Q9P0V3 (SH3B4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	963 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Membrane › clathrin-coated pit. Cytoplasmic vesicle › clathrin-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 process	Endocytosis
Cellular component	Coated pit Cytoplasmic vesicle Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular 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 cascade 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
Cellular_component	clathrin-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 nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GDP-dissociation inhibitor activity Inferred from mutant phenotype Ref.11. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CIZ1	Q9ULV3	2	EBI-1049513,EBI-2652948
PLEKHA1	Q9HB21	2	EBI-1049513,EBI-2652984

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 963	963	SH3 domain-binding protein 4		PRO_0000274574
Regions
	Domain	55 – 114	60	SH3
Amino acid modifications
	Modified residue	131	1	Phosphoserine Ref.8
	Modified residue	246	1	Phosphoserine Ref.9
	Modified residue	637	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	515 – 925	411	Missing in isoform 2.		VSP_022823
	Natural variant	155	1	M → T. Ref.2 Corresponds to variant rs3731644 [ dbSNP | Ensembl ].		VAR_030330
	Natural variant	197	1	A → T. Ref.2 Corresponds to variant rs3731646 [ dbSNP | Ensembl ].		VAR_030331
Experimental info
	Mutagenesis	92	1	W → 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 conflict	235	1	D → N in ABB18377. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 7F98200AC420F3D5	FASTA	963	107,496
	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
	Isoform 2 [UniParc]. Checksum: 1C9C5ABE339BFD7D	FASTA	552	60,337
	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 RQAPNPITKR WKHLTGTLIL VNSLDVLRAA 550 AFSPADQDDF VI

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.
IPI	IPI00005030. IPI00383564.
RefSeq	NP_055336.1. NM_014521.2.
UniGene	Hs.516777.
3D structure databases
HSSP	HSSP built from PDB template 1BU1 based on UniProtKB P08631.
ProteinModelPortal	Q9P0V3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9P0V3. 22 interactions.
MINT	MINT-1649163.
STRING	9606.ENSP00000340237.
PTM databases
PhosphoSite	Q9P0V3.
Polymorphism databases
DMDM	74753102.
Proteomic databases
PaxDb	Q9P0V3.
PRIDE	Q9P0V3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000344528; ENSP00000340237; ENSG00000130147. ENST00000392011; ENSP00000375867; ENSG00000130147. ENST00000409212; ENSP00000386862; ENSG00000130147.
GeneID	23677.
KEGG	hsa:23677.
UCSC	uc002vvp.3. human.
Organism-specific databases
CTD	23677.
GeneCards	GC02P235876.
HGNC	HGNC:10826. SH3BP4.
HPA	HPA037533.
MIM	605611. gene.
neXtProt	NX_Q9P0V3.
PharmGKB	PA35734.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46295.
HOGENOM	HOG000015297.
HOVERGEN	HBG057439.
InParanoid	Q9P0V3.
OMA	CRAELDS.
OrthoDB	EOG4M0F10.
PhylomeDB	Q9P0V3.
Gene expression databases
ArrayExpress	Q9P0V3.
Bgee	Q9P0V3.
CleanEx	HS_SH3BP4.
Genevestigator	Q9P0V3.
Family and domain databases
InterPro	IPR011511. SH3_2. IPR001452. SH3_domain. IPR000906. ZU5. [Graphical view]
Pfam	PF00018. SH3_1. 1 hit. PF07653. SH3_2. 1 hit. PF00791. ZU5. 1 hit. [Graphical view]
SMART	SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF50044. SH3. 1 hit.
PROSITE	PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SH3BP4. human.
GenomeRNAi	23677.
NextBio	46541.
SOURCE	Search...

Entry information

Entry name

SH3B4_HUMAN

Accession

Primary (citable) accession number: Q9P0V3
Secondary accession number(s): O95082 , Q309A3, Q53QD0, Q53TD1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 6, 2007
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 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.