SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000642 
UniProt Accession
Theoretical PI
6.4  
Molecular Weight
122102 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
MUC1 
Gene Synonyms/Alias
PUM 
Protein Name
Mucin-1 Mucin-1 subunit alpha Mucin-1 subunit beta 
Protein Synonyms/Alias
MUC-1 Breast carcinoma-associated antigen DF3; Carcinoma-associated mucin; Episialin; H23AG; Krebs von den Lungen-6;KL-6 PEMT; Peanut-reactive urinary mucin;PUM Polymorphic epithelial mucin;PEM Tumor-associated epithelial membrane antigen;EMA Tumor-associated mucin; CD_antigen=CD227;Contains:MUC1-NTMUC1-alphaContains:MUC1-beta MUC1-CT;Flags: Precursor 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:1;155158300-155162707;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
These results suggest a variable glycosylation of MUC1 mucin in differentiating germ cells, which is aberrant in pathological conditions. mucin1 expression might be closely related to spermatogenesis. Our findings should be substantiated by more direct evidence, such as mucin protein expression and localization. 
The information of related literatures
1. F. E. Franke, S. Kraus, C. Eiermann, K. Pauls, E. N. Lalani and M. Bergmann (2001) MUC1 in normal and impaired spermatogenesis. Mol Hum Reprod 7(6): 505-12. 

Abstract
The MUC1 mucin [also known as episialin, epithelial membrane antigen (EMA) or polymorphic epithelial mucin (PEM)] is a component of the mucosal glycocalyx, contributing to anti-adhesive and protective cell functions. MUC1 has been shown in a variety of epithelial cell types in the reproductive tracts of males and females, but this is the first report of its expression in human testis and non-epithelial cells of the germ cell lineage. Analysing 65 testes with normal or impaired spermatogenesis, we identified MUC1 protein in maturing germ cells by immunohistochemistry using the monoclonal antibodies HMFG1, HMFG2 and SM3 binding to different glycosylation variants. MUC1 expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis on tissue extracts of human testis, and RT-PCR of selected germ cells after UV laser-assisted cell picking. MUC1 glycosylation variants were selectively distributed during normal spermatogenesis. Whereas HMFG1 labelled certain groups of pachytene spermatocytes, HMFG2 labelled only spermatids. Low glycosylated forms of MUC1 mucin, recognized by SM3, were not found. In contrast to its weak expression during normal spermatogenesis, the HMFG1 glycosylation variant accumulated markedly in all spermatocytes showing abnormal or arrested maturation. These results suggest a variable glycosylation of MUC1 mucin in differentiating germ cells, which is aberrant in pathological conditions. PMID: [11385106] 

2. J. T. Seo, J. S. Lee, J. H. Jun and M. H. Yang (2005) Expression of mucin genes in the human testis and its relationship to spermatogenesis. Yonsei Med J 46(5): 667-72. 

Abstract
In this study we investigate the expression pattern of mucin genes in the human testis and evaluate the relationship between the expression of mucin genes and impaired spermatogenesis in the human testis. Thirty human testis tissues were collected from patients undergoing diagnostic testicular biopsy to investigate the cause of infertility. One part of the tissue underwent histological observation, and the other part of the tissue was subjected to semiquantitative RT-PCR of mucin genes, that is, mucin1, 2, 3, 4, and 9. The relative amount of mucin mRNAs was calculated by densitometry using glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as an internal control. The samples were histologically diagnosed as either obstructive azoospermia with normal spermatogenesis (n = 13) or non-obstructive azoospermia with impaired spermatogenesis (n = 17). In the human testis with normal spermatogenesis, mRNA expression of mucin1, 9, 13 and GAPDH were found, but RT-PCR products of mucin 2, 3 and 4 were not detected. In the testis with impaired spermatogenesis, however, RT-PCR product of mucin1 was not found. There was no difference in the other mucin mRNA expression patterns between the testis with either normal or impaired spermatogenesis. To our knowledge, this study is the first that has detected the mRNA of mucin9 and 13 in human testis. This study also shows that mucin1 expression might be closely related to spermatogenesis. Our findings should be substantiated by more direct evidence, such as mucin protein expression and localization. PMID: [16259065] 

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Figures for illustrating the function of this protein/gene
Function
The beta subunit contains a C-terminal domain which isinvolved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly orindirectly the Ras/MAPK pathway. Promotes tumor progression.Regulates TP53-mediated transcription and determines cell fate inthe genotoxic stress response. Binds, together with KLF4, the PE21promoter element of TP53 and represses TP53 activity. 
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Subcellular Location
Mucin-1 subunit beta: Cell membrane.Cytoplasm. Nucleus. Note=On EGF and PDGFRB stimulation,transported to the nucleus through interaction with CTNNB1, aprocess which is stimulated by phosphorylation. On HRGstimulation, colocalizes with JUP/gamma-catenin at the nucleus. 
Tissue Specificity
Expressed on the apical surface of epithelialcells, especially of airway passages, breast and uterus. Alsoexpressed in activated and unactivated T-cells. Overexpressed inepithelial tumors, such as breast or ovarian cancer and also innon-epithelial tumor cells. Isoform 7 is expressed in tumor cellsonly. 
Gene Ontology
GO IDGO termEvidence
GO:0016324 C:apical plasma membrane IBA:RefGenome.
GO:0009986 C:cell surface IBA:RefGenome.
GO:0005576 C:extracellular region IEA:UniProtKB-SubCell.
GO:0005796 C:Golgi lumen TAS:Reactome.
GO:0005887 C:integral to plasma membrane TAS:ProtInc.
GO:0000790 C:nuclear chromatin IDA:BHF-UCL.
GO:0000978 F:RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA:BHF-UCL.
GO:0003712 F:transcription cofactor activity IDA:BHF-UCL.
GO:0006916 P:anti-apoptosis IDA:BHF-UCL.
GO:0006977 P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest IDA:BHF-UCL.
GO:0006978 P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator IDA:BHF-UCL.
GO:0010944 P:negative regulation of transcription by competitive promoter binding IDA:BHF-UCL.
GO:0016266 P:O-glycan processing TAS:Reactome.
GO:0090240 P:positive regulation of histone H4 acetylation IDA:BHF-UCL.
GO:0036003 P:positive regulation of transcription from RNA polymerase II promoter in response to stress IDA:BHF-UCL.
GO:0043687 P:post-translational protein modification TAS:Reactome.
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Interpro
IPR023217;    Mucin-1.
IPR000082;    SEA.
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Pfam
PF01390;    SEA;    1.
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SMART
SM00200;    SEA;    1.
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PROSITE
PS50024;    SEA;    1.
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PRINTS
Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
SIGNAL        1     23
CHAIN        24   1255       Mucin-1.
                             /FTId=PRO_0000019277.
CHAIN        24   1097       Mucin-1 subunit alpha.
                             /FTId=PRO_0000317446.
CHAIN      1098   1255       Mucin-1 subunit beta.
                             /FTId=PRO_0000317447.
TOPO_DOM     24   1158       Extracellular (Potential).
TRANSMEM   1159   1181       Helical; (Potential).
TOPO_DOM   1182   1255       Cytoplasmic (Potential).
REPEAT       61     80       1; approximate.
REPEAT       81    100       2; approximate.
REPEAT      101    120       3.
REPEAT      121    140       4.
REPEAT      141    160       5.
REPEAT      161    180       6.
REPEAT      181    200       7.
REPEAT      201    220       8.
REPEAT      221    240       9.
REPEAT      241    260       10.
REPEAT      261    280       11.
REPEAT      281    300       12.
REPEAT      301    320       13.
REPEAT      321    340       14.
REPEAT      341    360       15.
REPEAT      361    380       16.
REPEAT      381    400       17.
REPEAT      401    420       18.
REPEAT      421    440       19.
REPEAT      441    460       20.
REPEAT      461    480       21.
REPEAT      481    500       22.
REPEAT      501    520       23.
REPEAT      521    540       24.
REPEAT      541    560       25.
REPEAT      561    580       26.
REPEAT      581    600       27.
REPEAT      601    620       28.
REPEAT      621    640       29.
REPEAT      641    660       30.
REPEAT      661    680       31.
REPEAT      681    700       32.
REPEAT      701    720       33.
REPEAT      721    740       34.
REPEAT      741    760       35.
REPEAT      761    780       36.
REPEAT      781    800       37.
REPEAT      801    820       38.
REPEAT      821    840       39.
REPEAT      841    860       40.
REPEAT      861    880       41.
REPEAT      881    900       42.
REPEAT      901    920       43.
REPEAT      921    940       44.
REPEAT      941    960       45.
REPEAT      961    980       46; approximate.
REPEAT      981   1000       47; approximate.
REPEAT     1001   1020       48; approximate.
DOMAIN     1034   1151       SEA.
REGION      126    965       42 X 20 AA approximate tandem repeats of
                             P-A-P-G-S-T-A-P-P-A-H-G-V-T-S-A-P-D-T-R.
REGION     1192   1228       Interaction with P53.
REGION     1223   1230       Required for interaction with GSK3B.
REGION     1233   1241       Required for interaction with beta- and
                             gamma-catenins.
MOTIF      1203   1206       Interaction with GRB2.
MOTIF      1229   1232       Interaction with SRC and ESR1.
MOTIF      1243   1246       Required for interaction with AP1S2.
SITE       1097   1098       Cleavage; by autolysis.
MOD_RES    1191   1191       Phosphotyrosine.
MOD_RES    1203   1203       Phosphotyrosine; by PDGFR.
MOD_RES    1209   1209       Phosphotyrosine.
MOD_RES    1212   1212       Phosphotyrosine.
MOD_RES    1218   1218       Phosphotyrosine; by PDGFR.
MOD_RES    1224   1224       Phosphothreonine; by PKC/PRKCD.
MOD_RES    1227   1227       Phosphoserine; by GSK3-beta.
MOD_RES    1229   1229       Phosphotyrosine; by CSK, EGFR and SRC.
MOD_RES    1243   1243       Phosphotyrosine.
LIPID      1184   1184       S-palmitoyl cysteine.
LIPID      1186   1186       S-palmitoyl cysteine.
CARBOHYD    131    131       O-linked (GalNAc...) (Probable).
CARBOHYD    139    139       O-linked (GalNAc...) (Probable).
CARBOHYD    140    140       O-linked (GalNAc...) (Potential).
CARBOHYD    144    144       O-linked (GalNAc...) (Potential).
CARBOHYD    957    957       N-linked (GlcNAc...) (Potential).
CARBOHYD    975    975       N-linked (GlcNAc...) (Potential).
CARBOHYD   1029   1029       N-linked (GlcNAc...) (Potential).
CARBOHYD   1055   1055       N-linked (GlcNAc...) (Potential).
CARBOHYD   1133   1133       N-linked (GlcNAc...) (Potential).
VAR_SEQ      19     21       Missing (in isoform 3).
                             /FTId=VSP_003281.
VAR_SEQ      19     19       T -> TATTAPKPAT (in isoform 2).
                             /FTId=VSP_003280.
VAR_SEQ      20     31       Missing (in isoform 4).
                             /FTId=VSP_003282.
VAR_SEQ      54   1053       Missing (in isoform 7).
                             /FTId=VSP_003285.
VAR_SEQ      54   1035       Missing (in isoform 8 and isoform 9).
                             /FTId=VSP_003286.
VAR_SEQ      54     87       VSMTSSVLSSHSPGSGSSTTQGQDVTLAPATEPA -> IPA
                             PTTTKSCRETFLKCFCRFINKGVFWASPILS (in
                             isoform 10).
                             /FTId=VSP_035046.
VAR_SEQ      54     70       VSMTSSVLSSHSPGSGS -> IPAPTTTKSCRETFLKW
                             (in isoform 6).
                             /FTId=VSP_003283.
VAR_SEQ      71   1095       Missing (in isoform 6).
                             /FTId=VSP_003284.
VAR_SEQ      88   1139       Missing (in isoform 10).
                             /FTId=VSP_035047.
VAR_SEQ    1077   1181       Missing (in isoform 9).
                             /FTId=VSP_003287.
VAR_SEQ    1077   1087       FLQIYKQGGFL -> VSIGLSFPMLP (in isoform
                             5).
                             /FTId=VSP_003288.
VAR_SEQ    1088   1255       Missing (in isoform 5).
                             /FTId=VSP_003289.
VARIANT    1117   1117       V -> M (in dbSNP:rs1611770).
                             /FTId=VAR_019390.
VARIANT    1142   1142       S -> N (in dbSNP:rs11465207).
                             /FTId=VAR_019391.
MUTAGEN    1098   1098       S->A,D,E,F,G,H,I,K,L,M,N,P,Q,R,V,W,Y:
                             Completely abrogates cleavage.
MUTAGEN    1098   1098       S->C,T: Almost complete cleavage.
MUTAGEN    1116   1116       D->A: Greatly reduced formation of
                             isoform 5/isoform 7 complex.
MUTAGEN    1116   1116       D->E: No effect on formation of isoform
                             5/isoform 7 complex.
MUTAGEN    1184   1184       C->A: S-palmitoylation reduced by 50%.
                             Complete loss of palmitoylation, no
                             effect on endocytosis, recycling
                             inhibited and AP1S1 binding reduced by
                             30%; when associated with C-1186.
                             Accumulates in intracellular
                             compartments; when associated with C-1186
                             and N-1203.
MUTAGEN    1186   1186       C->A: S-palmitoylation reduced by 50%.
                             Complete loss of palmitoylation, no
                             effect on endocytosis, recycling
                             inhibited, and AP1S1 binding reduced by
                             30%; when associated with C-1184.
                             Accumulates in intracellular
                             compartments; when associated with C-1184
                             and N-1203.
MUTAGEN    1187   1189       RRK->AAA: No nuclear targeting of HRG-
                             stimulated MUC1 C-terminal nor JUP/gamma-
                             catenin. No effect on interaction with
                             JUP/gamma-catenin.
MUTAGEN    1187   1189       RRK->QQQ: No effect on palmitoylation.
MUTAGEN    1191   1191       Y->F: No effect on EGFR-mediated
                             phosphorylation.
MUTAGEN    1191   1191       Y->N: No effect on endocytosis.
MUTAGEN    1203   1203       Y->E: No effect on nuclear colocalization
                             of MUC1CT and CTNNB1. No effect on in
                             vitro PDFGR-induced cell invasiveness.
MUTAGEN    1203   1203       Y->F: No effect on EGFR-mediated
                             phosphorylation. No nuclear localization
                             of MUC1CT. Reduced in vitro PDGFR-induced
                             cell invasiveness.
MUTAGEN    1203   1203       Y->N: Reduced endocytosis by 30%. Greatly
                             reduced binding to AP1S2 and GRB2.
                             Binding AP1S1 reduced by 25%. Reduced
                             endocytosis by 77%; when associated with
                             N-1243. Accumulates in intracellular
                             compartments; when associated with C-1184
                             and C-1186.
MUTAGEN    1209   1209       Y->F: Some reduction in EGFR-mediated
                             phosphorylation.
MUTAGEN    1218   1218       Y->F: No effect on EGFR-mediated
                             phosphorylation. No nuclear
                             colocalization of MUC1CT and CTNNB1.
MUTAGEN    1223   1223       S->A: No change in PRKCD- nor GSK3B-
                             mediated phosphorylation.
MUTAGEN    1224   1224       T->A: Loss of PRKCD-mediated
                             phosphorylation. Decreased PRKCD binding.
                             No increased binding to CTNNB1 in the
                             presence of autophosphorylated PRKCD.
                             Increases formation of E-cadherin/beta-
                             catenin complex.
MUTAGEN    1227   1227       S->A: No change in PRKCD-mediated
                             phosphorylation. Loss of GSK3B-mediated
                             phosphorylation. CTNNB1.
MUTAGEN    1229   1229       Y->F: Greatly reduced EGFR- and Src-
                             mediated phosphorylation. No nuclear
                             localization of MUC1CT. Reduced in vitro
                             PDGFR-mediated phosphorylation. Decreased
                             Src-binding.
MUTAGEN    1229   1229       Y->N: No effect on endocytosis.
MUTAGEN    1243   1243       Y->N: Reduces binding to AP1S2 by 33%.
                             Greatly reduced binding to GRB2. Reduced
                             endocytosis by 50%. Reduced endocytosis
                             by 77%; when associated with N-1203.
CONFLICT      2      2       T -> A (in Ref. 20; AAD14369).
CONFLICT    134    134       P -> Q (in Ref. 18; AAA35757).
CONFLICT    154    154       P -> Q (in Ref. 18).
CONFLICT   1021   1021       S -> T (in Ref. 2 and 3).
CONFLICT   1193   1193       Q -> L (in Ref. 11; AAK30142).
CONFLICT   1231   1231       K -> T (in Ref. 9; AAD10858).
CONFLICT   1251   1251       T -> A (in Ref. 1; AAA60019).
STRAND     1042   1052
HELIX      1056   1059
HELIX      1064   1080
TURN       1082   1085
STRAND     1086   1096
STRAND     1099   1107
TURN       1109   1111
HELIX      1114   1132
STRAND     1136   1142
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Nucleotide Sequence
Length: 4139 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 1255 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
ABL1MINT 
APCBioGRID 
GRB2BioGRID 
_BioGRID 
CTNNB1BioGRID 
CTNND1BioGRID 
EGFRBioGRID 
ESR1BioGRID 
GALNT4BioGRID 
GALNT12BioGRID 
GRB2BioGRID 
GSK3BBioGRID 
JUNIntAct 
PRKCDBioGRID 
LYNBioGRID 
ABL1MINT 
GRB2BioGRID 
CTNNB1BioGRID 
Ctnnb1BioGRID 
CTNND1BioGRID 
EGFRBioGRID 
ERBB2BioGRID 
ERBB3BioGRID 
ERBB4BioGRID 
ESR1BioGRID 
GRB2BioGRID 
GSK3BBioGRID 
PRKCDBioGRID 
JUPBioGRID 
GSK3BBioGRID 
_BioGRID 
SOS1BioGRID 
SRCBioGRID 
APCBioGRID 
FTT_0715IntAct 
GSK3BBioGRID 
LYNBioGRID 
_BioGRID 
SRCBioGRID 
Other Protein-Protein interaction resources
String database  
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