SPD2B_HUMAN
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 03-AUG-2022, entry version 121.
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}.
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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; 53.
DR IntAct; A1X283; 11.
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; A1X283; -.
DR PeptideAtlas; A1X283; -.
DR PRIDE; A1X283; -.
DR ProteomicsDB; 156; -.
DR ABCD; A1X283; 20 sequenced antibodies.
DR Antibodypedia; 49665; 92 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 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; 1183210at2759; -.
DR PhylomeDB; A1X283; -.
DR TreeFam; TF329347; -.
DR PathwayCommons; A1X283; -.
DR SignaLink; A1X283; -.
DR SIGNOR; A1X283; -.
DR BioGRID-ORCS; 285590; 16 hits in 1069 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 153 other tissues.
DR ExpressionAtlas; A1X283; baseline and differential.
DR Genevisible; A1X283; HS.
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; -; 1.
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; IPR030512; SH3PXD2B.
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:SF19; PTHR15706:SF19; 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; SSF50044; SSF50044; 4.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 4.
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
