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Protein

SH3 and PX domain-containing protein 2A

Gene

Sh3pxd2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-MMU-8941237. Invadopodia formation.

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 and PX domain-containing protein 2A
Alternative name(s):
Five SH3 domain-containing protein
SH3 multiple domains protein 1
Tyrosine kinase substrate with five SH3 domains
Gene namesi
Name:Sh3pxd2a
Synonyms:Fish, Sh3md1, Tks5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1298393. Sh3pxd2a.

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

Pathology & Biotechi

Disruption phenotypei

Shows significant decrease in total cellular reactive oxygen species (ROS) and in podosome formation.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002784891 – 1124SH3 and PX domain-containing protein 2AAdd BLAST1124

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei256PhosphothreonineCombined sources1
Modified residuei405PhosphoserineBy similarity1
Modified residuei420PhosphoserineBy similarity1
Modified residuei546PhosphoserineCombined sources1
Modified residuei566PhosphoserineBy similarity1
Modified residuei592PhosphoserineBy similarity1
Modified residuei643PhosphoserineCombined sources1
Modified residuei728PhosphothreonineBy similarity1
Modified residuei764PhosphoserineCombined sources1
Modified residuei766PhosphoserineCombined sources1
Modified residuei812PhosphoserineCombined sources1
Modified residuei822PhosphothreonineCombined sources1
Modified residuei993PhosphoserineCombined sources1
Modified residuei1007PhosphoserineCombined sources1
Modified residuei1008PhosphoserineCombined sources1
Modified residuei1029PhosphoserineCombined sources1

Post-translational modificationi

Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory role in the protein localization. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region. Phosphorylated on serine upon DNA damage, probably by ATM or ATR (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO89032.
PaxDbiO89032.
PeptideAtlasiO89032.
PRIDEiO89032.

PTM databases

iPTMnetiO89032.
PhosphoSitePlusiO89032.

Expressioni

Tissue specificityi

Widely expressed. Not found in the spleen and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000053617.
CleanExiMM_SH3PXD2A.
GenevisibleiO89032. MM.

Interactioni

Subunit structurei

Interacts with ADAM12, ADAM15 and ADAM19 (By similarity). Interacts with NOXO1 (By similarity). Interacts (via SH3 domains) with NOXA1; the interaction is direct (By similarity). Interacts (via N-terminus) with CYBA. Interacts with FASLG (By similarity).By similarity

Protein-protein interaction databases

BioGridi199678. 1 interactor.
IntActiO89032. 2 interactors.
STRINGi10090.ENSMUSP00000080325.

Structurei

3D structure databases

ProteinModelPortaliO89032.
SMRiO89032.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 128PXPROSITE-ProRule annotationAdd BLAST125
Domaini166 – 225SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini266 – 325SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini447 – 506SH3 3PROSITE-ProRule annotationAdd BLAST60
Domaini833 – 892SH3 4PROSITE-ProRule annotationAdd BLAST60
Domaini1063 – 1124SH3 5PROSITE-ProRule annotationAdd BLAST62

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili907 – 937Sequence analysisAdd BLAST31

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi633 – 709Ser-richAdd BLAST77

Domaini

The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns4P), phosphatidylinositol 5-phosphate (PtdIns5P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity).By similarity
The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19.By similarity

Sequence similaritiesi

Belongs to the SH3PXD2 family.Curated

Keywords - Domaini

Coiled coil, Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG4773. Eukaryota.
ENOG410YBFF. LUCA.
GeneTreeiENSGT00530000063010.
HOGENOMiHOG000154376.
HOVERGENiHBG089589.
InParanoidiO89032.
OMAiNGWWYCQ.
OrthoDBiEOG091G00YX.
TreeFamiTF329347.

Family and domain databases

CDDicd12074. SH3_Tks5_1. 1 hit.
cd12077. SH3_Tks5_2. 1 hit.
cd12079. SH3_Tks5_3. 1 hit.
cd12019. SH3_Tks5_4. 1 hit.
cd12020. SH3_Tks5_5. 1 hit.
Gene3Di3.30.1520.10. 1 hit.
InterProiView protein in InterPro
IPR001683. Phox.
IPR036871. PX_dom_sf.
IPR036028. SH3-like_dom_sf.
IPR001452. SH3_domain.
IPR034917. SH3PXD2A.
IPR035450. SH3PXD2A_SH3_1.
IPR035452. SH3PXD2A_SH3_2.
IPR035449. SH3PXD2A_SH3_3.
IPR035453. SH3PXD2A_SH3_4.
IPR035454. SH3PXD2A_SH3_5.
PANTHERiPTHR15706:SF7. PTHR15706:SF7. 3 hits.
PfamiView protein in Pfam
PF00787. PX. 1 hit.
PF00018. SH3_1. 4 hits.
SMARTiView protein in SMART
SM00312. PX. 1 hit.
SM00326. SH3. 5 hits.
SUPFAMiSSF50044. SSF50044. 5 hits.
SSF64268. SSF64268. 1 hit.
PROSITEiView protein in PROSITE
PS50195. PX. 1 hit.
PS50002. SH3. 5 hits.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O89032-1) [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
MLAYCVQDAT VVDVEKRRSP SKHYVYIINV TWSDSTSQTI YRRYSKFFDL
60 70 80 90 100
QMQLLDKFPI EGGQKDPKQR IIPFLPGKIL FRRSHIRDVA VKRLKPIDEY
110 120 130 140 150
CRALVRLPPH ISQCDEVFRF FEARPEDVNP PKEDYGSSKR KSVWLSSWAE
160 170 180 190 200
SPKKDVTGAD TNAEPMILEQ YVVVSNYKKQ ENSELSLQAG EVVDVIEKNE
210 220 230 240 250
SGWWFVSTSE EQGWVPATYL EAQNGTRDDS DINTSKTGEV SKRRKAHLRR
260 270 280 290 300
LDRRWTLGGM VNRQHSREEK YVTVQPYTSQ SKDEIGFEKG VTVEVIRKNL
310 320 330 340 350
EGWWYIRYLG KEGWAPASYL KKAKDDLPTR KKNLAGPVEI IGNIMEISNL
360 370 380 390 400
LNKKASGDKE APAEGEGSEA PITKKEISLP ILCNASNGSA LAIPERTTSK
410 420 430 440 450
LAQGSPAVAR IAPQRAQISS PNLRTRPPPR RESSLGFQLP KPPEPPSVEV
460 470 480 490 500
EYYTIAEFQS CISDGISFRG GQKAEVIDKN SGGWWYVQIG EKEGWAPASY
510 520 530 540 550
IDKRKKPNLS RRTSTLTRPK VPPPAPPSKP KEAEENPVGA CESQGSPLKV
560 570 580 590 600
KYEEPEYDVP AFGFDSEPEM NEEPSGDRGS GDKHPAQPRR ISPASSLQRA
610 620 630 640 650
HFKVGESSED VALEEETIYE NEGFRPYTED TLSARGSSGD SDSPGSSSLS
660 670 680 690 700
LAVKNSPKSD SPKSSSLLKL KAEKNAQAEL GKNQSNISFS SSVTISTTCS
710 720 730 740 750
SSSSSSSLSK NNGDLKPRSA SDAGIRDTPK VGTKKDPDVK AGLASCARAK
760 770 780 790 800
PSVRPKPVLN RAESQSQEKM DISSLRRQLR PTGQLRGGLK GSRSEDSELP
810 820 830 840 850
PQMASEGSRR GSADIIPLTA TTPPCVPKKE WEGQGATYVT CSAYQKVQDS
860 870 880 890 900
EISFPEGAEV HVLEKAESGW WYVRFGELEG WAPSHYLVAE ENQQPDTASK
910 920 930 940 950
EGDTGKSSQN EGKSDSLEKI EKRVQALNTV NQSKRATPPI PSKPPGGFGK
960 970 980 990 1000
TSGTVAVKMR NGVRQVAVRP QSVFVSPPPK DNNLSCALRR NESLTATDSL
1010 1020 1030 1040 1050
RGVRRNSSFS TARSAAAEAK GRLAERAASQ GSESPLLPTQ RKGIPVSPVR
1060 1070 1080 1090 1100
PKPIEKSQFI HNNLKDVYIS IADYEGDEET AGFQEGVSME VLEKNPNGWW
1110 1120
YCQILDEVKP FKGWVPSNYL EKKN
Length:1,124
Mass (Da):124,201
Last modified:July 27, 2011 - v2
Checksum:i2A06118D1CE7C567
GO
Isoform 2 (identifier: O89032-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     240-267: Missing.

Show »
Length:1,096
Mass (Da):120,748
Checksum:iC08302C4647E6B19
GO
Isoform 3 (identifier: O89032-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     143-157: Missing.
     240-267: Missing.

Show »
Length:1,081
Mass (Da):119,033
Checksum:iF80206E3CDEB6C1A
GO

Sequence cautioni

The sequence AAI18023 differs from that shown. Reason: Frameshift at position 786.Curated
The sequence AAI18023 differs from that shown. Reason: Frameshift at position 788.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti867E → V in CAA07416 (PubMed:9687503).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023314143 – 157Missing in isoform 3. CuratedAdd BLAST15
Alternative sequenceiVSP_023315240 – 267Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ007012 mRNA. Translation: CAA07416.1.
AC132268 Genomic DNA. No translation available.
AC132288 Genomic DNA. No translation available.
BC118022 mRNA. Translation: AAI18023.1. Frameshift.
CCDSiCCDS29891.1. [O89032-1]
CCDS50464.1. [O89032-2]
RefSeqiNP_001158189.1. NM_001164717.1. [O89032-2]
NP_032044.2. NM_008018.4. [O89032-1]
UniGeneiMm.127560.

Genome annotation databases

EnsembliENSMUST00000081619; ENSMUSP00000080325; ENSMUSG00000053617. [O89032-1]
ENSMUST00000111800; ENSMUSP00000107430; ENSMUSG00000053617. [O89032-2]
GeneIDi14218.
KEGGimmu:14218.
UCSCiuc008huy.2. mouse. [O89032-1]
uc008hva.2. mouse. [O89032-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSPD2A_MOUSE
AccessioniPrimary (citable) accession number: O89032
Secondary accession number(s): E9QKJ2, Q148Q8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: July 27, 2011
Last modified: November 22, 2017
This is version 136 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families