Details for: SRRD

Gene ID: 402055

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: SRRD

Ensembl ID: ENSG00000100104

Description: SRR1 domain containing

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conventional dendritic cell CL0000990
    CSI 26.66
    rCSI 22.25%
    PRS 99.72
  • pericyte CL0000669
    CSI 16.66
    rCSI 44.36%
    PRS 99.59
  • chondrocyte CL0000138
    CSI 16.5
    rCSI 26.24%
    PRS 99.93
  • innate lymphoid cell CL0001065
    CSI 14.52
    rCSI 29.98%
    PRS 99.79
  • helper T cell CL0000912
    CSI 13.92
    rCSI 19.69%
    PRS 99.78
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 13.85
    rCSI 16.78%
    PRS 99.47
  • basal cell of epidermis CL0002187
    CSI 13.4
    rCSI 23.75%
    PRS 99.36
  • melanocyte of skin CL1000458
    CSI 12.78
    rCSI 17.42%
    PRS 99.57
  • suprabasal keratinocyte CL4033013
    CSI 11.21
    rCSI 18.29%
    PRS 99.65
  • mast cell CL0000097
    CSI 9.64
    rCSI 20.82%
    PRS 99.82
  • regulatory T cell CL0000815
    CSI 9.14
    rCSI 10.6%
    PRS 99.74
  • endothelial cell of vascular tree CL0002139
    CSI 6.71
    rCSI 36.67%
    PRS 99.83
  • ependymal cell CL0000065
    CSI 6.26
    rCSI 12.69%
    PRS 99.85
  • neural progenitor cell CL0011020
    CSI 5.94
    rCSI 26.13%
    PRS 99.16
  • common myeloid progenitor CL0000049
    CSI 5.65
    rCSI 4.57%
    PRS 100
  • radial glial cell CL0000681
    CSI 5.2
    rCSI 7.22%
    PRS 100
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 4.16
    rCSI 7.35%
    PRS 99.99
  • cytotoxic T cell CL0000910
    CSI 2.63
    rCSI 15.06%
    PRS 99.84

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.

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  • 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 [SRRD](/details-gene/402055), or SRR1 domain containing, is a protein-coding gene located on chromosome 22q12.1. It is primarily involved in fundamental metabolic and regulatory processes, including the biosynthesis of heme and the regulation of circadian rhythms. Functional data indicates the protein is localized to both the cytoplasm and nucleus, consistent with a dual role in metabolic pathways and gene expression control ([Link](https://doi.org/10.1016/j.abb.2017.08.006)). Its expression profile suggests a broad but significant role across diverse cell lineages, with the highest significance observed in immune cells, particularly [conventional dendritic cells (CL0000990)](/details-cell/CL0000990), as well as in structural cell types like [pericytes (CL0000669)](/details-cell/CL0000669) and [chondrocytes (CL0000138)](/details-cell/CL0000138). ## Cellular Roles and Expression Landscape [SRRD](/details-gene/402055) exhibits a distinct and broad expression pattern, pointing to its involvement in a variety of specialized cellular functions. **Overall**, its most significant expression is observed in [conventional dendritic cells (CL0000990)](/details-cell/CL0000990) (CSI: 26.66), suggesting a key role in the metabolic regulation that underpins antigen presentation and the initiation of adaptive immunity. Beyond this primary immune context, [SRRD](/details-gene/402055) is also highly significant in several mesenchymal and structural cell types, including [pericytes (CL0000669)](/details-cell/CL0000669) and [chondrocytes (CL0000138)](/details-cell/CL0000138). Its expression is also notable across a wide range of lymphocyte populations, such as [innate lymphoid cells (CL0001065)](/details-cell/CL0001065), [helper T cells (CL0000912)](/details-cell/CL0000912), and various memory and regulatory T cell subsets. This widespread presence within the immune system points to a general role in immune cell biology and homeostasis. Furthermore, its expression in skin-resident cells like [basal cells of the epidermis (CL0002187)](/details-cell/CL0002187) and [melanocytes (CL1000458)](/details-cell/CL1000458) implies functions related to skin homeostasis and rhythmic processes influenced by environmental cues. ## Pathways and Molecular Function The molecular functions of [SRRD](/details-gene/402055) are strongly linked to metabolic control and biological timing. Gene Ontology annotations highlight its critical role in the '[Heme biosynthetic process (GO:0006783)](https://www.ebi.ac.uk/QuickGO/term/GO:0006783)' and its regulation ([GO:0070453](https://www.ebi.ac.uk/QuickGO/term/GO:0070453)). Heme is an essential prosthetic group for many proteins involved in oxygen transport and cellular respiration, and its synthesis is vital for highly metabolically active cells. The high significance of [SRRD](/details-gene/402055) in immune cells like dendritic and T cells may be directly related to their high energetic demands during activation. In parallel, [SRRD](/details-gene/402055) is implicated in the '[Regulation of circadian rhythm (GO:0042752)](https://www.ebi.ac.uk/QuickGO/term/GO:0042752)' and more broadly in '[Rhythmic process (GO:0048511)](https://www.ebi.ac.uk/QuickGO/term/GO:0048511)'. Research has established SRRD as a heme-dependent protein that links the cellular heme pool to the core circadian clock machinery ([Link](https://doi.org/10.1016/j.abb.2017.08.006)). This dual function suggests it acts as a molecular sensor, coordinating cellular metabolic status with daily physiological rhythms. The protein's localization in both the [cytoplasm (GO:0005737)](https://www.ebi.ac.uk/QuickGO/term/GO:0005737) and the [nucleus (GO:0005634)](https://www.ebi.ac.uk/QuickGO/term/GO:0005634) is consistent with its proposed roles in cytoplasmic metabolic pathways and nuclear regulation of gene expression. ## Research Directions The unique position of [SRRD](/details-gene/402055) at the intersection of immunity, metabolism, and circadian biology opens up several avenues for future investigation. **Proposed Hypotheses:** 1. **Metabolic Gating of Dendritic Cell Function:** Given its top expression in [conventional dendritic cells (CL0000990)](/details-cell/CL0000990) and its role in heme synthesis, [SRRD](/details-gene/402055) may function as a metabolic checkpoint that controls dendritic cell activation. We hypothesize that SRRD-mediated heme production is essential for meeting the bioenergetic demands required for antigen processing, co-stimulatory molecule expression, and cytokine production, thereby gating the initiation of T cell responses. 2. **Circadian Control of Skin Homeostasis:** The significant expression of [SRRD](/details-gene/402055) in epidermal cells, which are constantly exposed to diurnal light-dark cycles, suggests a role in local chronobiology. We hypothesize that in [basal cells (CL0002187)](/details-cell/CL0002187) and [melanocytes (CL1000458)](/details-cell/CL1000458), [SRRD](/details-gene/402055) integrates environmental light cues with cellular metabolism to regulate the timing of DNA repair, proliferation, and pigment production, contributing to the skin's rhythmic protective functions. **Key Experimental Approach:** To test the first hypothesis regarding the role of [SRRD](/details-gene/402055) in dendritic cell function, a loss-of-function study could be performed. Specifically, CRISPR-Cas9 could be used to knock out [SRRD](/details-gene/402055) in primary human monocytes before their differentiation into [conventional dendritic cells (CL0000990)](/details-cell/CL0000990). The functional consequences could then be assessed by challenging these knockout cells with Toll-like receptor agonists (e.g., LPS) and measuring key outputs, including cytokine secretion (e.g., IL-12, TNF-α) via ELISA and the upregulation of co-stimulatory molecules (CD80, CD86) using flow cytometry. A mixed lymphocyte reaction assay would further determine if the absence of [SRRD](/details-gene/402055) impairs their capacity to activate T cells. **Therapeutic Potential:** As an intracellular protein integral to core metabolic pathways, [SRRD](/details-gene/402055) is a potential target for small-molecule modulators. Its dysregulation could be relevant in diseases characterized by altered metabolism or circadian disruption, such as certain cancers or chronic inflammatory conditions. Depending on the specific pathology, either inhibition (to restrict heme availability in hyperproliferative states) or activation (to restore metabolic or rhythmic homeostasis) could be a viable therapeutic strategy. However, its broad expression across multiple essential cell types warns that systemic targeting could carry a risk of off-target effects, suggesting that future therapeutic development would likely require cell-type-specific delivery mechanisms or highly targeted approaches.

Genular Protein ID: 1716458046

Symbol: SRR1L_HUMAN

Name: SRR1-like protein

UniProtKB Accession Codes:

Q9UH36 Q6NXP8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 1 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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: 28802827

Title: The novel heme-dependent inducible protein, SRRD regulates heme biosynthesis and circadian rhythms.

PubMed ID: 28802827

DOI: 10.1016/j.abb.2017.08.006

Sequence Information:

  • Length: 339
  • Mass: 38573
  • Checksum: 9DDF4C81ED940468
  • Sequence:
    • MAAAAAAALE SWQAAAPRKR RSAARRPRRR EAAPRGREAA PRGREAAPRG PEAEFESDSG 
VVLRRIWEAE KDLFISDFWS SALETINRCL TKHLEQLKAP VGTLSDIFGN LHLDSLPEES 
DVATDSIPRE ILVTGTCHLK CVCYGIGNFA TCIVARNQLT FLLLLLEKCQ IPRSHCWVYD 
PLFSQLEIEV LNTLGVTVLS ENEEGKRSIR GEPTIFYMLH CGTALYNNLL WSNWSVDALS 
KMVIIGNSFK GLEERLLARI LQKNYPYIAK ILKGLEELEF PQTSQYMDIF NDTSVHWFPV 
QKLEQLSIDI WEFREEPDYQ DCEDLEIIRN KREDPSATD