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A2AAY5 (SPD2B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 65. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SH3 and PX domain-containing protein 2B
Alternative name(s):
Factor for adipocyte differentiation 49
Tyrosine kinase substrate with four SH3 domains
Gene names
Name:Sh3pxd2b
Synonyms:Fad49, Tks4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length908 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.8 Ref.9

Subunit structure

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. Ref.7

Subcellular location

Cytoplasm. Cell projectionpodosome. Note: Cytoplasmic in normal cells and localizes to podosomes in SRC-transformed cells. Ref.1 Ref.7 Ref.8

Tissue specificity

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. Ref.1 Ref.7 Ref.8

Developmental stage

Expression increases quickly after induction of adipocyte differentiation, reaches a maximum after 3 hours and decreases by 12 hours. Expressed from embryonic day E10.5 in heart and hindbrain, followed by an increased expression at E12.5 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 E14.5, expression is present in developing bones (proximal ribs, lower jaw and clavicle), but the expression in the heart is no longer detectable. At stages E16.5 and E18.5, 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 E16.5 is highly specific for the ganglion cell layer. Ref.1 Ref.10

Domain

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. Ref.1

Post-translational modification

Phosphorylated in SRC-transformed cells. Ref.8

Disruption phenotype

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. Ref.9 Ref.10

Sequence similarities

Belongs to the SH3PXD2 family.

Contains 1 PX (phox homology) domain.

Contains 4 SH3 domains.

Sequence caution

The sequence BAC40843.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processDifferentiation
   Cellular componentCell junction
Cell projection
Cytoplasm
   DomainRepeat
SH3 domain
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadipose tissue development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

bone development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix disassembly

Inferred from electronic annotation. Source: Ensembl

eye development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

heart development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

podosome assembly

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of fat cell differentiation

Inferred from mutant phenotype Ref.1. Source: UniProtKB

protein localization to membrane

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal system development

Inferred from mutant phenotype Ref.10. Source: UniProtKB

superoxide metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell projection

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay Ref.1Ref.8Ref.7. Source: UniProtKB

podosome

Inferred from direct assay Ref.8Ref.7. Source: UniProtKB

   Molecular_functionSH2 domain binding

Inferred from direct assay Ref.1. Source: UniProtKB

phosphatidylinositol-3,5-bisphosphate binding

Inferred from direct assay Ref.1. Source: UniProtKB

phosphatidylinositol-3-phosphate binding

Inferred from mutant phenotype Ref.1. Source: UniProtKB

phosphatidylinositol-4-phosphate binding

Inferred from direct assay Ref.1. Source: UniProtKB

phosphatidylinositol-5-phosphate binding

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 908908SH3 and PX domain-containing protein 2B
PRO_0000312202

Regions

Domain5 – 129125PX
Domain152 – 21160SH3 1
Domain221 – 28060SH3 2
Domain368 – 42760SH3 3
Domain846 – 90863SH3 4
Compositional bias718 – 77760Pro-rich

Amino acid modifications

Modified residue251Phosphotyrosine Probable
Modified residue2791Phosphoserine By similarity
Modified residue2911Phosphoserine By similarity
Modified residue6611Phosphotyrosine Ref.5
Modified residue8401Phosphoserine Ref.6

Experimental info

Mutagenesis251Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-373 and F-508. Ref.8
Mutagenesis3731Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-508. Ref.8
Mutagenesis5081Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-373. Ref.8
Sequence conflict4641V → M in BAG81976. Ref.1
Sequence conflict4641V → M in AAI15765. Ref.4
Sequence conflict7441V → VSV in BAG81976. Ref.1
Sequence conflict7441V → VSV in BAE42425. Ref.2
Sequence conflict7491L → Q in BAG81976. Ref.1
Sequence conflict7491L → Q in BAE42425. Ref.2

Sequences

Sequence LengthMass (Da)Tools
A2AAY5 [UniParc].

Last modified February 20, 2007. Version 1.
Checksum: 83341ABA6DF639AB

FASTA908101,517
        10         20         30         40         50         60 
MPPRRSIVEV KVLDVQKRRV PNKHYVYIIR VTWSSGATEA IYRRYSKFFD LQMQMLDKFP 

        70         80         90        100        110        120 
MEGGQKDPKQ RIIPFLPGKI LFRRSHIRDV AVKRLIPIDE YCKALIQLPP YISQCDEVLQ 

       130        140        150        160        170        180 
FFETRPEDLN PPKEEHIGKK KSGNDPTSVD PMVLEQYVVV ADYQKQESSE ISLSVGQVVD 

       190        200        210        220        230        240 
IIEKNESGWW FVSTAEEQGW VPATCLEGQD GVQDEFSLQP EEEEKYTVIY PYTARDQDEM 

       250        260        270        280        290        300 
NLERGAVVEV VQKNLEGWWK IRYQGKEGWA PASYLKKNSG EPLPPKLGPS SPAHSGALDL 

       310        320        330        340        350        360 
DGVSRHQNAM GREKELLNNQ RDGRFEGRLV PDGDVKQRSP KMRQRPPPRR DMTIPRGLNL 

       370        380        390        400        410        420 
PKPPIPPQVE EEYYTIAEFQ TTIPDGISFQ AGLKVEVIEK SLSGWWYIQM EDKEGWAPAT 

       430        440        450        460        470        480 
FIDKYKKTSS ASRPNFLAPL PHEMTQLRLG DAAATENNTG PEAVGPSRPL PEAPHGAVDS 

       490        500        510        520        530        540 
GMLWSKDWKG GKEAPRKASS DLSASTGYEE ISDPTQEEKP SLPPRKESII KSEEELLERE 

       550        560        570        580        590        600 
RQKMEPLRGS SPKPPGMILP MIPAKHAPLA RDSRKPEPKL DKSKFPLRND MGLECGHKVL 

       610        620        630        640        650        660 
AKEVKKPNLR PISRSKAELS EEKVDPTSQN LFMKSRPQVR PKPTPSPKTE PAQSEDHVDI 

       670        680        690        700        710        720 
YNLRSKLRPA KSQEKALLDG ESHHAAGSHD TALSRSFLPG EGPGHGQDRS GRQDGLSPKE 

       730        740        750        760        770        780 
TPCRAPPRPA KTTDPGPKNV PVPVQEATLQ QRPVVPPRRP PPPKKTSSSP LSCRPLPEVR 

       790        800        810        820        830        840 
GAQREESRVA PAAGRALLVP PKAKPFLSNS SVGQDDMRGK GGLGPRVTGK VGETREKAAS 

       850        860        870        880        890        900 
FLNADGPKDS LYVAVANFEG DEDTSSFQEG TVFEVREKNS SGWWFCQVLS GAPSWEGWIP 


SNYLRKKP 

« Hide

References

« Hide 'large scale' references
[1]"A novel gene, fad49, plays a crucial role in the immediate early stage of adipocyte differentiation via involvement in mitotic clonal expansion."
Hishida T., Eguchi T., Osada S., Nishizuka M., Imagawa M.
FEBS J. 275:5576-5588(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Dendritic cell.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-647.
[5]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-661, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-840, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"The podosomal-adaptor protein SH3PXD2B is essential for normal postnatal development."
Mao M., Thedens D.R., Chang B., Harris B.S., Zheng Q.Y., Johnson K.R., Donahue L.R., Anderson M.G.
Mamm. Genome 20:462-475(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ADAM15.
[8]"The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation."
Buschman M.D., Bromann P.A., Cejudo-Martin P., Wen F., Pass I., Courtneidge S.A.
Mol. Biol. Cell 20:1302-1311(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, MUTAGENESIS OF TYR-25; TYR-373 AND TYR-508, SUBCELLULAR LOCATION.
[9]"Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity."
Gianni D., Diaz B., Taulet N., Fowler B., Courtneidge S.A., Bokoch G.M.
Sci. Signal. 2:RA54-RA54(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[10]"Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome."
Iqbal Z., Cejudo-Martin P., de Brouwer A., van der Zwaag B., Ruiz-Lozano P., Scimia M.C., Lindsey J.D., Weinreb R., Albrecht B., Megarbane A., Alanay Y., Ben-Neriah Z., Amenduni M., Artuso R., Veltman J.A., van Beusekom E., Oudakker A., Millan J.L. expand/collapse author list , Hennekam R., Hamel B., Courtneidge S.A., van Bokhoven H.
Am. J. Hum. Genet. 86:254-261(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB430861 mRNA. Translation: BAG81976.1.
AK089330 mRNA. Translation: BAC40843.1. Frameshift.
AK171384 mRNA. Translation: BAE42425.1.
AL662780 Genomic DNA. Translation: CAM22517.1.
BC115711 mRNA. Translation: AAI15712.1.
BC115764 mRNA. Translation: AAI15765.1.
RefSeqNP_796338.2. NM_177364.3.
UniGeneMm.227616.

3D structure databases

ProteinModelPortalA2AAY5.
SMRA2AAY5. Positions 7-132, 153-432, 846-907.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActA2AAY5. 1 interaction.
MINTMINT-4110712.

PTM databases

PhosphoSiteA2AAY5.

Proteomic databases

PaxDbA2AAY5.
PRIDEA2AAY5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000038753; ENSMUSP00000044276; ENSMUSG00000040711.
GeneID268396.
KEGGmmu:268396.
UCSCuc007ijq.1. mouse.

Organism-specific databases

CTD285590.
MGIMGI:2442062. Sh3pxd2b.

Phylogenomic databases

eggNOGNOG148927.
GeneTreeENSGT00530000063010.
HOGENOMHOG000154376.
HOVERGENHBG107128.
InParanoidA2AAY5.
OMAGHKVLAK.
OrthoDBEOG7H4DSQ.
PhylomeDBA2AAY5.
TreeFamTF329347.

Gene expression databases

ArrayExpressA2AAY5.
BgeeA2AAY5.
CleanExMM_SH3PXD2B.
GenevestigatorA2AAY5.

Family and domain databases

Gene3D3.30.1520.10. 1 hit.
InterProIPR001683. Phox.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00787. PX. 1 hit.
PF00018. SH3_1. 3 hits.
PF07653. SH3_2. 1 hit.
[Graphical view]
SMARTSM00312. PX. 1 hit.
SM00326. SH3. 4 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 4 hits.
SSF64268. SSF64268. 1 hit.
PROSITEPS50195. PX. 1 hit.
PS50002. SH3. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio392275.
PROA2AAY5.
SOURCESearch...

Entry information

Entry nameSPD2B_MOUSE
AccessionPrimary (citable) accession number: A2AAY5
Secondary accession number(s): B6F0V1 expand/collapse secondary AC list , Q1LZL8, Q1LZM5, Q3TB89, Q8BIC6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot