SRY is the Y-linked testis-determining factor of therian mammals, a 204-residue transcription factor with a single central HMG box, derived in evolution from SOX3. Expressed briefly in supporting-cell precursors of the bipotential embryonic gonad, it binds the [AT]AACAA[AT] motif by partial intercalation in the DNA minor groove, sharply bending the DNA, and, together with SF1, activates the SOX9 testis enhancer, so committing these cells to the Sertoli lineage and initiating testis development. Nuclear entry uses two nuclear localization signals flanking the HMG box: the N-terminal signal binds calmodulin and the C-terminal one importin-beta, and exportin-4 also imports SRY; acetylation by p300 favours nuclear localization and deacetylation by HDAC3 cytoplasmic retention. The C terminus of human SRY binds the PDZ protein NHERF2. Loss-of-function variants, many de novo in the HMG box and some impairing nuclear import, cause 46,XY complete or partial gonadal dysgenesis, while translocation of SRY onto the X chromosome causes 46,XX testicular or ovotesticular differences of sex development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: SRY binds its target sequences in chromatin; the ISA row transfers the SOX-family chromatin location. Reason: Consistent with its role as a sequence-specific DNA-binding transcription factor acting on gonadal enhancers such as the SOX9 TES; chromatin is an appropriate location for the active protein. Supporting Evidence: file:human/SRY/SRY-uniprot.txt Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: SRY binds the [AT]AACAA[AT] motif in cis-regulatory regions of RNA polymerase II genes, including the SOX9 testis enhancer. Reason: Core molecular function; the IBA is consistent with experimental DNA-binding and SOX9-enhancer data for human SRY. Supporting Evidence: file:human/SRY/SRY-uniprot.txt Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | ACCEPT | Summary: SRY activates the human SOX9 testis-specific enhancer (hTES) together with SF1 in NT2/D1 cells, and patient alleles fail to do so. Reason: Direct experimental support for SRY as an RNA polymerase II-specific DNA-binding transcription factor; this is the core activity. Supporting Evidence: PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. PMID:21412441 Together, SRY and SF1 co-operate to activate hTES by ∼16-fold. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: Sequence-similarity transfer of DNA-binding transcription factor activity within the SOX/SRY family. Reason: Consistent with the direct evidence (PMID:21412441); same claim as the IDA row. Supporting Evidence: PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: SRY acts as a transcriptional activator of RNA polymerase II targets, most clearly SOX9. Reason: Supported by activation of the hTES enhancer with SF1; the IBA places the activity in the SRY/SOX clade, which human SRY clearly belongs to. Supporting Evidence: PMID:21412441 Together, SRY and SF1 co-operate to activate hTES by ∼16-fold. |
| GO:0003677 DNA binding | IDA PMID:1425584 SRY, like HMG1, recognizes sharp angles in DNA. | MODIFY | Summary: SRY binds DNA through its HMG box in a sequence-specific way, by partial intercalation in the minor groove, and sharply bends it. Reason: DNA binding is correct but uninformative. The experiments show the two specific activities that define the SRY HMG box: sequence-specific binding of cis-regulatory elements and DNA bending. Refined to both. Proposed replacements: DNA binding, bending RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:1425584 when SRY binds to linear duplex DNA containing its specific target AACAAAG, it produces a sharp bend file:human/SRY/SRY-uniprot.txt Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' |
| GO:0003677 DNA binding | IDA PMID:8265659 The SRY high-mobility-group box recognizes DNA by partial in... | MODIFY | Summary: SRY binds DNA through its HMG box in a sequence-specific way, by partial intercalation in the minor groove, and sharply bends it. Reason: DNA binding is correct but uninformative. The experiments show the two specific activities that define the SRY HMG box: sequence-specific binding of cis-regulatory elements and DNA bending. Refined to both. Proposed replacements: DNA binding, bending RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8265659 The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove PMID:1425584 when SRY binds to linear duplex DNA containing its specific target AACAAAG, it produces a sharp bend |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: SRY binds DNA through its HMG box in a sequence-specific way, by partial intercalation in the minor groove, and sharply bends it. Reason: DNA binding is correct but uninformative. The experiments show the two specific activities that define the SRY HMG box: sequence-specific binding of cis-regulatory elements and DNA bending. Refined to both. Proposed replacements: DNA binding, bending RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/SRY/SRY-uniprot.txt Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' PMID:1425584 when SRY binds to linear duplex DNA containing its specific target AACAAAG, it produces a sharp bend |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO transfer of generic DNA-binding transcription factor activity from the HMG box. Reason: Correct but less specific than the RNA polymerase II-specific activity that human SRY is shown to have (PMID:21412441). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. |
| GO:0005515 protein binding | IPI PMID:16166090 NHERF2/SIP-1 interacts with mouse SRY via a different mechan... | MODIFY | Summary: NHERF2 (SIP-1) binds SRY through its PDZ1 domain; for human SRY the binding site is the C-terminal seven residues. Reason: Bare protein binding is uninformative. The interaction is mapped to the SRY C terminus and the PDZ domains of NHERF2, so PDZ domain binding describes it. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:9054412 Interacting domains were mapped to the C-terminal seven amino acids of SRY and to the PDZ domains of SIP-1, respectively. PMID:16166090 previously isolated SIP-1/NHERF2 as a human SRY-interacting protein |
| GO:0005515 protein binding | IPI PMID:9054412 The human testis determining factor SRY binds a nuclear fact... | MODIFY | Summary: Yeast two-hybrid, in vitro and co-immunoprecipitation evidence that human SRY binds the PDZ protein SIP-1 (NHERF2) via its C-terminal seven amino acids. Reason: Bare protein binding is uninformative; the interaction is mapped to PDZ domains of SIP-1, so PDZ domain binding is the informative term. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:9054412 Interacting domains were mapped to the C-terminal seven amino acids of SRY and to the PDZ domains of SIP-1, respectively. |
| GO:0005634 nucleus | EXP PMID:15297880 Regulation of human SRY subcellular distribution by its acet... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:15297880 We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. |
| GO:0005634 nucleus | EXP PMID:15746192 Defective calmodulin-mediated nuclear transport of the sex-d... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:15746192 The SRY N-terminal NLS (n-NLS) binds calmodulin (CaM) in vitro, and here we show that this protein interaction is reduced in vivo by calmidazolium, a CaM antagonist. |
| GO:0005634 nucleus | EXP PMID:16762365 SRY-directed DNA bending and human sex reversal: reassessmen... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:16762365 Our results suggest that male development is robust to subtle alterations in SRY-DNA architecture but depends critically on nuclear localization. |
| GO:0005634 nucleus | EXP PMID:19349578 Exportin 4 mediates a novel nuclear import pathway for Sox f... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:19349578 Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. The IBA agrees with the experimental rows. Supporting Evidence: PMID:19349578 Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY PMID:16762365 Our results suggest that male development is robust to subtle alterations in SRY-DNA architecture but depends critically on nuclear localization. |
| GO:0005634 nucleus | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:21412441 Overlap of SRY (green) and H3 Me3K4 in NT2/D1 cells reveals co-localization (yellow) within nuclear compartments. |
| GO:0005634 nucleus | IDA PMID:28030592 A Novel Missense Mutation 224G>T (R75M) in SRY Coding Region... | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:28030592 the mutated SRY is greatly accumulated in cytoplasm while the wild type SRY is mostly localized in nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: SRY is a nuclear transcription factor imported by calmodulin-, importin-beta- and exportin-4-dependent pathways. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:15297880 We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. |
| GO:0005634 nucleus | NAS PMID:1425584 SRY, like HMG1, recognizes sharp angles in DNA. | ACCEPT | Summary: Nuclear location inferred by the authors from the DNA-binding HMG box. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:1425584 when SRY binds to linear duplex DNA containing its specific target AACAAAG, it produces a sharp bend |
| GO:0005634 nucleus | NAS PMID:8265659 The SRY high-mobility-group box recognizes DNA by partial in... | ACCEPT | Summary: Nuclear location inferred by the authors from sequence-specific DNA binding. Reason: SRY acts on chromatin in the nucleus; patient alleles that leave SRY in the cytoplasm cause sex reversal, so nuclear localization is the core location of its function. Supporting Evidence: PMID:8265659 The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5626938 | ACCEPT | Summary: Reactome places SRY binding to beta-catenin in the nucleoplasm. Reason: Nucleoplasm is a more specific nuclear location consistent with the experimental data; kept as a correct location. Supporting Evidence: Reactome:R-HSA-5626938 Human SRY binds beta-catenin through a N-terminal domain |
| GO:0005737 cytoplasm | EXP PMID:15297880 Regulation of human SRY subcellular distribution by its acet... | KEEP AS NON CORE | Summary: HDAC3 deacetylation relocates SRY to the cytoplasm, and SRY was cytoplasmic in somatic cells of an 8-week embryonic gonad. Reason: A real, regulated pool, but the function of SRY is exerted in the nucleus; cytoplasm is a peripheral location. Supporting Evidence: PMID:15297880 We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. PMID:15297880 However, in the 8-week human male embryonic gonad, SRY displayed a cytoplasmic localisation in the somatic cell compartment |
| GO:0005737 cytoplasm | EXP PMID:19349578 Exportin 4 mediates a novel nuclear import pathway for Sox f... | KEEP AS NON CORE | Summary: SRY is found partly in the cytoplasm before exportin-4-mediated import. Reason: Peripheral location; the active pool is nuclear. Supporting Evidence: PMID:19349578 Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to cytoplasm. Reason: Same claim as the experimental cytoplasm rows; peripheral to the nuclear function. Supporting Evidence: PMID:15297880 We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. |
| GO:0010628 positive regulation of gene expression | IDA PMID:24681825 The NLR-related protein NWD1 is associated with prostate can... | MODIFY | Summary: In HEK293T and prostate cancer cells, NWD1 expression is up-regulated by SRY-family proteins acting on predicted SRY sites in its promoter. Reason: Weak, overexpression-based evidence in non-gonadal cell lines; the general term positive regulation of gene expression is better captured as positive regulation of transcription by RNA polymerase II, which is the established mechanism for SRY. NWD1 is not an established in vivo target. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:24681825 Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) family proteins. PMID:21412441 Together, SRY and SF1 co-operate to activate hTES by ∼16-fold. |
| GO:0016607 nuclear speck | EXP PMID:11818535 A direct role of SRY and SOX proteins in pre-mRNA splicing. | KEEP AS NON CORE | Summary: SRY colocalizes with splicing factors in nuclear speckles in NT2/D1 cells. Reason: Experimental but contested: another study found no colocalization of Flag-SRY with the speckle marker SC-35. A role in pre-mRNA splicing is not established, so nuclear speck is kept as a peripheral location. Supporting Evidence: PMID:11818535 Here we show that SRY and the Sox protein SOX6 colocalize with splicing factors in the nucleus PMID:21412441 Flag-SRY protein does not co-localize with splicing factor SC-35 |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to nuclear speck. Reason: Same claim as the experimental speckle row; kept non-core because the observation is contested (PMID:21412441). Supporting Evidence: PMID:11818535 Here we show that SRY and the Sox protein SOX6 colocalize with splicing factors in the nucleus PMID:21412441 Flag-SRY protein does not co-localize with splicing factor SC-35 |
| GO:0030154 cell differentiation | IBA GO_REF:0000033 | MODIFY | Summary: SRY directs bipotential supporting-cell precursors to differentiate as Sertoli cells. Reason: Cell differentiation is correct but very general; the specific process SRY initiates is Sertoli cell differentiation. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000030384 SUPPORTS TRANSFER SOX/SRY clade node; cell differentiation is true for SRY but general, since its specific process is Sertoli cell differentiation. Proposed replacements: Sertoli cell differentiation Supporting Evidence: file:human/SRY/SRY-uniprot.txt It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells file:human/SRY/SRY-deep-research-openscientist.md Within the pre-Sertoli cells of the bipotential gonad, SRY commits the organ to the testicular fate rather than the default ovarian fate. |
| GO:0030238 male sex determination | IBA GO_REF:0000033 | ACCEPT | Summary: SRY is the testis-determining factor: de novo loss-of-function mutations cause 46,XY sex reversal. Reason: Core biological process. SRY does the initiating work of male sex determination by activating SOX9 in pre-Sertoli cells. Supporting Evidence: file:human/SRY/SRY-uniprot.txt It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells PMID:2247149 the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. |
| GO:0030238 male sex determination | IEA GO_REF:0000002 | ACCEPT | Summary: SRY is the testis-determining factor: de novo loss-of-function mutations cause 46,XY sex reversal. Reason: Core biological process. SRY does the initiating work of male sex determination by activating SOX9 in pre-Sertoli cells. Supporting Evidence: PMID:2247149 the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. file:human/SRY/SRY-uniprot.txt It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells |
| GO:0030238 male sex determination | NAS PMID:1695712 A gene from the human sex-determining region encodes a prote... | ACCEPT | Summary: SRY is the testis-determining factor: de novo loss-of-function mutations cause 46,XY sex reversal. Reason: Core biological process. SRY does the initiating work of male sex determination by activating SOX9 in pre-Sertoli cells. Supporting Evidence: PMID:1695712 This gene has been termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-determining gene, TDF. PMID:2247149 the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | MODIFY | Summary: SRY with SF1 activates the human SOX9 testis enhancer about 16-fold in NT2/D1 cells. Reason: Correct, but the experiment shows activation of an RNA polymerase II gene enhancer; refined to the specific child term. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:21412441 Together, SRY and SF1 co-operate to activate hTES by ∼16-fold. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: SRY positively regulates RNA polymerase II transcription of SOX9. Reason: Core process, consistent with the hTES activation data. Supporting Evidence: PMID:21412441 Together, SRY and SF1 co-operate to activate hTES by ∼16-fold. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:16582099 The high-mobility-group domain of Sox proteins interacts wit... | KEEP AS NON CORE | Summary: In GST pulldowns, fragments of the human SRY HMG box bound the DNA-binding domains of several transcription factors identified as Sox8/Sox10 partners. Reason: The biochemistry is real, but the partners are mostly neural/glial factors identified for Sox8 and Sox10 and tested on isolated HMG-box fragments; no SRY-specific physiological role follows. The term is already specific, so it is kept but non-core. Supporting Evidence: PMID:16582099 In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. PMID:16582099 amino acids 58–84 or 84–133 of human SRY (SRY A and SRY B) in frame behind the GST coding sequence |
| GO:2000020 positive regulation of male gonad development | IDA PMID:21412441 Failure of SOX9 regulation in 46XY disorders of sex developm... | ACCEPT | Summary: SRY promotes male gonad development by activating SOX9 through its testis enhancer; patient SRY alleles fail to do so. Reason: Supported by direct enhancer activation data and by the disease genetics; a core process consistent with male sex determination. Supporting Evidence: PMID:21412441 SRY and SF1 co-operate to activate the human SOX9 homologous TES (hTES), a process dependent on phosphorylated SF1. PMID:2247149 the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination. |
| GO:0005516 calmodulin binding | IDA PMID:15746192 Defective calmodulin-mediated nuclear transport of the sex-d... | NEW | Summary: The SRY N-terminal nuclear localization signal binds calmodulin, and calmodulin antagonism reduces the interaction and SRY nuclear import. Reason: Calmodulin binding by the n-NLS is the basis of one of the two SRY nuclear import pathways, and sex-reversing alleles impair it; an informative binding function not present in GOA. Supporting Evidence: PMID:15746192 The SRY N-terminal NLS (n-NLS) binds calmodulin (CaM) in vitro, and here we show that this protein interaction is reduced in vivo by calmidazolium, a CaM antagonist. |
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Download this section (compressed HTML)Q: For individual patient alleles, how much of the sex-reversing effect comes from reduced DNA bending and how much from reduced nuclear import, given that M64I was first explained by a reduced bend and later by a localization defect?
Q: Is the reported localization of SRY to splicing speckles, and a role in pre-mRNA splicing, reproducible in human pre-Sertoli cells, given conflicting results in NT2/D1 cells?
Q: What is the direct genome-wide target set of human SRY in fetal gonadal supporting cells, beyond SOX9?
Experiment: ChIP-seq or CUT&RUN for endogenous SRY in human fetal gonad or iPSC-derived supporting-like cells, with matched patient alleles, to define direct targets and test enhancer occupancy at the SOX9 TES and Enh13 regions.
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