A1X283 (SPD2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	911 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 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 projection › podosome 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 process	Differentiation
Cellular component	Cell junction Cell projection Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat SH3 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adipose tissue development Inferred from sequence or structural similarity. 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 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: Compara protein localization to membrane Inferred from direct assay Ref.8. Source: UniProtKB superoxide metabolic process Inferred from direct assay Ref.8. 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 sequence or structural similarity. Source: UniProtKB podosome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	SH2 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: Compara phosphatidylinositol-5-phosphate binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 911	911	SH3 and PX domain-containing protein 2B		PRO_0000312201
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	849 – 911	63	SH3 4
	Compositional bias	729 – 806	78	Pro-rich
Amino acid modifications
	Modified residue	279	1	Phosphoserine Ref.10
	Modified residue	291	1	Phosphoserine Ref.6 Ref.10
	Modified residue	528	1	Phosphoserine By similarity
	Modified residue	675	1	Phosphoserine By similarity
	Modified residue	843	1	Phosphoserine By similarity
Natural variations
	Natural variant	43	1	R → W in FTHS. Ref.9		VAR_063764
	Natural variant	101	1	Y → F. Corresponds to variant rs6880739 [ dbSNP | Ensembl ].		VAR_046226
Experimental info
	Sequence conflict	28	1	I → V in AAZ99795. Ref.2
	Sequence conflict	72	1	I → T in AAZ99795. Ref.2
	Sequence conflict	712	1	R → G in AAZ99795. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	A1X283 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: A5AA524F9AA21318	FASTA	911	101,579
	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

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].
[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. , 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, MASS SPECTROMETRY. 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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00023832.
RefSeq	NP_001017995.1. NM_001017995.2.
UniGene	Hs.285666.
3D structure databases
ProteinModelPortal	A1X283.
ModBase	Search...
Protein-protein interaction databases
IntAct	A1X283. 2 interactions.
STRING	9606.ENSP00000309714.
PTM databases
PhosphoSite	A1X283.
Proteomic databases
PaxDb	A1X283.
PRIDE	A1X283.
Protocols and materials databases
DNASU	285590.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000311601; ENSP00000309714; ENSG00000174705.
GeneID	285590.
KEGG	hsa:285590.
UCSC	uc003mbr.3. human.
Organism-specific databases
CTD	285590.
GeneCards	GC05M171693.
H-InvDB	HIX0005417.
HGNC	HGNC:29242. SH3PXD2B.
HPA	HPA036471.
MIM	249420. phenotype. 613293. gene.
neXtProt	NX_A1X283.
Orphanet	137834. Frank-Ter Haar syndrome.
PharmGKB	PA134864119.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG148927.
HOGENOM	HOG000154376.
HOVERGEN	HBG107128.
InParanoid	A1X283.
OMA	GHKVLAK.
OrthoDB	EOG4ZS92S.
Gene expression databases
ArrayExpress	A1X283.
Bgee	A1X283.
CleanEx	HS_SH3PXD2B.
Genevestigator	A1X283.
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
ChiTaRS	SH3PXD2B. human.
GenomeRNAi	285590.
NextBio	95625.
SOURCE	Search...

Entry information

Entry name

SPD2B_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 60 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.