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Q9Z0R4 (ITSN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Intersectin-1
Alternative name(s):
EH and SH3 domains protein 1
Gene names
Name:Itsn1
Synonyms:Ese1, Itsn
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1714 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Inhibits ARHGAP31 activity toward RAC1. Acts as guanine nucleotide exchange factor (GEF) specific for the CDC42 GTPase. Ref.11

Subunit structure

Interacts with dynamin, CDC42, SNAP25 and SNAP23. Clusters several dynamin in a manner that is regulated by alternative splicing. Interacts with clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31. Interacts with ADAM15. Ref.4 Ref.10

Subcellular location

Endomembrane system By similarity. Cell junctionsynapsesynaptosome By similarity. Cell projectionlamellipodium By similarity. Membraneclathrin-coated pit By similarity. Note: Colocalizes with SGIP1 at the plasma membrane in structures corresponding most problably to clathrin-coated pits By similarity.

Tissue specificity

Widely expressed. Expressed at high levels in brain, heart and skeletal muscle.

Domain

SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin By similarity. SH3-1 and SH3-4 bind to ARHGAP31. Ref.11

The KLERQ domain binds to SNAP-25 and SNAP-23 By similarity. Ref.11

In an autoinhibited form the SH3 domain 5 may bind intramolecularly to the DH domain, thus blocking the CDC42-binding site (Ref.11). Ref.11

Miscellaneous

Overexpression results in the inhibition of the transferrin uptake and the blockage of the clathrin-mediated endocytosis.

Sequence similarities

Contains 1 C2 domain.

Contains 1 DH (DBL-homology) domain.

Contains 2 EF-hand domains.

Contains 2 EH domains.

Contains 1 PH domain.

Contains 5 SH3 domains.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell junction
Cell projection
Coated pit
Membrane
Synapse
Synaptosome
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
SH3 domain
   LigandCalcium
Metal-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 17875942. Source: MGI

positive regulation of phosphorylation

Inferred from direct assay PubMed 17875942. Source: GOC

positive regulation of protein kinase B signaling

Inferred from direct assay PubMed 17875942. Source: MGI

small GTPase mediated signal transduction

Inferred from direct assay Ref.4. Source: MGI

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

endocytic vesicle

Inferred from direct assay PubMed 17875942. Source: MGI

lamellipodium

Inferred from direct assay Ref.4. Source: MGI

neuron projection

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: Ensembl

synapse

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionRho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

calcium ion binding

Inferred from electronic annotation. Source: InterPro

kinase activator activity

Inferred from direct assay PubMed 17875942. Source: MGI

protein binding

Inferred from physical interaction PubMed 17182770PubMed 21349274PubMed 18692052. Source: IntAct

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9Z0R4-1)

Also known as: Ese1L;

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: Q9Z0R4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1214-1714: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17141714Intersectin-1
PRO_0000080958

Regions

Domain21 – 10989EH 1
Domain53 – 8836EF-hand 1
Domain221 – 31090EH 2
Domain254 – 28936EF-hand 2
Domain738 – 79962SH3 1
Domain906 – 96459SH3 2
Domain995 – 105359SH3 3
Domain1067 – 113165SH3 4
Domain1148 – 120760SH3 5
Domain1230 – 1416187DH
Domain1455 – 1564110PH
Domain1576 – 167297C2
Calcium binding66 – 78131 Potential
Calcium binding267 – 279132 Potential
Region326 – 702377KLERQ
Coiled coil352 – 662311 Potential
Compositional bias321 – 3244Poly-Ser

Amino acid modifications

Modified residue2031Phosphoserine Ref.5
Modified residue3341Phosphoserine Ref.7
Modified residue3351Phosphoserine Ref.7
Modified residue8951Phosphoserine Ref.7
Modified residue8971Phosphoserine Ref.7
Modified residue9771Phosphothreonine Ref.7
Modified residue11301Phosphoserine Ref.6

Natural variations

Alternative sequence1214 – 1714501Missing in isoform 2.
VSP_004296

Experimental info

Sequence conflict1791L → W in AAD19749. Ref.1
Sequence conflict1791L → W in AAD19746. Ref.1
Sequence conflict4021R → A in AAD19749. Ref.1
Sequence conflict4021R → A in AAD19746. Ref.1

Secondary structure

....................................... 1714
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Ese1L) [UniParc].

Last modified October 3, 2012. Version 2.
Checksum: BCF5038160E8208E

FASTA1,714194,297
        10         20         30         40         50         60 
MAQFPTPFGG SLDVWAITVE ERAKHDQQFL SLKPIAGFIT GDQARNFFFQ SGLPQPVLAQ 

        70         80         90        100        110        120 
IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSTLPP VMKQQPVAIS SAPAFGIGGI 

       130        140        150        160        170        180 
ASMPPLTAVA PVPMGSIPVV GMSPPLVSSV PPAAVPPLAN GAPPVIQPLP AFAHPAATLP 

       190        200        210        220        230        240 
KSSSFSRSGP GSQLNTKLQK AQSFDVASAP PAAEWAVPQS SRLKYRQLFN SHDKTMSGHL 

       250        260        270        280        290        300 
TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP 

       310        320        330        340        350        360 
PEYIPPSFRR VRSGSGMSVI SSSSVDQRLP EEPSSEDEQQ PEKKLPVTFE DKKRENFERG 

       370        380        390        400        410        420 
SVELEKRRQA LLEQQRKEQE RLAQLERAEQ ERKERERQEQ ERKRQLELEK QLEKQRELER 

       430        440        450        460        470        480 
QREEERRKEI ERREAAKREL ERQRQLEWER NRRQELLNQR NKEQEGTVVL KARRKTLEFE 

       490        500        510        520        530        540 
LEALNDKKHQ LEGKLQDIRC RLATQRQEIE STNKSRELRI AEITHLQQQL QESQQMLGRL 

       550        560        570        580        590        600 
IPEKQILSDQ LKQVQQNSLH RDSLLTLKRA LEAKELARQQ LREQLDEVER ETRSKLQEID 

       610        620        630        640        650        660 
VFNNQLKELR EIHSKQQLQK QRSLEAARLK QKEQERKSLE LEKQKEDAQR RVQERDKQWL 

       670        680        690        700        710        720 
EHVQQEEQPR PRKPHEEDRL KREDSVRKKE AEERAKPEMQ DKQSRLFHPH QEPAKLATQA 

       730        740        750        760        770        780 
PWSTTEKGPL TISAQESVKV VYYRALYPFE SRSHDEITIQ PGDIVMVDES QTGEPGWLGG 

       790        800        810        820        830        840 
ELKGKTGWFP ANYAEKIPEN EVPTPAKPVT DLTSAPAPKL ALRETPAPLP VTSSEPSTTP 

       850        860        870        880        890        900 
NNWADFSSTW PSSSNEKPET DNWDTWAAQP SLTVPSAGQL RQRSAFTPAT ATGSSPSPVL 

       910        920        930        940        950        960 
GQGEKVEGLQ AQALYPWRAK KDNHLNFNKS DVITVLEQQD MWWFGEVQGQ KGWFPKSYVK 

       970        980        990       1000       1010       1020 
LISGPVRKST SIDTGPTESP ASLKRVASPA AKPAIPGEEF IAMYTYESSE QGDLTFQQGD 

      1030       1040       1050       1060       1070       1080 
VIVVTKKDGD WWTGTVGDKS GVFPSNYVRL KDSEGSGTAG KTGSLGKKPE IAQVIASYAA 

      1090       1100       1110       1120       1130       1140 
TGPEQLTLAP GQLILIRKKN PGGWWEGELQ ARGKKRQIGW FPANYVKLLS PGTSKITPTE 

      1150       1160       1170       1180       1190       1200 
LPKTAVQPAV CQVIGMYDYT AQNDDELAFS KGQIINVLNK EDPDWWKGEV SGQVGLFPSN 

      1210       1220       1230       1240       1250       1260 
YVKLTTDMDP SQQWCSDLHL LDMLTPTERK RQGYIHELIV TEENYVNDLQ LVTEIFQKPL 

      1270       1280       1290       1300       1310       1320 
TESELLTEKE VAMIFVNWKE LIMCNIKLLK ALRVRKKMSG EKMPVKMIGD ILSAQLPHMQ 

      1330       1340       1350       1360       1370       1380 
PYIRFCSCQL NGAALIQQKT DEAPDFKEFV KRLAMDPRCK GMPLSSFILK PMQRVTRYPL 

      1390       1400       1410       1420       1430       1440 
IIKNILENTP ENHPDHSHLK HALEKAEELC SQVNEGVREK ENSDRLEWIQ AHVQCEGLSE 

      1450       1460       1470       1480       1490       1500 
QLVFNSVTNC LGPRKFLHSG KLYKAKSNKE LYGFLFNDFL LLTQITKPLG SSGTDKVFSP 

      1510       1520       1530       1540       1550       1560 
KSNLQYKMYK TPIFLNEVLV KLPTDPSGDE PIFHISHIDR VYTLRAESIN ERTAWVQKIK 

      1570       1580       1590       1600       1610       1620 
AASELYIETE KKKREKAYLV RSQRATGIGR LMVNVVEGIE LKPCRSHGKS NPYCEVTMGS 

      1630       1640       1650       1660       1670       1680 
QCHITKTIQD TLNPKWNSNC QFFIRDLEQE VLCITVFERD QFSPDDFLGR TEIRVADIKK 

      1690       1700       1710 
DQGSKGPVTK CLLLHEVPTG EIVVRLDLQL FDEP 

« Hide

Isoform 2 [UniParc].

Checksum: 1376AD0DFBD503C2
Show »

FASTA1,213136,607

References

« Hide 'large scale' references
[1]"The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15."
Sengar A.S., Wang W., Bishay J., Cohen S., Egan S.E.
EMBO J. 18:1159-1171(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"Mouse homologues of human chromosome 21 genes."
Skripkina I.Y., Tsyba L.O., Anoprienko O.V., Slavov D., Tassone F., Rynditch A.V., Gardiner K.
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 966-1714, NUCLEOTIDE SEQUENCE [MRNA] OF 545-599 (ISOFORMS 1 AND 2).
Strain: 129/Ola.
Tissue: Spleen.
[4]"The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin."
Jenna S., Hussain N.K., Danek E.I., Triki I., Wasiak S., McPherson P.S., Lamarche-Vane N.
J. Biol. Chem. 277:6366-6373(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARHGAP31.
[5]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[6]"Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334; SER-335; SER-895; SER-897 AND THR-977, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[9]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"FCHo proteins are nucleators of clathrin-mediated endocytosis."
Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., McMahon H.T.
Science 328:1281-1284(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FCHO2.
[11]"The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin."
Ahmad K.F., Lim W.A.
PLoS ONE 5:E11291-E11291(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1151-1431, SH3 DOMAIN, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF132481 mRNA. Translation: AAD19749.1.
AF132478 mRNA. Translation: AAD19746.1.
AC126053 Genomic DNA. No translation available.
AC131691 Genomic DNA. No translation available.
AC134837 Genomic DNA. No translation available.
AF169621 mRNA. Translation: AAD48848.1.
AF356517 Genomic DNA. Translation: AAK40228.1.
CCDSCCDS37402.1. [Q9Z0R4-1]
CCDS49913.1. [Q9Z0R4-2]
RefSeqNP_001103745.1. NM_001110275.1. [Q9Z0R4-2]
NP_034717.2. NM_010587.2. [Q9Z0R4-1]
UniGeneMm.40546.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3HS8X-ray1.90P840-851[»]
3JV3X-ray2.40A/B1151-1431[»]
ProteinModelPortalQ9Z0R4.
SMRQ9Z0R4. Positions 1-111, 210-312, 909-962, 998-1053, 1063-1574, 1588-1711.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200851. 10 interactions.
IntActQ9Z0R4. 11 interactions.
MINTMINT-86500.
STRING10090.ENSMUSP00000066361.

PTM databases

PhosphoSiteQ9Z0R4.

Proteomic databases

MaxQBQ9Z0R4.
PaxDbQ9Z0R4.
PRIDEQ9Z0R4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000056482; ENSMUSP00000056011; ENSMUSG00000022957. [Q9Z0R4-2]
ENSMUST00000114002; ENSMUSP00000109635; ENSMUSG00000022957. [Q9Z0R4-1]
GeneID16443.
KEGGmmu:16443.

Organism-specific databases

CTD6453.
MGIMGI:1338069. Itsn1.

Phylogenomic databases

eggNOGCOG5422.
GeneTreeENSGT00750000117388.
HOGENOMHOG000010175.
HOVERGENHBG052159.
TreeFamTF324293.

Gene expression databases

ArrayExpressQ9Z0R4.
CleanExMM_ITSN1.
GenevestigatorQ9Z0R4.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR000219. DH-domain.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EPS15_homology.
IPR001331. GDS_CDC24_CS.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 1 hit.
PF14604. SH3_9. 4 hits.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00239. C2. 1 hit.
SM00054. EFh. 2 hits.
SM00027. EH. 2 hits.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 5 hits.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF50044. SSF50044. 5 hits.
PROSITEPS50004. C2. 1 hit.
PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
PS50031. EH. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSITSN1. mouse.
EvolutionaryTraceQ9Z0R4.
NextBio289695.
PROQ9Z0R4.
SOURCESearch...

Entry information

Entry nameITSN1_MOUSE
AccessionPrimary (citable) accession number: Q9Z0R4
Secondary accession number(s): F8VQE5, Q9R143
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: October 3, 2012
Last modified: July 9, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot