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Q99962 (SH3G2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endophilin-A1
Alternative name(s):
EEN-B1
Endophilin-1
SH3 domain protein 2A
SH3 domain-containing GRB2-like protein 2
Gene names
Name:SH3GL2
Synonyms:CNSA2, SH3D2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature.

Subunit structure

Monomer; in cytoplasm. Homodimer; when associated with membranes By similarity. Interacts with OPHN1 By similarity. Interacts with SYNJ1 and DNM1. Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation. Interacts with PDCD6IP. Interacts with ATX2. Interacts with ADAM9 and ADAM15 cytoplasmic tails. Interacts with BIN2. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Note: Concentrated in presynaptic nerve terminals in neurons.

Tissue specificity

Brain, mostly in frontal cortex. Expressed at high level in fetal cerebellum.

Domain

An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface. Ref.14

Miscellaneous

HeLa cells expressing the N-BAR domain of SH3GL2 show tubulation of the plasma membrane. The N-BAR domain binds liposomes and induces formation of tubules from liposomes. The N-terminal amphipathic helix is required for liposome binding. The second amphipathic helix enhances liposome tubulation.

Sequence similarities

Belongs to the endophilin family.

Contains 1 BAR domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCytoplasm
Membrane
   DomainCoiled coil
SH3 domain
   LigandLipid-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of exogenous peptide antigen via MHC class II

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

central nervous system development

Traceable author statement Ref.1. Source: ProtInc

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

membrane organization

Traceable author statement. Source: Reactome

negative regulation of epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

post-Golgi vesicle-mediated transport

Traceable author statement. Source: Reactome

regulation of receptor internalization

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

synaptic vesicle endocytosis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

clathrin-coated endocytic vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionidentical protein binding

Inferred from physical interaction PubMed 16115810. Source: IntAct

lipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 352352Endophilin-A1
PRO_0000146747

Regions

Domain18 – 249232BAR
Domain290 – 34960SH3
Region1 – 125125Binds and tubulates liposomes By similarity
Region1 – 2121Membrane-binding amphipathic helix
Region60 – 8728Required for dimerization upon membrane association By similarity
Coiled coil181 – 24868 Potential

Experimental info

Mutagenesis631A → S: Reduced tubulation of liposomes, 3-fold increase in tubule diameter, no effect on liposome binding; when associated with S-66 or with S-66 and Q-70. Ref.14
Mutagenesis661A → D: Loss of tubulation of liposomes, no effect on liposome binding. Ref.14
Mutagenesis661A → S: Reduced tubulation of liposomes, 3-fold increase in tubule diameter, no effect on liposome binding; when associated with S-63 or with S-63 and Q-70. Ref.14
Mutagenesis661A → W: Vesiculation of liposomes, no effect on liposome binding, indol ring located in hydrophobic core of the membrane. Ref.14
Mutagenesis701M → Q: Reduced tubulation of liposomes, 3-fold increase in tubule diameter, no effect on liposome binding; when associated with S-63 and S-66. Ref.14
Mutagenesis2021F → W: No effect. Indol ring not associated with the membrane. Ref.14

Secondary structure

................... 352
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99962 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: F3AE2353E1EB7CF3

FASTA35239,962
        10         20         30         40         50         60 
MSVAGLKKQF HKATQKVSEK VGGAEGTKLD DDFKEMERKV DVTSRAVMEI MTKTIEYLQP 

        70         80         90        100        110        120 
NPASRAKLSM INTMSKIRGQ EKGPGYPQAE ALLAEAMLKF GRELGDDCNF GPALGEVGEA 

       130        140        150        160        170        180 
MRELSEVKDS LDIEVKQNFI DPLQNLHDKD LREIQHHLKK LEGRRLDFDY KKKRQGKIPD 

       190        200        210        220        230        240 
EELRQALEKF DESKEIAESS MFNLLEMDIE QVSQLSALVQ AQLEYHKQAV QILQQVTVRL 

       250        260        270        280        290        300 
EERIRQASSQ PRREYQPKPR MSLEFPTGDS TQPNGGLSHT GTPKPSGVQM DQPCCRALYD 

       310        320        330        340        350 
FEPENEGELG FKEGDIITLT NQIDENWYEG MLHGHSGFFP INYVEILVAL PH 

« Hide

References

« Hide 'large scale' references
[1]"A novel SH3-containing human gene family preferentially expressed in the central nervous system."
Giachino C., Lantelme E., Lanzetti L., Saccone S., Della Valle G., Migone N.
Genomics 41:427-434(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"A family of EEN-like genes coding for SH3-domain containing proteins are preferentially expressed in human brain."
So C.W., So C.K.C., Sham M.H., Chan L.C.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1."
Howard L., Nelson K.K., Maciewicz R.A., Blobel C.P.
J. Biol. Chem. 274:31693-31699(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADAM9 AND ADAM15.
[9]"The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity."
Cestra G., Castagnoli L., Dente L., Minenkova O., Petrelli A., Migone N., Hoffmueller U., Schneider-Mergener J., Cesareni G.
J. Biol. Chem. 274:32001-32007(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYNJ1.
[10]"Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding."
Fisher R.D., Chung H.Y., Zhai Q., Robinson H., Sundquist W.I., Hill C.P.
Cell 128:841-852(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDCD6IP.
[11]"Ataxin-2 associates with the endocytosis complex and affects EGF receptor trafficking."
Nonis D., Schmidt M.H., van de Loo S., Eich F., Dikic I., Nowock J., Auburger G.
Cell. Signal. 20:1725-1739(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATX2.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis."
Sanchez-Barrena M.J., Vallis Y., Clatworthy M.R., Doherty G.J., Veprintsev D.B., Evans P.R., McMahon H.T.
PLoS ONE 7:E52401-E52401(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BIN2.
[14]"Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms."
Masuda M., Takeda S., Sone M., Ohki T., Mori H., Kamioka Y., Mochizuki N.
EMBO J. 25:2889-2897(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-247, DOMAIN, MUTAGENESIS OF ALA-63; ALA-66; MET-70 AND PHE-202.
[15]"Solution structures of the SH3 domain of human SH3-containing GRB2-like protein 2."
RIKEN structural genomics initiative (RSGI)
Submitted (DEC-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 293-352.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X99657 mRNA. Translation: CAA67971.1.
AF036268 mRNA. Translation: AAC04764.1.
CR542086 mRNA. Translation: CAG46883.1.
CR542102 mRNA. Translation: CAG46899.1.
BT019682 mRNA. Translation: AAV38488.1.
AK312400 mRNA. Translation: BAG35315.1.
AL139115, AL133214 Genomic DNA. Translation: CAB92765.2.
AL133214, AL139115 Genomic DNA. Translation: CAH70742.1.
CH471071 Genomic DNA. Translation: EAW58661.1.
RefSeqNP_003017.1. NM_003026.2.
UniGeneHs.75149.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X03X-ray3.10A1-247[»]
1X04X-ray2.90A1-247[»]
2D4CX-ray2.40A/B/C/D1-247[»]
2DBMNMR-A293-352[»]
ProteinModelPortalQ99962.
SMRQ99962. Positions 26-247, 293-352.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112353. 59 interactions.
DIPDIP-30996N.
IntActQ99962. 43 interactions.
MINTMINT-108776.
STRING9606.ENSP00000369981.

PTM databases

PhosphoSiteQ99962.

Polymorphism databases

DMDM10720276.

Proteomic databases

PaxDbQ99962.
PRIDEQ99962.

Protocols and materials databases

DNASU6456.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380607; ENSP00000369981; ENSG00000107295.
GeneID6456.
KEGGhsa:6456.
UCSCuc003zna.3. human.

Organism-specific databases

CTD6456.
GeneCardsGC09P017569.
HGNCHGNC:10831. SH3GL2.
HPACAB010056.
HPA026685.
MIM604465. gene.
neXtProtNX_Q99962.
PharmGKBPA35737.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307129.
HOGENOMHOG000231641.
HOVERGENHBG052866.
InParanoidQ99962.
KOK11247.
OMASESHNGG.
OrthoDBEOG7G1V6H.
PhylomeDBQ99962.
TreeFamTF313281.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkQ99962.

Gene expression databases

ArrayExpressQ99962.
BgeeQ99962.
CleanExHS_SH3GL2.
GenevestigatorQ99962.

Family and domain databases

Gene3D1.20.1270.60. 1 hit.
InterProIPR027267. AH/BAR-dom.
IPR004148. BAR_dom.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]
PfamPF03114. BAR. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.
SMARTSM00721. BAR. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS51021. BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ99962.
GeneWikiSH3GL2.
GenomeRNAi6456.
NextBio25093.
PROQ99962.
SOURCESearch...

Entry information

Entry nameSH3G2_HUMAN
AccessionPrimary (citable) accession number: Q99962
Secondary accession number(s): B2R618, Q9NQK5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1997
Last modified: April 16, 2014
This is version 133 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM