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A1X283 (SPD2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 67. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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):
Adapter protein HOFI
Factor for adipocyte differentiation 49
Tyrosine kinase substrate with four SH3 domains
Gene names
Name:SH3PXD2B
Synonyms:FAD49, KIAA1295, TKS4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length911 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 By similarity. Ref.5 Ref.8 Ref.11

Subunit structure

Interacts with ADAM15 By similarity. Interacts with NOXO1. Interacts (via SH3 domains) with NOXA1; the interaction is direct. Interacts with FASLG. Ref.5 Ref.7 Ref.8 Ref.11

Subcellular location

Cytoplasm By similarity. Cell projectionpodosome By similarity. Note: Cytoplasmic in normal cells and localizes to podosomes in SRC-transformed cells By similarity. Ref.5

Tissue specificity

Expressed in fibroblasts. 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.5

Post-translational modification

Phosphorylated in SRC-transformed cells By similarity.

Involvement in disease

Frank-Ter Haar syndrome (FTHS) [MIM:249420]: A syndrome characterized by brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones and flexion deformity of the fingers.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the SH3PXD2 family.

Contains 1 PX (phox homology) domain.

Contains 4 SH3 domains.

Ontologies

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

Inferred from sequence or structural similarity. Source: UniProtKB

bone development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix disassembly

Inferred from mutant phenotype Ref.8. Source: UniProtKB

eye development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

heart development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

podosome assembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

protein localization to membrane

Inferred from direct assay Ref.8. Source: UniProtKB

skeletal system development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

superoxide metabolic process

Inferred from direct assay Ref.8. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell projection

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

podosome

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionSH2 domain binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3,5-bisphosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-3-phosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol-4-phosphate binding

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-5-phosphate binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 911911SH3 and PX domain-containing protein 2B
PRO_0000312201

Regions

Domain5 – 129125PX
Domain152 – 21160SH3 1
Domain221 – 28060SH3 2
Domain368 – 42760SH3 3
Domain849 – 91163SH3 4
Compositional bias729 – 80678Pro-rich

Amino acid modifications

Modified residue2791Phosphoserine Ref.10
Modified residue2911Phosphoserine Ref.6 Ref.10
Modified residue8431Phosphoserine By similarity

Natural variations

Natural variant431R → W in FTHS. Ref.9
VAR_063764
Natural variant1011Y → F.
Corresponds to variant rs6880739 [ dbSNP | Ensembl ].
VAR_046226

Experimental info

Sequence conflict281I → V in AAZ99795. Ref.2
Sequence conflict721I → T in AAZ99795. Ref.2
Sequence conflict7121R → G in AAZ99795. Ref.2

Sequences

Sequence LengthMass (Da)Tools
A1X283 [UniParc].

Last modified May 5, 2009. Version 3.
Checksum: A5AA524F9AA21318

FASTA911101,579
        10         20         30         40         50         60 
MPPRRSIVEV KVLDVQKRRV PNKHYVYIIR VTWSSGSTEA IYRRYSKFFD LQMQMLDKFP 

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

       130        140        150        160        170        180 
FFETRPEDLN PPKEEHIGKK KSGGDQTSVD PMVLEQYVVV ANYQKQESSE ISLSVGQVVD 

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

       250        260        270        280        290        300 
NLERGAVVEV IQKNLEGWWK IRYQGKEGWA PASYLKKNSG EPLPPKPGPG SPSHPGALDL 

       310        320        330        340        350        360 
DGVSRQQNAV GREKELLSSQ RDGRFEGRPV PDGDAKQRSP KMRQRPPPRR DMTIPRGLNL 

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

       430        440        450        460        470        480 
FIDKYKKTSN ASRPNFLAPL PHEVTQLRLG EAAALENNTG SEATGPSRPL PDAPHGVMDS 

       490        500        510        520        530        540 
GLPWSKDWKG SKDVLRKASS DMSASAGYEE ISDPDMEEKP SLPPRKESII KSEGELLERE 

       550        560        570        580        590        600 
RERQRTEQLR GPTPKPPGVI LPMMPAKHIP PARDSRRPEP KPDKSRLFQL KNDMGLECGH 

       610        620        630        640        650        660 
KVLAKEVKKP NLRPISKSKT DLPEEKPDAT PQNPFLKSRP QVRPKPAPSP KTEPPQGEDQ 

       670        680        690        700        710        720 
VDICNLRSKL RPAKSQDKSL LDGEGPQAVG GQDVAFSRSF LPGEGPGRAQ DRTGKQDGLS 

       730        740        750        760        770        780 
PKEISCRAPP RPAKTTDPVS KSVPVPLQEA PQQRPVVPPR RPPPPKKTSS SSRPLPEVRG 

       790        800        810        820        830        840 
PQCEGHESRA APTPGRALLV PPKAKPFLSN SLGGQDDTRG KGSLGPWGTG KIGENREKAA 

       850        860        870        880        890        900 
AASVPNADGL KDSLYVAVAD FEGDKDTSSF QEGTVFEVRE KNSSGWWFCQ VLSGAPSWEG 

       910 
WIPSNYLRKK P 

« 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].
[2]"Identification and characterization of HOFI, a novel homolog of FISH."
Lanyi A., Geiszt M.
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 362-911.
Tissue: Brain.
[5]"The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells."
Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., Courtneidge S.A.
J. Biol. Chem. 278:16844-16851(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN PX, INTERACTION WITH ADAM12; ADAM15 AND ADAM19.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-291, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
Voss M., Lettau M., Janssen O.
BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FASLG.
[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, INTERACTION WITH NOXA1.
[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. 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: TISSUE SPECIFICITY, VARIANT FTHS TRP-43.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-279 AND SER-291, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Direct interaction between Tks proteins and the N-terminal proline-rich region (PRR) of NoxA1 mediates Nox1-dependent ROS generation."
Gianni D., Dermardirossian C., Bokoch G.M.
Eur. J. Cell Biol. 90:164-171(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NOXA1 AND NOXO1.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB430862 mRNA. Translation: BAG81977.1.
DQ109556 mRNA. Translation: AAZ99795.1.
AC008671 Genomic DNA. No translation available.
AC011407 Genomic DNA. No translation available.
AC090064 Genomic DNA. No translation available.
AB037716 mRNA. Translation: BAA92533.1.
RefSeqNP_001017995.1. NM_001017995.2.
UniGeneHs.285666.

3D structure databases

ProteinModelPortalA1X283.
SMRA1X283. Positions 7-132, 153-550, 842-910.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid130149. 6 interactions.
IntActA1X283. 2 interactions.
STRING9606.ENSP00000309714.

PTM databases

PhosphoSiteA1X283.

Proteomic databases

PaxDbA1X283.
PRIDEA1X283.

Protocols and materials databases

DNASU285590.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000311601; ENSP00000309714; ENSG00000174705.
GeneID285590.
KEGGhsa:285590.
UCSCuc003mbr.3. human.

Organism-specific databases

CTD285590.
GeneCardsGC05M171693.
H-InvDBHIX0005417.
HGNCHGNC:29242. SH3PXD2B.
HPAHPA036471.
MIM249420. phenotype.
613293. gene.
neXtProtNX_A1X283.
Orphanet137834. Frank-Ter Haar syndrome.
PharmGKBPA134864119.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148927.
HOGENOMHOG000154376.
HOVERGENHBG107128.
InParanoidA1X283.
OMAGHKVLAK.
OrthoDBEOG7H4DSQ.
PhylomeDBA1X283.
TreeFamTF329347.

Gene expression databases

ArrayExpressA1X283.
BgeeA1X283.
CleanExHS_SH3PXD2B.
GenevestigatorA1X283.

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

ChiTaRSSH3PXD2B. human.
GenomeRNAi285590.
NextBio95625.
PROA1X283.
SOURCESearch...

Entry information

Entry nameSPD2B_HUMAN
AccessionPrimary (citable) accession number: A1X283
Secondary accession number(s): B6F0V2, Q9P2Q1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: May 5, 2009
Last modified: April 16, 2014
This is version 67 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM