Q99963 (SH3G3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endophilin-A3

Alternative name(s):
EEN-B2
Endophilin-3
SH3 domain protein 2C
SH3 domain-containing GRB2-like protein 3

Gene names

Name:	SH3GL3
Synonyms:	CNSA3, SH3D2C

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	347 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Implicated in endocytosis. May recruit other proteins to membranes with high curvature By similarity.
Subunit structure	Interacts with ARC By similarity. Interacts with DNM1, SGIP1 and SYNJ1. Interacts with the huntingtin exon 1 protein (HDEX1P) containing a glutamine repeat in the pathological range and promotes formation of insoluble polyglutamine-containing aggregates in vivo. Interacts with DYDC1. Interacts with FASLG. Interacts with ATX2. Interacts with BIN2. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.10
Subcellular location	Cytoplasm By similarity. Early endosome membrane; Peripheral membrane protein By similarity. Note: Associated with postsynaptic endosomes in hippocampal neurons. Associated with presynaptic endosomes in olfactory neurons By similarity.
Tissue specificity	Brain and testis.
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 By similarity.
Sequence similarities	Belongs to the endophilin family. Contains 1 BAR domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cytoplasm Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil SH3 domain
Ligand	Lipid-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Traceable author statement Ref.1. Source: ProtInc endocytosis Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-473910,EBI-473910
ATXN2	Q99700	7	EBI-473910,EBI-697691
HTT	P42858	4	EBI-473910,EBI-466029
SH3GL1	Q99961	3	EBI-473910,EBI-697911
SH3GL2	Q99962	4	EBI-473910,EBI-77938

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99963-1)

Also known as: EEN-B2-L1;

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: Q99963-2)

Also known as: EEN-B2-L2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.

Isoform 3 (identifier: Q99963-3)

Also known as: EEN-B2-L3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MSVAGLKKQFHKAS → MDGIFAGIICNQANRCLTWTSQ

Isoform 4 (identifier: Q99963-4)

Also known as: EEN-B2-L4;

The sequence of this isoform differs from the canonical sequence as follows:
     311-347: IITLTNQIDENWYEGMIHGESGFFPINYVEVIVPLPQ → GTFRKIKRETKIKMCRKKIVNIYKLKDQQH

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 347

347

Endophilin-A3

PRO_0000146750

Regions

Domain

18 – 249

232

BAR

Domain

285 – 344

60

SH3

Region

1 – 21

21

Membrane-binding amphipathic helix By similarity

Region

60 – 87

28

Required for dimerization upon membrane association By similarity

Region

218 – 254

37

Interaction with ARC By similarity

Coiled coil

181 – 201

21

Potential

Natural variations

Alternative sequence

1 – 69

69

Missing in isoform 2.

VSP_001441

Alternative sequence

1 – 14

14

MSVAG…FHKAS → MDGIFAGIICNQANRCLTWT SQ in isoform 3.

VSP_001440

Alternative sequence

311 – 347

37

IITLT…VPLPQ → GTFRKIKRETKIKMCRKKIV NIYKLKDQQH in isoform 4.

VSP_001442

Secondary structure

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347

Helix Strand Turn

Details...

Helix

31 – 58

28

Helix

62 – 69

8

Helix

89 – 104

16

Helix

109 – 138

30

Helix

140 – 148

9

Helix

150 – 172

23

Turn

173 – 176

4

Helix

180 – 206

27

Helix

209 – 246

38

Beta strand

289 – 294

6

Beta strand

311 – 327

17

Beta strand

330 – 335

6

Helix

336 – 338

3

Beta strand

339 – 342

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (EEN-B2-L1) [UniParc]. Last modified May 1, 1997. Version 1. Checksum: D68DA7B28574C4E6	FASTA	347	39,285
	10 20 30 40 50 60 MSVAGLKKQF HKASQLFSEK ISGAEGTKLD DEFLDMERKI DVTNKVVAEI LSKTTEYLQP 70 80 90 100 110 120 NPAYRAKLGM LNTVSKIRGQ VKTTGYPQTE GLLGDCMLKY GKELGEDSTF GNALIEVGES 130 140 150 160 170 180 MKLMAEVKDS LDINVKQTFI DPLQLLQDKD LKEIGHHLKK LEGRRLDYDY KKKRVGKIPD 190 200 210 220 230 240 EEVRQAVEKF EESKELAERS MFNFLENDVE QVSQLAVFIE AALDYHRQST EILQELQSKL 250 260 270 280 290 300 QMRISAASSV PRREYKPRPV KRSSSELNGV STTSVVKTTG SNIPMDQPCC RGLYDFEPEN 310 320 330 340 QGELGFKEGD IITLTNQIDE NWYEGMIHGE SGFFPINYVE VIVPLPQ
	Isoform 2 (EEN-B2-L2) [UniParc]. Checksum: E0C2DDBD871FBB09	FASTA	278	31,587
	10 20 30 40 50 60 MLNTVSKIRG QVKTTGYPQT EGLLGDCMLK YGKELGEDST FGNALIEVGE SMKLMAEVKD 70 80 90 100 110 120 SLDINVKQTF IDPLQLLQDK DLKEIGHHLK KLEGRRLDYD YKKKRVGKIP DEEVRQAVEK 130 140 150 160 170 180 FEESKELAER SMFNFLENDV EQVSQLAVFI EAALDYHRQS TEILQELQSK LQMRISAASS 190 200 210 220 230 240 VPRREYKPRP VKRSSSELNG VSTTSVVKTT GSNIPMDQPC CRGLYDFEPE NQGELGFKEG 250 260 270 DIITLTNQID ENWYEGMIHG ESGFFPINYV EVIVPLPQ
	Isoform 3 (EEN-B2-L3) [UniParc]. Checksum: AB91D787F6C13AFC	FASTA	355	40,196
	10 20 30 40 50 60 MDGIFAGIIC NQANRCLTWT SQQLFSEKIS GAEGTKLDDE FLDMERKIDV TNKVVAEILS 70 80 90 100 110 120 KTTEYLQPNP AYRAKLGMLN TVSKIRGQVK TTGYPQTEGL LGDCMLKYGK ELGEDSTFGN 130 140 150 160 170 180 ALIEVGESMK LMAEVKDSLD INVKQTFIDP LQLLQDKDLK EIGHHLKKLE GRRLDYDYKK 190 200 210 220 230 240 KRVGKIPDEE VRQAVEKFEE SKELAERSMF NFLENDVEQV SQLAVFIEAA LDYHRQSTEI 250 260 270 280 290 300 LQELQSKLQM RISAASSVPR REYKPRPVKR SSSELNGVST TSVVKTTGSN IPMDQPCCRG 310 320 330 340 350 LYDFEPENQG ELGFKEGDII TLTNQIDENW YEGMIHGESG FFPINYVEVI VPLPQ
	Isoform 4 (EEN-B2-L4) [UniParc]. Checksum: BC523D052F3E0114	FASTA	340	38,739
	10 20 30 40 50 60 MSVAGLKKQF HKASQLFSEK ISGAEGTKLD DEFLDMERKI DVTNKVVAEI LSKTTEYLQP 70 80 90 100 110 120 NPAYRAKLGM LNTVSKIRGQ VKTTGYPQTE GLLGDCMLKY GKELGEDSTF GNALIEVGES 130 140 150 160 170 180 MKLMAEVKDS LDINVKQTFI DPLQLLQDKD LKEIGHHLKK LEGRRLDYDY KKKRVGKIPD 190 200 210 220 230 240 EEVRQAVEKF EESKELAERS MFNFLENDVE QVSQLAVFIE AALDYHRQST EILQELQSKL 250 260 270 280 290 300 QMRISAASSV PRREYKPRPV KRSSSELNGV STTSVVKTTG SNIPMDQPCC RGLYDFEPEN 310 320 330 340 QGELGFKEGD GTFRKIKRET KIKMCRKKIV NIYKLKDQQH

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] (ISOFORM 1). 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] (ISOFORMS 1; 2; 3 AND 4). Tissue: Brain.
[3]	"SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates." Sittler A., Walter S., Wedemeyer N., Hasenbank R., Scherzinger E., Eickhoff H., Bates G.P., Lehrach H., Wanker E.E. Mol. Cell 2:427-436(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUNTINGTIN EXON 1 PROTEIN.
[4]	"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.
[5]	"Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance." Trevaskis J., Walder K., Foletta V., Kerr-Bayles L., McMillan J., Cooper A., Lee S., Bolton K., Prior M., Fahey R., Whitecross K., Morton G.J., Schwartz M.W., Collier G.R. Endocrinology 146:3757-3764(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SGIP1.
[6]	"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.
[7]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[8]	"Interaction of SH3P13 and DYDC1 protein: a germ cell component that regulates acrosome biogenesis during spermiogenesis." Li S., Qiao Y., Di Q., Le X., Zhang L., Zhang X., Zhang C., Cheng J., Zong S., Koide S.S., Miao S., Wang L. Eur. J. Cell Biol. 88:509-520(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DYDC1.
[9]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"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.
[11]	"Crystal structure of BAR domain of endophilin-III." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 22-256.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X99664 mRNA. Translation: CAA67978.1.
AF036269 mRNA. Translation: AAC04765.1.
AF036270 mRNA. Translation: AAC04766.1.
AF036271 mRNA. Translation: AAC04767.1.
AF036272 mRNA. Translation: AAC04768.1.

IPI

IPI00019172.
IPI00216201.
IPI00216202.
IPI00216203.

RefSeq

NP_003018.3. NM_003027.3.

UniGene

Hs.270055.
Hs.666365.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EW3	NMR	-	A	285-345	[»]
2Z0V	X-ray	2.49	A/B	22-256	[»]

ProteinModelPortal

Q99963.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99963. 29 interactions.

MINT

MINT-128532.

STRING

9606.ENSP00000391372.

PTM databases

PhosphoSite

Q99963.

Polymorphism databases

DMDM

12643798.

Proteomic databases

PaxDb

Q99963.

PRIDE

Q99963.

Protocols and materials databases

DNASU

6457.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000324537; ENSP00000320092; ENSG00000140600.
ENST00000427482; ENSP00000391372; ENSG00000140600.
ENST00000434347; ENSP00000397871; ENSG00000140600.

GeneID

6457.

KEGG

hsa:6457.

UCSC

uc002bju.3. human.
uc002bjw.3. human.

Organism-specific databases

CTD

6457.

GeneCards

GC15P084115.

H-InvDB

HIX0026775.

HGNC

HGNC:10832. SH3GL3.

HPA

HPA039381.

MIM

603362. gene.

neXtProt

NX_Q99963.

PharmGKB

PA35738.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG307129.

HOGENOM

HOG000231641.

HOVERGEN

HBG052866.

InParanoid

Q99963.

KO

K11247.

OMA

GMLNTMS.

OrthoDB

EOG4C2H9V.

Gene expression databases

ArrayExpress

Q99963.

Bgee

Q99963.

CleanEx

HS_SH3GL3.

Genevestigator

Q99963.

GermOnline

ENSG00000140600. Homo sapiens.

Family and domain databases

Gene3D

1.20.1270.60. 1 hit.

InterPro

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

Pfam

PF03114. BAR. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.

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

Q99963.

GenomeRNAi

6457.

NextBio

25097.

SOURCE

Search...

Entry information

Entry name

SH3G3_HUMAN

Accession

Primary (citable) accession number: Q99963
Secondary accession number(s): O43553, O43554

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 125 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.