O89032

FUNCTION: 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 (By similarity). SUBUNIT: Interacts with ADAM12, ADAM15 and ADAM19 (By similarity). Interacts with NOXO1 (By similarity). Interacts (via SH3 domains) with NOXA1; the interaction is direct (By similarity). Interacts (via N-terminus) with CYBA. Interacts with FASLG (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Cell projection, podosome (By similarity). Note=Cytoplasmic in normal cells and localizes to podosomes in Src-transformed cells (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Comment=Additional isoforms seem to exist; Name=1; IsoId=O89032-1; Sequence=Displayed; Name=2; IsoId=O89032-2; Sequence=VSP_023315; Name=3; IsoId=O89032-3; Sequence=VSP_023314, VSP_023315; TISSUE SPECIFICITY: Widely expressed. Not found in the spleen and testis. DOMAIN: The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4- phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity). DOMAIN: The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19 (By similarity). PTM: 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 (By similarity). DISRUPTION PHENOTYPE: Shows significant decrease in total cellular reactive oxygen species (ROS) and in podosome formation. SIMILARITY: Belongs to the SH3PXD2 family. SIMILARITY: Contains 1 PX (phox homology) domain. SIMILARITY: Contains 5 SH3 domains. SEQUENCE CAUTION: Sequence=AAI18023.1; Type=Frameshift; Positions=786; Sequence=AAI18023.1; Type=Frameshift; Positions=788; GENE SYNONYMS:Sh3pxd2a Fish Sh3md1 Tks5. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 1124 AA; 124201 MW; 2A06118D1CE7C567 CRC64;

SPD2A_MOUSE

urn:biopax:ModificationFeature:SPD2A_MOUSE_1, urn:biopax:ModificationFeature:SPD2A_MOUSE_10, urn:biopax:ModificationFeature:SPD2A_MOUSE_11, urn:biopax:ModificationFeature:SPD2A_MOUSE_12, urn:biopax:ModificationFeature:SPD2A_MOUSE_13, urn:biopax:ModificationFeature:SPD2A_MOUSE_2, urn:biopax:ModificationFeature:SPD2A_MOUSE_3, urn:biopax:ModificationFeature:SPD2A_MOUSE_4, urn:biopax:ModificationFeature:SPD2A_MOUSE_5, urn:biopax:ModificationFeature:SPD2A_MOUSE_6, urn:biopax:ModificationFeature:SPD2A_MOUSE_7, urn:biopax:ModificationFeature:SPD2A_MOUSE_8, urn:biopax:ModificationFeature:SPD2A_MOUSE_9

MLAYCVQDATVVDVEKRRSPSKHYVYIINVTWSDSTSQTIYRRYSKFFDLQMQLLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHISQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADTNAEPMILEQYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTRDDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEIGFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGNIMEISNLLNKKASGDKEAPAEGEGSEAPITKKEISLPILCNASNGSALAIPERTTSKLAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEFQSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTLTRPKVPPPAPPSKPKEAEENPVGACESQGSPLKVKYEEPEYDVPAFGFDSEPEMNEEPSGDRGSGDKHPAQPRRISPASSLQRAHFKVGESSEDVALEEETIYENEGFRPYTEDTLSARGSSGDSDSPGSSSLSLAVKNSPKSDSPKSSSLLKLKAEKNAQAELGKNQSNISFSSSVTISTTCSSSSSSSSLSKNNGDLKPRSASDAGIRDTPKVGTKKDPDVKAGLASCARAKPSVRPKPVLNRAESQSQEKMDISSLRRQLRPTGQLRGGLKGSRSEDSELPPQMASEGSRRGSADIIPLTATTPPCVPKKEWEGQGATYVTCSAYQKVQDSEISFPEGAEVHVLEKAESGWWYVRFGELEGWAPSHYLVAEENQQPDTASKEGDTGKSSQNEGKSDSLEKIEKRVQALNTVNQSKRATPPIPSKPPGGFGKTSGTVAVKMRNGVRQVAVRPQSVFVSPPPKDNNLSCALRRNESLTATDSLRGVRRNSSFSTARSAAAEAKGRLAERAASQGSESPLLPTQRKGIPVSPVRPKPIEKSQFIHNNLKDVYISIADYEGDEETAGFQEGVSMEVLEKNPNGWWYCQILDEVKPFKGWVPSNYLEKKN