Q99962 (SH3G2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	352 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Endocytosis
Cellular component	Cytoplasm Membrane
Domain	Coiled coil SH3 domain
Ligand	Lipid-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class II Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome cellular membrane organization 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 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: Compara synaptic vesicle endocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi 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_function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-77938,EBI-77938
ADAM15	Q13444	2	EBI-77938,EBI-77818
ADAM9	Q13443	2	EBI-77938,EBI-77903
ATXN2	Q99700	4	EBI-77938,EBI-697691
EMD	P50402	2	EBI-77938,EBI-489887
LRRK2	Q5S007	2	EBI-77938,EBI-5323863
SH3GL3	Q99963	4	EBI-77938,EBI-473910

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 352

352

Endophilin-A1

PRO_0000146747

Regions

Domain

18 – 249

232

BAR

Domain

290 – 349

60

SH3

Region

1 – 125

125

Binds and tubulates liposomes By similarity

Region

1 – 21

21

Membrane-binding amphipathic helix

Region

60 – 87

28

Required for dimerization upon membrane association By similarity

Coiled coil

181 – 248

68

Potential

Experimental info

Mutagenesis

63

1

A → 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

Mutagenesis

66

1

A → D: Loss of tubulation of liposomes, no effect on liposome binding. Ref.14

Mutagenesis

66

1

A → 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

Mutagenesis

66

1

A → W: Vesiculation of liposomes, no effect on liposome binding, indol ring located in hydrophobic core of the membrane. Ref.14

Mutagenesis

70

1

M → 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

Mutagenesis

202

1

F → W: No effect. Indol ring not associated with the membrane. Ref.14

Secondary structure

1

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352

Helix Strand Turn

Details...

Helix

12 – 21

10

Helix

24 – 58

35

Helix

62 – 64

3

Helix

65 – 68

4

Helix

89 – 104

16

Beta strand

106 – 109

4

Helix

110 – 138

29

Helix

140 – 148

9

Helix

150 – 175

26

Helix

180 – 246

67

Beta strand

294 – 299

6

Beta strand

316 – 318

3

Beta strand

323 – 332

10

Beta strand

335 – 348

14

Sequences

	Sequence		Length	Mass (Da)
	Q99962 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: F3AE2353E1EB7CF3	FASTA	352	39,962
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00019171.

RefSeq

NP_003017.1. NM_003026.2.

UniGene

Hs.75149.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X03	X-ray	3.10	A	1-247	[»]
1X04	X-ray	2.90	A	1-247	[»]
2D4C	X-ray	2.40	A/B/C/D	1-247	[»]
2DBM	NMR	-	A	293-352	[»]

ProteinModelPortal

Q99962.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-30996N.

IntAct

Q99962. 16 interactions.

MINT

MINT-108776.

STRING

9606.ENSP00000369981.

PTM databases

PhosphoSite

Q99962.

Polymorphism databases

DMDM

10720276.

Proteomic databases

PaxDb

Q99962.

PRIDE

Q99962.

Protocols and materials databases

DNASU

6456.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380607; ENSP00000369981; ENSG00000107295.

GeneID

6456.

KEGG

hsa:6456.

UCSC

uc003zna.3. human.

Organism-specific databases

CTD

6456.

GeneCards

GC09P017569.

HGNC

HGNC:10831. SH3GL2.

HPA

CAB010056.
HPA026685.

MIM

604465. gene.

neXtProt

NX_Q99962.

PharmGKB

PA35737.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG307129.

HOGENOM

HOG000231641.

HOVERGEN

HBG052866.

InParanoid

Q99962.

KO

K11247.

OMA

RELGDEC.

OrthoDB

EOG4C2H9V.

PhylomeDB

Q99962.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.
REACT_6900. Immune System.

SignaLink

Q99962.

Gene expression databases

ArrayExpress

Q99962.

Bgee

Q99962.

CleanEx

HS_SH3GL2.

Genevestigator

Q99962.

GermOnline

ENSG00000107295. Homo sapiens.

Family and domain databases

Gene3D

1.20.1270.60. 1 hit.

InterPro

IPR027267. AH/BAR-dom.
IPR004148. BAR_dom.
IPR011511. SH3_2.
IPR001452. SH3_domain.
IPR013315. Spectrin_alpha_SH3.
[Graphical view]

Pfam

PF03114. BAR. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.
PR01887. SPECTRNALPHA.

SMART

SM00721. BAR. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS51021. BAR. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q99962.

GenomeRNAi

6456.

NextBio

25093.

SOURCE

Search...

Entry information

Entry name

SH3G2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 126 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.