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Protein

SH3 domain-binding protein 1

Gene

SH3BP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin-plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563).4 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • semaphorin receptor binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

  • actin filament organization Source: UniProtKB
  • cell junction assembly Source: UniProtKB
  • cell migration Source: UniProtKB
  • establishment of epithelial cell apical/basal polarity Source: UniProtKB
  • filopodium assembly Source: Ensembl
  • negative regulation of small GTPase mediated signal transduction Source: UniProtKB
  • phagocytosis, engulfment Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of actin filament depolymerization Source: UniProtKB
  • regulation of blood vessel endothelial cell migration Source: UniProtKB
  • semaphorin-plexin signaling pathway Source: UniProtKB

Keywordsi

Molecular functionGTPase activation
Biological processPhagocytosis

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 domain-binding protein 1Imported
Gene namesi
Name:SH3BP1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100092.20.
HGNCiHGNC:10824. SH3BP1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Nucleus, Tight junction

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi312R → A: Probable loss of the GTPase activator activity. Loss of function in cell migration. 1 Publication1

Organism-specific databases

DisGeNETi23616.
OpenTargetsiENSG00000100092.
PharmGKBiPA35732.

Polymorphism and mutation databases

BioMutaiSH3BP1.
DMDMi51338841.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000567231 – 701SH3 domain-binding protein 1Add BLAST701

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei175PhosphoserineCombined sources1
Modified residuei262PhosphoserineCombined sources1
Modified residuei264PhosphoserineCombined sources1
Modified residuei544PhosphoserineCombined sources1
Modified residuei550PhosphoserineCombined sources1
Modified residuei601PhosphothreonineBy similarity1
Modified residuei626PhosphothreonineCombined sources1
Modified residuei641PhosphoserineBy similarity1
Modified residuei653PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y3L3.
PaxDbiQ9Y3L3.
PeptideAtlasiQ9Y3L3.
PRIDEiQ9Y3L3.

PTM databases

iPTMnetiQ9Y3L3.
PhosphoSitePlusiQ9Y3L3.

Expressioni

Gene expression databases

BgeeiENSG00000100092.
CleanExiHS_SH3BP1.
ExpressionAtlasiQ9Y3L3. baseline and differential.
GenevisibleiQ9Y3L3. HS.

Organism-specific databases

HPAiHPA000757.

Interactioni

Subunit structurei

Interacts with RAC1 (By similarity). Interacts with the exocyst via EXOC4 and EXOC8; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells (PubMed:21658605). Interacts with CD2AP and CGNL1; probably part of a complex at cell junctions (PubMed:22891260). Interacts with CAPZA1; recruits CAPZA1 to forming cell junctions (PubMed:22891260). May interact with AFDN (PubMed:22891260). Interacts with PLXND1; they dissociate upon SEMA3E binding to PLXND1 allowing SH3BP1 to transduce downstream signal through RAC1 inactivation (PubMed:24841563). Interacts with ABL1, GRB2 and SRC (via SH3 domain) (By similarity).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • semaphorin receptor binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi117149. 20 interactors.
IntActiQ9Y3L3. 8 interactors.
MINTiMINT-2823406.
STRINGi9606.ENSP00000350018.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J9DX-ray1.50B/D/F616-625[»]
4J9FX-ray1.09B/D/F616-625[»]
ProteinModelPortaliQ9Y3L3.
SMRiQ9Y3L3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 262BARPROSITE-ProRule annotationAdd BLAST246
Domaini276 – 469Rho-GAPPROSITE-ProRule annotationAdd BLAST194

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 275Interaction with CGNL11 PublicationAdd BLAST275
Regioni470 – 701Interaction with CD2AP1 PublicationAdd BLAST232

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi616 – 625SH3-bindingBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi500 – 693Pro-richPROSITE-ProRule annotationAdd BLAST194

Domaini

The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration (PubMed:21658605). It also mediates the interaction with PLXND1 (PubMed:24841563).2 Publications

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG4270. Eukaryota.
ENOG410XRR2. LUCA.
GeneTreeiENSGT00760000118863.
HOGENOMiHOG000179193.
HOVERGENiHBG000015.
InParanoidiQ9Y3L3.
KOiK20652.
OMAiAGALKCY.
OrthoDBiEOG091G02YP.
PhylomeDBiQ9Y3L3.
TreeFamiTF316514.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
1.20.1270.60. 1 hit.
InterProiView protein in InterPro
IPR027267. AH/BAR_dom_sf.
IPR004148. BAR_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
PfamiView protein in Pfam
PF03114. BAR. 1 hit.
PF00620. RhoGAP. 1 hit.
SMARTiView protein in SMART
SM00721. BAR. 1 hit.
SM00324. RhoGAP. 1 hit.
SUPFAMiSSF103657. SSF103657. 2 hits.
SSF48350. SSF48350. 1 hit.
PROSITEiView protein in PROSITE
PS51021. BAR. 1 hit.
PS50238. RHOGAP. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q9Y3L3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MMKRQLHRMR QLAQTGSLGR TPETAEFLGE DLLQVEQRLE PAKRAAHNIH
60 70 80 90 100
KRLQACLQGQ SGADMDKRVK KLPLMALSTT MAESFKELDP DSSMGKALEM
110 120 130 140 150
SCAIQNQLAR ILAEFEMTLE RDVLQPLSRL SEEELPAILK HKKSLQKLVS
160 170 180 190 200
DWNTLKSRLS QATKNSGSSQ GLGGSPGSHS HTTMANKVET LKEEEEELKR
210 220 230 240 250
KVEQCRDEYL ADLYHFVTKE DSYANYFIRL LEIQADYHRR SLSSLDTALA
260 270 280 290 300
ELRENHGQAD HSPSMTATHF PRVYGVSLAT HLQELGREIA LPIEACVMML
310 320 330 340 350
LSEGMKEEGL FRLAAGASVL KRLKQTMASD PHSLEEFCSD PHAVAGALKS
360 370 380 390 400
YLRELPEPLM TFDLYDDWMR AASLKEPGAR LQALQEVCSR LPPENLSNLR
410 420 430 440 450
YLMKFLARLA EEQEVNKMTP SNIAIVLGPN LLWPPEKEGD QAQLDAASVS
460 470 480 490 500
SIQVVGVVEA LIQSADTLFP GDINFNVSGL FSAVTLQDTV SDRLASEELP
510 520 530 540 550
STAVPTPATT PAPAPAPAPA PAPALASAAT KERTESEVPP RPASPKVTRS
560 570 580 590 600
PPETAAPVED MARRTKRPAP ARPTMPPPQV SGSRSSPPAP PLPPGSGSPG
610 620 630 640 650
TPQALPRRLV GSSLRAPTVP PPLPPTPPQP ARRQSRRSPA SPSPASPGPA
660 670 680 690 700
SPSPVSLSNP AQVDLGAATA EGGAPEAISG VPTPPAIPPQ PRPRSLASET

N
Length:701
Mass (Da):75,713
Last modified:August 16, 2004 - v3
Checksum:i877D144E81F0F974
GO
Isoform 2 (identifier: Q9Y3L3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     440-452: DQAQLDAASVSSI → TEPARELGSQTLC
     453-701: Missing.

Show »
Length:452
Mass (Da):50,820
Checksum:iA2C33CFBB2532FD0
GO
Isoform Long BGIN1 Publication (identifier: Q6ZT62-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q6ZT62.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Based on a naturally occurring readthrough transcript which produces a SH3BP1-PDXP fusion protein. Translation initiation occurs at a non-canonical CUG codon.1 Publication
Length:677
Mass (Da):73,599
GO
Isoform Short BGIN1 Publication (identifier: Q6ZT62-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q6ZT62.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation at Met-73 of isoform long BGIN.1 Publication
Length:605
Mass (Da):66,180
GO

Sequence cautioni

The sequence AAH08282 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC85842 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC85842 differs from that shown. Reason: Erroneous termination at position 56. Translated as Cys.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033450511P → L. Corresponds to variant dbSNP:rs929038Ensembl.1
Natural variantiVAR_033451656S → F. Corresponds to variant dbSNP:rs2269548Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011373440 – 452DQAQL…SVSSI → TEPARELGSQTLC in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_011374453 – 701Missing in isoform 2. 1 PublicationAdd BLAST249

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR456576 mRNA. Translation: CAG30462.1.
AK124370 mRNA. Translation: BAC85842.1. Sequence problems.
Z83844 Genomic DNA. No translation available.
BC008282 mRNA. Translation: AAH08282.1. Different initiation.
AL157480 mRNA. Translation: CAB75671.2.
CCDSiCCDS13952.2. [Q9Y3L3-1]
PIRiT46916.
RefSeqiNP_061830.3. NM_018957.3. [Q9Y3L3-1]
UniGeneiHs.601143.

Genome annotation databases

EnsembliENST00000357436; ENSP00000350018; ENSG00000100092. [Q9Y3L3-1]
ENST00000417536; ENSP00000411979; ENSG00000100092. [Q9Y3L3-2]
GeneIDi23616.
KEGGihsa:23616.
UCSCiuc003atg.2. human. [Q9Y3L3-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry namei3BP1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y3L3
Secondary accession number(s): Q5R3N0
, Q6IBZ2, Q6ZVL9, Q96HQ5, Q9NSQ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: August 16, 2004
Last modified: November 22, 2017
This is version 160 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references