SMN2

SMN2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1G5V, 1MHN, 2LEH, 3S6N, 4A4E, 4A4G, 4GLI, 4NL6, 4NL7, 4QQ6
Identifikatori
Aliasi	SMN2
Vanjski ID-jevi	OMIM: 601627 MGI: 109257 HomoloGene: 292 GeneCards: SMN2
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	70,078,522 bp
Lokacija gena (miš)
Hrom.	Hromosom 13 (miš)
Kraj	100,274,198 bp
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 discdkac; • 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
	6607
	20595
	ENSG00000277773; ENSG00000205571; ENSG00000273772
	ENSMUSG00000021645
	Q16637
	P97801
	NM_017411; NM_022875; NM_022876; NM_022877
	NM_001252629; NM_011420
NP_059107; NP_075013; NP_075014; NP_075015; NP_000335;
	NP_001284644; NP_075012
	NP_001239558; NP_035550
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Gen preživljavanja motornog neurona 2 (SMN2) je gen koji kod ljudi kodira SMN protein (pun i krnji). Genski lokus nalazi se na hromosomu 5.^[5]^[6]

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

Gen SMN2 dio je 500 kb-ne obrnute duplikacije na hromosomu 5q13. 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. Telomerne (SMN1) i centromerne (SMN2) kopije ovog gena su gotovo identične i kodiraju isti protein. . Kritična razlika u sekvenci između dva gena je jedan nukleotid, tj. tačkasta mutacija u egzonu 7, za koji se smatra da je pojačivač prerade egzona. Supstitucija nukleotida u SMN2 rezultira da je oko 80-90% njegovih transkripata nepotpuni, nestabilni proteini bez biološke funkcije (Δ7SMN), a samo 10-20% njegovih transkripata su protein pune dužine (fl- SMN).

Devet egzona i telomerne i centromerijske kopije historijski označeno je kao egzoni 1, 2a, 2b i 3-8. Smatra se da pojave konverzije gena mogu uključivati oba gena, što dovodi do različitog broja kopija svakog gena.^[6]

Klinički značaj

Dok su mutacije u telomernoj kopiji povezane sa spinalnom mišićnom atrofijom, mutacije u centromernoj kopiji ovog gena ne dovode do bolesti. Ovaj gen može biti modifikator bolesti uzrokovane mutacijom u telomernoj kopiji.

Reference

^ ^a ^b ^c ENSG00000205571, ENSG00000273772 GRCh38: Ensembl release 89: ENSG00000277773, ENSG00000205571, ENSG00000273772 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021645 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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. S2CID 14291056.
^ ^a ^b "Entrez Gene: SMN2 survival of motor neuron 2, centromeric".
^ "UniProt, Q16637" (jezik: engleski). Pristupljeno 20. 10. 2021.

Dopunska literarura

Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, Tang TH, Zabidi-Hussin ZA, Nishio H, Zilfalil BA (januar 2009). "Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy". Brain & Development. 31 (1): 42–5. doi:10.1016/j.braindev.2008.08.012. PMID 18842367. S2CID 206312220.
Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AH, Kissel JT (septembar 2009). "A positive modifier of spinal muscular atrophy in the SMN2 gene". American Journal of Human Genetics. 85 (3): 408–13. doi:10.1016/j.ajhg.2009.08.002. PMC 2771537. PMID 19716110.
Coady TH, Baughan TD, Shababi M, Passini MA, Lorson CL (2008). Valcarcel J (ured.). "Development of a single vector system that enhances trans-splicing of SMN2 transcripts". PLOS ONE. 3 (10): e3468. Bibcode:2008PLoSO...3.3468C. doi:10.1371/journal.pone.0003468. PMC 2565107. PMID 18941511.
Elsheikh B, Prior T, Zhang X, Miller R, Kolb SJ, Moore D, Bradley W, Barohn R, Bryan W, Gelinas D, Iannaccone S, Leshner R, Mendell JR, Mendoza M, Russman B, Smith S, King W, Kissel JT (oktobar 2009). "An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy". Muscle & Nerve. 40 (4): 652–6. doi:10.1002/mus.21350. PMID 19760790. S2CID 44901599.
Workman E, Saieva L, Carrel TL, Crawford TO, Liu D, Lutz C, Beattie CE, Pellizzoni L, Burghes AH (juni 2009). "A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice". Human Molecular Genetics. 18 (12): 2215–29. doi:10.1093/hmg/ddp157. PMC 2685758. PMID 19329542.
Bose JK, Wang IF, Hung L, Tarn WY, Shen CK (oktobar 2008). "TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing". The Journal of Biological Chemistry. 283 (43): 28852–9. doi:10.1074/jbc.M805376200. PMC 2661999. PMID 18703504.
Hauke J, Riessland M, Lunke S, Eyüpoglu IY, Blümcke I, El-Osta A, Wirth B, Hahnen E (januar 2009). "Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition". Human Molecular Genetics. 18 (2): 304–17. doi:10.1093/hmg/ddn357. PMC 2638778. PMID 18971205.
Corcia P, Camu W, Praline J, Gordon PH, Vourch P, Andres C (2009). "The importance of the SMN genes in the genetics of sporadic ALS". Amyotrophic Lateral Sclerosis. 10 (5–6): 436–40. doi:10.3109/17482960902759162. PMID 19922137. S2CID 2326464.
Tiziano FD, Pinto AM, Fiori S, Lomastro R, Messina S, Bruno C, Pini A, Pane M, D'Amico A, Ghezzo A, Bertini E, Mercuri E, Neri G, Brahe C (januar 2010). "SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR". European Journal of Human Genetics. 18 (1): 52–8. doi:10.1038/ejhg.2009.116. PMC 2987170. PMID 19603064.
Jedrzejowska M, Milewski M, Zimowski J, Borkowska J, Kostera-Pruszczyk A, Sielska D, Jurek M, Hausmanowa-Petrusewicz I (2009). "Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease". Acta Biochimica Polonica. 56 (1): 103–8. doi:10.18388/abp.2009_2521. PMID 19287802.
Arkblad E, Tulinius M, Kroksmark AK, Henricsson M, Darin N (maj 2009). "A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy". Acta Paediatrica. 98 (5): 865–72. doi:10.1111/j.1651-2227.2008.01201.x. PMID 19154529. S2CID 3134264.
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.
Farooq F, Balabanian S, Liu X, Holcik M, MacKenzie A (novembar 2009). "p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR". Human Molecular Genetics. 18 (21): 4035–45. doi:10.1093/hmg/ddp352. PMID 19648294.
Hasanzad M, Golkar Z, Kariminejad R, Hadavi V, Almadani N, Afroozan F, Salahshurifar I, Shafeghati Y, Kahrizi K, Najmabadi H (februar 2009). "Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy". Annals of the Academy of Medicine, Singapore. 38 (2): 139–41. PMID 19271042.
Martins de Araújo M, Bonnal S, Hastings ML, Krainer AR, Valcárcel J (april 2009). "Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP". RNA. 15 (4): 515–23. doi:10.1261/rna.1273209. PMC 2661831. PMID 19244360.
Song F, Qu YJ, Zou LP, Wang LW, Long MJ, Wang X, Yang YL, Chen Q, Wang H, Jin YW (decembar 2008). "[Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy]". Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics. 46 (12): 919–23. PMID 19134255.
Irimura S, Kitamura K, Kato N, Saiki K, Takeuchi A, Matsuo M, Nishio H, Lee MJ (2009). "HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1". The Kobe Journal of Medical Sciences. 54 (5): E227-36. PMID 19628962.
Yong J, Wan L, Dreyfuss G (maj 2004). "Why do cells need an assembly machine for RNA-protein complexes?". Trends in Cell Biology. 14 (5): 226–32. doi:10.1016/j.tcb.2004.03.010. PMID 15130578.
Chen HH, Chang JG, Lu RM, Peng TY, Tarn WY (novembar 2008). "The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene". Molecular and Cellular Biology. 28 (22): 6929–38. doi:10.1128/MCB.01332-08. PMC 2573304. PMID 18794368.
Cogulu O, Durmaz B, Pehlivan S, Alpman A, Ozkinay F (juni 2009). "Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy". Genetic Testing and Molecular Biomarkers. 13 (3): 287–8. doi:10.1089/gtmb.2008.0139. PMID 19397406.

Vanjski linkovi

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

[refGRCh38Ensembl-1] ENSG00000205571, ENSG00000273772 GRCh38: Ensembl release 89: ENSG00000277773, ENSG00000205571, ENSG00000273772 - Ensembl, maj 2017

[refGRCm38Ensembl-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.

[pmid7813012-5] 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. S2CID 14291056.

[entrez-6] "Entrez Gene: SMN2 survival of motor neuron 2, centromeric".

[UniProt-7] "UniProt, Q16637" (jezik: engleski). Pristupljeno 20. 10. 2021.

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