Q9Z0R4

EV
Gene name
Itsn1 (Ese1)
Protein name
Intersectin-1
Names
EH and SH3 domains protein 1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:16443
EC number
Protein Class
RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR AT 64C, ISOFORM A (PTHR46006)

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 (SH3E) being sufficient for the bulk of the autoinhibitory effect. The actual autoinhibited structure contains the related intramolecular SH3E-DH interaction, which may block or distort the GTPase binding region of the DH domain.
SH3A is involved in the interaction of Itsn1 with synapsin and it is autoinhibited by its adjacent N-terminal and C-terminal sequences.

Autoinhibitory domains (AIDs)

719-738 (N-terminal linker of SH3A) EV

Target domain

739-796 (SH3A domain)

Relief mechanism

Assay

Structural analysis, Deletion assay, Split protein assay

797-833 (C-terminal linker of SH3A) EV

Target domain

739-796 (SH3A domain)

Relief mechanism

PTM

Assay

Structural analysis, Deletion assay, Split protein assay

1151-1203 (SH3E domain) EV

Target domain

1230-1416 (DH domain)

Relief mechanism

Partner binding, Ligand binding

Assay

Deletion assay, Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

3 structures for Q9Z0R4

Entry ID Method Resolution Chain Position Source
3HS8 X-ray 190 A P 840-851 PDB
3JV3 X-ray 240 A A/B 1151-1431 PDB
AF-Q9Z0R4-F1 Predicted AlphaFoldDB

15 variants for Q9Z0R4

Variant ID(s) Position Change Description Diseaes Association Provenance
rs238282963 162 A>T No Ensembl
rs231683120 337 D>E No Ensembl
rs252251426 344 K>R No Ensembl
rs263959163 361 S>N No Ensembl
rs213234804 362 V>L No Ensembl
rs220054936 387 R>G No Ensembl
rs33602308 506 R>K No Ensembl
rs228954227 539 R>K No Ensembl
rs252241684 691 A>T No Ensembl
rs219767048 704 S>I No Ensembl
rs259490235 712 E>D No Ensembl
rs248034470 716 L>P No Ensembl
rs265829309 718 T>I No Ensembl
rs212699777 754 H>Q No Ensembl
rs222355269 1225 T>S No Ensembl

No associated diseases with Q9Z0R4

4 regional properties for Q9Z0R4

Type Name Position InterPro Accession
ptm P-type ATPase, phosphorylation site 454 - 460 IPR018303
domain P-type ATPase, C-terminal 917 - 1171 IPR032630
domain P-type ATPase, N-terminal 79 - 142 IPR032631
domain P-type ATPase, haloacid dehalogenase domain 436 - 940 IPR044492

Functions

Description
EC Number
Subcellular Localization
  • Endomembrane system
  • Synapse, synaptosome
  • Cell projection, lamellipodium
  • Cell membrane
  • Membrane, clathrin-coated pit
  • Recycling endosome
  • Endosome
  • Cytoplasmic vesicle
  • Colocalizes with SGIP1 at the plasma membrane in structures corresponding most probably to clathrin-coated pits
  • Colocalizes with RAB13 on cytoplasmic vesicles that are most likely recycling endosomes
PANTHER Family PTHR46006 RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR AT 64C, ISOFORM A
PANTHER Subfamily PTHR46006:SF9 INTERSECTIN-2 ISOFORM X1
PANTHER Protein Class guanyl-nucleotide exchange factor
G-protein modulator
protein-binding activity modulator
PANTHER Pathway Category No pathway information available

17 GO annotations of cellular component

Name Definition
apical dendrite A dendrite that emerges near the apical pole of a neuron. In bipolar neurons, apical dendrites are located on the opposite side of the soma from the axon.
calyx of Held The terminal specialization of a calyciferous axon which forms large synapses in the mammalian auditory central nervous system.
clathrin-coated pit A part of the endomembrane system in the form of an invagination of a membrane upon which a clathrin coat forms, and that can be converted by vesicle budding into a clathrin-coated vesicle. Coated pits form on the plasma membrane, where they are involved in receptor-mediated selective transport of many proteins and other macromolecules across the cell membrane, in the trans-Golgi network, and on some endosomes.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendritic spine A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
endocytic vesicle A membrane-bounded intracellular vesicle formed by invagination of the plasma membrane around an extracellular substance. Endocytic vesicles fuse with early endosomes to deliver the cargo for further sorting.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
intracellular vesicle Any vesicle that is part of the intracellular region.
lamellipodium A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
nuclear envelope The double lipid bilayer enclosing the nucleus and separating its contents from the rest of the cytoplasm; includes the intermembrane space, a gap of width 20-40 nm (also called the perinuclear space).
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic actin cytoskeleton The actin cytoskeleton that is part of a postsynapse.
presynaptic endocytic zone A specialized region of the plasma membrane and underlying cytoplasm which surround the the active zone, into which synaptic vesicle membranes are recycled following exocytosis. It is especially enriched in endocytic proteins following intense activity.
recycling endosome An organelle consisting of a network of tubules that functions in targeting molecules, such as receptors transporters and lipids, to the plasma membrane.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

5 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.
kinase activator activity Binds to and increases the activity of a kinase, an enzyme which catalyzes of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
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.
proline-rich region binding Binding to a proline-rich region, i.e. a region that contains a high proportion of proline residues, in a protein.

13 GO annotations of biological process

Name Definition
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.
endocytosis A vesicle-mediated transport process in which cells take up external materials or membrane constituents by the invagination of a small region of the plasma membrane to form a new membrane-bounded vesicle.
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.
exocytosis A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell.
negative regulation of neuron apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
positive regulation of caveolin-mediated endocytosis Any process that activates or increases the frequency, rate or extent of caveolin-mediated endocytosis.
positive regulation of dendritic spine development Any process that increases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
positive regulation of growth hormone secretion Any process that increases the frequency, rate or extent of the regulated release of growth hormone from a cell.
positive regulation of protein kinase B signaling Any process that activates or increases the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
protein transport The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
regulation of modification of postsynaptic actin cytoskeleton Any process that modulates the frequency, rate or extent of modification of postsynaptic actin cytoskeleton.
small GTPase mediated signal transduction The series of molecular signals in which a small monomeric GTPase relays a signal.
synaptic vesicle endocytosis A vesicle-mediated transport process, in which the synaptic vesicle membrane constituents are retrieved from the presynaptic membrane on the axon terminal after neurotransmitter secretion by exocytosis. Synaptic vesicle endocytosis can occur via clathrin-dependent and clathrin-independent mechanisms.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
E1BKY4 ITSN1 Intersectin 1 Bos taurus (Bovine) SS
A0A2I2U1K8 ITSN1 Intersectin 1 Felis catus (Cat) (Felis silvestris catus) SS
A0A2I3T257 ITSN1 Intersectin 1 Pan troglodytes (Chimpanzee) SS
Q9NZM3 ITSN2 Intersectin-2 Homo sapiens (Human) SS
Q15811 ITSN1 Intersectin-1 Homo sapiens (Human) EV SS
Q80XA6 Reps2 RalBP1-associated Eps domain-containing protein 2 Mus musculus (Mouse) PR
Q9Z0R6 Itsn2 Intersectin-2 Mus musculus (Mouse) SS
Q9WVE9 Itsn1 Intersectin-1 Rattus norvegicus (Rat) SS
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