A2AAY5 (SPD2B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Protein existence	Evidence 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.7 Ref.8
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.6
Subcellular location	Cytoplasm. Cell projection › podosome. Note: Cytoplasmic in normal cells and localizes to podosomes in SRC-transformed cells. Ref.1 Ref.6 Ref.7
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.6 Ref.7
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.9
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.7
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.8 Ref.9
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 process	Differentiation
Cellular component	Cell junction Cell projection Cytoplasm
Domain	Repeat SH3 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adipose tissue development Inferred from mutant phenotype Ref.9. Source: UniProtKB bone development Inferred from mutant phenotype Ref.9. Source: UniProtKB cell communication Inferred from electronic annotation. Source: InterPro cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW extracellular matrix disassembly Inferred from electronic annotation. Source: Compara eye development Inferred from mutant phenotype Ref.9. Source: UniProtKB heart development Inferred from mutant phenotype Ref.9. Source: UniProtKB podosome assembly Inferred from mutant phenotype Ref.7. 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 superoxide metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell projection Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay Ref.1Ref.7Ref.6. Source: UniProtKB podosome Inferred from direct assay Ref.7Ref.6. Source: UniProtKB
Molecular_function	SH2 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 908	908	SH3 and PX domain-containing protein 2B		PRO_0000312202
Regions
	Domain	5 – 129	125	PX
	Domain	152 – 211	60	SH3 1
	Domain	221 – 280	60	SH3 2
	Domain	368 – 427	60	SH3 3
	Domain	846 – 908	63	SH3 4
	Compositional bias	718 – 777	60	Pro-rich
Amino acid modifications
	Modified residue	25	1	Phosphotyrosine Probable
	Modified residue	279	1	Phosphoserine By similarity
	Modified residue	291	1	Phosphoserine By similarity
	Modified residue	528	1	Phosphoserine Ref.5
	Modified residue	672	1	Phosphoserine Ref.5
	Modified residue	840	1	Phosphoserine Ref.5
Experimental info
	Mutagenesis	25	1	Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-373 and F-508. Ref.7
	Mutagenesis	373	1	Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-508. Ref.7
	Mutagenesis	508	1	Y → F: Reduced phosphorylation. Almost complete loss of phosphorylation; when associated with F-25 and F-373. Ref.7
	Sequence conflict	464	1	V → M in BAG81976. Ref.1
	Sequence conflict	464	1	V → M in AAI15765. Ref.4
	Sequence conflict	744	1	V → VSV in BAG81976. Ref.1
	Sequence conflict	744	1	V → VSV in BAE42425. Ref.2
	Sequence conflict	749	1	L → Q in BAG81976. Ref.1
	Sequence conflict	749	1	L → Q in BAE42425. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	A2AAY5 [UniParc]. Last modified February 20, 2007. Version 1. Checksum: 83341ABA6DF639AB	FASTA	908	101,517
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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-528; SER-672 AND SER-840, MASS SPECTROMETRY. Tissue: Macrophage.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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. , 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.
IPI	IPI00222090.
RefSeq	NP_796338.2. NM_177364.3.
UniGene	Mm.227616.
3D structure databases
ProteinModelPortal	A2AAY5.
SMR	A2AAY5. Positions 7-132, 153-278, 370-432, 844-907.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4110712.
PTM databases
PhosphoSite	A2AAY5.
Proteomic databases
PaxDb	A2AAY5.
PRIDE	A2AAY5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000038753; ENSMUSP00000044276; ENSMUSG00000040711.
GeneID	268396.
KEGG	mmu:268396.
UCSC	uc007ijq.1. mouse.
Organism-specific databases
CTD	285590.
MGI	MGI:2442062. Sh3pxd2b.
Phylogenomic databases
eggNOG	NOG148927.
GeneTree	ENSGT00530000063010.
HOGENOM	HOG000154376.
HOVERGEN	HBG107128.
InParanoid	A2AAY5.
OMA	GHKVLAK.
OrthoDB	EOG4ZS92S.
Gene expression databases
ArrayExpress	A2AAY5.
Bgee	A2AAY5.
CleanEx	MM_SH3PXD2B.
Genevestigator	A2AAY5.
Family and domain databases
Gene3D	3.30.1520.10. 1 hit.
InterPro	IPR001683. Phox. IPR011511. SH3_2. IPR001452. SH3_domain. [Graphical view]
Pfam	PF00787. PX. 1 hit. PF00018. SH3_1. 3 hits. PF07653. SH3_2. 1 hit. [Graphical view]
SMART	SM00312. PX. 1 hit. SM00326. SH3. 4 hits. [Graphical view]
SUPFAM	SSF64268. PX. 1 hit. SSF50044. SH3. 4 hits.
PROSITE	PS50195. PX. 1 hit. PS50002. SH3. 4 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	392275.
SOURCE	Search...

Entry information

Entry name

SPD2B_MOUSE

Accession

Primary (citable) accession number: A2AAY5
Secondary accession number(s): B6F0V1 , Q1LZL8, Q1LZM5, Q3TB89, Q8BIC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 4, 2007
Last sequence update:	February 20, 2007
Last modified:	May 29, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program