O35179 (SH3G2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endophilin-A1

Alternative name(s):
Endophilin-1
SH3 domain protein 2A
SH3 domain-containing GRB2-like protein 2
SH3p4

Gene names

Name:	Sh3gl2
Synonyms:	Sh3d2a, Sh3p4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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. Ref.5 Ref.10
Subunit structure	Monomer; in cytoplasm. Homodimer; when associated with membranes By similarity. Interacts with SYNJ1 and DNM1. Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation. Interacts with PDCD6IP By similarity. Interacts with OPHN1. Interacts with ADAM9 and ADAM15 cytoplasmic tails. Interacts with BIN2 By similarity. Ref.3 Ref.4 Ref.8 Ref.10
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note: Concentrated in presynaptic nerve terminals in neurons. Ref.3
Tissue specificity	Brain. Expressed at low level in the kidney. Ref.3
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.5 Ref.9 Ref.10
Miscellaneous	The N-BAR domain binds liposomes and mediates dimerization of BAR domains upon liposome binding. It induces formation of tubules from liposomes as well as fusion of liposome tubules. Cells overexpressing Sh3gl2 show no effect on transferrin uptake.
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	regulation of receptor internalization Inferred from electronic annotation. Source: Compara synaptic vesicle endocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell 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
Dnm1	P21575	2	EBI-1149197,EBI-80070
Synj1	Q62910	2	EBI-1149197,EBI-1149123

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 352

352

Endophilin-A1

PRO_0000146749

Regions

Domain

18 – 249

232

BAR

Domain

290 – 349

60

SH3

Region

1 – 125

125

Binds and tubulates liposomes

Region

1 – 21

21

Membrane-binding amphipathic helix

Region

60 – 87

28

Required for dimerization upon membrane association

Coiled coil

181 – 250

70

Potential

Experimental info

Mutagenesis

263

1

L → P: Confers inhibition of transferrin uptake comparable to Sh3gl3 upon overexpression. Ref.6

Sequence conflict

78

1

R → H in AI044966. Ref.1

Secondary structure

1

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352

Helix Strand Turn

Details...

Helix

31 – 58

28

Helix

62 – 64

3

Helix

89 – 104

16

Beta strand

106 – 109

4

Helix

110 – 138

29

Helix

140 – 173

34

Turn

174 – 177

4

Helix

180 – 205

26

Helix

208 – 245

38

Beta strand

294 – 299

6

Beta strand

316 – 322

7

Beta strand

324 – 332

9

Beta strand

335 – 340

6

Helix

341 – 343

3

Beta strand

344 – 348

5

Sequences

	Sequence		Length	Mass (Da)
	O35179 [UniParc]. Last modified October 23, 2007. Version 2. Checksum: 382B6F651885B679	FASTA	352	39,899
	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 LDMEVKQNFI DPLQNLHDKD LREIQHHLKK LEGRRLDFDY KKKRQGKIPD 190 200 210 220 230 240 EELRQALEKF DESKEIAESS MFNLLEMDIE QVSQLSALVQ AQLEYHKQAV QILQQVTVRL 250 260 270 280 290 300 EERIRQASSQ PRREYQPKPR MSLEFATGDG TQPNGGLSHT GTPKPAGVQM DQPCCRALYD 310 320 330 340 350 FEPENEGELG FKEGDIITLT NQIDENWYEG MLHGQSGFFP INYVEILVAL PH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Normalization and subtraction: two approaches to facilitate gene discovery." Bonaldo M.F., Lennon G., Soares M.B. Genome Res. 6:791-806(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-79.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 15-352. Strain: Brown Norway.
[3]	"The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain." Ringstad N., Nemoto Y., De Camilli P. Proc. Natl. Acad. Sci. U.S.A. 94:8569-8574(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 105-352, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DNM1 AND SYNJ1. Tissue: Brain.
[4]	"Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase." Ramjaun A.R., Angers A., Legendre-Guillemin V., Tong X.-K., McPherson P.S. J. Biol. Chem. 276:28913-28919(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP4K3; SYNJ1 AND DNM1.
[5]	"Generation of high curvature membranes mediated by direct endophilin bilayer interactions." Farsad K., Ringstad N., Takei K., Floyd S.R., Rose K., De Camilli P. J. Cell Biol. 155:193-200(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN.
[6]	"Inhibitory role of endophilin 3 in receptor-mediated endocytosis." Sugiura H., Iwata K., Matsuoka M., Hayashi H., Takemiya T., Yasuda S., Ichikawa M., Yamauchi T., Mehlen P., Haga T., Yamagata K. J. Biol. Chem. 279:23343-23348(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LEU-263.
[7]	"Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission." Gallop J.L., Butler P.J., McMahon H.T. Nature 438:675-678(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SHOWS THAT SH3GL2 HAS NO LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE ACTIVITY.
[8]	"The Rho-linked mental retardation protein OPHN1 controls synaptic vesicle endocytosis via endophilin A1." Nakano-Kobayashi A., Kasri N.N., Newey S.E., Van Aelst L. Curr. Biol. 19:1133-1139(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH OPHN1.
[9]	"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: STRUCTURE BY NMR OF 291-352, DOMAIN.
[10]	"Mechanism of endophilin N-BAR domain-mediated membrane curvature." Gallop J.L., Jao C.C., Kent H.M., Butler P.J., Evans P.R., Langen R., McMahon H.T. EMBO J. 25:2898-2910(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 25-247, FUNCTION, SUBUNIT, DOMAIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AI044966 mRNA. No translation available.
AC112121 mRNA. No translation available.
AF009603 mRNA. Translation: AAC14883.1.

IPI

IPI00358767.

RefSeq

NP_446387.1. NM_053935.1.

UniGene

Rn.10787.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C08	X-ray	2.90	A	25-247	[»]
2KNB	NMR	-	B	291-352	[»]
3IQL	X-ray	1.40	A/B	291-352	[»]

ProteinModelPortal

O35179.

SMR

O35179. Positions 9-247, 293-352.

ModBase

Search...

Protein-protein interaction databases

IntAct

O35179. 2 interactions.

MINT

MINT-1037287.

STRING

10116.ENSRNOP00000008999.

Proteomic databases

PaxDb

O35179.

PRIDE

O35179.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

116743.

KEGG

rno:116743.

UCSC

RGD:620276. rat.

Organism-specific databases

CTD

6456.

RGD

620276. Sh3gl2.

Phylogenomic databases

eggNOG

NOG307129.

HOGENOM

HOG000231641.

HOVERGEN

HBG052866.

InParanoid

O35179.

KO

K11247.

Enzyme and pathway databases

Reactome

REACT_111984. Signal Transduction.

Gene expression databases

ArrayExpress

O35179.

Genevestigator

O35179.

GermOnline

ENSRNOG00000006761. Rattus norvegicus.

Family and domain databases

Gene3D

1.20.1270.60. 1 hit.

InterPro

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

Pfam

PF03114. BAR. 1 hit.
PF00018. SH3_1. 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

O35179.

NextBio

619680.

Entry information

Entry name

SH3G2_RAT

Accession

Primary (citable) accession number: O35179

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	October 23, 2007
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program