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Protein

SH3 and PX domain-containing protein 2A

Gene

SH3PXD2A

Organism
Homo sapiens (Human)
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 beta-amyloid peptide.5 Publications

GO - Molecular functioni

GO - Biological processi

  • osteoclast fusion Source: CACAO
  • oxidation-reduction process Source: GO_Central
  • podosome assembly Source: GO_Central
  • superoxide metabolic process Source: UniProtKB
Complete GO annotation...

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

HGNCiHGNC:23664. SH3PXD2A.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cell projection Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB-SubCell
  • podosome Source: UniProtKB
Complete GO annotation...

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.
OpenTargetsiENSG00000107957.
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.

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.
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

WithEntry#Exp.IntActNotes
ADAM15Q134442EBI-2483234,EBI-77818
Dnm1P215752EBI-7014859,EBI-80070From a different organism.
SOS1Q078895EBI-7014859,EBI-297487

Protein-protein interaction databases

BioGridi115002. 17 interactors.
IntActiQ5TCZ1. 13 interactors.
MINTiMINT-2792114.
STRINGi9606.ENSP00000348215.

Structurei

Secondary structure

11133
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi181 – 184Combined sources4
Beta strandi194 – 198Combined sources5
Beta strandi202 – 207Combined sources6
Beta strandi212 – 216Combined sources5
Helixi217 – 219Combined sources3
Beta strandi221 – 223Combined sources3
Beta strandi268 – 272Combined sources5
Beta strandi292 – 295Combined sources4
Beta strandi300 – 308Combined sources9
Beta strandi311 – 316Combined sources6
Helixi317 – 319Combined sources3
Beta strandi843 – 847Combined sources5
Beta strandi866 – 872Combined sources7
Beta strandi876 – 882Combined sources7
Beta strandi885 – 890Combined sources6
Turni891 – 893Combined sources3
Beta strandi1075 – 1079Combined sources5
Beta strandi1087 – 1089Combined sources3
Beta strandi1097 – 1100Combined sources4
Beta strandi1107 – 1113Combined sources7
Beta strandi1116 – 1118Combined sources3
Beta strandi1120 – 1125Combined sources6
Helixi1126 – 1128Combined sources3
Beta strandi1129 – 1131Combined sources3

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...

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
Domaini1071 – 1133SH3 5PROSITE-ProRule annotationAdd BLAST63

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
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation
Contains 5 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG4773. Eukaryota.
ENOG410YBFF. LUCA.
GeneTreeiENSGT00530000063010.
HOGENOMiHOG000154376.
HOVERGENiHBG089589.
InParanoidiQ5TCZ1.
OMAiLESGWWY.
OrthoDBiEOG091G00YX.
PhylomeDBiQ5TCZ1.
TreeFamiTF329347.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR001683. Phox.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00787. PX. 1 hit.
PF00018. SH3_1. 4 hits.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00326. SH3. 5 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 5 hits.
SSF64268. SSF64268. 1 hit.
PROSITEiPS50195. PX. 1 hit.
PS50002. SH3. 5 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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 rs11818820dbSNPEnsembl.1
Natural variantiVAR_0307821035R → Q.Corresponds to variant rs3781365dbSNPEnsembl.1
Natural variantiVAR_0569931073L → P.Corresponds to variant rs12764700dbSNPEnsembl.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, AL133355 Genomic DNA. Translation: CAI13961.1.
AL121929, AL133355 Genomic DNA. Translation: CAI13962.1.
AL121929 Genomic DNA. Translation: CAI13963.1.
AL133355, AL121929 Genomic DNA. Translation: CAI15351.1.
AL133355, AL121929 Genomic DNA. Translation: CAI15352.1.
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. [Q5TCZ1-1]
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007878 mRNA. Translation: BAA24848.2. Different initiation.
AL121929, AL133355 Genomic DNA. Translation: CAI13961.1.
AL121929, AL133355 Genomic DNA. Translation: CAI13962.1.
AL121929 Genomic DNA. Translation: CAI13963.1.
AL133355, AL121929 Genomic DNA. Translation: CAI15351.1.
AL133355, AL121929 Genomic DNA. Translation: CAI15352.1.
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. [Q5TCZ1-1]
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. 17 interactors.
IntActiQ5TCZ1. 13 interactors.
MINTiMINT-2792114.
STRINGi9606.ENSP00000348215.

PTM databases

iPTMnetiQ5TCZ1.
PhosphoSitePlusiQ5TCZ1.

Polymorphism and mutation databases

BioMutaiSH3PXD2A.
DMDMi74746151.

Proteomic databases

EPDiQ5TCZ1.
MaxQBiQ5TCZ1.
PaxDbiQ5TCZ1.
PeptideAtlasiQ5TCZ1.
PRIDEiQ5TCZ1.

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.
GeneCardsiSH3PXD2A.
HGNCiHGNC:23664. SH3PXD2A.
HPAiHPA037922.
HPA037923.
neXtProtiNX_Q5TCZ1.
OpenTargetsiENSG00000107957.
PharmGKBiPA134956816.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4773. Eukaryota.
ENOG410YBFF. LUCA.
GeneTreeiENSGT00530000063010.
HOGENOMiHOG000154376.
HOVERGENiHBG089589.
InParanoidiQ5TCZ1.
OMAiLESGWWY.
OrthoDBiEOG091G00YX.
PhylomeDBiQ5TCZ1.
TreeFamiTF329347.

Miscellaneous databases

ChiTaRSiSH3PXD2A. human.
EvolutionaryTraceiQ5TCZ1.
GeneWikiiSH3PXD2A.
GenomeRNAii9644.
PROiQ5TCZ1.

Gene expression databases

BgeeiENSG00000107957.
CleanExiHS_SH3PXD2A.
ExpressionAtlasiQ5TCZ1. baseline and differential.
GenevisibleiQ5TCZ1. HS.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiIPR001683. Phox.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00787. PX. 1 hit.
PF00018. SH3_1. 4 hits.
[Graphical view]
SMARTiSM00312. PX. 1 hit.
SM00326. SH3. 5 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 5 hits.
SSF64268. SSF64268. 1 hit.
PROSITEiPS50195. PX. 1 hit.
PS50002. SH3. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPD2A_HUMAN
AccessioniPrimary (citable) accession number: Q5TCZ1
Secondary accession number(s): D3DR98
, O43302, Q5TCZ2, Q5TDQ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: December 21, 2004
Last modified: November 2, 2016
This is version 122 of the entry and version 1 of the sequence. [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 10
    Human chromosome 10: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.