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Protein

SH3 and PX domain-containing protein 2A

Gene

SH3PXD2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.5 Publications

GO - Molecular functioni

GO - Biological processi

  • extracellular matrix organization Source: Reactome
  • osteoclast fusion Source: CACAO
  • superoxide metabolic process Source: UniProtKB

Enzyme and pathway databases

ReactomeiR-HSA-8941237 Invadopodia formation

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 and PX domain-containing protein 2A
Alternative name(s):
Adapter protein TKS5
Five SH3 domain-containing protein
SH3 multiple domains protein 1
Tyrosine kinase substrate with five SH3 domains
Gene namesi
Name:SH3PXD2A
Synonyms:FISH, KIAA0418, SH3MD1, TKS5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000107957.16
HGNCiHGNC:23664 SH3PXD2A
neXtProtiNX_Q5TCZ1

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42R → A: Loss of binding to (PtdIns(3)P) and (PtdIns(3,4)P2). 1 Publication1
Mutagenesisi93R → A: Loss of binding to (PtdIns(3)P) and (PtdIns(3,4)P2). 1 Publication1

Organism-specific databases

DisGeNETi9644
MalaCardsiSH3PXD2A
OpenTargetsiENSG00000107957
Orphaneti3148 Malignant peripheral nerve sheath tumor
PharmGKBiPA134956816

Polymorphism and mutation databases

BioMutaiSH3PXD2A
DMDMi74746151

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002784881 – 1133SH3 and PX domain-containing protein 2AAdd BLAST1133

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei256PhosphothreonineBy similarity1
Modified residuei406PhosphoserineCombined sources1
Modified residuei421PhosphoserineCombined sources1
Modified residuei547PhosphoserineCombined sources1
Modified residuei567PhosphoserineCombined sources1
Modified residuei593PhosphoserineCombined sources1
Modified residuei644PhosphoserineCombined sources1
Modified residuei731PhosphothreonineCombined sources1
Modified residuei767PhosphoserineBy similarity1
Modified residuei769PhosphoserineBy similarity1
Modified residuei819PhosphoserineBy similarity1
Modified residuei829PhosphothreonineBy similarity1
Modified residuei1002PhosphoserineCombined sources1
Modified residuei1016PhosphoserineCombined sources1
Modified residuei1017PhosphoserineCombined sources1
Modified residuei1038PhosphoserineCombined 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.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5TCZ1
MaxQBiQ5TCZ1
PaxDbiQ5TCZ1
PeptideAtlasiQ5TCZ1
PRIDEiQ5TCZ1
ProteomicsDBi64997
64998 [Q5TCZ1-2]
64999 [Q5TCZ1-3]

PTM databases

iPTMnetiQ5TCZ1
PhosphoSitePlusiQ5TCZ1

Expressioni

Tissue specificityi

Found in several cancer cell lines, particularly invasive breast carcinomas and melanomas.1 Publication

Gene expression databases

BgeeiENSG00000107957 Expressed in 219 organ(s), highest expression level in uterine cervix
CleanExiHS_SH3PXD2A
ExpressionAtlasiQ5TCZ1 baseline and differential
GenevisibleiQ5TCZ1 HS

Organism-specific databases

HPAiHPA037922
HPA037923

Interactioni

Subunit structurei

Interacts (via N-terminus) with CYBA (By similarity). Interacts with ADAM12, ADAM15 and ADAM19. Interacts with NOXO1. Interacts (via SH3 domains) with NOXA1. Interacts with FASLG.By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115002, 90 interactors
IntActiQ5TCZ1, 14 interactors
MINTiQ5TCZ1
STRINGi9606.ENSP00000348215

Structurei

Secondary structure

11133
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ5TCZ1
SMRiQ5TCZ1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5TCZ1

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
Domaini448 – 507SH3 3PROSITE-ProRule annotationAdd BLAST60
Domaini840 – 899SH3 4PROSITE-ProRule annotationAdd BLAST60
Domaini1072 – 1133SH3 5PROSITE-ProRule annotationAdd BLAST62

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili917 – 946Sequence analysisAdd BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi634 – 724Ser-richAdd BLAST91

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 ADAM19.2 Publications

Sequence similaritiesi

Belongs to the SH3PXD2 family.Curated

Keywords - Domaini

Coiled coil, Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG4773 Eukaryota
ENOG410YBFF LUCA
GeneTreeiENSGT00530000063010
HOGENOMiHOG000154376
HOVERGENiHBG089589
InParanoidiQ5TCZ1
OMAiPTQRNGI
OrthoDBiEOG091G00YX
PhylomeDBiQ5TCZ1
TreeFamiTF329347

Family and domain databases

CDDicd06888 PX_FISH, 1 hit
cd12074 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
IPR037961 SH3PXD2_PX
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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q5TCZ1-1) [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 VVDVEKRRNP 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 ATAEPMILEQ 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 TPPAEGEGHE APIAKKEISL PILCNASNGS AVGVPDRTVS
410 420 430 440 450
RLAQGSPAVA RIAPQRAQIS SPNLRTRPPP RRESSLGFQL PKPPEPPSVE
460 470 480 490 500
VEYYTIAEFQ SCISDGISFR GGQKAEVIDK NSGGWWYVQI GEKEGWAPAS
510 520 530 540 550
YIDKRKKPNL SRRTSTLTRP KVPPPAPPSK PKEAEEGPTG ASESQDSPRK
560 570 580 590 600
LKYEEPEYDI PAFGFDSEPE LSEEPVEDRA SGERRPAQPH RPSPASSLQR
610 620 630 640 650
ARFKVGESSE DVALEEETIY ENEGFRPYAE DTLSARGSSG DSDSPGSSSL
660 670 680 690 700
SLTRKNSPKS GSPKSSSLLK LKAEKNAQAE MGKNHSSASF SSSITINTTC
710 720 730 740 750
CSSSSSSSSS LSKTSGDLKP RSASDAGIRG TPKVRAKKDA DANAGLTSCP
760 770 780 790 800
RAKPSVRPKP FLNRAESQSQ EKMDISTLRR QLRPTGQLRG GLKGSKSEDS
810 820 830 840 850
ELPPQTASEA PSEGSRRSSS DLITLPATTP PCPTKKEWEG PATSYMTCSA
860 870 880 890 900
YQKVQDSEIS FPAGVEVQVL EKQESGWWYV RFGELEGWAP SHYLVLDENE
910 920 930 940 950
QPDPSGKELD TVPAKGRQNE GKSDSLEKIE RRVQALNTVN QSKKATPPIP
960 970 980 990 1000
SKPPGGFGKT SGTPAVKMRN GVRQVAVRPQ SVFVSPPPKD NNLSCALRRN
1010 1020 1030 1040 1050
ESLTATDGLR GVRRNSSFST ARSAAAEAKG RLAERAASQG SDSPLLPAQR
1060 1070 1080 1090 1100
NSIPVSPVRP KPIEKSQFIH NNLKDVYVSI ADYEGDEETA GFQEGVSMEV
1110 1120 1130
LERNPNGWWY CQILDGVKPF KGWVPSNYLE KKN
Length:1,133
Mass (Da):125,289
Last modified:December 21, 2004 - v1
Checksum:iD485F49E9192359C
GO
Isoform 2 (identifier: Q5TCZ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-165: Missing.
     240-267: Missing.

Show »
Length:940
Mass (Da):102,618
Checksum:i1CA24D7BC03B8AC3
GO
Isoform 3 (identifier: Q5TCZ1-3) [UniParc]FASTAAdd to basket

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

Note: Gene prediction based on similarity to mouse ortholog and partial transcript data.
Show »
Length:1,105
Mass (Da):121,836
Checksum:i384ECB9785EE3FAB
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y507H0Y507_HUMAN
SH3 and PX domain-containing protei...
SH3PXD2A
1,060Annotation score:

Sequence cautioni

The sequence BAA24848 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030781659K → Q. Corresponds to variant dbSNP:rs11818820Ensembl.1
Natural variantiVAR_0307821035R → Q. Corresponds to variant dbSNP:rs3781365Ensembl.1
Natural variantiVAR_0569931073L → P. Corresponds to variant dbSNP:rs12764700Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0233121 – 165Missing in isoform 2. 1 PublicationAdd BLAST165
Alternative sequenceiVSP_023313240 – 267Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007878 mRNA Translation: BAA24848.2 Different initiation.
AL121929 Genomic DNA No translation available.
AL133355 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49623.1
CH471066 Genomic DNA Translation: EAW49624.1
CCDSiCCDS31278.1 [Q5TCZ1-3]
PIRiT00056
RefSeqiNP_055446.2, NM_014631.2 [Q5TCZ1-3]
XP_005270351.1, XM_005270294.4
UniGeneiHs.678727

Genome annotation databases

EnsembliENST00000355946; ENSP00000348215; ENSG00000107957 [Q5TCZ1-3]
ENST00000369774; ENSP00000358789; ENSG00000107957 [Q5TCZ1-1]
GeneIDi9644
KEGGihsa:9644
UCSCiuc001kxj.2 human [Q5TCZ1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007878 mRNA Translation: BAA24848.2 Different initiation.
AL121929 Genomic DNA No translation available.
AL133355 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49623.1
CH471066 Genomic DNA Translation: EAW49624.1
CCDSiCCDS31278.1 [Q5TCZ1-3]
PIRiT00056
RefSeqiNP_055446.2, NM_014631.2 [Q5TCZ1-3]
XP_005270351.1, XM_005270294.4
UniGeneiHs.678727

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DNUNMR-A268-325[»]
2EGANMR-A168-224[»]
2EGCNMR-A1072-1133[»]
2EKHNMR-A842-908[»]
ProteinModelPortaliQ5TCZ1
SMRiQ5TCZ1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115002, 90 interactors
IntActiQ5TCZ1, 14 interactors
MINTiQ5TCZ1
STRINGi9606.ENSP00000348215

PTM databases

iPTMnetiQ5TCZ1
PhosphoSitePlusiQ5TCZ1

Polymorphism and mutation databases

BioMutaiSH3PXD2A
DMDMi74746151

Proteomic databases

EPDiQ5TCZ1
MaxQBiQ5TCZ1
PaxDbiQ5TCZ1
PeptideAtlasiQ5TCZ1
PRIDEiQ5TCZ1
ProteomicsDBi64997
64998 [Q5TCZ1-2]
64999 [Q5TCZ1-3]

Protocols and materials databases

DNASUi9644
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355946; ENSP00000348215; ENSG00000107957 [Q5TCZ1-3]
ENST00000369774; ENSP00000358789; ENSG00000107957 [Q5TCZ1-1]
GeneIDi9644
KEGGihsa:9644
UCSCiuc001kxj.2 human [Q5TCZ1-1]

Organism-specific databases

CTDi9644
DisGeNETi9644
EuPathDBiHostDB:ENSG00000107957.16
GeneCardsiSH3PXD2A
HGNCiHGNC:23664 SH3PXD2A
HPAiHPA037922
HPA037923
MalaCardsiSH3PXD2A
neXtProtiNX_Q5TCZ1
OpenTargetsiENSG00000107957
Orphaneti3148 Malignant peripheral nerve sheath tumor
PharmGKBiPA134956816
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4773 Eukaryota
ENOG410YBFF LUCA
GeneTreeiENSGT00530000063010
HOGENOMiHOG000154376
HOVERGENiHBG089589
InParanoidiQ5TCZ1
OMAiPTQRNGI
OrthoDBiEOG091G00YX
PhylomeDBiQ5TCZ1
TreeFamiTF329347

Enzyme and pathway databases

ReactomeiR-HSA-8941237 Invadopodia formation

Miscellaneous databases

ChiTaRSiSH3PXD2A human
EvolutionaryTraceiQ5TCZ1
GeneWikiiSH3PXD2A
GenomeRNAii9644
PROiPR:Q5TCZ1

Gene expression databases

BgeeiENSG00000107957 Expressed in 219 organ(s), highest expression level in uterine cervix
CleanExiHS_SH3PXD2A
ExpressionAtlasiQ5TCZ1 baseline and differential
GenevisibleiQ5TCZ1 HS

Family and domain databases

CDDicd06888 PX_FISH, 1 hit
cd12074 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
IPR037961 SH3PXD2_PX
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
ProtoNetiSearch...

Entry informationi

Entry nameiSPD2A_HUMAN
AccessioniPrimary (citable) accession number: Q5TCZ1
Secondary accession number(s): D3DR98
, O43302, Q5TCZ2, Q5TDQ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: December 21, 2004
Last modified: November 7, 2018
This is version 137 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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