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SG ID |
SG00000889 |
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UniProt Accession |
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Theoretical PI |
4.79
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Molecular Weight |
30645 Da
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Genbank Nucleotide ID |
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Genbank Protein ID |
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Gene Name |
Kitlg |
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Gene Synonyms/Alias |
Kitl, Mgf, Sl, Slf |
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Protein Name |
Kit ligand Soluble KIT ligand |
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Protein Synonyms/Alias |
Hematopoietic growth factor KL; Mast cell growth factor;MGF Steel factor; Stem cell factor;SCF c-Kit ligand;Contains:sKITLGFlags: Precursor |
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Organism |
Mus musculus (Mouse) |
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NCBI Taxonomy ID |
10090 |
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Chromosome Location |
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Function in Stage |
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Function in Cell Type |
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Description |
The Kit receptor and its ligand KL, which together constitute an essential effector at various stages of embryonic development, are both present during adult gametogenesis. In the testis, KL is expressed in Sertoli cells, and Kit in germ cells, starting at the premeiotic stages.The c-kit/SCF signal transduction system appears to be necessary for the maintenance and proliferation of differentiated c-kit receptor-positive spermatogonia but not for the initial step of spermatogonial cell differentiation. |
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The information of related literatures |
1. H. Ohta, A. Tohda and Y. Nishimune (2003) Proliferation and differentiation of spermatogonial stem cells in the w/wv mutant mouse testis. Biol Reprod 69(6): 1815-21. Abstract Mutations in the dominant-white spotting (W; c-kit) and stem cell factor (Sl; SCF) genes, which encode the transmembrane tyrosine kinase receptor and its ligand, respectively, affect both the proliferation and differentiation of many types of stem cells. Almost all homozygous W or Sl mutant mice are sterile because of the lack of differentiated germ cells or spermatogonial stem cells. To characterize spermatogenesis in c-kit/SCF mutants and to understand the role of c-kit signal transduction in spermatogonial stem cells, the existence, proliferation, and differentiation of spermatogonia were examined in the W/Wv mutant mouse testis. In the present study, some of the W/Wv mutant testes completely lacked spermatogonia, and many of the remaining testes contained only a few spermatogonia. Examination of the proliferative activity of the W/Wv mutant spermatogonia by transplantation of enhanced green fluorescent protein (eGFP)-labeled W/Wv spermatogonia into the seminiferous tubules of normal SCF (W/Wv) or SCF mutant (Sl/Sld) mice demonstrated that the W/Wv spermatogonia had the ability to settle and proliferate, but not to differentiate, in the recipient seminiferous tubules. Although the germ cells in the adult W/Wv testis were c-kit-receptor protein-negative undifferentiated type A spermatogonia, the juvenile germ cells were able to differentiate into spermatogonia that expressed the c-kit-receptor protein. Furthermore, differentiated germ cells with the c-kit-receptor protein on the cell surface could be induced by GnRH antagonist treatment, even in the adult W/Wv testis. These results indicate that all the spermatogonial stem cell characteristics of settlement, proliferation, and differentiation can be demonstrated without stimulating the c-kit-receptor signal. The c-kit/SCF signal transduction system appears to be necessary for the maintenance and proliferation of differentiated c-kit receptor-positive spermatogonia but not for the initial step of spermatogonial cell differentiation. PMID: [12890724] 2. D. G. de Rooij, M. Okabe and Y. Nishimune (1999) Arrest of spermatogonial differentiation in jsd/jsd, Sl17H/Sl17H, and cryptorchid mice. Biol Reprod 61(3): 842-7. Abstract The nature of the spermatogenic arrest in cryptorchid C57Bl mice and in jsd/jsd and Sl17H/Sl17H mutant mice was identified by studying whole mounts of seminiferous tubules. In all three types of mice, virtually only A spermatogonia were found, topographically arranged in clones of 1 to 16 (rarely more) cells. These clonal sizes are typical for undifferentiated spermatogonia. The proportion of these cells lying in chains of more than 2 cells (50-70%) was comparable to that seen in epithelial stages VII-VIII in the normal epithelium. It is concluded that in all three types of mice, spermatogenesis is arrested at the point where the undifferentiated A spermatogonia, specifically A(al) spermatogonia, differentiate into the first generation of the differentiating-type spermatogonia, the A1 spermatogonia. The remaining A spermatogonia were proliferating, but no accumulation of spermatogonia was present, as spermatogonial apoptosis also took place. Spermatogonial clones of all sizes were seen to undergo apoptosis, but there were relatively many large apoptotic clones, indicating that the clones became more vulnerable when they became larger. In contrast to what is seen in the normal epithelium, odd-numbered clones, not composed of 2(n) cells, were present, as well as clumps of 2 or more spermatogonial nuclei in the same cytoplasm, in all three types of mice. This indicates a lack of integrity of spermatogonial clones, also observed in other situations with a relative paucity of cells on the basal membrane. It is concluded that the differentiation of the undifferentiated spermatogonia, affected in all three types of mice as well as in vitamin A-deficient animals, is a rather vulnerable point in the spermatogenic developmental pathway. PMID: [10456866] 3. S. Vincent, D. Segretain, S. Nishikawa, S. I. Nishikawa, J. Sage, F. Cuzin and M. Rassoulzadegan (1998) Stage-specific expression of the Kit receptor and its ligand (KL) during male gametogenesis in the mouse. Development 125(22): 4585-93. Abstract The Kit receptor and its ligand KL, which together constitute an essential effector at various stages of embryonic development, are both present during adult gametogenesis. In the testis, KL is expressed in Sertoli cells, and Kit in germ cells, starting at the premeiotic stages. A series of observations indicated previously a role in spermatogonia survival, without excluding a possible function at later stages. We identified a complex pattern of expression of the two components in the adult murine testis, suggestive of a role in the meiotic progression of spermatocytes. At stages VII-VIII of the cycle of the seminiferous epithelium, the time when spermatocytes enter meiosis, the membrane-associated form of KL extends on the Sertoli cell from the peripheral to the adluminal compartment of the tubule. We also found that the receptor is present on the surface of germ cells up to the pachytene stage. The availability of differentiated Sertoli cell lines, which express the KL protein and support part of the maturation of germ cells in coculture, allowed us to ask whether, in the in vitro reconstructed system, transit of spermatocytes through meiosis requires the Kit-KL interaction. Addition of a blocking monoclonal antibody against the Kit receptor (ACK2) inhibited extensively the appearance of haploid cells and the expression of a haploid-phase-specific gene (Prm1). Recognition of the supporting Sertoli cell by germ cells was not affected, indicating a requirement for the activity of the receptor for either entering or completing meiosis. Involvement of the membrane-associated form of the ligand was suggested by the observation that addition of the soluble form of KL was equally inhibitory. PMID: [9778516] 4. S. Deshpande, V. Agosti, K. Manova, M. A. Moore, M. P. Hardy and P. Besmer (2010) Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis. Dev Biol 337(2): 199-210. Abstract Juxtamembrane signaling via the membrane growth factor KitL is critical for Kit mediated functions. KitL has a conserved cytoplasmic domain and has been shown to possess a monomeric leucine-dependent basolateral targeting signal. To investigate the consequences in vivo of impaired basolateral KitL targeting in polarized epithelial cells, we have mutated this critical leucine to alanine using a knock-in strategy. KitL(L263A/L263A) mutant mice are pigmented normally and steady-state hematopoiesis is unaffected although peritoneal and skin mast cell numbers are significantly increased. KitL localization is affected in the Sertoli cells of the KitL(L263A/L263A) testis and testis size is reduced in these mice due to aberrant spermatogonial proliferation. Furthermore, the effect of the KitL L263A mutation on the testicular phenotype is dosage dependent. The tubules of hemizygous KitL(L263A/Sl) mice completely lack germ cells in contrast to the weaker testicular phenotype of KitL(L263A/L263A) mice. The onset of the testis phenotype coincides with the formation of tight junctions between Sertoli cells during postnatal development. Thus, the altered sorting of KitL is dispensable for hematopoietic and melanogenic lineages, yet is crucial in the testicular environment, where the basal membranes of adjacent polarized Sertoli cells form a niche for the proliferating spermatogonia. PMID: [19874813] Back to Top |
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Figures for illustrating the function of this protein/gene |
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Function |
Ligand for the receptor-type protein-tyrosine kinaseKIT. Plays an essential role in the regulation of cell survivaland proliferation, hematopoiesis, stem cell maintenance,gametogenesis, mast cell development, migration and function, andin melanogenesis. KITLG/SCF binding can activate several signalingpathways. Promotes phosphorylation of PIK3R1, the regulatorysubunit of phosphatidylinositol 3-kinase, and subsequentactivation of the kinase AKT1. KITLG/SCF and KIT also transmitsignals via GRB2 and activation of RAS, RAF1 and the MAP kinasesMAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activationof STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KITpromote activation of PLCG1, leading to the production of thecellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with othercytokines, probably interleukins. Back to Top |
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Subcellular Location |
Soluble KIT ligand: Secreted (Bysimilarity). |
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Tissue Specificity |
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Gene Ontology |
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Interpro |
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Pfam |
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SMART |
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PROSITE |
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PRINTS |
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Created Date |
18-Oct-2012 |
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Record Type |
Experiment identified |
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Protein sequence Annotation |
SIGNAL 1 25 CHAIN 26 273 Kit ligand. /FTId=PRO_0000031914. CHAIN 26 190 Soluble KIT ligand (By similarity). /FTId=PRO_0000403392. TOPO_DOM 26 214 Extracellular (Potential). TRANSMEM 215 237 Helical; (Potential). TOPO_DOM 238 273 Cytoplasmic (Potential). CARBOHYD 90 90 N-linked (GlcNAc...) (Potential). CARBOHYD 97 97 N-linked (GlcNAc...) (Potential). CARBOHYD 145 145 N-linked (GlcNAc...) (Potential). CARBOHYD 195 195 N-linked (GlcNAc...) (Potential). DISULFID 29 114 DISULFID 68 163 VAR_SEQ 174 202 DSRVSVTKPFMLPPVAASSLRNDSSSSNR -> G (in isoform 2). /FTId=VSP_006023. VARIANT 122 122 N -> S (in MGFSL-3NEU). VARIANT 193 193 L -> P. VARIANT 207 207 A -> S. CONFLICT 215 215 W -> L (in Ref. 2; AAB22555/AAB22554). HELIX 35 39 HELIX 40 45 STRAND 53 57 TURN 59 63 HELIX 66 68 HELIX 70 85 HELIX 97 118 STRAND 131 135 HELIX 137 151 TURN 153 156 Back to Top |
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Nucleotide Sequence |
Length: 619 bp Go to nucleotide: FASTA |
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Protein Sequence |
Length: 273 bp Go to amino acid: FASTA |
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The verified Protein-Protein interaction information |
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Other Protein-Protein interaction resources |
String database |
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View Microarray data |
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Comments |
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