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FLASH GENE

Symbol

SMN2

contributors: shn/pgu - updated : 31-08-2016

HGNC name	survival of motor neuron 2, centromeric
HGNC id	11118

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	a single nucleotide change in exon 7 resulting in the splicing out of this exon from most of the transcripts from SMN2 (PMID: 10655541)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_017411 9 - 1634 NP_059107 31.7 294 - 1996 8808598 also called SMN2-Id or variant d NM_022875 8 splicing 1580 NP_075013 30.3 282 - 1996 8808598 also called SMN2-Ia also called variant a lacking exon 7 SMN delta7, that does not oligomerize efficiently and is unstable (PMID: 19716110) NM_022876 8 splicing 1538 NP_075014 28.4 262 - 1996 8808598 also called SMN2-Ib or variant b lacking exon 5 NM_022877 7 splicing 1484 NP_075015 27 250 - 1996 8808598 also called SMN2-Ic or variant c lacking exons 5-7

EXPRESSION

Type	ubiquitous

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue     highly   stomach       highly Lymphoid/Immune thymus       highly Reproductive female system uterus cervix   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a proline-rich motif at the C terminus
	Tudor domain

HOMOLOGY

interspecies

ortholog to SMN2, Pan troglodytes

Homologene

FAMILY

SMN family

CATEGORY

motor/contractile , RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm,nuclear bodies,coiled bodies (Cajal)
text	localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs)

basic FUNCTION	important roles in RNA metabolism
	may be a modifier of disease caused by mutation in the telomeric copy
	expresses only limited amounts of full-length transcript due to skipping of exon 7 caused by disruption of an SF2/ASF binding ESE (exonic splicing enhancer)
	truncated protein that lacks exon 7, unstable and quickly degraded, however maintains the ability to rescue viability but cannot overcome neurological defects

CELLULAR PROCESS

nucleotide, RNA splicing

PHYSIOLOGICAL PROCESS

text	SMN2 is not fully functional compared with normal SMN1 protein, including a diminished oligomerization and binding to protein substrates such as the snRNP Sm proteins
	degraded by the proteasome

PATHWAY

metabolism

signaling

a component	heteromeric complexes with proteins such as SIP1 and GEMIN4
	forming sub-complexes with gemin proteins, complexes that localise to both stationary and dynamic neurite granules

INTERACTION

DNA

RNA

small molecule

protein	HDAC1 and HDAC2
	SMN1
	SYNCRIP
	GAR1
	binding KHDRBS1, through its UUUUA consensus site in SMN2 exon-7 (binding of KHDRBS1 to the UUUUA consensus in the SMN2 exon-7 is required for efficient skipping)
	interacting with HNRNPA1 (HNRNPA1 can inhibit splicing of SMN2 exon 7 by direct binding to the 3prime ss sequence)
	HNRNPM promotes exon 7 inclusion of SMN1 and SMN2 pre-mRNA through targeting an enhancer on exon 7 through recruiting U2AF2

cell & other

REGULATION

induced by

inhibition of an individual HDAC which is sufficient to increase SMN2 transcription as well as promote the inclusion of exon 7

Other	transcriptional regulation during cellular differentiation and development
	modulated expression of SMN2 by histone acetylation (through HDAC2 or HDAC1)

ASSOCIATED DISORDERS

corresponding disease(s)

AMCSMA1 , SMA , SMA2 , SMA3 , SMA4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     in one case with spinal muscular atrophy, without any detectable lesion of SMN1 constitutional   deletion     homozygously deleted in sporadic SLA with shorter time of survival

Susceptibility

to spinal muscular amyotrophy splicing defect in SMN2 causes SMN deficiency because it fortuitously creates a degron resulting in major perturbations in RNA metabolism

Variant & Polymorphism

Candidate gene	an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one
Marker
Therapy target
	System Type Disorder Pubmed neuromuscular spinal muscular atrophy   in SMN-deficient mice expression of an increasing copy number of SMN2 cDNA transgenes proportionately lessens SMA severity neuromuscular spinal muscular atrophy   inhibition of SMN2 gene silencing conferred by DNA methylation might represent a promising strategy for pharmacologic SMA therapy neuromuscular spinal muscular atrophy   potential therapeutic benefit in increasing the SMN2 gene expression in order to decrease the severity of the SMA neuromuscular spinal muscular atrophy   use of single-stranded oligonucleotides to direct genetic conversion of SMN2 to SMN1 in human cells from SMA patients neuromuscular spinal muscular atrophy   inhibition of KHDRBS1 activity, through competition with dominant-negative mutants, provides a valuable approach for the rescue of SMN activity

ANIMAL & CELL MODELS