UniProtKB - A2AAY5 (SPD2B_MOUSE)
Protein
SH3 and PX domain-containing protein 2B
Gene
Sh3pxd2b
Organism
Mus musculus (Mouse)
Status
Functioni
Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation. 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. Plays a role in mitotic clonal expansion during the immediate early stage of adipocyte differentiation.3 Publications
GO - Molecular functioni
- phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
- phosphatidylinositol-3-phosphate binding Source: UniProtKB
- phosphatidylinositol-4-phosphate binding Source: UniProtKB
- phosphatidylinositol-5-phosphate binding Source: UniProtKB
- SH2 domain binding Source: UniProtKB
- superoxide-generating NADPH oxidase activator activity Source: GO_Central
GO - Biological processi
- adipose tissue development Source: UniProtKB
- bone development Source: UniProtKB
- cranial skeletal system development Source: UniProtKB
- extracellular matrix disassembly Source: MGI
- eye development Source: UniProtKB
- heart development Source: UniProtKB
- osteoblast fate commitment Source: UniProtKB
- podosome assembly Source: UniProtKB
- positive regulation of adipose tissue development Source: UniProtKB
- positive regulation of fat cell differentiation Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of multicellular organism growth Source: UniProtKB
- positive regulation of stress fiber assembly Source: UniProtKB
- protein localization to membrane Source: UniProtKB
- regulation of brood size Source: UniProtKB
- skeletal system development Source: UniProtKB
- skeletal system morphogenesis Source: UniProtKB
- superoxide metabolic process Source: UniProtKB
Keywordsi
Biological process | Differentiation |
Names & Taxonomyi
Protein namesi | Recommended name: SH3 and PX domain-containing protein 2BAlternative name(s): Factor for adipocyte differentiation 49 Tyrosine kinase substrate with four SH3 domains |
Gene namesi | Name:Sh3pxd2b Synonyms:Fad49, Tks4 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2442062, Sh3pxd2b |
Subcellular locationi
Cytoskeleton
- podosome Source: UniProtKB
Other locations
- cell junction Source: UniProtKB-KW
- cell projection Source: UniProtKB-KW
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cell junction, Cell projection, CytoplasmPathology & Biotechi
Disruption phenotypei
Exhibit skeletal, cardiac and eye phenotypes. Mice have glaucoma and suffer growth retardation as well as craniofacial defects. Skeletons show marked kyphosis, poorly aligned teeth, anomalies in the iliac crest, and a prominent xiphisternum. Mice show loss of adipose tissue as well as cardiac deficiencies, such as dysmorphic ventricular chambers, thin mitral valves and immature and disarrayed trabeculae with frequent apical indentation. Mice show loss of ROS formation.2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 25 | Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-373 and F-508. 1 Publication | 1 | |
Mutagenesisi | 373 | Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-508. 1 Publication | 1 | |
Mutagenesisi | 508 | Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-373. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000312202 | 1 – 908 | SH3 and PX domain-containing protein 2BAdd BLAST | 908 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 25 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 279 | PhosphoserineBy similarity | 1 | |
Modified residuei | 291 | PhosphoserineBy similarity | 1 | |
Modified residuei | 499 | PhosphoserineCombined sources | 1 | |
Modified residuei | 528 | PhosphoserineCombined sources | 1 | |
Modified residuei | 661 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 840 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Phosphorylated in SRC-transformed cells.1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | A2AAY5 |
MaxQBi | A2AAY5 |
PaxDbi | A2AAY5 |
PeptideAtlasi | A2AAY5 |
PRIDEi | A2AAY5 |
PTM databases
iPTMneti | A2AAY5 |
PhosphoSitePlusi | A2AAY5 |
Expressioni
Tissue specificityi
Highly expressed in the stromal-vascular fraction of white adipose tissue with moderate expression in heart, skeletal muscle and the mature adipocyte fraction of white adipose tissue. Also expressed in brain, spleen, kidney and liver. Expressed in white and brown adipose tissues, eye, lung, heart, brain, spleen, stomach, liver and skeletal muscle (at protein level). Not expressed in kidney or bone marrow.3 Publications
Developmental stagei
Expression increases quickly after induction of adipocyte differentiation, reaches a maximum after 3 hours and decreases by 12 hours. Expressed from embryonic day 10.5 dpc in heart and hindbrain, followed by an increased expression at 12.5 dpc that also involves a subset of cells on the luminal side of the left ventricular wall in the case of the heart and neuroepithelium in the case of the brain. At 14.5 dpc, expression is present in developing bones (proximal ribs, lower jaw and clavicle), but the expression in the heart is no longer detectable. At stages 16.5 dpc and 18.5 dpc, strong expression is seen in the long bones of the limbs, particularly in the growth plates, as well as in the facial and cranial bones and the primordial incisor. Expression in the ribs is seen in the proximal regions in those areas where the transition from cartilage to bone is expected to occur. Expression in the eye at 16.5 dpc is highly specific for the ganglion cell layer.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000040711, Expressed in ear vesicle and 227 other tissues |
Genevisiblei | A2AAY5, MM |
Interactioni
Subunit structurei
Interacts with NOXO1 (By similarity).
Interacts (via SH3 domains) with NOXA1; the interaction is direct (By similarity).
Interacts with ADAM15.
Interacts with FASLG (By similarity).
By similarityGO - Molecular functioni
- SH2 domain binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 234494, 3 interactors |
IntActi | A2AAY5, 2 interactors |
MINTi | A2AAY5 |
STRINGi | 10090.ENSMUSP00000044276 |
Miscellaneous databases
RNActi | A2AAY5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 5 – 129 | PXPROSITE-ProRule annotationAdd BLAST | 125 | |
Domaini | 152 – 211 | SH3 1PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 221 – 280 | SH3 2PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 368 – 427 | SH3 3PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 847 – 908 | SH3 4PROSITE-ProRule annotationAdd BLAST | 62 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 718 – 777 | Pro-richAdd BLAST | 60 |
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
Sequence similaritiesi
Belongs to the SH3PXD2 family.Curated
Keywords - Domaini
Repeat, SH3 domainPhylogenomic databases
eggNOGi | KOG0905, Eukaryota |
GeneTreei | ENSGT00940000158396 |
HOGENOMi | CLU_013051_1_0_1 |
InParanoidi | A2AAY5 |
OMAi | PMIPTKH |
OrthoDBi | 1183210at2759 |
PhylomeDBi | A2AAY5 |
TreeFami | TF329347 |
Family and domain databases
CDDi | cd06888, PX_FISH, 1 hit cd12075, SH3_Tks4_1, 1 hit cd12076, SH3_Tks4_2, 1 hit cd12078, SH3_Tks4_3, 1 hit cd12018, SH3_Tks4_4, 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 IPR030512, SH3PXD2B IPR035477, SH3PXD2B_SH3_1 IPR035478, SH3PXD2B_SH3_2 IPR035479, SH3PXD2B_SH3_3 IPR035480, SH3PXD2B_SH3_4 |
PANTHERi | PTHR15706:SF19, PTHR15706:SF19, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF00018, SH3_1, 3 hits PF07653, SH3_2, 1 hit |
SMARTi | View protein in SMART SM00312, PX, 1 hit SM00326, SH3, 4 hits |
SUPFAMi | SSF50044, SSF50044, 4 hits SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit PS50002, SH3, 4 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
A2AAY5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPPRRSIVEV KVLDVQKRRV PNKHYVYIIR VTWSSGATEA IYRRYSKFFD
60 70 80 90 100
LQMQMLDKFP MEGGQKDPKQ RIIPFLPGKI LFRRSHIRDV AVKRLIPIDE
110 120 130 140 150
YCKALIQLPP YISQCDEVLQ FFETRPEDLN PPKEEHIGKK KSGNDPTSVD
160 170 180 190 200
PMVLEQYVVV ADYQKQESSE ISLSVGQVVD IIEKNESGWW FVSTAEEQGW
210 220 230 240 250
VPATCLEGQD GVQDEFSLQP EEEEKYTVIY PYTARDQDEM NLERGAVVEV
260 270 280 290 300
VQKNLEGWWK IRYQGKEGWA PASYLKKNSG EPLPPKLGPS SPAHSGALDL
310 320 330 340 350
DGVSRHQNAM GREKELLNNQ RDGRFEGRLV PDGDVKQRSP KMRQRPPPRR
360 370 380 390 400
DMTIPRGLNL PKPPIPPQVE EEYYTIAEFQ TTIPDGISFQ AGLKVEVIEK
410 420 430 440 450
SLSGWWYIQM EDKEGWAPAT FIDKYKKTSS ASRPNFLAPL PHEMTQLRLG
460 470 480 490 500
DAAATENNTG PEAVGPSRPL PEAPHGAVDS GMLWSKDWKG GKEAPRKASS
510 520 530 540 550
DLSASTGYEE ISDPTQEEKP SLPPRKESII KSEEELLERE RQKMEPLRGS
560 570 580 590 600
SPKPPGMILP MIPAKHAPLA RDSRKPEPKL DKSKFPLRND MGLECGHKVL
610 620 630 640 650
AKEVKKPNLR PISRSKAELS EEKVDPTSQN LFMKSRPQVR PKPTPSPKTE
660 670 680 690 700
PAQSEDHVDI YNLRSKLRPA KSQEKALLDG ESHHAAGSHD TALSRSFLPG
710 720 730 740 750
EGPGHGQDRS GRQDGLSPKE TPCRAPPRPA KTTDPGPKNV PVPVQEATLQ
760 770 780 790 800
QRPVVPPRRP PPPKKTSSSP LSCRPLPEVR GAQREESRVA PAAGRALLVP
810 820 830 840 850
PKAKPFLSNS SVGQDDMRGK GGLGPRVTGK VGETREKAAS FLNADGPKDS
860 870 880 890 900
LYVAVANFEG DEDTSSFQEG TVFEVREKNS SGWWFCQVLS GAPSWEGWIP
SNYLRKKP
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A5F8MPP7 | A0A5F8MPP7_MOUSE | SH3 and PX domain-containing protei... | Sh3pxd2b | 936 | Annotation score: |
Sequence cautioni
The sequence BAC40843 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 464 | V → M in BAG81976 (PubMed:18959745).Curated | 1 | |
Sequence conflicti | 464 | V → M in AAI15765 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 744 | V → VSV in BAG81976 (PubMed:18959745).Curated | 1 | |
Sequence conflicti | 744 | V → VSV in BAE42425 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 749 | L → Q in BAG81976 (PubMed:18959745).Curated | 1 | |
Sequence conflicti | 749 | L → Q in BAE42425 (PubMed:16141072).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB430861 mRNA Translation: BAG81976.1 AK089330 mRNA Translation: BAC40843.1 Frameshift. AK171384 mRNA Translation: BAE42425.1 AL662780 Genomic DNA No translation available. BC115711 mRNA Translation: AAI15712.1 BC115764 mRNA Translation: AAI15765.1 |
CCDSi | CCDS24526.1 |
RefSeqi | NP_796338.2, NM_177364.3 |
Genome annotation databases
Ensembli | ENSMUST00000038753; ENSMUSP00000044276; ENSMUSG00000040711 |
GeneIDi | 268396 |
KEGGi | mmu:268396 |
UCSCi | uc007ijq.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB430861 mRNA Translation: BAG81976.1 AK089330 mRNA Translation: BAC40843.1 Frameshift. AK171384 mRNA Translation: BAE42425.1 AL662780 Genomic DNA No translation available. BC115711 mRNA Translation: AAI15712.1 BC115764 mRNA Translation: AAI15765.1 |
CCDSi | CCDS24526.1 |
RefSeqi | NP_796338.2, NM_177364.3 |
3D structure databases
SMRi | A2AAY5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 234494, 3 interactors |
IntActi | A2AAY5, 2 interactors |
MINTi | A2AAY5 |
STRINGi | 10090.ENSMUSP00000044276 |
PTM databases
iPTMneti | A2AAY5 |
PhosphoSitePlusi | A2AAY5 |
Proteomic databases
jPOSTi | A2AAY5 |
MaxQBi | A2AAY5 |
PaxDbi | A2AAY5 |
PeptideAtlasi | A2AAY5 |
PRIDEi | A2AAY5 |
Protocols and materials databases
Antibodypediai | 49665, 84 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000038753; ENSMUSP00000044276; ENSMUSG00000040711 |
GeneIDi | 268396 |
KEGGi | mmu:268396 |
UCSCi | uc007ijq.1, mouse |
Organism-specific databases
CTDi | 285590 |
MGIi | MGI:2442062, Sh3pxd2b |
Phylogenomic databases
eggNOGi | KOG0905, Eukaryota |
GeneTreei | ENSGT00940000158396 |
HOGENOMi | CLU_013051_1_0_1 |
InParanoidi | A2AAY5 |
OMAi | PMIPTKH |
OrthoDBi | 1183210at2759 |
PhylomeDBi | A2AAY5 |
TreeFami | TF329347 |
Miscellaneous databases
BioGRID-ORCSi | 268396, 1 hit in 17 CRISPR screens |
PROi | PR:A2AAY5 |
RNActi | A2AAY5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000040711, Expressed in ear vesicle and 227 other tissues |
Genevisiblei | A2AAY5, MM |
Family and domain databases
CDDi | cd06888, PX_FISH, 1 hit cd12075, SH3_Tks4_1, 1 hit cd12076, SH3_Tks4_2, 1 hit cd12078, SH3_Tks4_3, 1 hit cd12018, SH3_Tks4_4, 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 IPR030512, SH3PXD2B IPR035477, SH3PXD2B_SH3_1 IPR035478, SH3PXD2B_SH3_2 IPR035479, SH3PXD2B_SH3_3 IPR035480, SH3PXD2B_SH3_4 |
PANTHERi | PTHR15706:SF19, PTHR15706:SF19, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF00018, SH3_1, 3 hits PF07653, SH3_2, 1 hit |
SMARTi | View protein in SMART SM00312, PX, 1 hit SM00326, SH3, 4 hits |
SUPFAMi | SSF50044, SSF50044, 4 hits SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit PS50002, SH3, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SPD2B_MOUSE | |
Accessioni | A2AAY5Primary (citable) accession number: A2AAY5 Secondary accession number(s): B6F0V1 Q8BIC6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 4, 2007 |
Last sequence update: | February 20, 2007 | |
Last modified: | December 2, 2020 | |
This is version 108 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families