Details for: PKDCC

Gene ID: 91461

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: PKDCC

Ensembl ID: ENSG00000162878

Description: protein kinase domain containing, cytoplasmic

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • peripheral nervous system neuron CL2000032
    CSI 5.54
    rCSI 7.55%
    PRS 84.82
  • neural progenitor cell CL0011020
    CSI 5.29
    rCSI 23.28%
    PRS 80.57
  • hepatic stellate cell CL0000632
    CSI 3.89
    rCSI 14.58%
    PRS 86.39
  • subcutaneous adipocyte CL0002521
    CSI 3.6
    rCSI 18.43%
    PRS 92.63
  • myofibroblast cell CL0000186
    CSI 3.2
    rCSI 4.43%
    PRS 87.7
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.07
    rCSI 3.36%
    PRS 92.19
  • intestine goblet cell CL0019031
    CSI 2.77
    rCSI 2.46%
    PRS 88.58
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.67
    rCSI 16.65%
    PRS 84.88
  • vascular leptomeningeal cell CL4023051
    CSI 2.64
    rCSI 4.63%
    PRS 87.34
  • colon epithelial cell CL0011108
    CSI 2.63
    rCSI 2.75%
    PRS 88.73
  • stem cell CL0000034
    CSI 2.62
    rCSI 2.53%
    PRS 86.95
  • mesodermal cell CL0000222
    CSI 2.58
    rCSI 3.1%
    PRS 89.75
  • adipocyte CL0000136
    CSI 2.52
    rCSI 3.24%
    PRS 82.92
  • intestinal epithelial cell CL0002563
    CSI 2.39
    rCSI 2.5%
    PRS 88.56
  • BEST4+ enteroycte CL4030026
    CSI 2.39
    rCSI 2.97%
    PRS 90.65
  • transit amplifying cell of colon CL0009011
    CSI 2.38
    rCSI 2.79%
    PRS 90.89
  • M cell of gut CL0000682
    CSI 2.36
    rCSI 2.51%
    PRS 92.86
  • enteroendocrine cell CL0000164
    CSI 2.29
    rCSI 3.13%
    PRS 89.39
  • alveolar adventitial fibroblast CL4028006
    CSI 2.1
    rCSI 3.32%
    PRS 91.63
  • enterocyte CL0000584
    CSI 2.08
    rCSI 3.36%
    PRS 88
  • enteric smooth muscle cell CL0002504
    CSI 2.07
    rCSI 2.96%
    PRS 90.91
  • goblet cell CL0000160
    CSI 2.04
    rCSI 1.92%
    PRS 88.77
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.01
    rCSI 4.88%
    PRS 76.16
  • intestinal tuft cell CL0019032
    CSI 1.91
    rCSI 2.92%
    PRS 92.56
  • epicardial adipocyte CL1000309
    CSI 1.84
    rCSI 5.99%
    PRS 88.17
  • paneth cell CL0000510
    CSI 1.79
    rCSI 2.65%
    PRS 95.66
  • fibroblast of cardiac tissue CL0002548
    CSI 1.79
    rCSI 8.57%
    PRS 91.58
  • retinal rod cell CL0000604
    CSI 1.57
    rCSI 2.77%
    PRS 86.97
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.46
    rCSI 3.77%
    PRS 88.18
  • basal cell of epidermis CL0002187
    CSI 1.41
    rCSI 2.5%
    PRS 62.69
  • stromal cell CL0000499
    CSI 1.28
    rCSI 3.6%
    PRS 87.06
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.23
    rCSI 3.31%
    PRS 92.89
  • transit amplifying cell CL0009010
    CSI 1.2
    rCSI 1.83%
    PRS 93.98
  • stromal cell of ovary CL0002132
    CSI 1.17
    rCSI 3.21%
    PRS 93.68
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.13
    rCSI 3.53%
    PRS 79.63
  • mesenchymal cell CL0008019
    CSI 1.09
    rCSI 2.77%
    PRS 85.96
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.98
    rCSI 5.67%
    PRS 88
  • transit amplifying cell of small intestine CL0009012
    CSI 0.97
    rCSI 4.25%
    PRS 93.83
  • enterocyte of epithelium of large intestine CL0002071
    CSI 0.94
    rCSI 4.92%
    PRS 92.57
  • podocyte CL0000653
    CSI 0.93
    rCSI 4.11%
    PRS 91.15
  • type EC enteroendocrine cell CL0000577
    CSI 0.91
    rCSI 3.23%
    PRS 92.02
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.91
    rCSI 3.27%
    PRS 76.32
  • enteroendocrine cell of colon CL0009042
    CSI 0.79
    rCSI 3.69%
    PRS 92.93
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.78
    rCSI 2.26%
    PRS 90.07
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 0.74
    rCSI 4.23%
    PRS 92.48
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.74
    rCSI 2.3%
    PRS 81.3
  • tracheobronchial serous cell CL0019001
    CSI 0.67
    rCSI 2.91%
    PRS 93.07
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.61
    rCSI 4.6%
    PRS 94.96
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.54
    rCSI 3.15%
    PRS 78.74
  • mesenchymal stem cell CL0000134
    CSI 0.49
    rCSI 5.34%
    PRS 92.64

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 [PKDCC](/details-gene/91461) (Protein Kinase Domain Containing, Cytoplasmic) is a protein-coding gene located on chromosome 2p21 that encodes a protein tyrosine kinase. Uniquely, evidence suggests this kinase is secreted and acts in the extracellular environment, phosphorylating substrates outside the cell ([Link](https://doi.org/10.1016/j.cell.2014.06.048)). Its functions are strongly linked to developmental processes, including [skeletal system development](/details-go/GO:0001501), [limb morphogenesis](/details-go/GO:0035108), and [bone mineralization](/details-go/GO:0030282). Consistent with this, biallelic mutations in [PKDCC](/details-gene/91461) are associated with a human skeletal disorder ([Link](https://doi.org/10.1136/jmedgenet-2018-105639)). Expression data indicates its most significant roles are in neural and mesenchymal-derived cell types. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PKDCC](/details-gene/91461) highlights its significance in a diverse set of cell types, with a particular prominence in neural and mesenchymal lineages. The gene shows the highest cell-type specific significance in the [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 5.54) and [neural progenitor cell](/details-cell/CL0011020) (CSI: 5.29), suggesting a crucial role in the development or function of the nervous system. Beyond the neural context, [PKDCC](/details-gene/91461) is a significant marker in several cells of mesenchymal origin, which are key players in structural tissue formation and remodeling. These include [hepatic stellate cell](/details-cell/CL0000632) (CSI: 3.89), [subcutaneous adipocyte](/details-cell/CL0002521) (CSI: 3.60), and [myofibroblast cell](/details-cell/CL0000186) (CSI: 3.20). This expression pattern is consistent with its established role in skeletal and limb development. The gene also shows notable expression in various specialized epithelial and structural cells, such as [intestine goblet cell](/details-cell/CL0019031) (CSI: 2.77) and [regular ventricular cardiac myocyte](/details-cell/CL0002131) (CSI: 2.67), indicating a broader role in tissue organization and function. ## Pathways and Molecular Function Functionally, [PKDCC](/details-gene/91461) is annotated as a protein kinase with [non-membrane spanning protein tyrosine kinase activity](/details-go/GO:0004715) and [ATP binding](/details-go/GO:0005524) capabilities. Its cellular localization within the [Golgi apparatus](/details-go/GO:0005794) and the [extracellular region](/details-go/GO:0005576) supports the model of a secreted kinase processed through the Golgi for export. The biological processes associated with [PKDCC](/details-gene/91461) are overwhelmingly related to organismal development. It plays a key role in [skeletal system development](/details-go/GO:0001501), including the [positive regulation of bone mineralization](/details-go/GO:0030501) and [chondrocyte differentiation](/details-go/GO:0032332). Its involvement extends to the morphogenesis of various structures, such as the limbs ([GO:0035108](/details-go/GO:0035108)), digestive tract ([GO:0048566](/details-go/GO:0048566)), lungs ([GO:0048286](/details-go/GO:0048286)), and palate ([GO:0060021](/details-go/GO:0060021)). This strong developmental signature aligns with the severe skeletal phenotypes observed in patients with mutations in this gene ([Link](https://doi.org/10.1136/jmedgenet-2018-105639)). ## Research Directions The unique nature of [PKDCC](/details-gene/91461) as a secreted tyrosine kinase opens several avenues for future research, particularly in understanding how extracellular phosphorylation events regulate cell-cell communication during development and disease. **Proposed Testable Hypotheses:** 1. Given its high expression in [hepatic stellate cell](/details-cell/CL0000632) and [myofibroblast cell](/details-cell/CL0000186), extracellular [PKDCC](/details-gene/91461) may act as a pro-fibrotic signaling molecule, promoting tissue remodeling by phosphorylating extracellular matrix proteins or cell surface receptors on mesenchymal cells in response to injury. 2. In the developing nervous system, [PKDCC](/details-gene/91461) secreted from [neural progenitor cell](/details-cell/CL0011020)s could function as a paracrine signal to guide the differentiation or migration of adjacent cell types, such as neural crest derivatives or mesenchymal precursors, thereby coordinating neuro-skeletal development. **Suggested Experimental Approach:** To test the hypothesis that [PKDCC](/details-gene/91461) promotes fibrosis, an *in vitro* study using primary human [hepatic stellate cell](/details-cell/CL0000632)s could be conducted. These cells would be stimulated with a known fibrotic agent like TGF-β. The role of [PKDCC](/details-gene/91461) could be interrogated by either adding recombinant [PKDCC](/details-gene/91461) to the culture medium or by knocking down its endogenous expression using shRNA. The impact on fibrosis would be quantified by measuring the expression of key markers such as alpha-smooth muscle actin (α-SMA) and Collagen Type I (COL1A1) via qPCR and Western blot. Further, mass spectrometry-based phosphoproteomics of the cell surface and conditioned media could identify the direct extracellular substrates of [PKDCC](/details-gene/91461) kinase activity. **Therapeutic Potential:** As a secreted protein, [PKDCC](/details-gene/91461) represents a highly accessible therapeutic target. If its role in promoting fibrosis is validated, **inhibition** of its kinase activity could be a viable strategy for treating fibrotic diseases of the liver, lung, or other organs. Its extracellular location makes it an ideal candidate for targeting with monoclonal antibodies that could neutralize its activity or with cell-impermeable small molecule inhibitors. This approach would have the advantage of avoiding potential off-target effects associated with inhibiting intracellular kinases.

Genular Protein ID: 1704189823

Symbol: PKDCC_HUMAN

Name: Protein kinase-like protein SgK493

UniProtKB Accession Codes:

Q504Y2 D6W5A0 Q96I09

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 7 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 Rhea 4 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 12471243

Title: The protein kinase complement of the human genome.

PubMed ID: 12471243

DOI: 10.1126/science.1075762

PubMed ID: 25171405

Title: A secreted tyrosine kinase acts in the extracellular environment.

PubMed ID: 25171405

DOI: 10.1016/j.cell.2014.06.048

PubMed ID: 30478137

Title: Biallelic disruption of PKDCC is associated with a skeletal disorder characterised by rhizomelic shortening of extremities and dysmorphic features.

PubMed ID: 30478137

DOI: 10.1136/jmedgenet-2018-105639

Sequence Information:

  • Length: 493
  • Mass: 54132
  • Checksum: 9E6F2AF7BECDA26C
  • Sequence:
    • MRRRRAAVAA GFCASFLLGS VLNVLFAPGS EPPRPGQSPE PSPAPGPGRR GGRGELARQI 
RARYEEVQRY SRGGPGPGAG RPERRRLMDL APGGPGLPRP RPPWARPLSD GAPGWPPAPG 
PGSPGPGPRL GCAALRNVSG AQYMGSGYTK AVYRVRLPGG AAVALKAVDF SGHDLGSCVR 
EFGVRRGCYR LAAHKLLKEM VLLERLRHPN VLQLYGYCYQ DSEDIPDTLT TITELGAPVE 
MIQLLQTSWE DRFRICLSLG RLLHHLAHSP LGSVTLLDFR PRQFVLVDGE LKVTDLDDAR 
VEETPCAGST DCILEFPARN FTLPCSAQGW CEGMNEKRNL YNAYRFFFTY LLPHSAPPSL 
RPLLDSIVNA TGELAWGVDE TLAQLEKVLH LYRSGQYLQN STASSSTEYQ CIPDSTIPQE 
DYRCWPSYHH GSCLLSVFNL AEAVDVCESH AQCRAFVVTN QTTWTGRQLV FFKTGWSQVV 
PDPNKTTYVK ASG