Reviewed, UniProtKB/Swiss-Prot P78314 (3BP2_HUMAN)

Names and origin

Protein names

Recommended name:
    SH3 domain-binding protein 2
      Short name=3BP-2

Gene names

Name:	SH3BP2
Synonyms:	3BP2
ORF Names:	RES4-23

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	561 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism.
Tissue specificity	Expressed in a variety of tissues including lung, liver, skeletal muscle, kidney and pancreas.
Involvement in disease	Defects in SH3BP2 are the cause of cherubism (CRBM) [MIM:118400]. CRBM is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.
Sequence similarities	Contains 1 PH domain. Contains 1 SH2 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	SH2 domain SH3-binding
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	signal transduction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW SH3/SH2 adaptor activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P78314-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P78314-2)

The sequence of this isoform differs from the canonical sequence as follows:
     81-97: VMRAAEETTSNNVFPFK → QPRPQPAQALSQTEAGP
     98-561: Missing.

Notes: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 561

561

SH3 domain-binding protein 2

PRO_0000064365

Regions

Domain

26 – 130

105

PH

Domain

457 – 555

99

SH2

Motif

201 – 210

10

SH3-binding

Compositional bias

205 – 212

8

Poly-Pro

Compositional bias

236 – 240

5

Poly-Pro

Amino acid modifications

Modified residue

278

1

Phosphoserine

Natural variations

Alternative sequence

81 – 97

17

VMRAA…VFPFK → QPRPQPAQALSQTEAGP in isoform Short.

VSP_004085

Alternative sequence

98 – 561

464

Missing in isoform Short.

VSP_004086

Natural variant

415

1

R → P in CRBM.

VAR_013257

Natural variant

415

1

R → Q in CRBM.

VAR_013258

Natural variant

418

1

P → H in CRBM.

VAR_013259

Natural variant

418

1

P → L in CRBM.

VAR_013260

Natural variant

418

1

P → R in CRBM.

VAR_013261

Natural variant

420

1

G → E in CRBM.

VAR_013262

Natural variant

420

1

G → R in CRBM.

VAR_013263

Experimental info

Sequence conflict

27

1

V → L in AAB59973. Ref.3

Sequence conflict

224

1

H → N in AAB59973. Ref.3

Sequence conflict

249

1

L → R in AAB59973. Ref.3

Sequence conflict

251

1

A → P in AAB59973. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

561

Helix Strand Turn

Details...

Turn

455 – 457

3

Helix

464 – 474

11

Beta strand

485 – 489

5

Beta strand

496 – 501

6

Turn

503 – 505

3

Beta strand

506 – 508

3

Beta strand

514 – 516

3

Beta strand

519 – 525

7

Beta strand

527 – 530

4

Helix

531 – 538

8

Beta strand

544 – 548

5

Beta strand

553 – 556

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 69E6846A4F6D8F15	FASTA	561	62,244
	10 20 30 40 50 60 MAAEEMHWPV PMKAIGAQNL LTMPGGVAKA GYLHKKGGTQ LQLLKWPLRF VIIHKRCVYY 70 80 90 100 110 120 FKSSTSASPQ GAFSLSGYNR VMRAAEETTS NNVFPFKIIH ISKKHRTWFF SASSEEERKS 130 140 150 160 170 180 WMALLRREIG HFHEKKDLPL DTSDSSSDTD SFYGAVERPV DISLSPYPTD NEDYEHDDED 190 200 210 220 230 240 DSYLEPDSPE PGRLEDALMH PPAYPPPPVP TPRKPAFSDM PRAHSFTSKG PGPLLPPPPP 250 260 270 280 290 300 KHGLPDVGLA AEDSKRDPLC PRRAEPCPRV PATPRRMSDP PLSTMPTAPG LRKPPCFRES 310 320 330 340 350 360 ASPSPEPWTP GHGACSTSSA AIMATATSRN CDKLKSFHLS PRGPPTSEPP PVPANKPKFL 370 380 390 400 410 420 KIAEEDPPRE AAMPGLFVPP VAPRPPALKL PVPEAMARPA VLPRPEKPQL PHLQRSPPDG 430 440 450 460 470 480 QSFRSFSFEK PRQPSQADTG GDDSDEDYEK VPLPNSVFVN TTESCEVERL FKATSPRGEP 490 500 510 520 530 540 QDGLYCIRNS STKSGKVLVV WDETSNKVRN YRIFEKDSKF YLEGEVLFVS VGSMVEHYHT 550 560 HVLPSHQSLL LRHPYGYTGP R
	Isoform Short [UniParc]. Checksum: 58CB0FBE9EB3A7FF		97	10,624
	10 20 30 40 50 60 MAAEEMHWPV PMKAIGAQNL LTMPGGVAKA GYLHKKGGTQ LQLLKWPLRF VIIHKRCVYY 70 80 90 FKSSTSASPQ GAFSLSGYNR QPRPQPAQAL SQTEAGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"3BP2 binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase c-FES to the cytoplasmic membrane in a phosphorylation dependent mechanism." Gokemeijer J., Deligiannidis K.E., Ligris K., Ernst T.J. Blood 88:473A-473A(1996) Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Tonsil.
[2]	"Identification and characterization of the human homologue of SH3BP2, an SH3 binding domain protein within a common region of deletion at 4p16.3 involved in bladder cancer." Bell S.M., Shaw M., Jou Y.-S., Myers R.M., Knowles M.A. Genomics 44:163-170(1997) [PubMed: 9299232] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[3]	"The primary structure and genomic organization of five novel transcripts located close to the Huntington's disease gene on human chromosome 4p16.3." Hadano S., Ishida Y., Ikeda J.-E. DNA Res. 5:177-186(1998) [PubMed: 9734812] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), TISSUE SPECIFICITY. Tissue: Brain.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). Tissue: Cervix.
[7]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, MASS SPECTROMETRY.
[9]	"Solution structure of the SH2 domain of human SH3BP2 protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 444-558.
[10]	"Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism." Ueki Y., Tiziani V., Santanna C., Fukai N., Maulik C., Garfinkle J., Ninomiya C., doAmaral C., Peters H., Habal M., Rhee-Morris L., Doss J.B., Kreiborg S., Olsen B.R., Reichenberger E. Nat. Genet. 28:125-126(2001) [PubMed: 11381256] [Abstract] Cited for: VARIANTS CRBM GLN-415; PRO-415; ARG-418; HIS-418; LEU-418; ARG-420 AND GLU-420.
[11]	"Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism." Lo B., Faiyaz-Ul-Haque M., Kennedy S., Aviv R., Tsui L.-C., Teebi A.S. Am. J. Med. Genet. A 121:37-40(2003) [PubMed: 12900899] [Abstract] Cited for: VARIANT CRBM ARG-420.
[12]	"A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism." Imai Y., Kanno K., Moriya T., Kayano S., Seino H., Matsubara Y., Yamada A. Cleft Palate Craniofac. J. 40:632-638(2003) [PubMed: 14577811] [Abstract] Cited for: VARIANT CRBM ARG-418.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF000936 mRNA. Translation: AAB59973.1.
U56386 mRNA. Translation: AAB72034.1.
AB000462 mRNA. Translation: BAA19119.1.
AB000463 mRNA. Translation: BAA19120.1.
AL121750 Genomic DNA. No translation available.
CH471131 Genomic DNA. Translation: EAW82509.1.
BC022996 mRNA. Translation: AAH22996.1.

RefSeq

NP_001116153.1.
NP_003014.3.

UniGene

Hs.167679

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CR4	NMR	-	A	444-558	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P78314.

PTM databases

PhosphoSite

P78314.

Genome annotation databases

Ensembl

ENSG00000087266. Homo sapiens. [Contig view]

GeneID

6452.

KEGG

hsa:6452.

Organism-specific databases

H-InvDB

HIX0004037.

HGNC

HGNC:10825. SH3BP2.

MIM

118400. phenotype.
602104. gene.

Orphanet

184. Cherubism.

PharmGKB

PA35733.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P78314.

Gene expression databases

ArrayExpress

P78314.

CleanEx

HS_SH3BP2.

GermOnline

ENSG00000087266. Homo sapiens.

Family and domain databases

InterPro

IPR001849. PH.
IPR011993. PH_type.
IPR000980. SH2.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF00169. PH. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

ProDom

PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

25079.

SOURCE

Search...

Entry information

Entry name

3BP2_HUMAN

Accession

Primary (citable) accession number: P78314
Secondary accession number(s): A6NNC2 , O00500, O15373, P78315

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	November 25, 2008
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)