SMN1

Gen 1 preživljavanja motornog neurona (SMN1), znan i kao komponenta GEMS-a 1 ili GEMIN1, jest gen koji se kod ljudi nalazi na hromosoma 5. Kodira protein SMN.^[5][6]

SMN1
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1G5V, 1MHN, 2LEH, 3S6N, 4A4E, 4A4G, 4GLI, 4NL6, 4NL7, 4QQ6
Identifikatori
Aliasi	SMN1
Vanjski ID-jevi	OMIM: 600354 MGI: 109257 HomoloGene: 292 GeneCards: SMN1
Lokacija gena (čovjek) Hrom. Hromosom 5 (čovjek)[1] Bend 5q13.2 Početak 70,925,030 bp[1] Kraj 70,953,942 bp[1]
Lokacija gena (miš) Hrom. Hromosom 13 (miš)[2] Bend 13 D1|13 52.99 cM Početak 100,261,360 bp[2] Kraj 100,274,198 bp[2]
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje sa RNK • vezivanje identičnih proteina Ćelijska komponenta • citoplazma • SMN-Sm protein complex • citosol • Cajal body • nukleoplazma • SMN complex • Z disc • neuron projection • cytoplasmic ribonucleoprotein granule • jedro • gemini of coiled bodies • perikaryon • projekcija ćelije Biološki proces • DNA-templated transcription, termination • mRNA processing • nervous system development • spliceosomal snRNP assembly • spliceosomal complex assembly • Prerada RNK • import into nucleus Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	6606	20595
Ensembl	ENSG00000275349 ENSG00000172062	ENSMUSG00000021645
UniProt	Q16637	P97801
RefSeq (mRNK)	NM_000344 NM_001297715 NM_022874	NM_001252629 NM_011420
RefSeq (bjelančevina)	NP_059107 NP_075013 NP_075014 NP_075015 NP_000335 NP_001284644 NP_075012	NP_001239558 NP_035550
Lokacija (UCSC)	Chr 5: 70.93 – 70.95 Mb	Chr 13: 100.26 – 100.27 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 294 aminokiseline, а molekulska težina 31.849 Da.^[7]

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MAMSSGGSGG		GVPEQEDSVL		FRRGTGQSDD		SDIWDDTALI		KAYDKAVASF
KHALKNGDIC		ETSGKPKTTP		KRKPAKKNKS		QKKNTAASLQ		QWKVGDKCSA
IWSEDGCIYP		ATIASIDFKR		ETCVVVYTGY		GNREEQNLSD		LLSPICEVAN
NIEQNAQENE		NESQVSTDES		ENSRSPGNKS		DNIKPKSAPW		NSFLPPPPPM
PGPRLGPGKP		GLKFNGPPPP		PPPPPPHLLS		CWLPPFPSGP		PIIPPPPPIC
PDSLDDADAL		GSMLISWYMS		GYHTGYYMGF		RQNQKEGRCS		HSLN

Gen

SMN1 telomerna kopija gena koji kodira protein SMN; centromerna kopija naziva se SMN2. SMN1 i SMN2 su dio obrnute duplikacije na hromosomskoj regiji 5q13, od 500 kbp. Ova duplicirana regija sadrži najmanje četiri gena i ponavljajući element koji ga čine sklonim preuređivanjima i delecijama. Ponavljanje i složenost sekvence također su uzrokovali poteškoće u određivanju organizacije ove genomske regije. SMN1 i SMN2 su gotovo identični i kodiraju isti protein.^[6] Kritična razlika u sekvenci između njih je jedan nukleotid u egzonu 7, za koji se smatra da je pojačivač splajsinga egzona. Smatra se da konverzije gena mogu uključivati dva gena, što dovodi do različitog broja kopija svakog od njih.^[6]

Klinički značaj

Mutacije u SMN1 povezane su sa spinalnom mišićnom atrofijom. Mutacije samo u SMN2 ne dovode do bolesti, iako mutacije i u SMN1 i u SMN2 rezultiraju umiranjem embriona.

Reference

1. ENSG00000172062 GRCh38: Ensembl release 89: ENSG00000275349, ENSG00000172062 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021645 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M (januar 1995). "Identification and characterization of a spinal muscular atrophy-determining gene". Cell. 80 (1): 155–65. doi:10.1016/0092-8674(95)90460-3. PMID 7813012.
6. "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
7. "UniProt, Q16637" (jezik: engleski). Pristupljeno 20. 10. 2021.

Dopunska literatura

• Hausmanowa-Petrusewicz I, Jedrzejowska M (2002). "Spinal muscular atrophy of childhood at the edge of the centuries". Functional Neurology. 16 (4 Suppl): 247–53. PMID 11996521.
• Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (juni 2002). "The SMN complex, an assemblyosome of ribonucleoproteins". Current Opinion in Cell Biology. 14 (3): 305–12. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652.
• van der Steege G, Draaijers TG, Grootscholten PM, Osinga J, Anzevino R, Velonà I, Den Dunnen JT, Scheffer H, Brahe C, van Ommen GJ (1995). "A provisional transcript map of the spinal muscular atrophy (SMA) critical region". European Journal of Human Genetics. 3 (2): 87–95. doi:10.1159/000472281. PMID 7552146. S2CID 46083524.
• Bussaglia E, Clermont O, Tizzano E, Lefebvre S, Bürglen L, Cruaud C, Urtizberea JA, Colomer J, Munnich A, Baiget M (novembar 1995). "A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients". Nature Genetics. 11 (3): 335–7. doi:10.1038/ng1195-335. PMID 7581461. S2CID 10588736.
• Gennarelli M, Lucarelli M, Capon F, Pizzuti A, Merlini L, Angelini C, Novelli G, Dallapiccola B (august 1995). "Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients". Biochemical and Biophysical Research Communications. 213 (1): 342–8. doi:10.1006/bbrc.1995.2135. PMID 7639755.
• Liu Q, Dreyfuss G (juli 1996). "A novel nuclear structure containing the survival of motor neurons protein". The EMBO Journal. 15 (14): 3555–65. doi:10.1002/j.1460-2075.1996.tb00725.x. PMC 451956. PMID 8670859.
• van der Steege G, Grootscholten PM, Cobben JM, Zappata S, Scheffer H, den Dunnen JT, van Ommen GJ, Brahe C, Buys CH (oktobar 1996). "Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5". American Journal of Human Genetics. 59 (4): 834–8. PMC 1914786. PMID 8808598.
• Bürglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, Melki J (mart 1996). "Structure and organization of the human survival motor neurone (SMN) gene". Genomics. 32 (3): 479–82. doi:10.1006/geno.1996.0147. PMID 8838816.
• Parsons DW, McAndrew PE, Monani UR, Mendell JR, Burghes AH, Prior TW (novembar 1996). "An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene". Human Molecular Genetics. 5 (11): 1727–32. doi:10.1093/hmg/5.11.1727. PMID 8922999.
• Talbot K, Ponting CP, Theodosiou AM, Rodrigues NR, Surtees R, Mountford R, Davies KE (mart 1997). "Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?". Human Molecular Genetics. 6 (3): 497–500. doi:10.1093/hmg/6.3.497. PMID 9147655.
• Hahnen E, Schönling J, Rudnik-Schöneborn S, Raschke H, Zerres K, Wirth B (maj 1997). "Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA)". Human Molecular Genetics. 6 (5): 821–5. doi:10.1093/hmg/6.5.821. PMID 9158159.
• Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH (august 1997). "The survival motor neuron protein in spinal muscular atrophy". Human Molecular Genetics. 6 (8): 1205–14. doi:10.1093/hmg/6.8.1205. PMID 9259265.
• Battaglia G, Princivalle A, Forti F, Lizier C, Zeviani M (oktobar 1997). "Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system". Human Molecular Genetics. 6 (11): 1961–71. doi:10.1093/hmg/6.11.1961. PMID 9302277.
• Liu Q, Fischer U, Wang F, Dreyfuss G (septembar 1997). "The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins". Cell. 90 (6): 1013–21. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129.
• Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (novembar 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature. 390 (6658): 413–7. Bibcode:1997Natur.390..413I. doi:10.1038/37144. PMID 9389483. S2CID 1936633.
• Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan J, Kang X, Lefebvre C, Ikeda JE, Korneluk RG, MacKenzie AE (februar 1998). "Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP". Genomics. 48 (1): 121–7. doi:10.1006/geno.1997.5141. PMID 9503025.
• Francis JW, Sandrock AW, Bhide PG, Vonsattel JP, Brown RH (maj 1998). "Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 6492–7. Bibcode:1998PNAS...95.6492F. doi:10.1073/pnas.95.11.6492. PMC 27826. PMID 9600994.
• Gambardella A, Mazzei R, Toscano A, Annesi G, Pasqua A, Annesi F, Quattrone F, Oliveri RL, Valentino P, Bono F, Aguglia U, Zappia M, Vita G, Quattrone A (novembar 1998). "Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene". Annals of Neurology. 44 (5): 836–9. doi:10.1002/ana.410440522. PMID 9818944. S2CID 22595601.
• Parsons DW, McAndrew PE, Iannaccone ST, Mendell JR, Burghes AH, Prior TW (decembar 1998). "Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number". American Journal of Human Genetics. 63 (6): 1712–23. doi:10.1086/302160. PMC 1377643. PMID 9837824.

Vanjski linkovi

• Prior TW, Russman BS (2013). Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong CT, Mefford HC, Smith RJ, Stephens K (ured.). "Spinal Muscular Atrophy". GeneReviews [Internet]. PMID 20301526.

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.