ID SPD2B_HUMAN Reviewed; 911 AA. AC A1X283; B6F0V2; Q9P2Q1; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 3. DT 27-MAR-2024, entry version 130. DE RecName: Full=SH3 and PX domain-containing protein 2B; DE AltName: Full=Adapter protein HOFI; DE AltName: Full=Factor for adipocyte differentiation 49; DE AltName: Full=Tyrosine kinase substrate with four SH3 domains; GN Name=SH3PXD2B; Synonyms=FAD49, KIAA1295, TKS4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=18959745; DOI=10.1111/j.1742-4658.2008.06682.x; RA Hishida T., Eguchi T., Osada S., Nishizuka M., Imagawa M.; RT "A novel gene, fad49, plays a crucial role in the immediate early stage of RT adipocyte differentiation via involvement in mitotic clonal expansion."; RL FEBS J. 275:5576-5588(2008). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Lanyi A., Geiszt M.; RT "Identification and characterization of HOFI, a novel homolog of FISH."; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 362-911. RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN PX, AND INTERACTION WITH ADAM12; RP ADAM15 AND ADAM19. RX PubMed=12615925; DOI=10.1074/jbc.m300267200; RA Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., RA Courtneidge S.A.; RT "The adaptor protein fish associates with members of the ADAMs family and RT localizes to podosomes of Src-transformed cells."; RL J. Biol. Chem. 278:16844-16851(2003). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-291, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [8] RP FUNCTION, AND INTERACTION WITH NOXA1. RX PubMed=19755710; DOI=10.1126/scisignal.2000370; RA Gianni D., Diaz B., Taulet N., Fowler B., Courtneidge S.A., Bokoch G.M.; RT "Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 RT (Nox1) activity."; RL Sci. Signal. 2:RA54-RA54(2009). RN [9] RP TISSUE SPECIFICITY, AND VARIANT FTHS TRP-43. RX PubMed=20137777; DOI=10.1016/j.ajhg.2010.01.009; RA Iqbal Z., Cejudo-Martin P., de Brouwer A., van der Zwaag B., RA Ruiz-Lozano P., Scimia M.C., Lindsey J.D., Weinreb R., Albrecht B., RA Megarbane A., Alanay Y., Ben-Neriah Z., Amenduni M., Artuso R., RA Veltman J.A., van Beusekom E., Oudakker A., Millan J.L., Hennekam R., RA Hamel B., Courtneidge S.A., van Bokhoven H.; RT "Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the RT skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar RT Syndrome."; RL Am. J. Hum. Genet. 86:254-261(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279 AND SER-291, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP FUNCTION, AND INTERACTION WITH NOXA1 AND NOXO1. RX PubMed=20609497; DOI=10.1016/j.ejcb.2010.05.007; RA Gianni D., Dermardirossian C., Bokoch G.M.; RT "Direct interaction between Tks proteins and the N-terminal proline-rich RT region (PRR) of NoxA1 mediates Nox1-dependent ROS generation."; RL Eur. J. Cell Biol. 90:164-171(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). CC -!- FUNCTION: Adapter protein involved in invadopodia and podosome CC formation and extracellular matrix degradation. Binds matrix CC metalloproteinases (ADAMs), NADPH oxidases (NOXs) and CC phosphoinositides. Acts as an organizer protein that allows NOX1- or CC NOX3-dependent reactive oxygen species (ROS) generation and ROS CC localization. Plays a role in mitotic clonal expansion during the CC immediate early stage of adipocyte differentiation (By similarity). CC {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:19755710, CC ECO:0000269|PubMed:20609497}. CC -!- SUBUNIT: Interacts with ADAM15 (By similarity). Interacts with NOXO1. CC Interacts (via SH3 domains) with NOXA1; the interaction is direct. CC Interacts with FASLG. {ECO:0000250, ECO:0000269|PubMed:12615925, CC ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:19807924, CC ECO:0000269|PubMed:20609497}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection, CC podosome {ECO:0000250}. Note=Cytoplasmic in normal cells and localizes CC to podosomes in SRC-transformed cells. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts. CC {ECO:0000269|PubMed:20137777}. CC -!- DOMAIN: The PX domain is required for podosome localization because of CC its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and CC phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser CC extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), CC phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol CC 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 CC domain (By similarity). {ECO:0000250}. CC -!- PTM: Phosphorylated in SRC-transformed cells. {ECO:0000250}. CC -!- DISEASE: Frank-Ter Haar syndrome (FTHS) [MIM:249420]: A syndrome CC characterized by brachycephaly, wide fontanels, prominent forehead, CC hypertelorism, prominent eyes, macrocornea with or without glaucoma, CC full cheeks, small chin, bowing of the long bones and flexion deformity CC of the fingers. {ECO:0000269|PubMed:20137777}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SH3PXD2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB430862; BAG81977.1; -; mRNA. DR EMBL; DQ109556; AAZ99795.1; -; mRNA. DR EMBL; AC008671; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011407; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090064; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB037716; BAA92533.1; -; mRNA. DR CCDS; CCDS34291.1; -. DR RefSeq; NP_001017995.1; NM_001017995.2. DR AlphaFoldDB; A1X283; -. DR SMR; A1X283; -. DR BioGRID; 130149; 73. DR IntAct; A1X283; 17. DR MINT; A1X283; -. DR STRING; 9606.ENSP00000309714; -. DR iPTMnet; A1X283; -. DR PhosphoSitePlus; A1X283; -. DR BioMuta; SH3PXD2B; -. DR EPD; A1X283; -. DR jPOST; A1X283; -. DR MassIVE; A1X283; -. DR MaxQB; A1X283; -. DR PaxDb; 9606-ENSP00000309714; -. DR PeptideAtlas; A1X283; -. DR ProteomicsDB; 156; -. DR Pumba; A1X283; -. DR ABCD; A1X283; 20 sequenced antibodies. DR Antibodypedia; 49665; 108 antibodies from 16 providers. DR DNASU; 285590; -. DR Ensembl; ENST00000311601.6; ENSP00000309714.5; ENSG00000174705.13. DR GeneID; 285590; -. DR KEGG; hsa:285590; -. DR MANE-Select; ENST00000311601.6; ENSP00000309714.5; NM_001017995.3; NP_001017995.1. DR UCSC; uc003mbr.3; human. DR AGR; HGNC:29242; -. DR CTD; 285590; -. DR DisGeNET; 285590; -. DR GeneCards; SH3PXD2B; -. DR HGNC; HGNC:29242; SH3PXD2B. DR HPA; ENSG00000174705; Low tissue specificity. DR MalaCards; SH3PXD2B; -. DR MIM; 249420; phenotype. DR MIM; 613293; gene. DR neXtProt; NX_A1X283; -. DR OpenTargets; ENSG00000174705; -. DR Orphanet; 137834; Frank-Ter Haar syndrome. DR PharmGKB; PA134864119; -. DR VEuPathDB; HostDB:ENSG00000174705; -. DR eggNOG; KOG0905; Eukaryota. DR GeneTree; ENSGT00940000158396; -. DR HOGENOM; CLU_013051_1_0_1; -. DR InParanoid; A1X283; -. DR OMA; PMIPTKH; -. DR OrthoDB; 2910367at2759; -. DR PhylomeDB; A1X283; -. DR TreeFam; TF329347; -. DR PathwayCommons; A1X283; -. DR SignaLink; A1X283; -. DR SIGNOR; A1X283; -. DR BioGRID-ORCS; 285590; 17 hits in 1147 CRISPR screens. DR ChiTaRS; SH3PXD2B; human. DR GenomeRNAi; 285590; -. DR Pharos; A1X283; Tbio. DR PRO; PR:A1X283; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; A1X283; Protein. DR Bgee; ENSG00000174705; Expressed in decidua and 155 other cell types or tissues. DR ExpressionAtlas; A1X283; baseline and differential. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0002102; C:podosome; ISS:UniProtKB. DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB. DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IBA:GO_Central. DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB. DR GO; GO:0060348; P:bone development; IMP:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0022617; P:extracellular matrix disassembly; IMP:UniProtKB. DR GO; GO:0001654; P:eye development; IMP:UniProtKB. DR GO; GO:0007507; P:heart development; IMP:UniProtKB. DR GO; GO:0071800; P:podosome assembly; ISS:UniProtKB. DR GO; GO:0072657; P:protein localization to membrane; IDA:UniProtKB. DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB. DR GO; GO:0042554; P:superoxide anion generation; IBA:GO_Central. DR GO; GO:0006801; P:superoxide metabolic process; IDA:UniProtKB. DR CDD; cd06888; PX_FISH; 1. DR CDD; cd12075; SH3_Tks4_1; 1. DR CDD; cd12076; SH3_Tks4_2; 1. DR CDD; cd12078; SH3_Tks4_3; 1. DR CDD; cd12018; SH3_Tks4_4; 1. DR Gene3D; 3.30.1520.10; Phox-like domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 4. DR InterPro; IPR001683; PX_dom. DR InterPro; IPR036871; PX_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR037961; SH3PXD2_PX. DR InterPro; IPR035477; SH3PXD2B_SH3_1. DR InterPro; IPR035478; SH3PXD2B_SH3_2. DR InterPro; IPR035479; SH3PXD2B_SH3_3. DR InterPro; IPR035480; SH3PXD2B_SH3_4. DR PANTHER; PTHR15706:SF25; SH3 AND PX DOMAIN-CONTAINING PROTEIN 2B; 1. DR PANTHER; PTHR15706; SH3 MULTIPLE DOMAIN; 1. DR Pfam; PF00787; PX; 1. DR Pfam; PF00018; SH3_1; 3. DR Pfam; PF07653; SH3_2; 1. DR SMART; SM00312; PX; 1. DR SMART; SM00326; SH3; 4. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 4. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 4. DR Genevisible; A1X283; HS. PE 1: Evidence at protein level; KW Cell junction; Cell projection; Cytoplasm; Differentiation; KW Disease variant; Phosphoprotein; Reference proteome; Repeat; SH3 domain. FT CHAIN 1..911 FT /note="SH3 and PX domain-containing protein 2B" FT /id="PRO_0000312201" FT DOMAIN 5..129 FT /note="PX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147" FT DOMAIN 152..211 FT /note="SH3 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 221..280 FT /note="SH3 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 368..427 FT /note="SH3 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 850..911 FT /note="SH3 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 275..366 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 458..834 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 315..350 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 512..549 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 570..590 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 598..626 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 751..770 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 25 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:A2AAY5" FT MOD_RES 279 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 291 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT MOD_RES 499 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2AAY5" FT MOD_RES 528 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2AAY5" FT MOD_RES 843 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:A2AAY5" FT VARIANT 43 FT /note="R -> W (in FTHS; dbSNP:rs267607046)" FT /evidence="ECO:0000269|PubMed:20137777" FT /id="VAR_063764" FT VARIANT 101 FT /note="Y -> F (in dbSNP:rs6880739)" FT /id="VAR_046226" FT CONFLICT 28 FT /note="I -> V (in Ref. 2; AAZ99795)" FT /evidence="ECO:0000305" FT CONFLICT 72 FT /note="I -> T (in Ref. 2; AAZ99795)" FT /evidence="ECO:0000305" FT CONFLICT 712 FT /note="R -> G (in Ref. 2; AAZ99795)" FT /evidence="ECO:0000305" SQ SEQUENCE 911 AA; 101579 MW; A5AA524F9AA21318 CRC64; MPPRRSIVEV KVLDVQKRRV PNKHYVYIIR VTWSSGSTEA IYRRYSKFFD LQMQMLDKFP MEGGQKDPKQ RIIPFLPGKI LFRRSHIRDV AVKRLIPIDE YCKALIQLPP YISQCDEVLQ FFETRPEDLN PPKEEHIGKK KSGGDQTSVD PMVLEQYVVV ANYQKQESSE ISLSVGQVVD IIEKNESGWW FVSTAEEQGW VPATCLEGQD GVQDEFSLQP EEEEKYTVIY PYTARDQDEM NLERGAVVEV IQKNLEGWWK IRYQGKEGWA PASYLKKNSG EPLPPKPGPG SPSHPGALDL DGVSRQQNAV GREKELLSSQ RDGRFEGRPV PDGDAKQRSP KMRQRPPPRR DMTIPRGLNL PKPPIPPQVE EEYYTIAEFQ TTIPDGISFQ AGLKVEVIEK NLSGWWYIQI EDKEGWAPAT FIDKYKKTSN ASRPNFLAPL PHEVTQLRLG EAAALENNTG SEATGPSRPL PDAPHGVMDS GLPWSKDWKG SKDVLRKASS DMSASAGYEE ISDPDMEEKP SLPPRKESII KSEGELLERE RERQRTEQLR GPTPKPPGVI LPMMPAKHIP PARDSRRPEP KPDKSRLFQL KNDMGLECGH KVLAKEVKKP NLRPISKSKT DLPEEKPDAT PQNPFLKSRP QVRPKPAPSP KTEPPQGEDQ VDICNLRSKL RPAKSQDKSL LDGEGPQAVG GQDVAFSRSF LPGEGPGRAQ DRTGKQDGLS PKEISCRAPP RPAKTTDPVS KSVPVPLQEA PQQRPVVPPR RPPPPKKTSS SSRPLPEVRG PQCEGHESRA APTPGRALLV PPKAKPFLSN SLGGQDDTRG KGSLGPWGTG KIGENREKAA AASVPNADGL KDSLYVAVAD FEGDKDTSSF QEGTVFEVRE KNSSGWWFCQ VLSGAPSWEG WIPSNYLRKK P //