SH3BP2 SH3-domain binding protein 2 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: SH3BP2provided by HGNC
Official Full Name: SH3-domain binding protein 2provided by HGNC
Primary source: HGNC:10825
Locus tag: RES4-23
See related: Ensembl:ENSG00000087266; HPRD:03657; MIM:602104; Vega:OTTHUMG00000160801
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: 3BP2; CRBM; CRPM; 3BP-2; RES4-23
Summary: The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Genomic context

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Location :: 4p16.3

Sequence :: Chromosome: 4; NC_000004.11 (2794750..2842823)

See SH3BP2 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

In the first family, a missense mutation Arg415Gln was found in exon 9 of SH3BP2 in all affected individuals. The unaffected individuals did not have the mutation. In the second family, a missense mutation Pro418Thr was identified in exon 9 of the SH3BP2
Title: Mutations of the SH3BP2 gene in 2 families of cherubism.
These results demonstrate that PARP1 regulates expression of SH3BP2.
Title: Cloning and characterization of the human SH3BP2 promoter.
P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules.
Title: Enhancement of B-cell receptor signaling by a point mutation of adaptor protein 3BP2 identified in human inherited disease cherubism.
if a primary genetic defect is the cause for CGCG it is either located in SH3BP2 gene exons not yet related to cherubism or in a different gene.
Title: SH3BP2-encoding exons involved in cherubism are not associated with central giant cell granuloma.
The SH-3BP-2 mutation may participate in the differentiation and maturation of osteoclast-like cells in the lesion of cherubism.
Title: [Gene mutation and expression of SH-3BP-2 in cherubism].
over expression of SH3BP2 in RAW 264.7 cells potentiates sRANKL-stimulated phosphorylation of PLCgamma1 and PLCgamma2.
Title: SH3BP2 mutations potentiate osteoclastogenesis via PLCγ.
No SH3BP2 gene mutation was found in PGCL.
Title: NFATc1 and TNFalpha expression in giant cell lesions of the jaws.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: New genetic associations detected in a host response study to hepatitis B vaccine.
3BP2 induces the protein complex with cellular signaling molecules through phosphorylation of Tyr(183) and SH2 domain leading to the activation of NFAT in B cells
Title: Tyrosine phosphorylation of 3BP2 regulates B cell receptor-mediated activation of NFAT.

Submit: New GeneRIF Correction See all (24)

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

Cherubism is characterized by progressive, painless, bilateral enlargement of the mandible and/or maxilla resulting from replacement of bone with multilocular cysts composed of fibrotic stromal cells and osteoclast-like cells. The enlargement is usually symmetric in nature. The phenotype ranges from no clinical manifestations to severe mandibular and maxillary overgrowth with respiratory, vision, speech, and swallowing problems. Onset is typically between ages two and five years. Other bones are usually not affected and the affected person is otherwise normal. The jaw lesions progress slowly until puberty when they stabilize and then regress. Dental abnormalities include congenitally missing teeth, premature exfoliation of the deciduous teeth, and displacement of permanent teeth by the jaw lesions. By age 30 years, facial abnormalities are no longer apparent; residual jaw deformity is rare.

Diagnosis Testing

Diagnosis depends on typical clinical findings and radiographic findings of well-defined, often extensive bilateral multilocular areas of diminished density in the mandible and/or maxilla. Molecular genetic testing of SH3BP2, the only gene in which mutation is currently known to cause cherubism, is clinically available. Sequence analysis of exon 9 is typically performed first as most missense mutations identified to date are in exon 9.

Genetic Counseling

Cherubism is inherited in an autosomal dominant manner. The proportion of cases caused by de novo mutations is unknown because of variable expressivity and reduced penetrance. Each child of an individual with cherubism has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible when the SH3BP2 disease-causing mutation has been identified in the family.

References

PMID: 20301316

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_003014.2		FGFR1	BIND	PubMed	An unspecified isoform of FGFR1 interacts with SH3BP2. This interaction was modeled on a demonstrated interaction between FGFR1 from an unspecified species and human SH3BP2.
P78314	P00519	ABL1	HPRD	PubMed
P78314	Q9UJU6	DBNL	HPRD	PubMed
P78314	P11362	FGFR1	HPRD	PubMed
P78314	P36888	FLT3	HPRD	PubMed
P78314	P06241	FYN	HPRD	PubMed
P78314	P62993	GRB2	HPRD	PubMed
P78314	O43561	LAT	HPRD	PubMed
P78314	P06239	LCK	HPRD	PubMed
P78314	P19174	PLCG1	HPRD	PubMed
P78314	P16885	PLCG2	HPRD	PubMed
P78314	Q96B97	SH3KBP1	HPRD	PubMed
P78314	P43405	SYK	HPRD	PubMed
P78314	P02787	TF	HPRD	PubMed
P78314	P15498	VAV1	HPRD	PubMed
P78314	P52735	VAV2	HPRD	PubMed
P78314	Q9UKW4	VAV3	HPRD	PubMed
P78314	P27348	YWHAQ	HPRD	PubMed
P78314	P43403	ZAP70	HPRD	PubMed
BioGRID:112350	BioGRID:107315	CBL	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112350	BioGRID:118809	DBNL	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:112350	BioGRID:108376	ERBB2	BioGRID	PubMed	Protein-peptide
BioGRID:112350	BioGRID:108810	FYN	BioGRID	PubMed	Two-hybrid
BioGRID:112350	BioGRID:109142	GRB2	BioGRID	PubMed	Reconstituted Complex
BioGRID:112350	BioGRID:117971	LAT	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112350	BioGRID:114682	PDLIM7	BioGRID	PubMed	Two-hybrid
BioGRID:112350	BioGRID:111351	PLCG1	BioGRID	PubMed	Far Western; Reconstituted Complex
BioGRID:112350	BioGRID:123598	RNF146	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112350	BioGRID:119029	SH3KBP1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Two-hybrid
BioGRID:112350	BioGRID:112592	SRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112350	BioGRID:112717	SYK	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:112350	BioGRID:114207	TNKS	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112350	BioGRID:123257	TNKS2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Co-crystal Structure
BioGRID:112350	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112350	BioGRID:113252	VAV1	BioGRID	PubMed	Affinity Capture-Western; Far Western; Two-hybrid
BioGRID:112350	BioGRID:113367	ZAP70	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Pathways from BioSystems

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B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
TCR signaling in naive CD4+ T cells, organism-specific biosystem
TCR signaling in naive CD4+ T cells

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

GDB:434012 (e-PCR)
- UniSTS:157204

D4S3283 (e-PCR)
- UniSTS:73495

D4S182 (e-PCR)
- UniSTS:147238

D8S2279 (e-PCR)
- UniSTS:473907

STS-H16766 (e-PCR)
- UniSTS:76346

SHGC-68227 (e-PCR)
- UniSTS:38034

RH68130 (e-PCR)
- UniSTS:35773

L17971 (e-PCR)
- UniSTS:43966

L30021 (e-PCR)
- UniSTS:3276

SH3BP2__6823 (e-PCR)
- UniSTS:466427

Genotypes

See SH3BP2 SNP Geneview Report
See SH3BP2 SNP Genotype Report
See SH3BP2 SNP Variation Viewer Report

Homology

Homologs of the SH3BP2 gene: The SH3BP2 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, and chicken.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ42079, FLJ54978

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
SH3 domain binding	IEA Inferred from Electronic Annotation more info
SH3/SH2 adaptor activity	TAS Traceable Author Statement more info	PubMed
phospholipid binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info

Process	Evidence Code	Pubs
signal transduction	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: SH3 domain-binding protein 2

Names: SH3 domain-binding protein 2; Abl-SH3 binding protein 2; TNFAIP3 interacting protein 2

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_011609.1 RefSeqGene

Range

5001..53074

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001122681.1 → NP_001116153.1 SH3 domain-binding protein 2 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents use of an alternative promoter and 5' UTR and uses a downstream translation start site, compared to variant 3. The resulting isoform (a) has a shorter N-terminus, compared to isoform b. Both variants 1 and 2 encode the same isoform.

Source sequence(s)

AK225497, AK312286, AL121750

Consensus CDS

CCDS33944.1

UniProtKB/Swiss-Prot

P78314

Conserved Domains (3) summary

PHA02777
Location:371 – 457
Blast Score: 89

PHA02777; major capsid L1 protein; Provisional

cd00821
Location:29 – 127
Blast Score: 168

PH; Pleckstrin homology (PH) domain

cd10359
Location:456 – 556
Blast Score: 471

SH2_SH3BP2; Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2)
NM_001145855.1 → NP_001139327.1 SH3 domain-binding protein 2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents use of an alternative promoter and 5' UTR and uses an alternate translation start site, compared to variant 3. The resulting isoform (c) has a shorter and distinct N-terminus, compared to isoform b.

Source sequence(s)

AK299996, AK312286, AL121750, DC391267

Consensus CDS

CCDS54715.1

UniProtKB/Swiss-Prot

P78314

Related

ENSP00000388152, ENST00000442312

Conserved Domains (3) summary

PHA02777
Location:399 – 485
Blast Score: 89

PHA02777; major capsid L1 protein; Provisional

cd00821
Location:57 – 155
Blast Score: 168

PH; Pleckstrin homology (PH) domain

cd10359
Location:484 – 584
Blast Score: 471

SH2_SH3BP2; Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2)
NM_001145856.1 → NP_001139328.1 SH3 domain-binding protein 2 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (b).

Source sequence(s)

AK225497, AL121750, U56386

Consensus CDS

CCDS54716.1

UniProtKB/TrEMBL

D6R919

UniProtKB/Swiss-Prot

P78314

Related

ENSP00000422168, ENST00000503393

Conserved Domains (3) summary

PHA02777
Location:428 – 514
Blast Score: 89

PHA02777; major capsid L1 protein; Provisional

cd00821
Location:86 – 184
Blast Score: 168

PH; Pleckstrin homology (PH) domain

cd10359
Location:513 – 613
Blast Score: 474

SH2_SH3BP2; Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2)
NM_003023.4 → NP_003014.3 SH3 domain-binding protein 2 isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents use of an alternative promoter and 5' UTR and uses a downstream translation start site, compared to variant 3. The resulting isoform (a) has a shorter N-terminus, compared to isoform b. Both variants 1 and 2 encode the same isoform.

Source sequence(s)

AB000462, AK312286, AL121750

Consensus CDS

CCDS33944.1

UniProtKB/Swiss-Prot

P78314

Related

ENSP00000348685, OTTHUMP00000219027, ENST00000356331, OTTHUMT00000362406

Conserved Domains (3) summary

PHA02777
Location:371 – 457
Blast Score: 89

PHA02777; major capsid L1 protein; Provisional

cd00821
Location:29 – 127
Blast Score: 168

PH; Pleckstrin homology (PH) domain

cd10359
Location:456 – 556
Blast Score: 471

SH2_SH3BP2; Src homology 2 domain found in c-Abl SH3 domain-binding protein-2 (SH3BP2)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

2794750..2842823

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

2733534..2781278

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

2776037..2823097

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01029485.1 (16277..18438)	None
genomic	ABBA01029486.1	None
genomic	ABBA01029487.1	None
genomic	ABBA01029488.1	None
genomic	ABBA01029489.1 (13130..13244)	None
genomic	AL121750.22 (55906..78760)	None
genomic	AMYH01013884.1 (149..47209)	None
genomic	CH471131.2	EAW82506.1
		EAW82507.1
		EAW82508.1
		EAW82509.1
		EAW82510.1
		EAW82511.1
		EAW82512.1
		EAW82513.1
genomic	CQ834812.1	CAH05621.1
mRNA	AB000462.1	BAA19119.1
mRNA	AB000463.1	BAA19120.1
mRNA	AF000936.1	AAB59973.1
mRNA	AK124073.1	BAC85767.1
mRNA	AK126537.1	BAC86582.1
mRNA	AK225497.1	None
mRNA	AK299996.1	BAG61816.1
mRNA	AK304752.1	BAH14252.1
mRNA	AK307106.1	None
mRNA	AK312286.1	BAG35213.1
mRNA	BC022996.1	AAH22996.1
mRNA	DC391267.1	None
mRNA	U56386.1	AAB72034.1