MUC1_HUMAN » Mucin-1

MUC1_HUMAN » Mucin-1
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Topology in Plasma membrane
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cytoplasmic side
MUC1_HUMAN » Mucin-1 » MUC-1; Breast carcinoma-associated antigen DF3;Cancer antigen 15-3;CA 15-3; 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 membr
Hydrophobic Thickness 35.6 ± 3.0 Å
Tilt Angle 29 ± 3°
ΔGtransfer -28.6 kcal/mol
ΔGfold -27.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 1159-1184 (1159-1189)
Pathways none
PDB 2acm (A=1042-1097, B=1098-1152), 2fo4 (P=140-146), 1sm3 (P=919-931)
OPM none
Complexes none
Interactions

BAX, Complex: MUC1:BAX, PubMed

EGFR, Complex: EGFR:MUC1, PubMed

ERBB2, Complex: ERBB2:MUC1, PubMed

ERBB3, Complex: ERBB3:MUC1, PubMed

ERBB4, Complex: MUC1:ERBB4, PubMed

ESR1, Complex: ESR1:MUC1, PubMed

FGFR3, Complex: MUC1:FGFR3, PubMed

GALT1, Complex: GALT1:MUC1, PubMed

GALT2, Complex: GALT2:MUC1, PubMed

GALT4, Complex: MUC1:GALT4, PubMed

GLT10, Complex: GLT10:MUC1, PubMed

GLT12, Complex: GLT12:MUC1, PubMed

MET, Complex: MUC1:MET, PubMed

SN, Complex: SN:MUC1, PubMed

TNR1A, Complex: MUC1:TNR1A, PubMed

Domains

AA: 1041-1137, PDBID: 2ACM, Subunit A, Seq Identity:100%, SEA domain

UniProt annotation for MUC1_HUMAN » Mucin-1
FUNCTION: The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.

FUNCTION: The beta subunit contains a C-terminal domain which is involved 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 or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.

SUBUNIT: The alpha subunit forms a tight, non-covalent heterodimeric complex with the proteolytically-released beta- subunit. Interaction, via the tandem repeat region, with domain 1 of ICAM1 is implicated in cell migration and metastases. Isoform 1 binds directly the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4. Interacts with P53 in response to DNA damage. Interacts with KLF4. Interacts with estrogen receptor alpha/ESR1, through its DNA- binding domain, and stimulates its transcription activity. Binds ADAM17. Isoform ZD forms disulfide-linked oligomers.

TISSUE SPECIFICITY: Expressed on the apical surface of epithelial cells, especially of airway passages, breast and uterus. Also expressed in activated and unactivated T-cells. Overexpressed in epithelial tumors, such as breast or ovarian cancer and also in non-epithelial tumor cells. Isoform 7 is expressed in tumor cells only.

DEVELOPMENTAL STAGE: During fetal development, expressed at low levels in the colonic epithelium from 13 weeks of gestation.

DISEASE: Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.

DISEASE: Medullary cystic kidney disease 1 (MCKD1) OMIM: A form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade. mutations affecting the gene represented in this entry.

MISCELLANEOUS: The name KL-6 was originally that of a murine monoclonal antibody reacting with pulmonary adenocarcinoma cell lines and pulmonary epithelial cells. This antibody recognizes a sialylated carbohydrate chain on MUC1.

UniProt features for MUC1_HUMAN » Mucin-1
SIGNAL 1 23
CHAIN 24 1255 Mucin-1.
CHAIN 24 1097 Mucin-1 subunit alpha.
CHAIN 1098 1255 Mucin-1 subunit beta.
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.
Amino Acid Sequence for MUC1_HUMAN » Mucin-1
MTPGTQSPFF LLLLLTVLTV VTGSGHASST PGGEKETSAT QRSSVPSSTE KNAVSMTSSV LSSHSPGSGS STTQGQDVTL APATEPASGS AATWGQDVTS VPVTRPALGS TTPPAHDVTS APDNKPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDNRPALGS TAPPVHNVTS ASGSASGSAS TLVHNGTSAR ATTTPASKST PFSIPSHHSD TPTTLASHST KTDASSTHHS SVPPLTSSNH STSPQLSTGV SFFFLSFHIS NLQFNSSLED PSTDYYQELQ RDISEMFLQI YKQGGFLGLS NIKFRPGSVV VQLTLAFREG TINVHDVETQ FNQYKTEAAS RYNLTISDVS VSDVPFPFSA QSGAGVPGWG IALLVLVCVL VALAIVYLIA LAVCQCRRKN YGQLDIFPAR DTYHPMSEYP TYHTHGRYVP PSSTDRSPYE KVSAGNGGSS LSYTNPAVAA ASANL