UniProtKB - Q5TCZ1 (SPD2A_HUMAN)
Protein
SH3 and PX domain-containing protein 2A
Gene
SH3PXD2A
Organism
Homo sapiens (Human)
Status
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
- phosphatidylinositol-3,4-bisphosphate binding Source: Ensembl
- phosphatidylinositol-3-phosphate binding Source: GO_Central
- phosphatidylinositol-4,5-bisphosphate binding Source: Ensembl
- phosphatidylinositol-4-phosphate binding Source: Ensembl
- phosphatidylinositol-5-phosphate binding Source: Ensembl
- protease binding Source: Ensembl
- superoxide-generating NADPH oxidase activator activity Source: GO_Central
GO - Biological processi
- extracellular matrix organization Source: Reactome
- in utero embryonic development Source: Ensembl
- osteoclast fusion Source: CACAO
- superoxide metabolic process Source: UniProtKB
Enzyme and pathway databases
PathwayCommonsi | Q5TCZ1 |
Reactomei | R-HSA-8941237, Invadopodia formation |
Names & Taxonomyi
Protein namesi | Recommended name: SH3 and PX domain-containing protein 2AAlternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23664, SH3PXD2A |
neXtProti | NX_Q5TCZ1 |
VEuPathDBi | HostDB:ENSG00000107957.16 |
Subcellular locationi
Cytoskeleton
- podosome Source: UniProtKB
Cytosol
- cytosol Source: Reactome
Other locations
- cell junction Source: UniProtKB-KW
- cell projection Source: UniProtKB-KW
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cell junction, Cell projection, CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 42 | R → A: Loss of binding to (PtdIns(3)P) and (PtdIns(3,4)P2). 1 Publication | 1 | |
Mutagenesisi | 93 | R → A: Loss of binding to (PtdIns(3)P) and (PtdIns(3,4)P2). 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9644 |
MalaCardsi | SH3PXD2A |
OpenTargetsi | ENSG00000107957 |
Orphaneti | 3148, Malignant peripheral nerve sheath tumor |
PharmGKBi | PA134956816 |
Miscellaneous databases
Pharosi | Q5TCZ1, Tbio |
Genetic variation databases
BioMutai | SH3PXD2A |
DMDMi | 74746151 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000278488 | 1 – 1133 | SH3 and PX domain-containing protein 2AAdd BLAST | 1133 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 256 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 406 | PhosphoserineCombined sources | 1 | |
Modified residuei | 421 | PhosphoserineCombined sources | 1 | |
Modified residuei | 547 | PhosphoserineCombined sources | 1 | |
Modified residuei | 567 | PhosphoserineCombined sources | 1 | |
Modified residuei | 593 | PhosphoserineCombined sources | 1 | |
Modified residuei | 644 | PhosphoserineCombined sources | 1 | |
Modified residuei | 731 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 767 | PhosphoserineBy similarity | 1 | |
Modified residuei | 769 | PhosphoserineBy similarity | 1 | |
Modified residuei | 819 | PhosphoserineBy similarity | 1 | |
Modified residuei | 829 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1002 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1016 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1017 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1038 | PhosphoserineCombined sources | 1 |
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
PhosphoproteinProteomic databases
EPDi | Q5TCZ1 |
jPOSTi | Q5TCZ1 |
MassIVEi | Q5TCZ1 |
MaxQBi | Q5TCZ1 |
PaxDbi | Q5TCZ1 |
PeptideAtlasi | Q5TCZ1 |
PRIDEi | Q5TCZ1 |
ProteomicsDBi | 64997 [Q5TCZ1-1] 64998 [Q5TCZ1-2] 64999 [Q5TCZ1-3] |
PTM databases
iPTMneti | Q5TCZ1 |
PhosphoSitePlusi | Q5TCZ1 |
Expressioni
Tissue specificityi
Found in several cancer cell lines, particularly invasive breast carcinomas and melanomas.1 Publication
Gene expression databases
Bgeei | ENSG00000107957, Expressed in uterine cervix and 230 other tissues |
ExpressionAtlasi | Q5TCZ1, baseline and differential |
Genevisiblei | Q5TCZ1, HS |
Organism-specific databases
HPAi | ENSG00000107957, Low tissue specificity |
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 PublicationsBinary interactionsi
Hide detailsQ5TCZ1
With | #Exp. | IntAct |
---|---|---|
ADAM15 [Q13444] | 4 | EBI-2483234,EBI-77818 |
Isoform 2 [Q5TCZ1-2]
With | #Exp. | IntAct |
---|---|---|
SOS1 [Q07889] | 5 | EBI-7014859,EBI-297487 |
Dnm1 [P21575] from Rattus norvegicus. | 2 | EBI-7014859,EBI-80070 |
GO - Molecular functioni
- protease binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 115002, 93 interactors |
IntActi | Q5TCZ1, 23 interactors |
MINTi | Q5TCZ1 |
STRINGi | 9606.ENSP00000348215 |
Miscellaneous databases
RNActi | Q5TCZ1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q5TCZ1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q5TCZ1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 128 | PXPROSITE-ProRule annotationAdd BLAST | 125 | |
Domaini | 166 – 225 | SH3 1PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 266 – 325 | SH3 2PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 448 – 507 | SH3 3PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 840 – 899 | SH3 4PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 1072 – 1133 | SH3 5PROSITE-ProRule annotationAdd BLAST | 62 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 917 – 946 | Sequence analysisAdd BLAST | 30 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 634 – 724 | Ser-richAdd BLAST | 91 |
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 domainPhylogenomic databases
eggNOGi | KOG0905, Eukaryota |
GeneTreei | ENSGT00940000157732 |
HOGENOMi | CLU_013051_0_0_1 |
InParanoidi | Q5TCZ1 |
OMAi | AKDSHYM |
PhylomeDBi | Q5TCZ1 |
TreeFami | TF329347 |
Family and domain databases
CDDi | cd06888, 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 |
Gene3Di | 3.30.1520.10, 1 hit |
InterProi | View protein in InterPro IPR001683, PX_dom 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 |
PANTHERi | PTHR15706:SF22, PTHR15706:SF22, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF00018, SH3_1, 4 hits |
SMARTi | View protein in SMART SM00312, PX, 1 hit SM00326, SH3, 5 hits |
SUPFAMi | SSF50044, SSF50044, 5 hits SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit PS50002, SH3, 5 hits |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0Y507 | H0Y507_HUMAN | SH3 and PX domain-containing protei... | SH3PXD2A | 1,060 | Annotation score: |
Sequence cautioni
The sequence BAA24848 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030781 | 659 | K → Q. Corresponds to variant dbSNP:rs11818820Ensembl. | 1 | |
Natural variantiVAR_030782 | 1035 | R → Q. Corresponds to variant dbSNP:rs3781365Ensembl. | 1 | |
Natural variantiVAR_056993 | 1073 | L → P. Corresponds to variant dbSNP:rs12764700Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_023312 | 1 – 165 | Missing in isoform 2. 1 PublicationAdd BLAST | 165 | |
Alternative sequenceiVSP_023313 | 240 – 267 | Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST | 28 |
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 |
CCDSi | CCDS31278.1 [Q5TCZ1-3] |
PIRi | T00056 |
RefSeqi | NP_055446.2, NM_014631.2 [Q5TCZ1-3] XP_005270351.1, XM_005270294.4 |
Genome annotation databases
Ensembli | ENST00000355946; ENSP00000348215; ENSG00000107957 [Q5TCZ1-3] ENST00000369774; ENSP00000358789; ENSG00000107957 [Q5TCZ1-1] |
GeneIDi | 9644 |
KEGGi | hsa:9644 |
UCSCi | uc001kxj.2, human [Q5TCZ1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS31278.1 [Q5TCZ1-3] |
PIRi | T00056 |
RefSeqi | NP_055446.2, NM_014631.2 [Q5TCZ1-3] XP_005270351.1, XM_005270294.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2DNU | NMR | - | A | 268-325 | [»] | |
2EGA | NMR | - | A | 168-224 | [»] | |
2EGC | NMR | - | A | 1072-1133 | [»] | |
2EKH | NMR | - | A | 842-908 | [»] | |
SMRi | Q5TCZ1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115002, 93 interactors |
IntActi | Q5TCZ1, 23 interactors |
MINTi | Q5TCZ1 |
STRINGi | 9606.ENSP00000348215 |
PTM databases
iPTMneti | Q5TCZ1 |
PhosphoSitePlusi | Q5TCZ1 |
Genetic variation databases
BioMutai | SH3PXD2A |
DMDMi | 74746151 |
Proteomic databases
EPDi | Q5TCZ1 |
jPOSTi | Q5TCZ1 |
MassIVEi | Q5TCZ1 |
MaxQBi | Q5TCZ1 |
PaxDbi | Q5TCZ1 |
PeptideAtlasi | Q5TCZ1 |
PRIDEi | Q5TCZ1 |
ProteomicsDBi | 64997 [Q5TCZ1-1] 64998 [Q5TCZ1-2] 64999 [Q5TCZ1-3] |
Protocols and materials databases
ABCDi | Q5TCZ1, 9 sequenced antibodies |
Antibodypediai | 46067, 153 antibodies |
DNASUi | 9644 |
Genome annotation databases
Ensembli | ENST00000355946; ENSP00000348215; ENSG00000107957 [Q5TCZ1-3] ENST00000369774; ENSP00000358789; ENSG00000107957 [Q5TCZ1-1] |
GeneIDi | 9644 |
KEGGi | hsa:9644 |
UCSCi | uc001kxj.2, human [Q5TCZ1-1] |
Organism-specific databases
CTDi | 9644 |
DisGeNETi | 9644 |
GeneCardsi | SH3PXD2A |
HGNCi | HGNC:23664, SH3PXD2A |
HPAi | ENSG00000107957, Low tissue specificity |
MalaCardsi | SH3PXD2A |
neXtProti | NX_Q5TCZ1 |
OpenTargetsi | ENSG00000107957 |
Orphaneti | 3148, Malignant peripheral nerve sheath tumor |
PharmGKBi | PA134956816 |
VEuPathDBi | HostDB:ENSG00000107957.16 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0905, Eukaryota |
GeneTreei | ENSGT00940000157732 |
HOGENOMi | CLU_013051_0_0_1 |
InParanoidi | Q5TCZ1 |
OMAi | AKDSHYM |
PhylomeDBi | Q5TCZ1 |
TreeFami | TF329347 |
Enzyme and pathway databases
PathwayCommonsi | Q5TCZ1 |
Reactomei | R-HSA-8941237, Invadopodia formation |
Miscellaneous databases
BioGRID-ORCSi | 9644, 11 hits in 874 CRISPR screens |
ChiTaRSi | SH3PXD2A, human |
EvolutionaryTracei | Q5TCZ1 |
GeneWikii | SH3PXD2A |
GenomeRNAii | 9644 |
Pharosi | Q5TCZ1, Tbio |
PROi | PR:Q5TCZ1 |
RNActi | Q5TCZ1, protein |
Gene expression databases
Bgeei | ENSG00000107957, Expressed in uterine cervix and 230 other tissues |
ExpressionAtlasi | Q5TCZ1, baseline and differential |
Genevisiblei | Q5TCZ1, HS |
Family and domain databases
CDDi | cd06888, 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 |
Gene3Di | 3.30.1520.10, 1 hit |
InterProi | View protein in InterPro IPR001683, PX_dom 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 |
PANTHERi | PTHR15706:SF22, PTHR15706:SF22, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF00018, SH3_1, 4 hits |
SMARTi | View protein in SMART SM00312, PX, 1 hit SM00326, SH3, 5 hits |
SUPFAMi | SSF50044, SSF50044, 5 hits SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit PS50002, SH3, 5 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SPD2A_HUMAN | |
Accessioni | Q5TCZ1Primary (citable) accession number: Q5TCZ1 Secondary accession number(s): D3DR98 Q5TDQ8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 20, 2007 |
Last sequence update: | December 21, 2004 | |
Last modified: | February 10, 2021 | |
This is version 153 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human variants curated from literature reports
Index of human variants curated from literature reports - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with genetic variants
List of human entries with genetic variants