UniProt functional annotation for Q16637



	UniProt functional annotation for Q16637

UniProt code: Q16637.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:23063131, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:9845364}.

Subunit: Homodimer (PubMed:14715275). Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:9323129). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (PubMed:12065586, PubMed:18984161). Component of an import snRNP complex composed of KPNB1, RNUT1, SMN1 and ZNF259 (PubMed:12095920). Interacts with DDX20, FBL, NOLA1, RNUT1, SYNCRIP and with several spliceosomal snRNP core Sm proteins, including SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE and ILF3 (PubMed:11574476, PubMed:12095920). Interacts with OSTF1, LSM10, LSM11 and RPP20/POP7 (PubMed:11551898, PubMed:12975319, PubMed:16087681, PubMed:14715275). Interacts (via C-terminal region) with ZPR1 (via C- terminal region) (PubMed:11283611). Interacts (via Tudor domain) with COIL (PubMed:11641277). Interacts with SETX; recruits SETX to POLR2A (PubMed:21700224, PubMed:26700805). Interacts with POLR2A (via the C- terminal domain (CTD)) (PubMed:26700805). Interacts with PRMT5 (PubMed:26700805). Interacts with XRN2 (PubMed:26700805). Interacts (via C-terminus) with FMR1 (via C-terminus); the interaction is direct and occurs in a RNA-independent manner (PubMed:18093976). Interacts (via Tudor domain) with SF3B2 ('Arg-508'-methylated form) (PubMed:25737013). Interacts with WRAP53/TCAB1 (PubMed:21072240). Interacts (via Tudor domain) with ELAVL4 in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (PubMed:21088113, PubMed:21389246, PubMed:29061699). {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:11551898, ECO:0000269|PubMed:11574476, ECO:0000269|PubMed:11641277, ECO:0000269|PubMed:12065586, ECO:0000269|PubMed:12095920, ECO:0000269|PubMed:12975319, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:16087681, ECO:0000269|PubMed:18093976, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:21389246, ECO:0000269|PubMed:21700224, ECO:0000269|PubMed:25737013, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:29061699, ECO:0000269|PubMed:9323129}.

Subcellular location: Nucleus, gem {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:8670859, ECO:0000305|PubMed:12067652}. Nucleus, Cajal body {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:21072240, ECO:0000305|PubMed:12067652}. Cytoplasm {ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:8670859, ECO:0000305|PubMed:12067652}. Cytoplasmic granule {ECO:0000269|PubMed:14715275}. Perikaryon {ECO:0000269|PubMed:18093976}. Cell projection, neuron projection {ECO:0000269|PubMed:18093976}. Cell projection, axon {ECO:0000250|UniProtKB:P97801}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P97801}. Note=Colocalizes with actin and at the Z-line of skeletal muscle (By similarity). Under stress conditions colocalizes with RPP20/POP7 in punctuated cytoplasmic granules (PubMed:14715275). Colocalized and redistributed with ZPR1 from the cytoplasm to nuclear gems (Gemini of coiled bodies) and Cajal bodies (PubMed:11283611). Colocalizes with FMR1 in cytoplasmic granules in the soma and neurite cell processes (PubMed:18093976). {ECO:0000250|UniProtKB:P97801, ECO:0000269|PubMed:11283611, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:18093976}.

Tissue specificity: Expressed in a wide variety of tissues. Expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. Also seen at high levels in spinal cord. Present in osteoclasts and mononuclear cells (at protein level). {ECO:0000269|PubMed:11551898, ECO:0000269|PubMed:9259265}.

Domain: The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.

Disease: Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:15249625, ECO:0000269|PubMed:15580564, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:21389246, ECO:0000269|PubMed:7813012, ECO:0000269|PubMed:9147655}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spinal muscular atrophy 2 (SMA2) [MIM:253550]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. {ECO:0000269|PubMed:10732802, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spinal muscular atrophy 3 (SMA3) [MIM:253400]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spinal muscular atrophy 4 (SMA4) [MIM:271150]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk. {ECO:0000269|PubMed:7658877, ECO:0000269|PubMed:8551862}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: The SMN gene is present in two highly homologous and functional copies (TelSMN/SMN1 and CenSMN/SMN2). The telomeric copy of SMN gene (TelSMN/SMN1) seems to be the SMA-determining gene while the centromeric copy seems unaffected.

Miscellaneous: [Isoform SMN]: Primarily derived from SMN1 gene.

Miscellaneous: [Isoform SMN-delta7]: Thought to be a non-functional protein that lacks the capacity to oligomerize and thus cannot interact with Sm proteins. Primarily derived from SMN2 gene. {ECO:0000305}.

Similarity: Belongs to the SMN family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269\|PubMed:18984161, ECO:0000269\|PubMed:23063131, ECO:0000269\|PubMed:26700805, ECO:0000269\|PubMed:9845364}.


Subunit:		Homodimer (PubMed:14715275). Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:9323129). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (PubMed:12065586, PubMed:18984161). Component of an import snRNP complex composed of KPNB1, RNUT1, SMN1 and ZNF259 (PubMed:12095920). Interacts with DDX20, FBL, NOLA1, RNUT1, SYNCRIP and with several spliceosomal snRNP core Sm proteins, including SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE and ILF3 (PubMed:11574476, PubMed:12095920). Interacts with OSTF1, LSM10, LSM11 and RPP20/POP7 (PubMed:11551898, PubMed:12975319, PubMed:16087681, PubMed:14715275). Interacts (via C-terminal region) with ZPR1 (via C- terminal region) (PubMed:11283611). Interacts (via Tudor domain) with COIL (PubMed:11641277). Interacts with SETX; recruits SETX to POLR2A (PubMed:21700224, PubMed:26700805). Interacts with POLR2A (via the C- terminal domain (CTD)) (PubMed:26700805). Interacts with PRMT5 (PubMed:26700805). Interacts with XRN2 (PubMed:26700805). Interacts (via C-terminus) with FMR1 (via C-terminus); the interaction is direct and occurs in a RNA-independent manner (PubMed:18093976). Interacts (via Tudor domain) with SF3B2 ('Arg-508'-methylated form) (PubMed:25737013). Interacts with WRAP53/TCAB1 (PubMed:21072240). Interacts (via Tudor domain) with ELAVL4 in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (PubMed:21088113, PubMed:21389246, PubMed:29061699). {ECO:0000269\|PubMed:11283611, ECO:0000269\|PubMed:11551898, ECO:0000269\|PubMed:11574476, ECO:0000269\|PubMed:11641277, ECO:0000269\|PubMed:12065586, ECO:0000269\|PubMed:12095920, ECO:0000269\|PubMed:12975319, ECO:0000269\|PubMed:14715275, ECO:0000269\|PubMed:16087681, ECO:0000269\|PubMed:18093976, ECO:0000269\|PubMed:18984161, ECO:0000269\|PubMed:21072240, ECO:0000269\|PubMed:21088113, ECO:0000269\|PubMed:21389246, ECO:0000269\|PubMed:21700224, ECO:0000269\|PubMed:25737013, ECO:0000269\|PubMed:26700805, ECO:0000269\|PubMed:29061699, ECO:0000269\|PubMed:9323129}.
Subcellular location:		Nucleus, gem {ECO:0000269\|PubMed:11283611, ECO:0000269\|PubMed:8670859, ECO:0000305\|PubMed:12067652}. Nucleus, Cajal body {ECO:0000269\|PubMed:11283611, ECO:0000269\|PubMed:21072240, ECO:0000305\|PubMed:12067652}. Cytoplasm {ECO:0000269\|PubMed:11283611, ECO:0000269\|PubMed:8670859, ECO:0000305\|PubMed:12067652}. Cytoplasmic granule {ECO:0000269\|PubMed:14715275}. Perikaryon {ECO:0000269\|PubMed:18093976}. Cell projection, neuron projection {ECO:0000269\|PubMed:18093976}. Cell projection, axon {ECO:0000250\|UniProtKB:P97801}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000250\|UniProtKB:P97801}. Note=Colocalizes with actin and at the Z-line of skeletal muscle (By similarity). Under stress conditions colocalizes with RPP20/POP7 in punctuated cytoplasmic granules (PubMed:14715275). Colocalized and redistributed with ZPR1 from the cytoplasm to nuclear gems (Gemini of coiled bodies) and Cajal bodies (PubMed:11283611). Colocalizes with FMR1 in cytoplasmic granules in the soma and neurite cell processes (PubMed:18093976). {ECO:0000250\|UniProtKB:P97801, ECO:0000269\|PubMed:11283611, ECO:0000269\|PubMed:14715275, ECO:0000269\|PubMed:18093976}.
Tissue specificity:		Expressed in a wide variety of tissues. Expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. Also seen at high levels in spinal cord. Present in osteoclasts and mononuclear cells (at protein level). {ECO:0000269\|PubMed:11551898, ECO:0000269\|PubMed:9259265}.
Domain:		The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.
Disease:		Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269\|PubMed:10732817, ECO:0000269\|PubMed:14715275, ECO:0000269\|PubMed:15249625, ECO:0000269\|PubMed:15580564, ECO:0000269\|PubMed:21088113, ECO:0000269\|PubMed:21389246, ECO:0000269\|PubMed:7813012, ECO:0000269\|PubMed:9147655}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spinal muscular atrophy 2 (SMA2) [MIM:253550]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. {ECO:0000269\|PubMed:10732802, ECO:0000269\|PubMed:14715275, ECO:0000269\|PubMed:21088113, ECO:0000269\|PubMed:9158159, ECO:0000269\|PubMed:9837824}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spinal muscular atrophy 3 (SMA3) [MIM:253400]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. {ECO:0000269\|PubMed:10732817, ECO:0000269\|PubMed:14715275, ECO:0000269\|PubMed:9158159, ECO:0000269\|PubMed:9837824}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spinal muscular atrophy 4 (SMA4) [MIM:271150]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk. {ECO:0000269\|PubMed:7658877, ECO:0000269\|PubMed:8551862}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		The SMN gene is present in two highly homologous and functional copies (TelSMN/SMN1 and CenSMN/SMN2). The telomeric copy of SMN gene (TelSMN/SMN1) seems to be the SMA-determining gene while the centromeric copy seems unaffected.
Miscellaneous:		[Isoform SMN]: Primarily derived from SMN1 gene.
Miscellaneous:		[Isoform SMN-delta7]: Thought to be a non-functional protein that lacks the capacity to oligomerize and thus cannot interact with Sm proteins. Primarily derived from SMN2 gene. {ECO:0000305}.
Similarity:		Belongs to the SMN family. {ECO:0000305}.