Details for: PSD

Gene ID: 5662

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PSD

Ensembl ID: ENSG00000059915

Description: pleckstrin and Sec7 domain containing

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • myofibroblast cell CL0000186
    CSI 11.48
    rCSI 15.9%
    PRS 80.94
  • lung neuroendocrine cell CL1000223
    CSI 7.08
    rCSI 10.47%
    PRS 87.29
  • astrocyte of the cerebral cortex CL0002605
    CSI 5.13
    rCSI 11.5%
    PRS 68.87
  • smooth muscle cell CL0000192
    CSI 4.56
    rCSI 10.88%
    PRS 79.93
  • enteric smooth muscle cell CL0002504
    CSI 4.27
    rCSI 6.09%
    PRS 85.09
  • interneuron CL0000099
    CSI 3.24
    rCSI 6.5%
    PRS 76.13
  • ON-bipolar cell CL0000749
    CSI 3.11
    rCSI 4.63%
    PRS 84
  • pancreatic D cell CL0000173
    CSI 2.93
    rCSI 2.88%
    PRS 86.53
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.46
    rCSI 3.17%
    PRS 69.18
  • retinal cone cell CL0000573
    CSI 2.37
    rCSI 3.82%
    PRS 75.38
  • cerebral cortex neuron CL0010012
    CSI 2.32
    rCSI 9.44%
    PRS 76.42
  • pancreatic A cell CL0000171
    CSI 2.28
    rCSI 2.39%
    PRS 87.4
  • sncg GABAergic cortical interneuron CL4023015
    CSI 2.22
    rCSI 3.56%
    PRS 69.41
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.17
    rCSI 7.82%
    PRS 65.94
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.04
    rCSI 4.95%
    PRS 65.8
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.01
    rCSI 2.5%
    PRS 65.92
  • rod bipolar cell CL0000751
    CSI 1.98
    rCSI 3.55%
    PRS 78.39
  • retinal rod cell CL0000604
    CSI 1.97
    rCSI 3.48%
    PRS 79.9
  • direct pathway medium spiny neuron CL4023026
    CSI 1.93
    rCSI 46.11%
    PRS 65.86
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.91
    rCSI 46.19%
    PRS 66.35
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.86
    rCSI 2.22%
    PRS 68.12
  • enteroendocrine cell CL0000164
    CSI 1.84
    rCSI 2.51%
    PRS 83.65
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.73
    rCSI 3.06%
    PRS 67.56
  • retinal bipolar neuron CL0000748
    CSI 1.67
    rCSI 3.12%
    PRS 73.9
  • inhibitory interneuron CL0000498
    CSI 1.63
    rCSI 3.77%
    PRS 73.13
  • neural cell CL0002319
    CSI 1.55
    rCSI 5.86%
    PRS 67.69
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.55
    rCSI 4.84%
    PRS 71.74
  • OFF-bipolar cell CL0000750
    CSI 1.5
    rCSI 2.05%
    PRS 85.09
  • amacrine cell CL0000561
    CSI 1.33
    rCSI 3.86%
    PRS 74.53
  • glutamatergic neuron CL0000679
    CSI 1.29
    rCSI 2.64%
    PRS 71.77
  • S cone cell CL0003050
    CSI 1.22
    rCSI 5.35%
    PRS 79.04
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.2
    rCSI 2.86%
    PRS 72.04
  • glycinergic amacrine cell CL4030028
    CSI 1.16
    rCSI 3.02%
    PRS 78.61
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.11
    rCSI 4.18%
    PRS 68.41
  • type B pancreatic cell CL0000169
    CSI 0.99
    rCSI 2.19%
    PRS 84.17
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.97
    rCSI 1.63%
    PRS 67.97
  • GABAergic neuron CL0000617
    CSI 0.97
    rCSI 3.23%
    PRS 68.94
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.92
    rCSI 5.42%
    PRS 68.44
  • central nervous system neuron CL2000029
    CSI 0.89
    rCSI 6.53%
    PRS 73.14
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.89
    rCSI 2.92%
    PRS 70.95
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.85
    rCSI 2.66%
    PRS 69.5
  • retinal ganglion cell CL0000740
    CSI 0.84
    rCSI 1.85%
    PRS 71.37
  • pancreatic PP cell CL0002275
    CSI 0.76
    rCSI 3.02%
    PRS 89.81
  • dopaminergic neuron CL0000700
    CSI 0.62
    rCSI 3.5%
    PRS 71.28
  • eye photoreceptor cell CL0000287
    CSI 0.47
    rCSI 5.25%
    PRS 90.04

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PSD](/details-gene/5662) (pleckstrin and Sec7 domain containing) is a protein-coding gene located on chromosome 10q24.32. It encodes a guanyl-nucleotide exchange factor (GEF), a key regulatory protein in cellular signal transduction. Specifically, [PSD](/details-gene/5662) is involved in the [regulation of ARF protein signal transduction](/details-go/GO:0032012), which controls critical processes such as membrane trafficking and cytoskeletal dynamics. **Overall**, expression data reveals its highest significance in [myofibroblast cell](/details-cell/CL0000186) and a wide range of neuronal and neuroendocrine cell types, including [lung neuroendocrine cell](/details-cell/CL1000223) and [astrocyte of the cerebral cortex](/details-cell/CL0002605). This expression pattern, combined with its function, suggests dual roles for [PSD](/details-gene/5662) in both tissue remodeling and nervous system development and function. ## Cellular Roles and Expression Landscape The expression profile of [PSD](/details-gene/5662) highlights its importance in two major biological systems: mesenchymal/structural cells and the neuroendocrine system. **Overall**, the gene shows its highest significance score by a large margin in [myofibroblast cell](/details-cell/CL0000186) (CSI: 11.48), with high significance also observed in [smooth muscle cell](/details-cell/CL0000192) and [enteric smooth muscle cell](/details-cell/CL0002504). This suggests a fundamental role in cells responsible for generating contractile force, synthesizing extracellular matrix, and mediating tissue repair and fibrosis. Its function as an ARF GEF is consistent with the need for dynamic cytoskeletal rearrangement and membrane trafficking during cell migration and contraction in these cell types. Concurrently, [PSD](/details-gene/5662) is a significant gene across a diverse array of cells in the central and peripheral nervous systems. High significance is noted in [astrocyte of the cerebral cortex](/details-cell/CL0002605), multiple classes of neurons such as [interneuron](/details-cell/CL0000099), [cerebral cortex neuron](/details-cell/CL0010012), and various glutamatergic cortical neurons. This is strongly supported by its annotated localization to key synaptic structures like the [dendritic spine](/details-go/GO:0043197) and the [postsynaptic density, intracellular component](/details-go/GO:0099092). Its role extends to sensory and endocrine cells, with notable significance in [retinal cone cell](/details-cell/CL0000573), [lung neuroendocrine cell](/details-cell/CL1000223), and pancreatic islet cells ([pancreatic D cell](/details-cell/CL0000173) and [pancreatic A cell](/details-cell/CL0000171)), implicating it in processes like photoreception and hormone secretion. Research has also shown its participation in cytokinesis via targeting to the [cleavage furrow](/details-go/GO:0032154) ([Link](https://doi.org/10.1016/j.febslet.2013.03.042)). ## Pathways and Molecular Function The molecular function of [PSD](/details-gene/5662) is centered on its [guanyl-nucleotide exchange factor activity](/details-go/GO:0005085). As first suggested by its sequence homology containing Sec7 and pleckstrin-homology domains ([Link](https://pubmed.ncbi.nlm.nih.gov/9417912/)), [PSD](/details-gene/5662) activates small GTPases of the ARF family by promoting the exchange of GDP for GTP. This activation is a critical switch in many cellular signaling pathways. The primary annotated biological process for [PSD](/details-gene/5662) is the [regulation of arf protein signal transduction](/details-go/GO:0032012). ARF proteins are master regulators of vesicle budding, membrane trafficking, and actin cytoskeleton remodeling. This function directly underlies its role in [neuron projection development](/details-go/GO:0031175), where the precise control of membrane addition and cytoskeletal dynamics is essential for the formation of axons, dendrites, and dendritic spines. In the context of its high expression in neurons, the GEF activity of [PSD](/details-gene/5662) likely coordinates the trafficking of receptors and structural components to the postsynaptic density, thereby modulating synaptic strength and plasticity. In myofibroblasts and smooth muscle cells, this same ARF-mediated regulation of the cytoskeleton is crucial for cell migration, adhesion, and contraction. ## Research Directions The dual role of [PSD](/details-gene/5662) in both neuronal function and tissue fibrosis presents unique avenues for investigation. While no overt clinical associations are detailed beyond a general OMIM entry ([602327](https://omim.org/entry/602327)), its specific cellular expression patterns allow for the formulation of targeted hypotheses. 1. **Hypothesis 1:** Given its enrichment in multiple neuronal subtypes and its localization to the postsynaptic density, [PSD](/details-gene/5662) is essential for synaptic plasticity. A reduction in [PSD](/details-gene/5662) function would impair dendritic spine maturation and long-term potentiation (LTP) by disrupting ARF-dependent trafficking of glutamate receptors to the synapse. 2. **Hypothesis 2:** Based on its exceptionally high significance in [myofibroblast cell](/details-cell/CL0000186), [PSD](/details-gene/5662) is a key regulator of myofibroblast activation during wound healing and fibrosis. Its GEF activity is required to orchestrate the cytoskeletal reorganization necessary for the transition of fibroblasts into contractile, matrix-secreting myofibroblasts. **Experimental Proposal for Hypothesis 1:** To test the role of [PSD](/details-gene/5662) in synaptic plasticity, a conditional knockout mouse model could be generated with Cre-recombinase expressed under a neuron-specific promoter (e.g., CamKIIa). Electrophysiological recordings from hippocampal slices of these mice could directly assess whether the loss of [PSD](/details-gene/5662) ablates or reduces LTP. In parallel, primary neuronal cultures from these mice could be analyzed using super-resolution microscopy to quantify changes in dendritic spine density, morphology, and the synaptic localization of AMPA and NMDA receptors. **Therapeutic Potential:** The significant and specific expression of [PSD](/details-gene/5662) in [myofibroblast cell](/details-cell/CL0000186) suggests it could be a novel therapeutic target for anti-fibrotic therapies. As an enzyme, its GEF activity is a plausible target for inhibition by small molecules. A selective inhibitor of [PSD](/details-gene/5662) could potentially block the activation of myofibroblasts, thereby reducing scar tissue formation in diseases like idiopathic pulmonary fibrosis, cirrhosis, or systemic sclerosis. However, the gene's widespread and critical role in the central nervous system would be a major safety concern, likely requiring targeted drug delivery strategies to avoid neurological side effects.

Genular Protein ID: 2388436014

Symbol: PSD1_HUMAN

Name: PH and SEC7 domain-containing protein 1

UniProtKB Accession Codes:

A5PKW4 B1AKX7 D3DR87 Q15673 Q8IVG0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugCentral 1 EMBL 7 Ensembl 3 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 7 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9417912

Title: Identification of a novel gene, PSD, adjacent to NFKB2/lyt-10, which contains Sec7 and pleckstrin-homology domains.

PubMed ID: 9417912

DOI: 10.1006/geno.1997.5022

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 23603394

Title: EFA6 activates Arf6 and participates in its targeting to the Flemming body during cytokinesis.

PubMed ID: 23603394

DOI: 10.1016/j.febslet.2013.03.042

Sequence Information:

  • Length: 1024
  • Mass: 109543
  • Checksum: 74583FEAAB0E4E01
  • Sequence:
    • MAQGAMRFCS EGDCAISPPR CPRRWLPEGP VPQSPPASMY GSTGSLLRRV AGPGPRGREL 
GRVTAPCTPL RGPPSPRVAP SPWAPSSPTG QPPPGAQSSV VIFRFVEKAS VRPLNGLPAP 
GGLSRSWDLG GVSPPRPTPA LGPGSNRKLR LEASTSDPLP ARGGSALPGS RNLVHGPPAP 
PQVGADGLYS SLPNGLGGPP ERLATLFGGP ADTGFLNQGD TWSSPREVSS HAQRIARAKW 
EFFYGSLDPP SSGAKPPEQA PPSPPGVGSR QGSGVAVGRA AKYSETDLDT VPLRCYRETD 
IDEVLAEREE ADSAIESQPS SEGPPGTAYP PAPRPGPLPG PHPSLGSGNE DEDDDEAGGE 
EDVDDEVFEA SEGARPGSRM PLKSPVPFLP GTSPSADGPD SFSCVFEAIL ESHRAKGTSY 
TSLASLEALA SPGPTQSPFF TFELPPQPPA PRPDPPAPAP LAPLEPDSGT SSAADGPWTQ 
RGEEEEAEAR AKLAPGREPP SPCHSEDSLG LGAAPLGSEP PLSQLVSDSD SELDSTERLA 
LGSTDTLSNG QKADLEAAQR LAKRLYRLDG FRKADVARHL GKNNDFSKLV AGEYLKFFVF 
TGMTLDQALR VFLKELALMG ETQERERVLA HFSQRYFQCN PEALSSEDGA HTLTCALMLL 
NTDLHGHNIG KRMTCGDFIG NLEGLNDGGD FPRELLKALY SSIKNEKLQW AIDEEELRRS 
LSELADPNPK VIKRISGGSG SGSSPFLDLT PEPGAAVYKH GALVRKVHAD PDCRKTPRGK 
RGWKSFHGIL KGMILYLQKE EYKPGKALSE TELKNAISIH HALATRASDY SKRPHVFYLR 
TADWRVFLFQ APSLEQMQSW ITRINVVAAM FSAPPFPAAV SSQKKFSRPL LPSAATRLSQ 
EEQVRTHEAK LKAMASELRE HRAAQLGKKG RGKEAEEQRQ KEAYLEFEKS RYSTYAALLR 
VKLKAGSEEL DAVEAALAQA GSTEDGLPPS HSSPSLQPKP SSQPRAQRHS SEPRPGAGSG 
RRKP

Genular Protein ID: 1822716364

Symbol: Q86YI3_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q86YI3

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 2 InterPro 7 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 4 PeptideAtlas 1 Pfam 2 RefSeq 1 SAM 1 SMART 2 SUPFAM 2

Citations:

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 927
  • Mass: 99721
  • Checksum: F9E5543BAC3B5A7B
  • Sequence:
    • QIWRCPLQHH AESAPPLPAL SWAQPLLCLS SVSALGEQRP TPALGPGSNR KLRLEASTSD 
PLPARGGSAL PGSRNLVHGP PAPPQVGADG LYSSLPNGLG GPPERLATLF GGPADTGFMN 
QGDTWSSPRE VSSHAQRIAR AKWEFFYGSL DPPSSGAKPP EQAPPSPPGV GSRQGSGVAV 
GRAAKYSETD LDTVPLRCYR ETDIDEVLAE REEADSAIES QPSSEGPPGT AYPPAPRPGP 
LPGPHPSLGS GNEDEDDDEA GGEEDVDDEV FEASEGARPG SRMPLKSPVP FLPGTSPSAD 
GPDSFSCVFE AILESHRAKG TSYTSLASLE ALASPGPTQS PFFTFELPPQ PPAPRPDPPA 
PAPLAPLEPD SGTSSAADGP WTQRGEEEEA EARAKLAPGR EPPSPCHSED SLGLGAAPLG 
SEPPLSQLVS DSDSELDSTE RLALGSTDTL SNGQKADLEA AQRLAKRLYR LDGFRKADVA 
RHLGKNNDFS KLVAGEYLKF FVFTGMTLDQ ALRVFLKELA LMGETQERER VLAHFSQRYF 
QCNPEALSSE DGAHTLTCAL MLLNTDLHGH NIGKRMTCGD FIGNLECLND GGDFPRELLK 
ALYSSIKNEK LQWAIDEEEL RRSLSELADP NPKVIKRISG GSGSGSSPFL DLTPEPGAAV 
YKHGALVRKV HADPDCRKTP RGKRGWKSFH GILKGMILYL QKEEYKPGKA LSETELKNAI 
SIHNALATRA SDYSKRPHVF YLRTADWRVF LFLAPSLEQM QSWITRINVV AAMFSAPPFP 
AAVSSQKKFS RPLLPSAATR LSQEEQVRTH EAKLKAMASE LREHRAAQLG KKGRGKEAEE 
QRQKEAYLEF EKSRYSTYAA LLRVKLKAGS EELDAVEAAL AQAGSTEDGL PPSHSSPSLQ 
PKPSSQPRAQ RHSSEPRPGA GSGRRKP