SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000638 
UniProt Accession
Theoretical PI
7.34  
Molecular Weight
23884 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
SRY 
Gene Synonyms/Alias
TDF 
Protein Name
Sex-determining region Y protein 
Protein Synonyms/Alias
Testis-determining factor; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:Y;2654896-2655740;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Individuals polymorphic for genes GSTM1 and GSTT1 are susceptible to reduction in sperm quality and infertility, possibly because oligozoo spermic individuals have been affected by GST polymorphism. The data presented here show that critical levels of WT1 + KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. 
The information of related literatures
1. D. Modi, C. Shah, G. Sachdeva, S. Gadkar, D. Bhartiya and C. Puri (2005) Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa. Reproduction 130(5): 603-13. 

Abstract
The sex-determining region on the Y (SRY) gene is unequivocally designated as the testis-determining factor in mammals; however, its roles beyond sex determination, if any, have been hitherto unknown. To determine whether SRY has any roles beyond sex determination, herein the expression of SRY mRNA was investigated in the midtrimester human fetal, infantile and adult testes as well as in ejaculated spermatozoa. High levels of SRY transcripts were in situ localized to the Sertoli cells of the developing testis at 9 weeks of gestation, and the expression persisted at comparable levels throughout the midtrimester (until 22 weeks) and also in the testis of an infant at 3 months of age. The germ cells and other somatic cells in the testes of fetuses and the infant were negative for SRY expression. The mRNA for SRY was detected in the spermatogenic cells, particularly the spermatogonia and the round spermatids; the expression was negligible in the meiotic stages. A single transcript of approximately 1.2 kb was detected in the adult testes and isolated spermatogonial cells. In the adult testis, in situ hybridization (ISH) studies revealed a switch in the cellular localization of SRY transcripts. SRY transcripts were also demonstrable by RT-PCR of RNA from ejaculated human spermatozoa. ISH revealed the presence of SRY transcripts in the midpiece of 50% of ejaculated sperm. These results suggest that SRY may have extensive roles in male reproductive physiology, such as maturation of fetal testis, spermatogenesis, sperm maturation and early embryonic development. PMID: [16264091] 

2. V. Schumacher, B. Gueler, L. H. Looijenga, J. U. Becker, K. Amann, R. Engers, J. Dotsch, H. Stoop, W. Schulz and B. Royer-Pokora (2008) Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. Mol Reprod Dev 75(9): 1484-94. 

Abstract
Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1 + KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial-spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as 'testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1 + KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. PMID: [18271004] 

Back to Top
Figures for illustrating the function of this protein/gene
Ref: D. Modi, C. Shah, G. Sachdeva, S. Gadkar, D. Bhartiya and C. Puri (2005) Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa. Reproduction 130(5): 603-13. PMID: [16264091]
Ref: D. Modi, C. Shah, G. Sachdeva, S. Gadkar, D. Bhartiya and C. Puri (2005) Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa. Reproduction 130(5): 603-13. PMID: [16264091]
Function
Transcriptional regulator that controls a genetic switchin male development. It is necessary and sufficient for initiatingmale sex determination by directing the development of supportingcell precursors (pre-Sertoli cells) as Sertoli rather thangranulosa cells (By similarity). In male adult brain involved inthe maintenance of motor functions of dopaminergic neurons (Bysimilarity). Involved in different aspects of gene regulationincluding promoter activation or repression (By similarity).Promotes DNA bending. SRY HMG box recognizes DNA by partialintercalation in the minor groove. Also involved in pre-mRNAsplicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. 
Back to Top
Subcellular Location
Nucleus speckle. Cytoplasm. Note=Colocalizeswith SOX6 in speckles. Colocalizes with CAML in the nucleus.Colocalizes in the nucleus with ZNF208 isoform KRAB-O and tyrosinehydroxylase (TH) (By similarity). 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005737 C:cytoplasm IDA:HPA.
GO:0016607 C:nuclear speck IEA:UniProtKB-SubCell.
GO:0005634 C:nucleus IDA:UniProtKB.
GO:0003677 F:DNA binding IDA:UniProtKB.
GO:0003705 F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity IDA:UniProtKB.
GO:0030154 P:cell differentiation IEA:UniProtKB-KW.
GO:0030238 P:male sex determination NAS:UniProtKB.
GO:2000020 P:positive regulation of male gonad development IDA:UniProtKB.
GO:0045893 P:positive regulation of transcription, DNA-dependent IDA:UniProtKB.
GO:0007548 P:sex differentiation IEA:UniProtKB-KW.
Back to Top
Interpro
IPR009071;    HMG_superfamily.
IPR017253;    TF_Sry.
Back to Top
Pfam
PF00505;    HMG_box;    1.
Back to Top
SMART
SM00398;    HMG;    1.
Back to Top
PROSITE
PS50118;    HMG_BOX_2;    1.
Back to Top
PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    204       Sex-determining region Y protein.
                             /FTId=PRO_0000048671.
DNA_BIND     60    128       HMG box.
REGION       59    136       Sufficient for interaction with KPNB1.
REGION       61     77       Required for nuclear localization.
REGION      107    139       Sufficient for interaction with EP300.
REGION      130    136       Required for nuclear localization.
REGION      138    155       Necessary for interaction with ZNF208
                             isoform KRAB-O.
REGION      198    204       Necessary for interaction with SLC9A3R2.
MOD_RES     136    136       N6-acetyllysine.
VARIANT       3      3       S -> L (in SRXY1).
                             /FTId=VAR_030019.
VARIANT      18     18       S -> N (in SRXY1; partial; also in two
                             patients with a Turner syndrome
                             phenotype).
                             /FTId=VAR_003717.
VARIANT      60     60       V -> A (in SRXY1).
                             /FTId=VAR_003718.
VARIANT      60     60       V -> L (in SRXY1).
                             /FTId=VAR_003719.
VARIANT      62     62       R -> G (in SRXY1).
                             /FTId=VAR_003720.
VARIANT      64     64       M -> I (in SRXY1; alters interaction with
                             DNA and DNA bending).
                             /FTId=VAR_003721.
VARIANT      64     64       M -> R (in SRXY1).
                             /FTId=VAR_017298.
VARIANT      67     67       F -> V (in SRXY1).
                             /FTId=VAR_017299.
VARIANT      68     68       I -> T (in SRXY1).
                             /FTId=VAR_003722.
VARIANT      76     76       R -> S (in SRXY1).
                             /FTId=VAR_017300.
VARIANT      78     78       M -> T (in SRXY1).
                             /FTId=VAR_003723.
VARIANT      87     87       N -> Y (in SRXY1).
                             /FTId=VAR_017301.
VARIANT      90     90       I -> M (in SRXY1).
                             /FTId=VAR_003724.
VARIANT      91     91       S -> G (in SRXY1).
                             /FTId=VAR_003725.
VARIANT      95     95       G -> E (in SRXY1).
                             /FTId=VAR_017302.
VARIANT      95     95       G -> R (in SRXY1).
                             /FTId=VAR_003726.
VARIANT     101    101       L -> H (in SRXY1).
                             /FTId=VAR_003727.
VARIANT     106    106       K -> I (in SRXY1).
                             /FTId=VAR_003728.
VARIANT     108    108       P -> R (in SRXY1).
                             /FTId=VAR_003729.
VARIANT     109    109       F -> S (in SRXY1).
                             /FTId=VAR_003730.
VARIANT     113    113       A -> T (in SRXY1).
                             /FTId=VAR_003731.
VARIANT     125    125       P -> L (in SRXY1).
                             /FTId=VAR_003732.
VARIANT     127    127       Y -> C (in SRXY1).
                             /FTId=VAR_003733.
VARIANT     127    127       Y -> F (in SRXY1).
                             /FTId=VAR_017303.
VARIANT     131    131       P -> R (in SRXY1).
                             /FTId=VAR_017304.
VARIANT     133    133       R -> W (in SRXY1).
                             /FTId=VAR_003734.
MUTAGEN      31     33       SSS->AAA: Abolishes its phosphorylation
                             by PKA. Does not enhance its DNA-binding
                             activity. Abolishes stimulation of
                             transcription repression.
MUTAGEN      62     62       R->G: Strongly reduces nuclear
                             localization. Strongly reduces nuclear
                             localization; when associated with W-133.
                             Reduces interaction with KPNB1. Abolishes
                             DNA-binding.
MUTAGEN      64     64       M->I: Abolishes nuclear localization.
MUTAGEN      75     75       R->N: Strongly reduces nuclear
                             localization. Abolishes DNA-binding. Does
                             not reduce interaction with KPNB1 and
                             CAML.
MUTAGEN      76     76       R->P: Reduces nuclear localization.
                             Reduces DNA-binding. Does not reduce
                             interaction with KPNB1 and CAML.
MUTAGEN     115    115       K->R: Does not abolish acetylation
                             activity.
MUTAGEN     123    123       K->R: Does not abolish acetylation.
MUTAGEN     128    128       K->R: Does not abolish acetylation.
MUTAGEN     133    133       R->W: Reduces nuclear localization.
                             Strongly reduces nuclear localization;
                             when associated with G-62. Reduces
                             interaction with KPNB1. Does not reduce
                             interaction with CAML. Does not abolish
                             DNA-binding.
MUTAGEN     134    134       K->R: Does not abolish acetylation.
MUTAGEN     136    136       K->R: Abolishes acetylation. Does not
                             abolish interaction with EP300. Does not
                             abolish DNA-binding. Enhances cytoplasmic
                             localization. Abolishes interaction with
                             KPNB1.
HELIX        66     81
STRAND       86     88
HELIX        89     99
HELIX       103    123
STRAND      124    126
Back to Top
Nucleotide Sequence
Length: 2151 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 204 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
Other Protein-Protein interaction resources
String database  
View Microarray data
Temporarily unavailable 
Comments