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Q9P0V3 (SH3B4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SH3 domain-binding protein 4
Alternative name(s):
EH-binding protein 10
Transferrin receptor-trafficking protein
Gene names
Name:SH3BP4
Synonyms:BOG25, EHB10, TTP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length963 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may acts as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy. Ref.2 Ref.11

Subunit structure

Homodimer or homooligomer. Interacts with DNM2, EPS15, clathrin, the adapter protein complex 2/AP-2 and TFRC. Interacts with the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; the interaction is most probably direct, preferentially occurs with their inactive GDP-bound form and is negatively regulated by amino acids. Ref.2 Ref.5 Ref.11

Subcellular location

Membraneclathrin-coated pit. Cytoplasmic vesicleclathrin-coated vesicle. Nucleus Probable. Note: Specifically associated with transferrin receptor-containing clathrin-coated pits and clathrin-coated vesicles. May also localize to the nucleus. Ref.2 Ref.6

Tissue specificity

Expressed in all tissues tested with higher expression in pancreas. Expressed by retinal pigment epithelial cells (at protein level). Ref.1 Ref.6

Domain

The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1.

Post-translational modification

Phosphorylated upon EGF stimulation. Phosphorylation prevents interaction with DNM2. Ref.2

Miscellaneous

Overexpression or depletion of SH3BP4 result in a specific decrease of the transferrin receptor endocytosis that can be rescued by DNM2 overexpression.

Sequence similarities

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCoated pit
Cytoplasmic vesicle
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3 domain
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to amino acid stimulus

Inferred from mutant phenotype Ref.11. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of GTPase activity

Inferred from direct assay Ref.11. Source: UniProtKB

negative regulation of TOR signaling

Inferred from mutant phenotype Ref.11. Source: UniProtKB

negative regulation of cell growth

Inferred from mutant phenotype Ref.11. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of autophagy

Inferred from mutant phenotype Ref.11. Source: UniProtKB

protein localization to lysosome

Inferred from mutant phenotype Ref.11. Source: UniProtKB

regulation of catalytic activity

Inferred from mutant phenotype Ref.11. Source: UniProtKB

   Cellular_componentclathrin-coated vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.11. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGDP-dissociation inhibitor activity

Inferred from mutant phenotype Ref.11. Source: UniProtKB

Ras GTPase binding

Inferred from physical interaction Ref.11. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.2. Source: IntAct

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9P0V3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9P0V3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     515-925: Missing.
Note: No experimental confirmation available. Dubious isoform produced through aberrant splice sites.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 963963SH3 domain-binding protein 4
PRO_0000274574

Regions

Domain55 – 11460SH3

Amino acid modifications

Modified residue1311Phosphoserine Ref.8
Modified residue2461Phosphoserine Ref.9
Modified residue6371Phosphoserine Ref.10

Natural variations

Alternative sequence515 – 925411Missing in isoform 2.
VSP_022823
Natural variant1551M → T. Ref.2
Corresponds to variant rs3731644 [ dbSNP | Ensembl ].
VAR_030330
Natural variant1971A → T. Ref.2
Corresponds to variant rs3731646 [ dbSNP | Ensembl ].
VAR_030331

Experimental info

Mutagenesis921W → A: Loss of function. Loss of targeting to the clathrin-coated pits and vesicles. Loss of interaction with DNM2, RRAGB and RRAGC. No effect on localization to the plasma membrane. Ref.2 Ref.11
Sequence conflict2351D → N in ABB18377. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 7F98200AC420F3D5

FASTA963107,496
        10         20         30         40         50         60 
MAAQRIRAAN SNGLPRCKSE GTLIDLSEGF SETSFNDIKV PSPSALLVDN PTPFGNAKEV 

        70         80         90        100        110        120 
IAIKDYCPTN FTTLKFSKGD HLYVLDTSGG EWWYAHNTTE MGYIPSSYVQ PLNYRNSTLS 

       130        140        150        160        170        180 
DSGMIDNLPD SPDEVAKELE LLGGWTDDKK VPGRMYSNNP FWNGVQTNPF LNGNVPVMPS 

       190        200        210        220        230        240 
LDELNPKSTV DLLLFDAGTS SFTESSSATT NSTGNIFDEL PVTNGLHAEP PVRRDNPFFR 

       250        260        270        280        290        300 
SKRSYSLSEL SVLQAKSDAP TSSSFFTGLK SPAPEQFQSR EDFRTAWLNH RKLARSCHDL 

       310        320        330        340        350        360 
DLLGQSPGWG QTQAVETNIV CKLDSSGGAV QLPDTSISIH VPEGHVAPGE TQQISMKALL 

       370        380        390        400        410        420 
DPPLELNSDR SCSISPVLEV KLSNLEVKTS IILEMKVSAE IKNDLFSKST VGLQCLRSDS 

       430        440        450        460        470        480 
KEGPYVSVPL NCSCGDTVQA QLHNLEPCMY VAVVAHGPSI LYPSTVWDFI NKKVTVGLYG 

       490        500        510        520        530        540 
PKHIHPSFKT VVTIFGHDCA PKTLLVSEVT RQAPNPAPVA LQLWGKHQFV LSRPQDLKVC 

       550        560        570        580        590        600 
MFSNMTNYEV KASEQAKVVR GFQLKLGKVS RLIFPITSQN PNELSDFTLR VQVKDDQEAI 

       610        620        630        640        650        660 
LTQFCVQTPQ PPPKSAIKPS GQRRFLKKNE VGKIILSPFA TTTKYPTFQD RPVSSLKFGK 

       670        680        690        700        710        720 
LLKTVVRQNK NHYLLEYKKG DGIALLSEER VRLRGQLWTK EWYIGYYQGR VGLVHTKNVL 

       730        740        750        760        770        780 
VVGRARPSLC SGPELSTSVL LEQILRPCKF LTYIYASVRT LLMENISSWR SFADALGYVN 

       790        800        810        820        830        840 
LPLTFFCRAE LDSEPERVAS VLEKLKEDCN NTENKERKSF QKELVMALLK MDCQGLVVRL 

       850        860        870        880        890        900 
IQDFVLLTTA VEVAQRWREL AEKLAKVSKQ QMDAYESPHR DRNGVVDSEA MWKPAYDFLL 

       910        920        930        940        950        960 
TWSHQIGDSY RDVIQELHLG LDKMKNPITK RWKHLTGTLI LVNSLDVLRA AAFSPADQDD 


FVI 

« Hide

Isoform 2 [UniParc].

Checksum: 1C9C5ABE339BFD7D
Show »

FASTA55260,337

References

« Hide 'large scale' references
[1]"Cloning, chromosomal localization, and characterization of cDNA from a novel gene, SH3BP4, expressed by human corneal fibroblasts."
Dunlevy J.R., Berryhill B.L., Vergnes J.-P., SundarRaj N., Hassell J.R.
Genomics 62:519-524(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Corneal fibroblast.
[2]"TTP specifically regulates the internalization of the transferrin receptor."
Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P., Tacchetti C., Di Fiore P.P.
Cell 123:875-888(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN ENDOCYTOSIS, INTERACTION WITH AP-2; CLATHRIN; DNM2; EPS15 AND TFRC, OLIGOMERIZATION, PHOSPHORYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-92, VARIANTS THR-155 AND THR-197.
Tissue: Placenta.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Eye.
[5]"Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module."
Salcini A.E., Confalonieri S., Doria M., Santolini E., Tassi E., Minenkova O., Cesareni G., Pelicci P.G., Di Fiore P.P.
Genes Dev. 11:2239-2249(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 74-963 (ISOFORM 2), INTERACTION WITH EPS15.
Tissue: Fibroblast.
[6]"Nuclear and plasma membrane localization of SH3BP4 in retinal pigment epithelial cells."
Khanobdee K., Kolberg J.B., Dunlevy J.R.
Mol. Vis. 10:933-942(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"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-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[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-637, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling."
Kim Y.M., Stone M., Hwang T.H., Kim Y.G., Dunlevy J.R., Griffin T.J., Kim D.H.
Mol. Cell 46:833-846(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTORC1 SIGNALING, INTERACTION WITH RRAGA; RRAGB; RRAGC AND RRAGD, MUTAGENESIS OF TRP-92.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF147747 mRNA. Translation: AAF33022.1.
DQ232895 mRNA. Translation: ABB18377.1.
AC010148 Genomic DNA. Translation: AAY14916.1.
AC114814 Genomic DNA. Translation: AAY24025.1.
BC057396 mRNA. Translation: AAH57396.1.
AF015043 mRNA. Translation: AAD01551.1.
RefSeqNP_055336.1. NM_014521.2.
UniGeneHs.516777.

3D structure databases

ProteinModelPortalQ9P0V3.
SMRQ9P0V3. Positions 61-112.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117194. 31 interactions.
IntActQ9P0V3. 29 interactions.
MINTMINT-1649163.
STRING9606.ENSP00000340237.

PTM databases

PhosphoSiteQ9P0V3.

Polymorphism databases

DMDM74753102.

Proteomic databases

PaxDbQ9P0V3.
PRIDEQ9P0V3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344528; ENSP00000340237; ENSG00000130147. [Q9P0V3-1]
ENST00000392011; ENSP00000375867; ENSG00000130147. [Q9P0V3-1]
ENST00000409212; ENSP00000386862; ENSG00000130147. [Q9P0V3-1]
GeneID23677.
KEGGhsa:23677.
UCSCuc002vvp.3. human. [Q9P0V3-1]

Organism-specific databases

CTD23677.
GeneCardsGC02P235876.
HGNCHGNC:10826. SH3BP4.
HPAHPA037533.
MIM605611. gene.
neXtProtNX_Q9P0V3.
PharmGKBPA35734.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46295.
HOGENOMHOG000015297.
HOVERGENHBG057439.
InParanoidQ9P0V3.
OMACRAELDS.
OrthoDBEOG7GJ6C4.
PhylomeDBQ9P0V3.
TreeFamTF105572.

Gene expression databases

ArrayExpressQ9P0V3.
BgeeQ9P0V3.
CleanExHS_SH3BP4.
GenevestigatorQ9P0V3.

Family and domain databases

InterProIPR011511. SH3_2.
IPR001452. SH3_domain.
IPR000906. ZU5.
[Graphical view]
PfamPF07653. SH3_2. 1 hit.
PF00791. ZU5. 1 hit.
[Graphical view]
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSH3BP4. human.
GeneWikiSH3BP4.
GenomeRNAi23677.
NextBio46541.
PROQ9P0V3.
SOURCESearch...

Entry information

Entry nameSH3B4_HUMAN
AccessionPrimary (citable) accession number: Q9P0V3
Secondary accession number(s): O95082 expand/collapse secondary AC list , Q309A3, Q53QD0, Q53TD1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 99 of the entry and version 1 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 2

Human chromosome 2: entries, gene names and cross-references to MIM