Q8K382

EV
Gene name
Dennd1a
Protein name
DENN domain-containing protein 1A
Names
Connecdenn 1, Connecdenn
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:227801
EC number
Protein Class
DENN DOMAIN-CONTAINING (PTHR13196)

Descriptions

Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. It appears that through an intramolecular interaction, the C-terminal region of connecdenn 1 obstructs substrate binding and reduces GEF activity. In the case of connecdenn 1, this activity is mediated by interaction of the DENN domain with a C-terminal region containing Ser-536 and Ser-538.

Autoinhibitory domains (AIDs)

527-547 (C-terminal autoinhibitory region) EV

Target domain

1-406 (DENN domain)

Relief mechanism

PTM

Assay

Deletion assay, Split protein assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8K382

Entry ID Method Resolution Chain Position Source
AF-Q8K382-F1 Predicted AlphaFoldDB

4 variants for Q8K382

Variant ID(s) Position Change Description Diseaes Association Provenance
rs261256160 483 L>F No Ensembl
rs257849049 689 T>A No Ensembl
rs232604594 802 T>S No Ensembl
rs221749747 1005 V>M No Ensembl

No associated diseases with Q8K382

3 regional properties for Q8K382

Type Name Position InterPro Accession
domain cDENN domain 92 - 273 IPR001194
domain uDENN domain 9 - 91 IPR005113
domain Tripartite DENN domain 13 - 378 IPR037516

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasmic vesicle, clathrin-coated vesicle membrane ; Peripheral membrane protein
  • Presynaptic cell membrane
  • Associates to membranes via lipid-binding activity
PANTHER Family PTHR13196 DENN DOMAIN-CONTAINING
PANTHER Subfamily PTHR13196:SF22 DENN DOMAIN-CONTAINING PROTEIN 1A
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
clathrin-coated vesicle A vesicle with a coat formed of clathrin connected to the membrane via one of the clathrin adaptor complexes.
clathrin-coated vesicle membrane The lipid bilayer surrounding a clathrin-coated vesicle.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
intracellular membrane-bounded organelle Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
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.
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
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.
phosphatidylinositol phosphate binding Binding to phosphatidylinositol phosphate.
phosphatidylinositol-3-phosphate binding Binding to phosphatidylinositol-3-phosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 3' position.
SH3 domain binding Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
small GTPase binding Binding to a small monomeric GTPase.

6 GO annotations of biological process

Name Definition
endocytic recycling The directed movement of membrane-bounded vesicles from endosomes back to the plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins.
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.
positive regulation of GTPase activity Any process that activates or increases the activity of a GTPase.
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 Rab protein signal transduction Any process that modulates the frequency, rate or extent of Rab protein signal transduction.
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.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q6P3S1 DENND1B DENN domain-containing protein 1B Homo sapiens (Human) SS
Q8TEH3 DENND1A DENN domain-containing protein 1A Homo sapiens (Human) SS
Q8C4S8 Dennd2a DENN domain-containing protein 2A Mus musculus (Mouse) PR
Q3U1T9 Dennd1b DENN domain-containing protein 1B Mus musculus (Mouse) PR
10 20 30 40 50 60
MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD
70 80 90 100 110 120
SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT
130 140 150 160 170 180
TKRQESQWNE LLETLHRLPI PDPGVSVHLS VHSYFTVPDS RELPSIPENR NLTEYFVAVD
190 200 210 220 230 240
VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC
250 260 270 280 290 300
APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV
310 320 330 340 350 360
STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFSEE AFVSHYRSGA MKQFLQNATQ
370 380 390 400 410 420
LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK
430 440 450 460 470 480
TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDITENGCV SSAEDPLPKT MPSPQAETQD
490 500 510 520 530 540
PRLREDRRPI TVHFGQVRPP RPHVVRRPKS NITVEGRRTS VSSPEQPQPY RTLKESDSAE
550 560 570 580 590 600
GDETESPEQL VREPWGPTPA PPDRAASIDL LEDVFSSLDV EAPLQPLGQA KSLEDLRAPK
610 620 630 640 650 660
DLREQPGSFD YQRLDLCRSE RGLSMAAALK LAHPYTKLWS LGQDDMAIPS KPSITSPEKP
670 680 690 700 710 720
SALLGTSPAL PLRPQNQEGI LSPSIKEETP IPTPGSITIP RPQGRKTPEL GIVPPPPTAR
730 740 750 760 770 780
PAKLQAAGGP LGDFSSEPLQ MDRERQAALS PALLSGLLPR AVPQGPTELL QPPSPAPGAA
790 800 810 820 830 840
GTGSDALLAL LDPLNTAWSG STIPSHPATP SAATPFIPQL SFPPTVTPTP FVQTPLNPFV
850 860 870 880 890 900
PSVPVVPPSM PLSSTPARPF GTPPASLGPA YAPSILLSSS GFYAPHRSQP NLSALSMPNL
910 920 930 940 950 960
FGQIPMGAHT SPLQPLGPPA VAPSRIRTLP LARSSARAAE AKQGLALRPG ESPLLPPRPP
970 980 990 1000 1010
QSLQPTPQPS VPTQARDPFE DLLRKTKQDV SPSPAPALAP ASTSVEQLRR QWETFE