SF3B4 splicing factor 3b subunit 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SF3B4provided by HGNC
Official Full Name: splicing factor 3b subunit 4provided by HGNC
Primary source: HGNC:HGNC:10771
See related: Ensembl:ENSG00000143368 MIM:605593
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AFD1; Hsh49; SAP49; SF3b49
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 26.0), bone marrow (RPKM 20.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (149923317..149927803, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (149895209..149899695, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nager syndrome in patient lacking acrofacial dysostosis: Expanding the phenotypic spectrum of SF3B4-related disease.
Title: Nager syndrome in patient lacking acrofacial dysostosis: Expanding the phenotypic spectrum of SF3B4-related disease.
Publicly available data from paired normal and tumor tissues in hepatocellular carcinoma (HCC) and results from patients with HCC suggest that SRSF3 and SF3B4 possess an inverse relationship. SRSF3 is a key molecule for determining SF3B4 levels in HCC cells
Title: SRSF3 Depletion Leads to an Increase in SF3B4 Expression in SNU-368 HCC Cells.
A unique system comprising a p180-SF3b4-mRNA complex facilitates the selective assembly of polyribosomes on the endoplasmic reticulum.
Title: Component of splicing factor SF3b plays a key role in translational control of polyribosomes on the endoplasmic reticulum.
MiRNA-133b not only regulates the endogenous expression of SF3B4 but also modulates SF3B4-mediated AS efficiency in HCC tumorigenesis.
Title: SF3B4 is regulated by microRNA-133b and promotes cell proliferation and metastasis in hepatocellular carcinoma.
SF3B4 indicates early-stage hepatocellular carcinoma in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.
Title: SF3B4 as an early-stage diagnostic marker and driver of hepatocellular carcinoma.
We identified two heterozygous frameshift mutations in the SF3B4 gene in three of the four fetuses investigated. The observed mutation was apparently de novo in one fetus for whom parental DNA was available. Thus, Acrofacial dysostosis syndrome of Rodriguez is an autosomal dominant condition and the recurrences identified in the initial report were likely due to gonadal mosaicism.
Title: Rodriguez acrofacial dysostosis is caused by apparently de novo heterozygous mutations in the SF3B4 gene.
A novel synonymous variant within exon 3 of the SF3B4 gene was identified in three members of a family affected by Nager syndrome.
Title: A synonymous splicing mutation in the SF3B4 gene segregates in a family with highly variable Nager syndrome.
Chemical shift mapping showed that the SF3b145 fragment spanning residues 598-631 interacts with SF3b49 RRM1, which adopts a canonical RRM fold with a topology of beta1-alpha1-beta2-beta3-alpha2-beta4.
Title: Solution structure of the first RNA recognition motif domain of human spliceosomal protein SF3b49 and its mode of interaction with a SF3b145 fragment.
SF3B4 mutations identified in Rodriguez Acrofacial Dysostosis patients disrupted mRNA splicing and reduced expression of DLX5, DLX6, SOX9, and SOX6 in cultured chondrocytes.
Title: Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis.
splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705.
Title: SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
A novel common variant in DCST2 is associated with length in early life and height in adulthood. GeneReviews: Not available
Hundreds of variants clustered in genomic loci and biological pathways affect human height. GeneReviews: Not available
Many sequence variants affecting diversity of adult human height. GeneReviews: Not available
Nager syndrome MedGen: C0265245 OMIM: 154400 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2014-07-17) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2014-07-17) ClinGen Genome Curation PagePubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify 49kDa subunit 4 of splicing factor 3b (SF3B4), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Vpr	vpr	Interaction of HIV-1 Vpr with SAP145 inhibits SAP145-SAP49 complex formation	PubMed
	vpr	HIV-1 Vpr induces checkpoint activation and G2 arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36569 (e-PCR)
- UniSTS:34638

PMC193924P1 (e-PCR)
- UniSTS:271763

RH69043 (e-PCR)
- UniSTS:76998

Homology

Homologs of the SF3B4 gene: The SF3B4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 383 organisms have orthologs with human gene SF3B4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables splicing factor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in RNA splicing	TAS Traceable Author Statement more info	PubMed
involved_in RNA splicing, via transesterification reactions	TAS Traceable Author Statement more info	PubMed
involved_in mRNA processing	TAS Traceable Author Statement more info	PubMed
involved_in mRNA splicing, via spliceosome	IC Inferred by Curator more info	PubMed
involved_in mRNA splicing, via spliceosome	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mRNA splicing, via spliceosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
part_of U12-type spliceosomal complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
part_of U12-type spliceosomal complex	IDA Inferred from Direct Assay more info	PubMed
part_of U2-type precatalytic spliceosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleolus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of spliceosomal complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: splicing factor 3B subunit 4

Names: SAP 49; SF3b50; pre-mRNA-splicing factor SF3b 49 kDa subunit; spliceosomal protein; spliceosome-associated protein (U2 snRNP); spliceosome-associated protein 49; splicing factor 3b, subunit 4, 49kD; splicing factor 3b, subunit 4, 49kDa

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032777.1 RefSeqGene

Range

5450..9936

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005850.5 → NP_005841.1 splicing factor 3B subunit 4

See identical proteins and their annotated locations for NP_005841.1

Status: REVIEWED

Source sequence(s)

AI925089, BC004273, DA535996

Consensus CDS

CCDS72900.1

UniProtKB/Swiss-Prot

Q15427

UniProtKB/TrEMBL

B3KUJ0

Related

ENSP00000271628.8, ENST00000271628.9

Conserved Domains (2) summary

cd12334
Location:15 → 88

RRM1_SF3B4; RNA recognition motif 1 (RRM1) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins

cd12335
Location:99 → 181

RRM2_SF3B4; RNA recognition motif 2 (RRM2) found in splicing factor 3B subunit 4 (SF3B4) and similar proteins