Descriptions
Intersection-1L (Itsn1) is a member of the Dbl homology (DH) domain quinine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Itsn1 is a GEF specific for Cdc42 and plays an important role in endocytosis. The five SH3 domains of Itsn1 are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. The actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction, which may block or distort the GTPase binding region of the DH domain.
Autoinhibitory domains (AIDs)
Target domain |
1162-1512 (DH-PH domains) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Ahmad KF et al. (2010) "The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin", PloS one, 5, e11291
- Murayama K et al. (2007) "Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism", The Journal of biological chemistry, 282, 4238-4242
- Kintscher C et al. (2010) "Autoinhibition of GEF activity in Intersectin 1 is mediated by the short SH3-DH domain linker", Protein science : a publication of the Protein Society, 19, 2164-74
- Gerth F et al. (2019) "Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain", Structure (London, England : 1993), 27, 977-987.e5
Autoinhibited structure
Activated structure
1 structures for Q9Z0R6
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9Z0R6-F1 | Predicted | AlphaFoldDB |
No variants for Q9Z0R6
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q9Z0R6 | |||||
No associated diseases with Q9Z0R6
12 regional properties for Q9Z0R6
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Receptor L-domain | 52 - 172 | IPR000494-1 |
| domain | Receptor L-domain | 366 - 484 | IPR000494-2 |
| domain | Protein kinase domain | 720 - 987 | IPR000719 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 722 - 975 | IPR001245 |
| domain | Furin-like cysteine-rich domain | 190 - 343 | IPR006211 |
| repeat | Furin-like repeat | 232 - 280 | IPR006212-1 |
| repeat | Furin-like repeat | 501 - 552 | IPR006212-2 |
| repeat | Furin-like repeat | 557 - 607 | IPR006212-3 |
| active_site | Tyrosine-protein kinase, active site | 841 - 853 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 726 - 753 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 720 - 976 | IPR020635 |
| domain | Growth factor receptor domain 4 | 511 - 642 | IPR032778 |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| intracellular vesicle | Any vesicle that is part of the intracellular region. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| presynaptic membrane | A specialized area of membrane of the axon terminal that faces the plasma membrane of the neuron or muscle fiber with which the axon terminal establishes a synaptic junction; many synaptic junctions exhibit structural presynaptic characteristics, such as conical, electron-dense internal protrusions, that distinguish it from the remainder of the axon plasma membrane. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| calcium ion binding | Binding to a calcium ion (Ca2+). |
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
| molecular adaptor activity | The binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way. |
4 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| clathrin-dependent synaptic vesicle endocytosis | Clathrin-dependent endocytosis of presynaptic membrane regions comprising synaptic vesicles' membrane constituents. This is a relatively slow process occurring in the range of tens of seconds. |
| endosomal transport | The directed movement of substances mediated by an endosome, a membrane-bounded organelle that carries materials enclosed in the lumen or located in the endosomal membrane. |
| positive regulation of Rho protein signal transduction | Any process that activates or increases the frequency, rate or extent of Rho protein signal transduction. |
6 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| E1BKY4 | ITSN1 | Intersectin 1 | Bos taurus (Bovine) | SS |
| Q15811 | ITSN1 | Intersectin-1 | Homo sapiens (Human) | EV SS |
| Q9NZM3 | ITSN2 | Intersectin-2 | Homo sapiens (Human) | SS |
| Q9Z0R4 | Itsn1 | Intersectin-1 | Mus musculus (Mouse) | EV |
| Q80XA6 | Reps2 | RalBP1-associated Eps domain-containing protein 2 | Mus musculus (Mouse) | PR |
| Q9WVE9 | Itsn1 | Intersectin-1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MMAQFPTAMN | GGPNMWAITS | EERTKHDKQF | DNLKPSGGYI | TGDQARTFFL | QSGLPAPVLA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EIWALSDLNK | DGKMDQQEFS | IAMKLIKLKL | QGQQLPVVLP | PIMKQPPMFS | PLISARFGMG |
| 130 | 140 | 150 | 160 | 170 | 180 |
| SMPNLSIHQP | LPPVAPIATP | LSSATSGTSI | PPLMMPAPLV | PSVSTSSLPN | GTASLIQPLS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| IPYSSSTLPH | ASSYSLMMGG | FGGASIQKAQ | SLIDLGSSSS | TSSTASLSGN | SPKTGTSEWA |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VPQPSRLKYR | QKFNSLDKGM | SGYLSGFQAR | NALLQSNLSQ | TQLATIWTLA | DIDGDGQLKA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EEFILAMHLT | DMAKAGQPLP | LTLPPELVPP | SFRGGKQVDS | VNGTLPSYQK | TQEEEPQKKL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PVTFEDKRKA | NYERGNMELE | KRRQVLMEQQ | QREAERKAQK | EKEEWERKQR | ELQEQEWKKQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LELEKRLEKQ | RELERQREEE | RRKEIERREA | AKQELERQRR | LEWERLRRQE | LLSQKTREQE |
| 490 | 500 | 510 | 520 | 530 | 540 |
| DIVRLSSRKK | SLHLELEAVN | GKHQQISGRL | QDVQIRKQTQ | KTELEVLDKQ | CDLEIMEIKQ |
| 550 | 560 | 570 | 580 | 590 | 600 |
| LQQELKEYQN | KLIYLVPEKQ | LLNERIKNMQ | LSNTPDSGIS | LLHKKSSEKE | ELCQRLKEQL |
| 610 | 620 | 630 | 640 | 650 | 660 |
| DALEKETASK | LSEMDSFNNQ | LKELRESYNT | QQLALEQLHK | IKRDKLKEIE | RKRLEQIQKK |
| 670 | 680 | 690 | 700 | 710 | 720 |
| KLEDEAARKA | KQGKENLWRE | SIRKEEEEKQ | KRLQEEKSQD | KTQEEERKAE | AKQSETASAL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| VNYRALYPFE | ARNHDEMSFS | SGDIIQVDEK | TVGEPGWLYG | SFQGKFGWFP | CNYVEKVLSS |
| 790 | 800 | 810 | 820 | 830 | 840 |
| EKALSPKKAL | LPPTVSLSAT | STSSQPPASV | TDYHNVSFSN | LTVNTTWQQK | SAFTRTVSPG |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SVSPIHGQGQ | AVENLKAQAL | CSWTAKKENH | LNFSKHDVIT | VLEQQENWWF | GEVHGGRGWF |
| 910 | 920 | 930 | 940 | 950 | 960 |
| PKSYVKLIPG | NEVQRGEPEA | LYAAVTKKPT | STAYPVTSTA | YPVGEDYIAL | YSYSSVEPGD |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| LTFTEGEEIL | VTQKDGEWWT | GSIGERTGIF | PSNYVRPKDQ | ENFGNASKSG | ASNKKPEIAQ |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| VTSAYAASGT | EQLSLAPGQL | ILILKKNTSG | WWQGELQARG | KKRQKGWFPA | SHVKLLGPSS |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| ERTMPTFHAV | CQVIAMYDYM | ANNEDELNFS | KGQLINVMNK | DDPDWWQGET | NGLTGLFPSN |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| YVKMTTDSDP | SQQWCADLQA | LDTMQPTERK | RQGYIHELIQ | TEERYMDDDL | QLVIEVFQKR |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| MAEEGFLTEA | DMALIFVNWK | ELIMSNTKLL | RALRVRKKTG | GEKMPVQMIG | DILAAELSHM |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| QAYIRFCSCQ | LNGATLLQQK | TDEDTDFKEF | LKKLASDPRC | KGMPLSSFLL | KPMQRITRYP |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| LLIRSILENT | PQSHVDHSSL | KLALERAEEL | CSQVNEGVRE | KENSDRLEWI | QAHVQCEGLA |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| EQLIFNSLTN | CLGPRKLLHS | GKLYKTKSNK | ELHAFLFNDF | LLLTYLVRQF | AAASGHEKLF |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| NSKSSAQFRM | YKTPIFLNEV | LVKLPTDPSG | DEPVFHISHI | DRVYTLRTDN | INERTAWVQK |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| IKGASEQYID | TEKKKREKAY | QARSQKTSGI | GRLMVHVIEA | TELKACKPNG | KSNPYCEVSM |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| GSQSYTTRTL | QDTLNPKWNF | NCQFFIKDLY | QDVLCLTMFD | RDQFSPDDFL | GRTEVPVAKI |
| 1630 | 1640 | 1650 | |||
| RTEQESKGPT | TRRLLLHEVP | TGEVWVRFDL | QLFEQKTLL |