda-interacting protein 61E3.4 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 3657 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Acts as part of the SMG1C complex, a mRNA surveillance complex that recognizes and degrades mRNAs containing premature translation termination codons (PTCs). The complex probably acts by associating with ribosomes during tranlation termination on mRNPs. If an exon junction complex (EJC) is located 50-55 or more nucleotides downstream from the termination codon, it phosphorylates UPF1/RENT1, triggering nonsense-mediated decay (NMD). Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate TP53/p53 and is required for optimal TP53/p53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. Ref.2 Ref.3 Ref.4 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Manganese. Ref.3 |
| Enzyme regulation | Inhibited by caffeine, LY294002 and wortmannin. Ref.2 Ref.3 Ref.4 |
| Subunit structure | Component of a post-splicing multiprotein NMD complex with UPF1/RENT1, UPF2/RENT2, EST1A (SMG5/7a), EST1B/SMG5 and UPF3 (UPF3A or UPF3B). Component of the SMG1C complex, at least composed of SMG1, SMG8 and SMG9. The SMG1C complex is then recruited on premature translation termination codons (PTCs) to form the ribosome:SURF complex, at least composed of ERF1, ERF3 (ERF3A or ERF3B), EEF2, UPF1/RENT1, SMG1, SMG8 and SMG9. Interacts with PRKCI. Ref.2 Ref.7 Ref.9 Ref.10 |
| Subcellular location | |
| Tissue specificity | Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver. Ref.4 Ref.7 |
| Post-translational modification | Autophosphorylated Probable. Phosphorylated upon DNA damage, probably by ATM or ATR. |
| Miscellaneous | This gene is located in a region of chromosome 16 that contains 2 segmental duplications. Other genes that are highly related to this exist, but they probably represent pseudogenes. |
| Sequence similarities | Belongs to the PI3/PI4-kinase family. Contains 1 FAT domain. Contains 1 FATC domain. Contains 1 HEAT repeat. Contains 1 PI3K/PI4K domain. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q96Q15-1) 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: Q96Q15-2) The sequence of this isoform differs from the canonical sequence as follows: 1-136: Missing. | ||||||
| Isoform 3 (identifier: Q96Q15-3) The sequence of this isoform differs from the canonical sequence as follows: 1-626: Missing. | ||||||
| Isoform 4 (identifier: Q96Q15-4) Also known as: BLIP; The sequence of this isoform differs from the canonical sequence as follows: 1-1265: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 3657 | 3657 | Serine/threonine-protein kinase SMG1 | PRO_0000229791 | |||||
Regions | |||||||||
| Domain | 1127 – 1862 | 736 | FAT | ||||||
| Repeat | 1813 – 1848 | 36 | HEAT | ||||||
| Domain | 2146 – 2474 | 329 | PI3K/PI4K | ||||||
| Domain | 3625 – 3657 | 33 | FATC | ||||||
Amino acid modifications | |||||||||
| Modified residue | 3546 | 1 | Phosphothreonine Ref.11 | ||||||
| Modified residue | 3552 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 3566 | 1 | Phosphoserine Ref.12 | ||||||
| Modified residue | 3572 | 1 | Phosphoserine Ref.12 | ||||||
| Modified residue | 3573 | 1 | Phosphothreonine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 1265 | 1265 | Missing in isoform 4. | VSP_017746 | |||||
| Alternative sequence | 1 – 626 | 626 | Missing in isoform 3. | VSP_017747 | |||||
| Alternative sequence | 1 – 136 | 136 | Missing in isoform 2. | VSP_017748 | |||||
| Natural variant | 31 | 1 | A → T Ref.15 | VAR_041623 | |||||
| Natural variant | 122 | 1 | R → C Ref.15 | VAR_041624 | |||||
| Natural variant | 140 | 1 | S → C Ref.4 Ref.15 | VAR_041625 | |||||
| Natural variant | 147 | 1 | N → Y Ref.15 | VAR_041626 | |||||
| Natural variant | 156 | 1 | D → N Ref.15 | VAR_041627 | |||||
| Natural variant | 163 | 1 | A → V Ref.15 | VAR_041628 | |||||
| Natural variant | 316 | 1 | D → G Ref.15 | VAR_041629 | |||||
| Natural variant | 461 | 1 | G → S Ref.15 | VAR_041630 | |||||
| Natural variant | 542 | 1 | H → R Ref.15 | VAR_041631 | |||||
| Natural variant | 584 | 1 | A → S Ref.15 | VAR_041632 | |||||
| Natural variant | 608 | 1 | K → I Ref.4 Ref.15 | VAR_041633 | |||||
| Natural variant | 749 | 1 | S → C Ref.15 | VAR_041634 | |||||
| Natural variant | 805 | 1 | S → C Ref.15 | VAR_041635 | |||||
| Natural variant | 808 | 1 | R → C Ref.15 | VAR_041636 | |||||
| Natural variant | 825 | 1 | V → I Ref.15 | VAR_041637 | |||||
| Natural variant | 828 | 1 | N → D Ref.15 | VAR_041638 | |||||
| Natural variant | 948 | 1 | A → G Ref.15 | VAR_041639 | |||||
| Natural variant | 965 | 1 | N → S Ref.15 | VAR_041640 | |||||
| Natural variant | 1012 | 1 | F → L Ref.15 | VAR_041641 | |||||
| Natural variant | 1025 | 1 | R → Q Ref.15 | VAR_041642 | |||||
| Natural variant | 1068 | 1 | T → S Ref.15 | VAR_041643 | |||||
| Natural variant | 1099 | 1 | N → H Ref.15 | VAR_041644 | |||||
| Natural variant | 1271 | 1 | P → R Ref.15 | VAR_041645 | |||||
| Natural variant | 1288 | 1 | Q → P Ref.15 | VAR_041646 | |||||
| Natural variant | 1328 | 1 | I → V Ref.15 | VAR_041647 | |||||
| Natural variant | 1354 | 1 | S → P Ref.15 | VAR_041648 | |||||
| Natural variant | 1414 | 1 | R → T Ref.15 | VAR_041649 | |||||
| Natural variant | 2167 | 1 | S → C in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.15 | VAR_041650 | |||||
| Natural variant | 2254 | 1 | G → S Ref.15 | VAR_041651 | |||||
| Natural variant | 2341 | 1 | M → K Ref.15 | VAR_041652 | |||||
| Natural variant | 2726 | 1 | Q → E Ref.15 | VAR_041653 | |||||
| Natural variant | 2885 | 1 | G → S Ref.15 | VAR_041654 | |||||
| Natural variant | 2895 | 1 | P → A Ref.15 | VAR_041655 | |||||
| Natural variant | 3235 | 1 | I → T in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.15 | VAR_041656 | |||||
| Natural variant | 3579 | 1 | K → Q in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.15 | VAR_041657 | |||||
Experimental info | |||||||||
| Mutagenesis | 2331 | 1 | D → A: Loss of function. Ref.2 Ref.3 Ref.4 | ||||||
| Sequence conflict | 682 | 1 | A → S Ref.3 | ||||||
| Sequence conflict | 682 | 1 | A → S Ref.4 | ||||||
| Sequence conflict | 739 | 1 | R → K Ref.3 | ||||||
| Sequence conflict | 739 | 1 | R → K Ref.4 | ||||||
| Sequence conflict | 1189 | 1 | F → C Ref.3 | ||||||
| Sequence conflict | 1189 | 1 | F → C Ref.4 | ||||||
| Sequence conflict | 2005 | 1 | K → R in BAB70696. Ref.2 | ||||||
| Sequence conflict | 2073 | 1 | S → N in AAK58892. Ref.1 | ||||||
Sequences
| ||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62." Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T. Mol. Cell. Biol. 18:3069-3080(1998) [PubMed: 9566925] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). |
| [2] | "Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay." Yamashita A., Ohnishi T., Kashima I., Taya Y., Ohno S. Genes Dev. 15:2215-2228(2001) [PubMed: 11544179] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PHOSPHORYLATION OF RENT1, ALTERNATIVE SPLICING, ENZYME REGULATION, PHOSPHORYLATION, INTERACTION WITH RENT1; UPF2 AND UPF3, MUTAGENESIS OF ASP-2331. |
| [3] | "Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein." Denning G., Jamieson L., Maquat L.E., Thompson E.A., Fields A.P. J. Biol. Chem. 276:22709-22714(2001) [PubMed: 11331269] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, PHOSPHORYLATION OF RENT1, COFACTOR, ENZYME REGULATION, MUTAGENESIS OF ASP-2331. |
| [4] | "The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells." Brumbaugh K.M., Otterness D.M., Geisen C., Oliveira V., Brognard J., Li X., Lejeune F., Tibbetts R.S., Maquat L.E., Abraham R.T. Mol. Cell 14:585-598(2004) [PubMed: 15175154] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, PHOSPHORYLATION OF TP53, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF ASP-2331, VARIANTS CYS-140 AND ILE-608. |
| [5] | "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed: 9455477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1670-3657. Tissue: Brain. |
| [6] | "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION. |
| [7] | "Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo." Diaz-Meco M.T., Municio M.M., Sanchez P., Lozano J., Moscat J. Mol. Cell. Biol. 16:105-114(1996) [PubMed: 8524286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2874-3657, TISSUE SPECIFICITY, INTERACTION WITH PRKCI. |
| [8] | "Divergent origins and concerted expansion of two segmental duplications on chromosome 16." Eichler E.E., Johnson M.E., Alkan C., Tuzun E., Sahinalp C., Misceo D., Archidiacono N., Rocchi M. J. Hered. 92:462-468(2001) [PubMed: 11948212] [Abstract] Cited for: DUPLICATION. |
| [9] | "Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7." Ohnishi T., Yamashita A., Kashima I., Schell T., Anders K.R., Grimson A., Hachiya T., Hentze M.W., Anderson P., Ohno S. Mol. Cell 12:1187-1200(2003) [PubMed: 14636577] [Abstract] Cited for: INTERACTION WITH SMG5. |
| [10] | "Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1." Chiu S.-Y., Serin G., Ohara O., Maquat L.E. RNA 9:77-87(2003) [PubMed: 12554878] [Abstract] Cited for: INTERACTION WITH RENT1; UPF2; EST1A AND UPF3B. |
| [11] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3546 AND SER-3552, MASS SPECTROMETRY. |
| [12] | "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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3566 AND SER-3572, MASS SPECTROMETRY. |
| [13] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [14] | "SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay." Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B., Katsuhata Y., Muramatsu R., Morita T., Iwamatsu A., Hachiya T., Kurata R., Hirano H., Anderson P., Ohno S. Genes Dev. 23:1091-1105(2009) [PubMed: 19417104] [Abstract] Cited for: CATALYTIC ACTIVITY, IDENTIFICATION IN THE SMG1C COMPLEX. |
| [15] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-31; CYS-122; CYS-140; TYR-147; ASN-156; VAL-163; GLY-316; SER-461; ARG-542; SER-584; ILE-608; CYS-749; CYS-805; CYS-808; ILE-825; ASP-828; GLY-948; SER-965; LEU-1012; GLN-1025; SER-1068; HIS-1099; ARG-1271; PRO-1288; VAL-1328; PRO-1354; THR-1414; CYS-2167; SER-2254; LYS-2341; GLU-2726; SER-2885; ALA-2895; THR-3235 AND GLN-3579. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF186377 mRNA. Translation: AAK58892.1. AB061371 mRNA. Translation: BAB70696.1. AY014957 mRNA. Translation: AAK00511.1. AF395444 mRNA. Translation: AAM73708.1. AB007881 mRNA. Translation: BAA24851.2. U32581 mRNA. Translation: AAA86535.2. Different initiation. | |
| IPI | IPI00183368. IPI00556369. IPI00639874. IPI00640955. |
| PIR | JC6084. |
| RefSeq | NP_055907.3. |
| UniGene | Hs.460179 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q96Q15. 3 interactions. |
PTM databases | |
| PhosphoSite | Q96Q15. |
Genome annotation databases | |
| Ensembl | ENSG00000157106. Homo sapiens. [Contig view] |
| GeneID | 23049. |
| KEGG | hsa:23049. |
Organism-specific databases | |
| GeneCards | GC16M018726. |
| H-InvDB | HIX0012849. HIX0012887. HIX0038531. HIX0038951. HIX0059633. |
| HGNC | HGNC:30045. SMG1. |
| HPA | HPA006870. |
| MIM | 607032. gene. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q96Q15. |
| HOVERGEN | Q96Q15. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 247. |
Gene expression databases | |
| ArrayExpress | Q96Q15. |
| Bgee | Q96Q15. |
| GermOnline | ENSG00000157106. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR015519. Ataxia_Telang_Mut. IPR003152. FATC. IPR000357. HEAT. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR014009. PIK_FAT. [Graphical view] |
| Gene3D | G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit. |
| PANTHER | PTHR11139:SF3. Ataxia_Telang_Mut. 1 hit. |
| Pfam | PF02260. FATC. 1 hit. PF02985. HEAT. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. [Graphical view] |
| SMART | SM00146. PI3Kc. 1 hit. [Graphical view] |
| PROSITE | PS51189. FAT. 1 hit. PS51190. FATC. 1 hit. PS50077. HEAT_REPEAT. False negative. PS00915. PI3_4_KINASE_1. False negative. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 44092. |
| SOURCE | Search... |
Entry information
| Entry name | SMG1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q96Q15 Secondary accession number(s): O43305 Q96RW3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| 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 |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


