ELM Details - LIG_SH3

LIG_SH3_2

Functional site class:	SH3 ligand
Functional site description:	This motif is involved in protein-protein interaction mediated by SH3 domains
ELM(s):	LIG_SH3_3, LIG_SH3_4, LIG_SH3_1, LIG_SH3_2, LIG_SH3_5
LIG_SH3_2 description:	this is the motif recognized by class II SH3 domains
Pattern:	P..P.[KR]
Present in taxon(s):	Homo sapiens Fungi/Metazoa group Bos taurus Mus musculus Rattus norvegicus Gallus gallus Pichia pastoris Saccharomyces cerevisiae
Not represented in taxon(s):

See instances for LIG_SH3_2

Abstract

SH3 (Src Homolgy 3) domains are small protein modules of about 50-60 residues. It is found in proteins involved in several biological processes as diverse as signal transduction pathways, cytoskeleton organization, membrane traffic or organelle assembly. SH3 domains bind to proline-rich peptides that form a left-handed polyproline type II helix (PPII) in one of two opposite orientations. Ligand orientation depends on the position of the positive residue in the target peptide. Peptides that bind in a type I orientation contain the consensus R/KXXPXXP, while the type II orientation conform to the PXXPXR/K consensus

Selected references

Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT, Edwards DP

Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases.

Mol Cell 2001 Aug;8(2) : 269-80.

PMID: 11545730

Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S

Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation.

J Biol Chem 2000 Dec 8;275(49) : 38131-4.

PMID: 11013230

Cestra G, Castagnoli L, Dente L, Minenkova O, Petrelli A, Migone N, Hoffmuller U, Schneider-Mergener J, Cesareni G

The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity.

J Biol Chem 1999 Nov 5;274(45) : 32001-7.

PMID: 10542231

Girzalsky W, Rehling P, Stein K, Kipper J, Blank L, Kunau WH, Erdmann R

Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2-dependent protein import into peroxisomes.

J Cell Biol 1999 Mar 22;144(6) : 1151-62.

PMID: 10087260

Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, De Camilli P

The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence.

J Biol Chem 1997 May 16;272(20) : 13419-25.

PMID: 9148966

Gregorieff A, Cloutier JF, Veillette A

Sequence requirements for association of protein-tyrosine phosphatase PEP with the Src homology 3 domain of inhibitory tyrosine protein kinase p50(csk).

J Biol Chem 1998 May 22;273(21) : 13217-22.

PMID: 9582365

Harte MT, Hildebrand JD, Burnham MR, Bouton AH, Parsons JT

p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase.

J Biol Chem 1996 Jun 7;271(23) : 13649-55.

PMID: 8662921

Kay BK, Williamson MP, Sudol M

The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains.

FASEB J 2000 Feb;14(2) : 231-41.

PMID: 10657980

Lai MM, Luo HR, Burnett PE, Hong JJ, Snyder SH

The calcineurin-binding protein cain is a negative regulator of synaptic vesicle endocytosis.

J Biol Chem 2000 Nov 3;275(44) : 34017-20.

PMID: 10931822

Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J

Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling.

Nature 1993 May 6;363(6424) : 85-8.

PMID: 8479541

Mayer BJ

SH3 domains: complexity in moderation.

J Cell Sci 2001 Apr;114() : 1253-63.

PMID: 11256992

Polte TR, Hanks SK

Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.

Proc Natl Acad Sci U S A 1995 Nov 7;92(23) : 10678-82.

PMID: 7479864

Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF

Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src.

Oncogene 1999 Aug 19;18(33) : 4647-53.

PMID: 10467411

Su YC, Han J, Xu S, Cobb M, Skolnik EY

NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain.

EMBO J 1997 Mar 17;16(6) : 1279-90.

PMID: 9135144

Suzuki A, Kadota N, Hara T, Nakagami Y, Izumi T, Takenawa T, Sabe H, Endo T

Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src.

Oncogene 2000 Nov 30;19(51) : 5842-50.

PMID: 11127814

Urquhart AJ, Kennedy D, Gould SJ, Crane DI

Interaction of Pex5p, the type 1 peroxisome targeting signal receptor, with the peroxisomal membrane proteins Pex14p and Pex13p.

J Biol Chem 2000 Feb 11;275(6) : 4127-36.

PMID: 10660573

Xu XX, Yi T, Tang B, Lambeth JD

Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2.

Oncogene 1998 Mar 26;16(12) : 1561-9.

PMID: 9569023

Zhao ZS, Manser E, Lim L

Interaction between PAK and nck: a template for Nck targets and role of PAK autophosphorylation.

Mol Cell Biol 2000 Jun;20(11) : 3906-17.

PMID: 10805734

de Mendez I, Homayounpour N, Leto TL

Specificity of p47phox SH3 domain interactions in NADPH oxidase assembly and activation.

Mol Cell Biol 1997 Apr;17(4) : 2177-85.

PMID: 9121467

This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process

  cell growth and/or maintenance

GO:0008150

  cell communication

GO:0007154

  signal transduction

GO:0007165

Cellular Component

  cytosol

GO:0005829

  plasma membrane

GO:0005886

  focal adhesion

GO:0005925

Molecular Function

  Binding

GO:0005488

  protein binding

GO:0005515

  protein domain specific binding

GO:0019904

  SH3-domain binding

GO:0017124

Instances for LIG_SH3_2

Sequence	Position	Subsequence (Click for evidence information)	PDB	Gene Name	Protein Description	Organism
NEF_HV1BR	72-77	GFPVTPQVPLRPMTYKA	-	Name=nef;	Protein Nef (Negative factor) (F-protein) (3'ORF) [Contains: C- terminal core protein].	Human immunodeficiency virus type 1 (isolate BRU/LAI group M subtype B) (HIV-1).
RPGF1_HUMAN	284-289	DNSPPPALPPKKRQSAP	1CKB	Name=RAPGEF1; Synonyms=GRF2;	Rap guanine nucleotide exchange factor 1 (Guanine nucleotide-releasing factor 2) (C3G protein) (CRK SH3-binding GNRP).	Homo sapiens (Human).
P85A_HUMAN	305-310	ERQPAPALPPKPPKPTT	-	Name=PIK3R1; Synonyms=GRB1;	Phosphatidylinositol 3-kinase regulatory subunit alpha (PI3-kinase p85 subunit alpha) (PtdIns-3-kinase p85-alpha) (PI3K).	Homo sapiens (Human).
P85A_HUMAN	308-313	PAPALPPKPPKPTTVAN	-	Name=PIK3R1; Synonyms=GRB1;	Phosphatidylinositol 3-kinase regulatory subunit alpha (PI3-kinase p85 subunit alpha) (PtdIns-3-kinase p85-alpha) (PI3K).	Homo sapiens (Human).
DYN1_HUMAN	833-838	PPPQVPSRPNRAPPGVP	-	Name=DNM1; Synonyms=DNM;	Dynamin-1 (EC 3.6.5.5).	Homo sapiens (Human).
PAK1_RAT	13-18	VQDKPPAPPMRNTSTMI	-	Name=Pak1;	Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (p21-activated kinase 1) (PAK-1) (p68-PAK) (Alpha-PAK) (Protein kinase MUK2).	Rattus norvegicus (Rat).
NCF1_HUMAN	363-368	RSKPQPAVPPRPSADLI	-	Name=NCF1; Synonyms=NOXO2, SH3PXD1A;	Neutrophil cytosol factor 1 (NCF-1) (Neutrophil NADPH oxidase factor 1) (47 kDa neutrophil oxidase factor) (p47-phox) (NCF-47K) (47 kDa autosomal chronic granulomatous disease protein) (Nox organizer 2) (Nox-organizing protein 2) (SH3 and PX domain-containing protein 1A).	Homo sapiens (Human).
PEX14_YEAST	87-92	YEAMPPTLPHRDWKDYF	-	Name=PEX14; OrderedLocusNames=YGL153W; ORFNames=G1870;	Peroxisomal membrane protein PEX14 (Peroxin-14).	Saccharomyces cerevisiae (Baker's yeast).
FAK1_MOUSE	750-755	GSDEAPPKPSRPGYPSP	-	Name=Ptk2; Synonyms=Fadk, Fak, Fak1;	Focal adhesion kinase 1 (EC 2.7.10.2) (FADK 1) (pp125FAK).	Mus musculus (Mouse).
SOS1_HUMAN	1151-1156	EVPVPPPVPPRRRPESA	-	Name=SOS1;	Son of sevenless homolog 1 (SOS-1).	Homo sapiens (Human).
SOS1_HUMAN	1152-1157	VPVPPPVPPRRRPESAP	-	Name=SOS1;	Son of sevenless homolog 1 (SOS-1).	Homo sapiens (Human).
PTN22_MOUSE	614-619	DDEIPPPLPERTPESFI	1JEG	Name=Ptpn22; Synonyms=Ptpn8;	Tyrosine-protein phosphatase non-receptor type 22 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP).	Mus musculus (Mouse).