SF3B4

Last updated
SF3B4
Protein SF3B4 PDB 1x5t.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SF3B4 , AFD1, Hsh49, SAP49, SF3b49, splicing factor 3b subunit 4
External IDs OMIM: 605593 MGI: 109580 HomoloGene: 134086 GeneCards: SF3B4
Orthologs
SpeciesHumanMouse
Entrez

10262

107701

Ensembl

ENSG00000143368

ENSMUSG00000068856

UniProt

Q15427
Q5SZ64

Q8QZY9

RefSeq (mRNA)

NM_005850

NM_153053

RefSeq (protein)

NP_005841

NP_694693

Location (UCSC) Chr 1: 149.92 – 149.93 Mb Chr 3: 96.08 – 96.08 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Splicing factor 3B subunit 4 is a protein that in humans is encoded by the SF3B4 gene. [5] [6]

Contents

Function

This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [6]

Disease associations

In 2012, Canadian researchers belonging to the FORGE (Finding of Rare disease GEnes) consortium identified new dominant mutations in SF3B4 as the cause of Nager syndrome, a rare type of mandibulofacial dysostosis with associated limb malformations. [7]

Interactions

SF3B4 has been shown to interact with CDC5L, [8] BMPR1A [9] and SF3B2. [5] [10]

Related Research Articles

RNA splicing Processing primary RNA to remove intron sequences and join the remaining exon sections

RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing introns and so joining together exons. For nuclear-encoded genes, splicing occurs in the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually needed to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing occurs in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). There exist self-splicing introns, that is, ribozymes that can catalyze their own excision from their parent RNA molecule.

Spliceosome Molecular machine that removes intron RNA from the primary transcript

A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specific proteins to form a small nuclear ribonucleoprotein complex, which in turn combines with other snRNPs to form a large ribonucleoprotein complex called a spliceosome. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. An analogy is a film editor, who selectively cuts out irrelevant or incorrect material from the initial film and sends the cleaned-up version to the director for the final cut.

snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

Minor spliceosome

The minor spliceosome is a ribonucleoprotein complex that catalyses the removal (splicing) of an atypical class of spliceosomal introns (U12-type) from eukaryotic messenger RNAs in plants, insects, vertebrates and some fungi. This process is called noncanonical splicing, as opposed to U2-dependent canonical splicing. U12-type introns represent less than 1% of all introns in human cells. However they are found in genes performing essential cellular functions.

U11 spliceosomal RNA

The U11 snRNA is an important non-coding RNA in the minor spliceosome protein complex, which activates the alternative splicing mechanism. The minor spliceosome is associated with similar protein components as the major spliceosome. It uses U11 snRNA to recognize the 5' splice site while U12 snRNA binds to the branchpoint to recognize the 3' splice site.

U4 spliceosomal RNA Non-coding RNA component of the spliceosome

The U4 small nuclear Ribo-Nucleic Acid is a non-coding RNA component of the major or U2-dependent spliceosome – a eukaryotic molecular machine involved in the splicing of pre-messenger RNA (pre-mRNA). It forms a duplex with U6, and with each splicing round, it is displaced from the U6 snRNA in an ATP-dependent manner, allowing U6 to re-fold and create the active site for splicing catalysis. A recycling process involving protein Brr2 releases U4 from U6, while protein Prp24 re-anneals U4 and U6. The crystal structure of a 5′ stem-loop of U4 in complex with a binding protein has been solved.

snRNP70

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the SNRNP70 gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.

PRPF8

Pre-mRNA-processing-splicing factor 8 is a protein that in humans is encoded by the PRPF8 gene.

Small nuclear ribonucleoprotein D2

Small nuclear ribonucleoprotein Sm D2 is a protein that in humans is encoded by the SNRPD2 gene. It belongs to the small nuclear ribonucleoprotein core protein family, and is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified.

SNRPD3

Small nuclear ribonucleoprotein Sm D3 is a protein that in humans is encoded by the SNRPD3 gene.

SF3A1

Splicing factor 3 subunit 1 is a protein that in humans is encoded by the SF3A1 gene.

PRPF3 Protein-coding gene in the species Homo sapiens

U4/U6 small nuclear ribonucleoprotein Prp3 is a protein that in humans is encoded by the PRPF3 gene.

SF3B1

Splicing factor 3B subunit 1 is a protein that in humans is encoded by the SF3B1 gene.

Small nuclear ribonucleoprotein polypeptide F

Small nuclear ribonucleoprotein F is a protein that in humans is encoded by the SNRPF gene.

SF3A2

Splicing factor 3A subunit 2 is a protein that in humans is encoded by the SF3A2 gene.

SF3B2

Splicing factor 3B subunit 2 is a protein that in humans is encoded by the SF3B2 gene.

SF3B3

Splicing factor 3B subunit 3 is a protein that in humans is encoded by the SF3B3 gene.

PRPF4 Protein-coding gene in the species Homo sapiens

U4/U6 small nuclear ribonucleoprotein Prp4 is a protein that in humans is encoded by the PRPF4 gene. The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. PRPF4 is 1 of several proteins that associate with U4 and U6 snRNPs.[supplied by OMIM]

SF3B14

Splicing factor 3B, 14 kDa subunit, also known as SF3B14, is a human gene.

PPIH Protein-coding gene in the species Homo sapiens

Peptidyl-prolyl cis-trans isomerase H is an enzyme that in humans is encoded by the PPIH gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000143368 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000068856 - Ensembl, May 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. 1 2 Champion-Arnaud P, Reed R (Aug 1994). "The prespliceosome components SAP 49 and SAP 145 interact in a complex implicated in tethering U2 snRNP to the branch site". Genes & Development. 8 (16): 1974–83. doi: 10.1101/gad.8.16.1974 . PMID   7958871.
  6. 1 2 "Entrez Gene: SF3B4 splicing factor 3b, subunit 4, 49kDa".
  7. ↑ Bernier FP, Caluseriu O, Ng S, Schwartzentruber J, Buckingham KJ, Innes AM, Jabs EW, Innis JW, Schuette JL, Gorski JL, Byers PH, Andelfinger G, Siu V, Lauzon J, Fernandez BA, McMillin M, Scott RH, Racher H, Majewski J, Nickerson DA, Shendure J, Bamshad MJ, Parboosingh JS (May 2012). "Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome". American Journal of Human Genetics. 90 (5): 925–33. doi:10.1016/j.ajhg.2012.04.004. PMC   3376638 . PMID   22541558.
  8. ↑ Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann M, Lamond AI (Dec 2000). "Functional analysis of the human CDC5L complex and identification of its components by mass spectrometry". The EMBO Journal. 19 (23): 6569–81. doi:10.1093/emboj/19.23.6569. PMC   305846 . PMID   11101529.
  9. ↑ Nishanian TG, Waldman T (Oct 2004). "Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor". Biochemical and Biophysical Research Communications. 323 (1): 91–7. doi:10.1016/j.bbrc.2004.08.060. PMID   15351706.
  10. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

Further reading


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