Details for: SHF

Gene ID: 90525

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: SHF

Ensembl ID: ENSG00000138606

Description: Src homology 2 domain containing F

Cell Significance Landscape

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 5.62
    rCSI 11.94%
    PRS 93.08
  • cerebellar granule cell CL0001031
    CSI 4.35
    rCSI 6.4%
    PRS 94.16
  • glial cell CL0000125
    CSI 4.01
    rCSI 15.26%
    PRS 93.47
  • melanocyte CL0000148
    CSI 3.62
    rCSI 2.68%
    PRS 95.36
  • stem cell CL0000034
    CSI 3.48
    rCSI 3.36%
    PRS 95.67
  • neural crest cell CL0011012
    CSI 3.48
    rCSI 2.75%
    PRS 94.59
  • interneuron CL0000099
    CSI 3.17
    rCSI 6.36%
    PRS 94.56
  • rod bipolar cell CL0000751
    CSI 2.73
    rCSI 4.91%
    PRS 94.3
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.5
    rCSI 3.21%
    PRS 95.11
  • peripheral nervous system neuron CL2000032
    CSI 2.4
    rCSI 3.27%
    PRS 93.93
  • cerebral cortex endothelial cell CL1001602
    CSI 2.4
    rCSI 4.15%
    PRS 94.85
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.36
    rCSI 2.82%
    PRS 91.29
  • enteroendocrine cell CL0000164
    CSI 2.2
    rCSI 3%
    PRS 95.22
  • retinal bipolar neuron CL0000748
    CSI 2.13
    rCSI 3.99%
    PRS 92.8
  • brush cell CL0002204
    CSI 2.12
    rCSI 4.19%
    PRS 96.99
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.09
    rCSI 6.16%
    PRS 96.76
  • inhibitory interneuron CL0000498
    CSI 1.83
    rCSI 4.23%
    PRS 92.33
  • serotonergic neuron CL0000850
    CSI 1.71
    rCSI 7.64%
    PRS 87.79
  • amacrine cell CL0000561
    CSI 1.46
    rCSI 4.22%
    PRS 92.51
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.99
    rCSI 2.4%
    PRS 89.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.88
    rCSI 2.76%
    PRS 91.89
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.78
    rCSI 2.94%
    PRS 91.17
  • cerebellar neuron CL1001611
    CSI 0.69
    rCSI 6.08%
    PRS 89.57
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.49
    rCSI 2.91%
    PRS 91.38

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 [SHF](/details-gene/90525), or Src homology 2 domain containing F, is a protein-coding gene located on chromosome 15q21.1. Functional annotations suggest it plays a role in intracellular signaling through its ability to bind phosphotyrosine residues, as part of the [apoptotic process](/details-go/GO:0006915) ([GO:0006915](https://www.ebi.ac.uk/QuickGO/term/GO:0006915)). **Overall**, expression data indicates that [SHF](/details-gene/90525) is a significant gene in the context of development and the nervous system, with its highest significance observed in [progenitor cell](/details-cell/CL0011026)s, [cerebellar granule cell](/details-cell/CL0001031)s, and [glial cell](/details-cell/CL0000125)s. The characterization of this gene is supported by large-scale cDNA sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1126/science.1058040)). ## Cellular Roles and Expression Landscape The expression profile of [SHF](/details-gene/90525) points to a specialized role in neural and developmental contexts. Its highest significance is in [progenitor cell](/details-cell/CL0011026)s (CSI: 5.62), with other developmental cell types such as [stem cell](/details-cell/CL0000034)s, [neural crest cell](/details-cell/CL0011012)s, and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s also showing high significance. This pattern suggests a potential function in cell fate determination, differentiation, or the maintenance of pluripotency. Concurrently, [SHF](/details-gene/90525) demonstrates a strong association with the nervous system. It is a highly significant gene in numerous mature neural and glial cell types, including [cerebellar granule cell](/details-cell/CL0001031)s (CSI: 4.35), [glial cell](/details-cell/CL0000125)s (CSI: 4.01), and various [interneuron](/details-cell/CL0000099)s. This co-expression in both developmental precursors and terminally differentiated neural cells suggests its function may be required throughout neurogenesis and for the maintenance of mature neuronal function. ## Pathways and Molecular Function The molecular function of [SHF](/details-gene/90525) is annotated as [phosphotyrosine residue binding](/details-go/GO:0001784) ([GO:0001784](https://www.ebi.ac.uk/QuickGO/term/GO:0001784)), a characteristic function of proteins containing an SH2 domain. This strongly implies that [SHF](/details-gene/90525) acts as an adaptor or scaffolding protein within signaling cascades initiated by receptor or non-receptor tyrosine kinases. Its involvement in the [apoptotic process](/details-go/GO:0006915) ([GO:0006915](https://www.ebi.ac.uk/QuickGO/term/GO:0006915)) connects this signaling role to a critical cellular outcome. This function is particularly relevant in the context of neurodevelopment, where tightly regulated apoptosis is essential for sculpting the nervous system. The protein may transduce survival or death signals downstream of neurotrophic factors in both developing [neuroblast (sensu Vertebrata)](/details-cell/CL0000031)s and mature neurons. ## Research Directions Based on its expression profile and annotated functions, [SHF](/details-gene/90525) presents several avenues for future research, particularly concerning its role in neurodevelopment and disease. **Proposed Hypotheses:** 1. Given its high significance in [progenitor cell](/details-cell/CL0011026)s and its link to apoptosis, [SHF](/details-gene/90525) may function as a critical regulator of the balance between self-renewal and differentiation in neural stem cells by mediating pro-survival signals downstream of tyrosine kinase receptors. 2. In mature neurons like [cerebellar granule cell](/details-cell/CL0001031)s, [SHF](/details-gene/90525) could be a necessary component of signaling pathways that maintain synaptic integrity or protect against excitotoxic or stress-induced apoptosis. Dysregulation of [SHF](/details-gene/90525) could therefore contribute to neurodegenerative processes. **Experimental Approach:** To test the first hypothesis regarding the role of [SHF](/details-gene/90525) in neural progenitor cell fate, a CRISPR-Cas9-mediated knockout of the gene could be performed in a human induced pluripotent stem cell (iPSC) line. These iPSCs would then be differentiated into neural progenitor cells (NPCs). The impact of [SHF](/details-gene/90525) loss could be assessed by comparing knockout and wild-type NPCs for differences in proliferation rates (via EdU incorporation), susceptibility to apoptosis under growth factor withdrawal (via cleaved caspase-3 staining), and the efficiency of subsequent differentiation into neurons and astrocytes (via immunocytochemistry for Tuj1 and GFAP markers). **Therapeutic Potential:** The role of [SHF](/details-gene/90525) in progenitor cell survival and apoptosis suggests it could be a relevant target in diseases characterized by aberrant cell proliferation, such as cancers of the nervous system (e.g., glioblastoma or neuroblastoma). If [SHF](/details-gene/90525) is found to be overexpressed and to promote the survival of cancer stem cells, it would represent a candidate for therapeutic **inhibition**. As an intracellular signaling adapter, targeting its SH2 domain with small molecule inhibitors to disrupt protein-protein interactions could be a viable strategy. However, its significant presence in healthy neural tissues raises concerns about potential neurotoxicity, suggesting that targeted drug delivery systems would be crucial for a favorable therapeutic index.

Genular Protein ID: 4261361613

Symbol: B3KTY1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KTY1

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 PharmGKB 1 RefSeq 5 SAM 1 SUPFAM 2

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 369
  • Mass: 40259
  • Checksum: 884DB45CA03A17CC
  • Sequence:
    • MQQEGGPVRS APCRTGTLEG SRQGSPGHRK RASPKGSLSS AQPHSWMLTP SPLNSHCAHR 
EPISSSPQPV ANGPKQKKKS NWRSTTRLRI IRLRDRLEPR PLAILEDYAD PFDVQETGEG 
SAGASGAPEK VPENDGYMEP YEAQKMMAEI RGSKETATQP LPLYDTPYEP EEDGATPEGE 
GAPWPRESRL PEDDERPPEE YDQPWEWKKE RISKAFAVDI KVIKDLPWPP PVGQLDSSPS 
LPDGDRDISG PASPLPEPSL EDSSAQFEGP EKSCLSPGRE EKGRLPPRLS AGNPKSAKPL 
SMEPSSPLGE WTDPALPLEN QVWYHGAISR TDAENLSGCA KRPATWCATV GPARMTSPSP 
SRAARDSCT

Genular Protein ID: 2551169687

Symbol: B4E1A9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4E1A9

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 RefSeq 3 SAM 1 SMART 1 SUPFAM 2

Sequence Information:

  • Length: 366
  • Mass: 40010
  • Checksum: CA5467891B71E17A
  • Sequence:
    • MLLSGAPPAA PPAPPPDILA AYRLQRERDF EDPYSGGSSG SAALATPVAP GPTPPPRHGS 
PPHRLIRVET PGPPAPPADE RISGPPASSD RLAILEDYAD PFDVQETGEG SAGASGAPEK 
VPENDGYMEP YEAQKMMAEI RGSKETATQP LPLYDTPYEP EEDGATPEGE GAPWPRESRL 
PEDDERPPEE YDQPWEWKKE RISKAFAAQF EGPEKSCLSP GREEKGRLPP RLSAGNPKSA 
KPLSMEPSSP LGEWTDPALP LENQVWYHGA ISRTDAENLL RLCKEASYLV RNSETSKNDF 
SLSLKSSQGF MHMKLSRTKE HKYVLGQNSP PFSSVPEIVH HYASRKLPIK GAEHMSLLYP 
VAIRTL

Genular Protein ID: 3784766867

Symbol: B4DWP8_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DWP8

Database IDs:

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

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

Sequence Information:

  • Length: 239
  • Mass: 27048
  • Checksum: 7FCFDCE2C46594BF
  • Sequence:
    • MEPYEAQKMM AEIRGSKETA TQPLPLYDTP YEPEEDGATP EGEGAPWPRE SRLPEDDERP 
PEEYDQPWEW KKERISKAFA AQFEGPEKSC LSPGREEKGR LPPRLSAGNP KSAKPLSMEP 
SSPLGEWTDP ALPLENQVWY HGAISRTDAE NLLRLCKEAS YLVRNSETSK NDFSLSLKSS 
QGFMHMKLSR TKEHKYVLGQ NSPPFSSVPE IVHHYASRKL PIKGAEHMSL LYPVAIRTL