SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000565 
UniProt Accession
Theoretical PI
8.97  
Molecular Weight
43008 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
GJA1 
Gene Synonyms/Alias
GJAL 
Protein Name
Gap junction alpha-1 protein 
Protein Synonyms/Alias
Connexin-43;Cx43 Gap junction 43 kDa heart protein; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:6;121756791-121770873;1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Severe spermatogenic impairment is associated with a population of Sertoli cells exhibiting a stage of differentiation deficiency. The alteration of Cx43 expression may be involved in spermatogenic impairment, and that the communication between Sertoli cells and germ cells through Cx43 may be important for maturation of spermatogenesis.  
The information of related literatures
1. K. Steger, F. Tetens and M. Bergmann (1999) Expression of connexin 43 in human testis. Histochem Cell Biol 112(3): 215-20. 

Abstract
In order to further characterize the Sertoli cell state of differentiation, we investigated the expression of connexin 43 (cx43) protein in the testis of adult men both with normal spermatogenesis and associated with spermatogenic impairment, since cx43 is first expressed during puberty. Cx43 protein was found as a single 43-kDa band on western blots of extracts of normal human testicular material. Cx43 immunoreactivity was generally present between Leydig cells. Within the normal seminiferous epithelium cx43 immunoreactivity was localized between adjacent Sertoli cells, except at stages II and III of the seminiferous epithelial cycle when primary spermatocytes cross from the basal to the adluminal compartment suggesting a stage-dependent Sertoli cell function. While testes with hypospermatogenesis and spermatogenic arrest at the level of round spermatids or spermatocytes revealed a staining pattern similar to that of normal adult testis, the seminiferous tubules showing spermatogenic arrest at the level of spermatogonia and Sertoli-cell-only syndrome were completely immunonegative. We therefore assume that severe spermatogenic impairment is associated with a population of Sertoli cells exhibiting a stage of differentiation deficiency. PMID: [10502068] 

2. Y. Matsuo, K. Nomata, J. Eguchi, D. Aoki, T. Hayashi, Y. Hishikawa, H. Kanetake, Y. Shibata and T. Koji (2007) Immunohistochemical analysis of connexin43 expression in infertile human testes. Acta Histochem Cytochem 40(3): 69-75. 

Abstract
Connexin43 (Cx43) is abundantly expressed in mammalian testes and implicated in the regulation of cell-to-cell interaction between germ cells and Sertoli cells, which is essential to the normal process of spermatogenesis. In the present study, we investigated the relation between Cx43 expression and the degree of spermatogenesis in infertile human testes. Immunohistochemical analysis of Cx43 was performed on testicular biopsies from 29 patients with azoospermia (n=23) and severe oligospermia (n=6), who gave informed consent to this experiment. The degree of testicular spermatogenesis was evaluated by Johnsen score. In the interstitium, immunostaining for Cx43 was localized to some focal parts of plasma membrane between neighboring Leydig cells. In seminiferous tubules with normal spermatogenesis, Cx43 expression was found between Sertoli cells and germ cells. However, Cx43 expression in maturation arrest was decreased and located mainly in the basal compartment of seminiferous tubules. Finally, there was a significant positive correlation between histological score of spermatogenesis and intensity of Cx43 (p=0.0294). These data suggest that the alteration of Cx43 expression may be involved in spermatogenic impairment, and that the communication between Sertoli cells and germ cells through Cx43 may be important for maturation of spermatogenesis. PMID: [17653298] 

3. M. Kotula-Balak, A. Hejmej, J. Sadowska and B. Bilinska (2007) Connexin 43 expression in human and mouse testes with impaired spermatogenesis. Eur J Histochem 51(4): 261-8. 

Abstract
Connexin 43 (Cx43) belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter's syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter's patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter's patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought. PMID: [18162455] 

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Figures for illustrating the function of this protein/gene
Function
Gap junction protein that acts as a regulator of bladdercapacity. A gap junction consists of a cluster of closely packedpairs of transmembrane channels, the connexons, through whichmaterials of low MW diffuse from one cell to a neighboring cell.May play a critical role in the physiology of hearing byparticipating in the recycling of potassium to the cochlearendolymph. Negative regulator of bladder functional capacity: actsby enhancing intercellular electrical and chemical transmission,thus sensitizing bladder muscles to cholinergic neural stimuli andcausing them to contract (By similarity). 
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Subcellular Location
Cell membrane; Multi-pass membrane protein.Cell junction, gap junction. 
Tissue Specificity
Expressed in the heart and fetal cochlea. 
Gene Ontology
GO IDGO termEvidence
GO:0005922 C:connexon complex TAS:ProtInc.
GO:0043292 C:contractile fiber IEA:Compara.
GO:0005829 C:cytosol IEA:Compara.
GO:0005769 C:early endosome IEA:Compara.
GO:0005789 C:endoplasmic reticulum membrane TAS:Reactome.
GO:0005916 C:fascia adherens IEA:Compara.
GO:0030660 C:Golgi-associated vesicle membrane TAS:Reactome.
GO:0005887 C:integral to plasma membrane TAS:UniProtKB.
GO:0014704 C:intercalated disc ISS:BHF-UCL.
GO:0005764 C:lysosome IEA:Compara.
GO:0005624 C:membrane fraction IEA:Compara.
GO:0045121 C:membrane raft ISS:BHF-UCL.
GO:0005741 C:mitochondrial outer membrane IEA:Compara.
GO:0005771 C:multivesicular body IEA:Compara.
GO:0005243 F:gap junction channel activity IEA:Compara.
GO:0015075 F:ion transmembrane transporter activity TAS:ProtInc.
GO:0004871 F:signal transducer activity IMP:UniProtKB.
GO:0007512 P:adult heart development IEA:Compara.
GO:0006915 P:apoptotic process IEA:Compara.
GO:0015867 P:ATP transport IEA:Compara.
GO:0048514 P:blood vessel morphogenesis IEA:Compara.
GO:0007267 P:cell-cell signaling TAS:ProtInc.
GO:0016044 P:cellular membrane organization TAS:Reactome.
GO:0002070 P:epithelial cell maturation IEA:Compara.
GO:0016264 P:gap junction assembly TAS:UniProtKB.
GO:0007507 P:heart development TAS:ProtInc.
GO:0001947 P:heart looping IEA:Compara.
GO:0001701 P:in utero embryonic development IEA:Compara.
GO:0060174 P:limb bud formation IEA:Compara.
GO:0006936 P:muscle contraction TAS:ProtInc.
GO:0008285 P:negative regulation of cell proliferation IEA:Compara.
GO:0010629 P:negative regulation of gene expression IEA:Compara.
GO:0001764 P:neuron migration IEA:Compara.
GO:0048812 P:neuron projection morphogenesis IEA:Compara.
GO:0010628 P:positive regulation of gene expression IEA:Compara.
GO:0043123 P:positive regulation of I-kappaB kinase/NF-kappaB cascade IMP:UniProtKB.
GO:0045732 P:positive regulation of protein catabolic process IEA:Compara.
GO:0045844 P:positive regulation of striated muscle tissue development IEA:Compara.
GO:0051259 P:protein oligomerization IEA:Compara.
GO:0051924 P:regulation of calcium ion transport IEA:Compara.
GO:0008016 P:regulation of heart contraction IEA:Compara.
GO:0043434 P:response to peptide hormone stimulus IEA:Compara.
GO:0009268 P:response to pH IEA:Compara.
GO:0043403 P:skeletal muscle tissue regeneration IEA:Compara.
GO:0010232 P:vascular transport IEA:Compara.
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Interpro
IPR000500;    Connexin.
IPR002261;    Connexin43.
IPR013124;    Connexin43_C.
IPR019570;    Connexin_CCC.
IPR017990;    Connexin_CS.
IPR013092;    Connexin_N.
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Pfam
PF00029;    Connexin;    1.
PF03508;    Connexin43;    1.
PF10582;    Connexin_CCC;    1.
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SMART
SM00037;    CNX;    1.
SM01089;    Connexin_CCC;    1.
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PROSITE
PS00407;    CONNEXINS_1;    1.
PS00408;    CONNEXINS_2;    1.
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PRINTS
PR00206;    CONNEXIN.;   
PR01132;    CONNEXINA1.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
INIT_MET      1      1       Removed (By similarity).
CHAIN         2    382       Gap junction alpha-1 protein.
                             /FTId=PRO_0000057801.
TOPO_DOM      2     13       Cytoplasmic (Potential).
TRANSMEM     14     36       Helical; (Potential).
TOPO_DOM     37     76       Extracellular (Potential).
TRANSMEM     77     99       Helical; (Potential).
TOPO_DOM    100    154       Cytoplasmic (Potential).
TRANSMEM    155    177       Helical; (Potential).
TOPO_DOM    178    208       Extracellular (Potential).
TRANSMEM    209    231       Helical; (Potential).
TOPO_DOM    232    382       Cytoplasmic (Potential).
MOD_RES     247    247       Phosphotyrosine.
MOD_RES     262    262       Phosphoserine.
MOD_RES     306    306       Phosphoserine (By similarity).
MOD_RES     313    313       Phosphotyrosine.
MOD_RES     314    314       Phosphoserine (By similarity).
MOD_RES     325    325       Phosphoserine; by CK1.
MOD_RES     326    326       Phosphothreonine (By similarity).
MOD_RES     328    328       Phosphoserine; by CK1.
MOD_RES     330    330       Phosphoserine; by CK1.
MOD_RES     365    365       Phosphoserine (By similarity).
MOD_RES     368    368       Phosphoserine; by PKC/PRKCG (By
                             similarity).
MOD_RES     369    369       Phosphoserine (By similarity).
MOD_RES     373    373       Phosphoserine (By similarity).
DISULFID     54    192
DISULFID    187    198
VARIANT       2      2       G -> V (in ODDD).
                             /FTId=VAR_058990.
VARIANT       7      7       L -> V (in ODDD).
                             /FTId=VAR_058991.
VARIANT      11     11       L -> P (in ODDD).
                             /FTId=VAR_058992.
VARIANT      17     17       Y -> S (in ODDD).
                             /FTId=VAR_015747.
VARIANT      18     18       S -> P (in ODDD).
                             /FTId=VAR_015748.
VARIANT      21     21       G -> R (in ODDD; involvement of only the
                             fourth and fifth fingers; SDTY3).
                             /FTId=VAR_015749.
VARIANT      22     22       G -> E (in ODDD; involvement of only the
                             fourth and fifth fingers; SDTY3).
                             /FTId=VAR_015750.
VARIANT      23     23       K -> T (in ODDD).
                             /FTId=VAR_015751.
VARIANT      27     27       S -> P (in ODDD).
                             /FTId=VAR_038356.
VARIANT      31     31       I -> M (in ODDD).
                             /FTId=VAR_038357.
VARIANT      40     40       A -> V (in ODDD).
                             /FTId=VAR_015752.
VARIANT      41     41       V -> L (in ectodermal and
                             oculodentodigital dysplasia; with skin
                             hyperkeratosis; associated with GJB2
                             variant His-127).
                             /FTId=VAR_058993.
VARIANT      49     49       Q -> K (in ODDD).
                             /FTId=VAR_015753.
VARIANT      49     49       Q -> P (in ODDD).
                             /FTId=VAR_058994.
VARIANT      49     49       Q -> QQ (in ODDD).
                             /FTId=VAR_058995.
VARIANT      52     52       F -> FF (in ODDD).
                             /FTId=VAR_015754.
VARIANT      59     59       P -> H (in ODDD).
                             /FTId=VAR_058996.
VARIANT      69     69       S -> Y (in ODDD).
                             /FTId=VAR_038358.
VARIANT      76     76       R -> H (in HSS; overlapping features with
                             oculodentodigital dysplasia).
                             /FTId=VAR_058997.
VARIANT      76     76       R -> S (in ODDD).
                             /FTId=VAR_015755.
VARIANT      90     90       L -> V (in ODDD).
                             /FTId=VAR_015756.
VARIANT      95     95       H -> R (in ODDD).
                             /FTId=VAR_058998.
VARIANT      96     96       V -> A (in ODDD).
                             /FTId=VAR_058999.
VARIANT      96     96       V -> E (in ODDD).
                             /FTId=VAR_059000.
VARIANT      96     96       V -> M (in ODDD; dbSNP:rs28931601).
                             /FTId=VAR_059001.
VARIANT      98     98       Y -> C (in ODDD).
                             /FTId=VAR_015757.
VARIANT     102    102       K -> N (in ODDD).
                             /FTId=VAR_015758.
VARIANT     106    106       L -> P (in ODDD).
                             /FTId=VAR_059002.
VARIANT     110    110       E -> D (in ODDD).
                             /FTId=VAR_059003.
VARIANT     113    113       L -> P (in ODDD).
                             /FTId=VAR_038359.
VARIANT     124    124       D -> E (in dbSNP:rs2228966).
                             /FTId=VAR_014094.
VARIANT     130    130       I -> T (in ODDD).
                             /FTId=VAR_015759.
VARIANT     134    134       K -> E (in ODDD).
                             /FTId=VAR_015760.
VARIANT     134    134       K -> N (in ODDD).
                             /FTId=VAR_038360.
VARIANT     138    138       G -> R (in ODDD).
                             /FTId=VAR_015761.
VARIANT     143    143       G -> S (in SDTY3; dbSNP:rs28931600).
                             /FTId=VAR_038361.
VARIANT     147    147       M -> T (in ODDD).
                             /FTId=VAR_059004.
VARIANT     148    148       R -> Q (in dbSNP:rs2228960).
                             /FTId=VAR_014095.
VARIANT     154    154       T -> A (in ODDD).
                             /FTId=VAR_059005.
VARIANT     154    154       T -> N (in ODDD).
                             /FTId=VAR_059006.
VARIANT     168    168       A -> T (in dbSNP:rs2228961).
                             /FTId=VAR_014096.
VARIANT     169    169       Missing (in ODDD).
                             /FTId=VAR_059007.
VARIANT     185    185       Y -> H (in dbSNP:rs2228962).
                             /FTId=VAR_014097.
VARIANT     194    194       H -> P (in ODDD; atypical form of ODDD
                             characterized by the predominance of the
                             ocular involvement and by the absence of
                             hand and/or foot syndactyly and absence
                             of any neurologic signs).
                             /FTId=VAR_059008.
VARIANT     201    201       S -> F (in ODDD).
                             /FTId=VAR_059009.
VARIANT     202    202       R -> C (in dbSNP:rs2228964).
                             /FTId=VAR_014098.
VARIANT     202    202       R -> H (in ODDD).
                             /FTId=VAR_015762.
VARIANT     204    204       T -> M (in dbSNP:rs2228965).
                             /FTId=VAR_014099.
VARIANT     216    216       V -> L (in ODDD).
                             /FTId=VAR_015763.
VARIANT     220    220       S -> Y (in ODDD).
                             /FTId=VAR_059010.
VARIANT     239    239       R -> W (in congenital heart
                             malformations; dbSNP:rs2227887).
                             /FTId=VAR_014100.
VARIANT     251    251       S -> T (in congenital heart
                             malformations).
                             /FTId=VAR_059011.
VARIANT     253    253       A -> P (in congenital heart
                             malformations).
                             /FTId=VAR_059012.
VARIANT     253    253       A -> V (in dbSNP:rs17653265).
                             /FTId=VAR_015764.
VARIANT     283    283       P -> L (in congenital heart
                             malformations; dbSNP:rs2228974).
                             /FTId=VAR_014101.
VARIANT     290    290       T -> N (in congenital heart
                             malformations; dbSNP:rs2227881).
                             /FTId=VAR_014102.
VARIANT     326    326       T -> A.
                             /FTId=VAR_059013.
VARIANT     352    352       E -> G (in heart malformations).
                             /FTId=VAR_059014.
VARIANT     362    362       R -> Q (in HLHS1 and AVSD3; associated
                             with Gln-376 in one individual with
                             atrioventricular septal defect; abolishes
                             phosphorylation by PKA and PKC;
                             dbSNP:rs2227885).
                             /FTId=VAR_032924.
VARIANT     364    364       S -> P (in heart malformations; shows
                             abnormalities in the regulation of cell-
                             cell communication as compared with cells
                             expressing normal GJA1).
                             /FTId=VAR_059015.
VARIANT     365    365       S -> N (in heart malformations).
                             /FTId=VAR_059016.
VARIANT     373    373       S -> G.
                             /FTId=VAR_059017.
VARIANT     376    376       R -> Q (in HLHS1 and AVSD3; associated
                             with Gln-362 in one individual with
                             atrioventricular septal defect; abolishes
                             phosphorylation by PKA and PKC).
                             /FTId=VAR_032925.
HELIX       240    242
HELIX       246    253
HELIX       255    257
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Nucleotide Sequence
Length: 3038 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 382 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
_BioGRID 
ADIPOR1String 
ADIPOR2String 
S100A1HPRD 
CSKHPRD 
PRKCAHPRD 
RUTBC3HPRD 
CAV1HPRD 
CDIPTString 
CSKHPRD 
_BioGRID 
ADIPOR1String 
ADIPOR2String 
CAV1BioGRID 
CDIPTString 
GJA1BioGRID 
GJA1BioGRID 
GJA3BioGRID 
GJA5BioGRID 
CSNK1DBioGRID 
PRKCEBioGRID 
MAPK7BioGRID 
CAV1BioGRID 
_BioGRID 
DKFZp686A1195BioGRID 
_BioGRID 
SRCMINT 
TFCP2IntAct 
TJP1BioGRID 
GJA3HPRD 
GJA5HPRD 
CSNK1DHPRD 
PRKCAHPRD 
PRKCBHPRD 
PRKCEHPRD 
PRKCGHPRD 
MAPK1HPRD 
MAPK3HPRD 
MAPK7HPRD 
NOVHPRD 
MAPK1HPRD 
CAV1HPRD 
MAPK1HPRD 
_HPRD 
DKFZp686A1195HPRD 
_BioGRID 
PRKCAHPRD 
S100A1HPRD 
SGSM3HPRD 
SRCHPRD 
TJP1HPRD 
Other Protein-Protein interaction resources
String database  
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