This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008] See more...

Aliases for SH3BP4 Gene

Aliases for SH3BP4 Gene

  • SH3 Domain Binding Protein 4 2 3 5
  • Transferrin Receptor-Trafficking Protein 3 4
  • SH3 Domain-Binding Protein 4 3 4
  • EH-Binding Protein 10 3 4
  • BOG25 3 4
  • TTP 3 4
  • EHB10 4

External Ids for SH3BP4 Gene

Previous GeneCards Identifiers for SH3BP4 Gene

  • GC02P233898
  • GC02P234542
  • GC02P235876
  • GC02P236147
  • GC02P235642
  • GC02P235525
  • GC02P227701

Summaries for SH3BP4 Gene

Entrez Gene Summary for SH3BP4 Gene

  • This gene encodes a protein with 3 Asn-Pro-Phe (NPF) motifs, an SH3 domain, a PXXP motif, a bipartite nuclear targeting signal, and a tyrosine phosphorylation site. This protein is involved in cargo-specific control of clathrin-mediated endocytosis, specifically controlling the internalization of a specific protein receptor. [provided by RefSeq, Jul 2008]

GeneCards Summary for SH3BP4 Gene

SH3BP4 (SH3 Domain Binding Protein 4) is a Protein Coding gene. Diseases associated with SH3BP4 include Molluscum Contagiosum and Cataract 8, Multiple Types. Among its related pathways are PI3K / Akt Signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and GDP-dissociation inhibitor activity. An important paralog of this gene is MACC1.

UniProtKB/Swiss-Prot Summary for SH3BP4 Gene

  • May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy.

Gene Wiki entry for SH3BP4 Gene

Additional gene information for SH3BP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SH3BP4 Gene

Genomics for SH3BP4 Gene

GeneHancer (GH) Regulatory Elements for SH3BP4 Gene

Promoters and enhancers for SH3BP4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J234948 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 754.1 +1.8 1822 10.2 ZBTB6 HLF AHR PRDM1 GLIS2 POLR2A ZBTB8A TCF7L2 PRDM10 ZEB2 SH3BP4 lnc-AGAP1-5 MG828606 lnc-ARL4C-13 HSALNG0023199 LOC105373938
GH02J234975 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 750.3 +31.5 31507 15 LCORL FOXA1 MLX RBPJ POLR2A NR2F1 NR2F6 NFYC HLF RAD21 AB372648 lnc-AGAP1-3 SH3BP4 HSALNG0023199 LOC105373939 lnc-AGAP1-4 lnc-ARL4C-11
GH02J235018 Promoter/Enhancer 1.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 750.2 +72.6 72557 12.9 E2F8 POLR2A SP1 PRDM1 FOSL2 ZIC2 RXRA PRDM10 FOXA2 CEBPB SH3BP4 lnc-AGAP1-2 HSALNG0023205
GH02J234288 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 5.4 -659.4 -659425 7.9 SP1 CTCF MLX MYC RELA HLF MAX RAD21 MNT CEBPG lnc-ARL4C-12 ARL4C HJURP SH3BP4 lnc-SPP2-8 HSALNG0023143 LOC105373933
GH02J234994 Enhancer 1.2 FANTOM5 ENCODE dbSUPER 4 +44.1 44060 3.9 RBPJ NR2F1 NR2F6 SP1 RERE ELF3 AHR MAFK PPARG SP5 lnc-AGAP1-2 SH3BP4 lnc-ARL4C-11 lnc-AGAP1-3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SH3BP4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the SH3BP4 gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • AP-2gamma
  • AREB6
  • C/EBPalpha
  • FOXO3
  • FOXO3a
  • FOXO3b
  • ZIC2

Genomic Locations for SH3BP4 Gene

Genomic Locations for SH3BP4 Gene
chr2:234,951,984-235,055,714
(GRCh38/hg38)
Size:
103,731 bases
Orientation:
Plus strand
chr2:235,860,617-235,964,358
(GRCh37/hg19)
Size:
103,742 bases
Orientation:
Plus strand

Genomic View for SH3BP4 Gene

Genes around SH3BP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SH3BP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SH3BP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SH3BP4 Gene

Proteins for SH3BP4 Gene

  • Protein details for SH3BP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P0V3-SH3B4_HUMAN
    Recommended name:
    SH3 domain-binding protein 4
    Protein Accession:
    Q9P0V3
    Secondary Accessions:
    • O95082
    • Q309A3
    • Q53QD0
    • Q53TD1

    Protein attributes for SH3BP4 Gene

    Size:
    963 amino acids
    Molecular mass:
    107496 Da
    Quaternary structure:
    • Homodimer or homooligomer. Interacts with DNM2, EPS15, clathrin, the adapter protein complex 2/AP-2 and TFRC. Interacts with the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; the interaction is most probably direct, preferentially occurs with their inactive GDP-bound form and is negatively regulated by amino acids.
    • (Microbial infection) Interacts with molluscum contagiosum virus protein MC159L; this interaction is important for the suppression of autophagy.
    Miscellaneous:
    • Overexpression or depletion of SH3BP4 result in a specific decrease of the transferrin receptor endocytosis that can be rescued by DNM2 overexpression.

    Alternative splice isoforms for SH3BP4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SH3BP4 Gene

Post-translational modifications for SH3BP4 Gene

  • Phosphorylated upon EGF stimulation. Phosphorylation prevents interaction with DNM2.
  • Ubiquitination at Lys657
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SH3BP4 Gene

Domains & Families for SH3BP4 Gene

Gene Families for SH3BP4 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for SH3BP4 Gene

Suggested Antigen Peptide Sequences for SH3BP4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ61205, highly similar to Homo sapiens SH3-domain binding protein 4 (SH3BP4), mRNA (B4E2S1_HUMAN)
  • Transferrin receptor-trafficking protein (SH3B4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P0V3

UniProtKB/Swiss-Prot:

SH3B4_HUMAN :
  • The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1.
Domain:
  • The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1.
genes like me logo Genes that share domains with SH3BP4: view

Function for SH3BP4 Gene

Molecular function for SH3BP4 Gene

UniProtKB/Swiss-Prot Function:
May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy.
GENATLAS Biochemistry:
SMC homology domain 3 (SH3) binding protein 4,expressed by corneal fibroblast and other tissues with higher levels in pancreas,placenta,heart,kidney,localized in the nucleus,may be involved in a newly cascade of proteins involved in endocytosis,intracellular sorting and the cell cycle

Phenotypes From GWAS Catalog for SH3BP4 Gene

Gene Ontology (GO) - Molecular Function for SH3BP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005092 GDP-dissociation inhibitor activity IMP 22575674
GO:0005515 protein binding IEA,IPI 16325581
GO:0017016 Ras GTPase binding IEA,IPI 22575674
GO:0042802 identical protein binding IPI 16325581
genes like me logo Genes that share ontologies with SH3BP4: view
genes like me logo Genes that share phenotypes with SH3BP4: view

Animal Models for SH3BP4 Gene

MGI Knock Outs for SH3BP4:
  • Sh3bp4 Sh3bp4<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SH3BP4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SH3BP4 Gene

Localization for SH3BP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SH3BP4 Gene

Membrane, clathrin-coated pit. Cytoplasmic vesicle, clathrin-coated vesicle. Nucleus. Note=Specifically associated with transferrin receptor-containing clathrin-coated pits and clathrin-coated vesicles. May also localize to the nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SH3BP4 gene
Compartment Confidence
nucleus 4
cytosol 2

Gene Ontology (GO) - Cellular Components for SH3BP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA,IBA 22575674
GO:0005905 clathrin-coated pit IEA --
GO:0016020 membrane IEA --
GO:0030136 clathrin-coated vesicle IEA --
genes like me logo Genes that share ontologies with SH3BP4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SH3BP4 Gene

Pathways & Interactions for SH3BP4 Gene

PathCards logo

SuperPathways for SH3BP4 Gene

SuperPathway Contained pathways
1 PI3K / Akt Signaling
genes like me logo Genes that share pathways with SH3BP4: view

Pathways by source for SH3BP4 Gene

1 Cell Signaling Technology pathway for SH3BP4 Gene

SIGNOR curated interactions for SH3BP4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for SH3BP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis IEA --
GO:0008285 negative regulation of cell proliferation IMP 22575674
GO:0010508 positive regulation of autophagy IMP 22575674
GO:0030308 negative regulation of cell growth IMP 22575674
GO:0032007 negative regulation of TOR signaling IMP,IEA 22575674
genes like me logo Genes that share ontologies with SH3BP4: view

Drugs & Compounds for SH3BP4 Gene

No Compound Related Data Available

Transcripts for SH3BP4 Gene

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SH3BP4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SH3BP4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c · 9d ^ 10 ^ 11a · 11b ^ 12a · 12b · 12c
SP1: - - - -
SP2: - - - - - -
SP3: - - - - - - - -
SP4: - - - -
SP5: -
SP6:
SP7: - - - - - - - -
SP8:
SP9: -
SP10:

Relevant External Links for SH3BP4 Gene

GeneLoc Exon Structure for
SH3BP4
ECgene alternative splicing isoforms for
SH3BP4

Expression for SH3BP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SH3BP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SH3BP4 Gene

This gene is overexpressed in Minor Salivary Gland (x4.3).

Protein differential expression in normal tissues from HIPED for SH3BP4 Gene

This gene is overexpressed in Plasma (23.8), Lung (8.6), Placenta (8.2), and Pancreas (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SH3BP4 Gene



NURSA nuclear receptor signaling pathways regulating expression of SH3BP4 Gene:

SH3BP4

SOURCE GeneReport for Unigene cluster for SH3BP4 Gene:

Hs.516777

mRNA Expression by UniProt/SwissProt for SH3BP4 Gene:

Q9P0V3-SH3B4_HUMAN
Tissue specificity: Expressed in all tissues tested with higher expression in pancreas. Expressed by retinal pigment epithelial cells (at protein level).

Evidence on tissue expression from TISSUES for SH3BP4 Gene

  • Liver(4.3)
  • Eye(4.2)
genes like me logo Genes that share expression patterns with SH3BP4: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SH3BP4 Gene

Orthologs for SH3BP4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SH3BP4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SH3BP4 33 32
  • 99.27 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SH3BP4 33 32
  • 87.84 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SH3BP4 33 32
  • 87.26 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SH3BP4 33
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia SH3BP4 33
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sh3bp4 32
  • 86.26 (n)
mouse
(Mus musculus)
Mammalia Sh3bp4 17 33 32
  • 85.92 (n)
chicken
(Gallus gallus)
Aves SH3BP4 33
  • 79 (a)
OneToOne
LOC100857104 32
  • 77.71 (n)
lizard
(Anolis carolinensis)
Reptilia SH3BP4 33
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia sh3bp4 32
  • 68.86 (n)
Str.458 32
zebrafish
(Danio rerio)
Actinopterygii sh3bp4a 33 32
  • 67.92 (n)
OneToMany
sh3bp4 33
  • 66 (a)
OneToMany
Dr.17077 32
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.7319 32
sea squirt
(Ciona savignyi)
Ascidiacea CSA.1683 33
  • 26 (a)
OneToMany
Species where no ortholog for SH3BP4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SH3BP4 Gene

ENSEMBL:
Gene Tree for SH3BP4 (if available)
TreeFam:
Gene Tree for SH3BP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SH3BP4: view image

Paralogs for SH3BP4 Gene

Paralogs for SH3BP4 Gene

(2) SIMAP similar genes for SH3BP4 Gene using alignment to 5 proteins:

  • SH3B4_HUMAN
  • C9JED2_HUMAN
  • C9JF25_HUMAN
  • C9JRG1_HUMAN
  • C9JWW6_HUMAN

Pseudogenes.org Pseudogenes for SH3BP4 Gene

genes like me logo Genes that share paralogs with SH3BP4: view

Variants for SH3BP4 Gene

Sequence variations from dbSNP and Humsavar for SH3BP4 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000006154 -- 234,990,634(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000024534 -- 235,038,662(+) A/C intron_variant
rs1000028771 -- 235,002,698(+) C/A/G intron_variant
rs1000137896 -- 234,987,032(+) AAA/AA genic_upstream_transcript_variant, intron_variant
rs1000140993 -- 235,033,315(+) C/A/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for SH3BP4 Gene

Variant ID Type Subtype PubMed ID
esv1367526 CNV deletion 17803354
esv2721678 CNV deletion 23290073
esv2721679 CNV deletion 23290073
esv2721680 CNV deletion 23290073
esv2721681 CNV deletion 23290073
esv2721682 CNV deletion 23290073
esv2721684 CNV deletion 23290073
esv3796 CNV loss 18987735
esv7240 CNV loss 19470904
esv993755 CNV deletion 20482838
nsv1072081 CNV deletion 25765185
nsv1072500 CNV deletion 25765185
nsv1072501 CNV deletion 25765185
nsv1136317 CNV deletion 24896259
nsv1143072 CNV deletion 24896259
nsv1143969 CNV deletion 24896259
nsv1151042 CNV insertion 26484159
nsv1151814 CNV deletion 26484159
nsv214423 CNV deletion 16902084
nsv3220 CNV insertion 18451855
nsv460140 CNV loss 19166990
nsv476127 CNV novel sequence insertion 20440878
nsv527654 CNV gain 19592680
nsv584719 CNV loss 21841781
nsv999839 CNV gain 25217958

Variation tolerance for SH3BP4 Gene

Residual Variation Intolerance Score: 70% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.60; 56.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SH3BP4 Gene

Human Gene Mutation Database (HGMD)
SH3BP4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SH3BP4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SH3BP4 Gene

Disorders for SH3BP4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for SH3BP4 Gene - From: HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
molluscum contagiosum
cataract 8, multiple types
  • ctrct8
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for SH3BP4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SH3BP4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SH3BP4 Gene

Publications for SH3BP4 Gene

  1. Cloning, chromosomal localization, and characterization of cDNA from a novel gene, SH3BP4, expressed by human corneal fibroblasts. (PMID: 10644451) Dunlevy JR … Hassell JR (Genomics 1999) 2 3 4 23 56
  2. MC159 of Molluscum Contagiosum Virus Suppresses Autophagy by Recruiting Cellular SH3BP4 via an SH3 Domain-Mediated Interaction. (PMID: 30842330) Schmotz C … Saksela K (Journal of virology 2019) 3 4 56
  3. Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. (PMID: 22419666) Shi M … Beaty TH (American journal of medical genetics. Part A 2012) 3 43 56
  4. SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling. (PMID: 22575674) Kim YM … Kim DH (Molecular cell 2012) 3 4 56
  5. Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. (PMID: 21546767) Murea M … Freedman BI (American journal of nephrology 2011) 3 43 56

Products for SH3BP4 Gene

Sources for SH3BP4 Gene