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Serine/threonine-protein kinase SMG1

 
Known also as: 61E3.4, Lambda/iota protein kinase C-interacting protein, Lambda-interacting protein

Known abbreviations: hSMG-1, SMG-1, SMG1, ATX, KIAA0421, LIP

 

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. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 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. 
 
CATALYTIC ACTIVITY:
 
ATP + a protein = ADP + a phosphoprotein. 
 
COFACTOR:
 
Manganese. 
 
ENZYME REGULATION:
 
Inhibited by caffeine, LY294002 and wortmannin. 
 
SUBUNIT STRUCTURE:
 
Component of the SMG1C complex composed of SMG1, SMG8 and SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large conformational change in the SMG1 C-terminal head domain containing the catalytic domain. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and RUVBL2. Interacts with UPF2. 
 
CELLULAR LOCALIZATION:
 
Nucleus. Cytoplasm 
 
TISSUE SPECIFICITY:
 
Widely expressed, with highest level in heart and skeletal muscle. Expressed in placenta, brain, lung and spleen, but not in liver. 
 
POST-TRANSLATIONAL MODIFICATION:
 
Autophosphorylated Probable. Phosphorylated upon DNA damage, probably by ATM or ATR. 



This protein can be a part of a given complexes: Activities in which Serine/threonine-protein kinase SMG1 is involved: Pathways in which Serine/threonine-protein kinase SMG1 is involved:

NCBI GI number(s): 62243658
219277632
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q96Q15 Q96Q15
BRENDA - -
KEGG hsa:23049 hsa:23049
PFAM: PF02260
PF00454
PF02260
PF00454
InterPro: IPR011989
IPR016024
IPR003152
IPR011009
IPR000403
IPR018936
IPR014009
IPR011989
IPR016024
IPR003152
IPR011009
IPR000403
IPR018936
IPR014009
CATH: - -
SCOP: - -


Protein sequence:
MSRRAPGSRLSSGGGGGGTKYPRSWNDWQPRTDSASADPDNLKYSSSRDR
GGSSSYGLQPSNSAVVSRQRHDDTRVHADIQNDEKGGYSVNGGSGENTYG
RKSLGQELRVNNVTSPEFTSVQHGSRALATKDMRKSQERSMSYSDESRLS
NLLRRITREDDRDRRLATVKQLKEFIQQPENKLVLVKQLDNILAAVHDVL
NESSKLLQELRQEGACCLGLLCASLSYEAEKIFKWIFSKFSSSAKDEVKL
LYLCATYKALETVGEKKAFSSVMQLVMTSLQSILENVDTPELLCKCVKCI
LLVARCYPHIFSTNFRDTVDILVGWHIDHTQKPSLTQQVSGWLQSLEPFW
VADLAFSTTLLGQFLEDMEAYAEDLSHVASGESVDEDVPPPSVSLPKLAA
LLRVFSTVVRSIGERFSPIRGPPITEAYVTDVLYRVMRCVTAANQVFFSE
AVLTAANECVGVLLGSLDPSMTIHCDMVITYGLDQLENCQTCGTDYIISV
LNLLTLIVEQINTKLPSSFVEKLFIPSSKLLFLRYHKEKEVVAVAHAVYQ
AVLSLKNIPVLETAYKLILGEMTCALNNLLHSLQLPEACSEIKHEAFKNH
VFNVDNAKFVVIFDLSALTTIGNAKNSLIGMWALSPTVFALLSKNLMIVH
SDLAVHFPAIQYAVLYTLYSHCTRHDHFISSSLSSSSPSLFDGAVISTVT
TATKKHFSIILNLLGILLKKDNLNQDTRKLLMTWALEAAVLMKKSETYAP
LFSLPSFHKFCKGLLANTLVEDVNICLQACSSLHALSSSLPDDLLQRCVD
VCRVQLVHSGTRIRQAFGKLLKSIPLDVVLSNNNHTEIQEISLALRSHMS
KAPSNTFHPQDFSDVISFILYGNSHRTGKDNWLERLFYSCQRLDKRDQST
IPRNLLKTDAVLWQWAIWEAAQFTVLSKLRTPLGRAQDTFQTIEGIIRSL
AAHTLNPDQDVSQWTTADNDEGHGNNQLRLVLLLQYLENLEKLMYNAYEG
CANALTSPPKVIRTFFYTNRQTCQDWLTRIRLSIMRVGLLAGQPAVTVRH
GFDLLTEMKTTSLSQGNELEVTIMMVVEALCELHCPEAIQGIAVWSSSIV
GKNLLWINSVAQQAEGRFEKASVEYQEHLCAMTGVDCCISSFDKSVLTLA
NAGRNSASPKHSLNGESRKTVLSKPTDSSPEVINYLGNKACECYISIADW
AAVQEWQNAIHDLKKSTSSTSLNLKADFNYIKSLSSFESGKFVECTEQLE
LLPGENINLLAGGSKEKIDMKKLLPNMLSPDPRELQKSIEVQLLRSSVCL
ATALNPIEQDQKWQSITENVVKYLKQTSRIAIGPLRLSTLTVSQSLPVLS
TLQLYCSSALENTVSNRLSTEDCLIPLFSEALRSCKQHDVRPWMQALRYT
MYQNQLLEKIKEQTVPIRSHLMELGLTAAKFARKRGNVSLATRLLAQCSE
VQLGKTTTAQDLVQHFKKLSTQGQVDEKWGPELDIEKTKLLYTAGQSTHA
MEMLSSCAISFCKSVKAEYAVAKSILTLAKWIQAEWKEISGQLKQVYRAQ
HQQNFTGLSTLSKNILTLIELPSVNTMEEEYPRIESESTVHIGVGEPDFI
LGQLYHLSSVQAPEVAKSWAALASWAYRWGRKVVDNASQGEGVRLLPREK
SEVQNLLPDTITEEEKERIYGILGQAVCRPAGIQDEDITLQITESEDNEE
DDMVDVIWRQLISSCPWLSELDESATEGVIKVWRKVVDRIFSLYKLSCSA
YFTFLKLNAGQIPLDEDDPRLHLSHRVEQSTDDMIVMATLRLLRLLVKHA
GELRQYLEHGLETTPTAPWRGIIPQLFSRLNHPEVYVRQSICNLLCRVAQ
DSPHLILYPAIVGTISLSSESQASGNKFSTAIPTLLGNIQGEELLVSECE
GGSPPASQDSNKDEPKSGLNEDQAMMQDCYSKIVDKLSSANPTMVLQVQM
LVAELRRVTVLWDELWLGVLLQQHMYVLRRIQQLEDEVKRVQNNNTLRKE
EKIAIMREKHTALMKPIVFALEHVRSITAAPAETPHEKWFQDNYGDAIEN
ALEKLKTPLNPAKPGSSWIPFKEIMLSLQQRAQKRASYILRLEEISPWLA
AMTNTEIALPGEVSARDTVTIHSVGGTITILPTKTKPKKLLFLGSDGKSY
PYLFKGLEDLHLDERIMQFLSIVNTMFATINRQETPRFHARHYSVTPLGT
RSGLIQWVDGATPLFGLYKRWQQREAALQAQKAQDSYQTPQNPGIVPRPS
ELYYSKIGPALKTVGLSLDVSRRDWPLHVMKAVLEELMEATPPNLLAKEL
WSSCTTPDEWWRVTQSYARSTAVMSMVGYIIGLGDRHLDNVLIDMTTGEV
VHIDYNVCFEKGKSLRVPEKVPFRMTQNIETALGVTGVEGVFRLSCEQVL
HIMRRGRETLLTLLEAFVYDPLVDWTAGGEAGFAGAVYGGGGQQAESKQS
KREMEREITRSLFSSRVAEIKVNWFKNRDEMLVVLPKLDGSLDEYLSLQE
QLTDVEKLQGKLLEEIEFLEGAEGVDHPSHTLQHRYSEHTQLQTQQRAVQ
EAIQVKLNEFEQWITHYQAAFNNLEATQLASLLQEISTQMDLGPPSYVPA
TAFLQNAGQAHLISQCEQLEGEVGALLQQRRSVLRGCLEQLHHYATVALQ
YPKAIFQKHRIEQWKTWMEELICNTTVERCQELYRKYEMQYAPQPPPTVC
QFITATEMTLQRYAADINSRLIRQVERLKQEAVTVPVCEDQLKEIERCIK
VFLHENGEEGSLSLASVIISALCTLTRRNLMMEGAASSAGEQLVDLTSRD
GAWFLEELCSMSGNVTCLVQLLKQCHLVPQDLDIPNPMEASETVHLANGV
YTSLQELNSNFRQIIFPEALRCLMKGEYTLESMLHELDGLIEQTTDGVPL
QTLVESLQAYLRNAAMGLEEETHAHYIDVARLLHAQYGELIQPRNGSVDE
TPKMSAGQMLLVAFDGMFAQVETAFSLLVEKLNKMEIPIAWRKIDIIREA
RSTQVNFFDDDNHRQVLEEIFFLKRLQTIKEFFRLCGTFSKTLSGSSSLE
DQNTVNGPVQIVNVKTLFRNSCFSEDQMAKPIKAFTADFVRQLLIGLPNQ
ALGLTLCSFISALGVDIIAQVEAKDFGAESKVSVDDLCKKAVEHNIQIGK
FSQLVMNRATVLASSYDTAWKKHDLVRRLETSISSCKTSLQRVQLHIAMF
QWQHEDLLINRPQAMSVTPPPRSAILTSMKKKLHTLSQIETSIATVQEKL
AALESSIEQRLKWAGGANPALAPVLQDFEATIAERRNLVLKESQRASQVT
FLCSNIIHFESLRTRTAEALNLDAALFELIKRCQQMCSFASQFNSSVSEL
ELRLLQRVDTGLEHPIGSSEWLLSAHKQLTQDMSTQRAIQTEKEQQIETV
CETIQNLVDNIKTVLTGHNRQLGDVKHLLKAMAKDEEAALADGEDVPYEN
SVRQFLGEYKSWQDNIQTVLFTLVQAMGQVRSQEHVEMLQEITPTLKELK
TQSQSIYNNLVSFASPLVTDATNECSSPTSSATYQPSFAAAVRSNTGQKT
QPDVMSQNARKLIQKNLATSADTPPSTVPGTGKSVACSPKKAVRDPKTGK
AVQERNSYAVSVWKRVKAKLEGRDVDPNRRMSVAEQVDYVIKEATNLDNL
AQLYEGWTAWV

Serine/threonine-protein kinase SMG1 (Homo sapiens) is product of expression of SMG1 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A, Hachiya T, Hentze MW, Anderson P, Ohno S Mol Cell 2003-11-01 (12) 14636577
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 2009-05-01 (23) 19417104
The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8. Arias-Palomo E, Yamashita A, Fernandez IS, Nunez-Ramirez R, Bamba Y, Izumi N, Ohno S, Llorca O Genes Dev 2011-02-15 (25) 21245168
Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. Chiu SY, Serin G, Ohara O, Maquat LE RNA 2003-02-01 (9) 12554878
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 2001-09-01 (15) 11544179
Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein. Denning G, Jamieson L, Maquat LE, Thompson EA, Fields AP J Biol Chem 2001-06-22 (276) 11331269
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem 2009-06-01 (81) 19413330
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science 2007-05-25 (316) 17525332
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science 2009-08-14 (325) 19608861
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A 2008-08-05 (105) 18669648
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 2002-06-01 (9) 12168954
Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Kashima I, Yamashita A, Izumi N, Kataoka N, Morishita R, Hoshino S, Ohno M, Dreyfuss G, Ohno S Genes Dev 2006-01-01 (20) 16452507
Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT Mol Cell Biol 1998-05-01 (18) 9566925
The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Brumbaugh KM, Otterness DM, Geisen C, Oliveira V, Brognard J, Li X, Lejeune F, Tibbetts RS, Maquat LE, Abraham RT Mol Cell 2004-06-04 (14) 15175154
The sequence and analysis of duplication-rich human chromosome 16. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M Nature 2004-12-23 (432) 15616553
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 1997-10-31 (4) 9455477
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 MT, Municio MM, Sanchez P, Lozano J, Moscat J Mol Cell Biol 1996-02-01 (16) 8524286
Divergent origins and concerted expansion of two segmental duplications on chromosome 16. Eichler EE, Johnson ME, Alkan C, Tuzun E, Sahinalp C, Misceo D, Archidiacono N, Rocchi M J Hered 2001-01-01 (92) 11948212
Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly. Kaizuka T, Hara T, Oshiro N, Kikkawa U, Yonezawa K, Takehana K, Iemura S, Natsume T, Mizushima N J Biol Chem 2010-06-25 (285) 20427287
A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Hurov KE, Cotta-Ramusino C, Elledge SJ Genes Dev 2010-09-01 (24) 20810650
AAA+ proteins RUVBL1 and RUVBL2 coordinate PIKK activity and function in nonsense-mediated mRNA decay. Izumi N, Yamashita A, Iwamatsu A, Kurata R, Nakamura H, Saari B, Hirano H, Anderson P, Ohno S Sci Signal 2010-01-01 (3) 20371770
Patterns of somatic mutation in human cancer genomes. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C Nature 2007-03-08 (446) 17344846



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Last modification of this entry: Sept. 25, 2012.

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