Mucin-4

UniProt data

UniProt name: MUC4_HUMAN (Q99102)

Gene name: MUC4

Organism: Homo sapiens (Human).

Function: May play a role in tumor progression. Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Has anti-adhesive properties. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ERBB2. Plays an important role in cell proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. The MUC4-ERBB2 complex causes site-specific phosphorylation of the ERBB2 'Tyr-1248'. In polarized epithelilal cells segragates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. {ECO:0000269|PubMed:12102554, ECO:0000269|PubMed:16049287, ECO:0000269|PubMed:16814944, ECO:0000269|PubMed:16914178}.

Subcellular location: Isoform 17: Cell membrane; Single-pass membrane protein.

Transmembrane domains:

  1. 2126-2146, 21 AA, Helical. {ECO:0000255}.

Sequence: 2169 AA

10 20 30 40 50 60 MKGARWRRVP WVSLSCLCLC LLPHVVPGTT EDTLITGSKT AAPVTSTGST TATLEGQSTA 70 80 90 100 110 120 ASSRTSNQDI SASSQNHQTK STETTSKAQT DTLTQMMTST LFSSPSVHNV METVTQETAP 130 140 150 160 170 180 PDEMTTSFPS SVTNTLMMTS KTITMTTSTD STLGNTEETS TAGTESSTPV TSAVSITAGQ 190 200 210 220 230 240 EGQSRTTSWR TSIQDTSASS QNHWTRSTQT TRESQTSTLT HRTTSTPSFS PSVHNVTGTV 250 260 270 280 290 300 SQKTSPSGET ATSSLCSVTN TSMMTSEKIT VTTSTGSTLG NPGETSSVPV TGSLMPVTSA 310 320 330 340 350 360 ALVTVDPEGQ SPATFSRTST QDTTAFSKNH QTQSVETTRV SQINTLNTLT PVTTSTVLSS 370 380 390 400 410 420 PSGFNPSGTV SQETFPSGET TISSPSSVSN TFLVTSKVFR MPISRDSTLG NTEETSLSVS 430 440 450 460 470 480 GTISAITSKV STIWWSDTLS TALSPSSLPP KISTAFHTQQ SEGAETTGRP HERSSFSPGV 490 500 510 520 530 540 SQEIFTLHET TTWPSSFSSK GHTTWSQTEL PSTSTGAATR LVTGNPSTRA AGTIPRVPSK 550 560 570 580 590 600 VSAIGEPGEP TTYSSHSTTL PKTTGAGAQT QWTQETGTTG EALLSSPSYS VIQMIKTATS 610 620 630 640 650 660 PSSSPMLDRH TSQQITTAPS TNHSTIHSTS TSPQESPAVS QRGHTRAPQT TQESQTTRSV 670 680 690 700 710 720 SPMTDTKTVT TPGSSFTASG HSPSEIVPQD APTISAATTF APAPTGNGHT TQAPTTALQA 730 740 750 760 770 780 APSSHDATLG PSGGTSLSKT GALTLANSVV STPGGPEGQW TSASASTSPD TAAAMTHTHQ 790 800 810 820 830 840 AESTEASGQT QTSEPASSGS RTTSAGTATP SSSGASGTTP SGSEGISTSG ETTRFSSNPS 850 860 870 880 890 900 RDSHTTQSTT ELLSASASHG AIPVSTGMAS SIVPGTFHPT LSEASTAGRP TGQSSPTSPS 910 920 930 940 950 960 ASPQETAAIS RMAQTQRTGT SRGSDTISLA SQATDTFSTV PPTPPSITSS GLTSPQTQTH 970 980 990 1000 1010 1020 TLSPSGSGKT FTTALISNAT PLPVTSTSSA STGHATPLAV SSATSASTVS SDSPLKMETS 1030 1040 1050 1060 1070 1080 GMTTPSLKTD GGRRTATSPP PTTSQTIIST IPSTAMHTRS TAAPIPILPE RGVSLFPYGA 1090 1100 1110 1120 1130 1140 GAGDLEFVRR TVDFTSPLFK PATGFPLGSS LRDSLYFTDN GQIIFPESDY QIFSYPNPLP 1150 1160 1170 1180 1190 1200 TGFTGRDPVA LVAPFWDDAD FSTGRGTTFY QEYETFYGEH SLLVQQAESW IRKMTNNGGY 1210 1220 1230 1240 1250 1260 KARWALKVTW VNAHAYPAQW TLGSNTYQAI LSTDGSRSYA LFLYQSGGMQ WDVAQRSGNP 1270 1280 1290 1300 1310 1320 VLMGFSSGDG YFENSPLMSQ PVWERYRPDR FLNSNSGLQG LQFYRLHREE RPNYRLECLQ 1330 1340 1350 1360 1370 1380 WLKSQPRWPS WGWNQVSCPC SWQQGRRDLR FQPVSIGRWG LGSRQLCSFT SWRGGVCCSY 1390 1400 1410 1420 1430 1440 GPWGEFREGW HVQRPWQLAQ ELEPQSWCCR WNDKPYLCAL YQQRRPHVGC ATYRPPQPAW 1450 1460 1470 1480 1490 1500 MFGDPHITTL DGVSYTFNGL GDFLLVGAQD GNSSFLLQGR TAQTGSAQAT NFIAFAAQYR 1510 1520 1530 1540 1550 1560 SSSLGPVTVQ WLLEPHDAIR VLLDNQTVTF QPDHEDGGGQ ETFNATGVLL SRNGSEVSAS 1570 1580 1590 1600 1610 1620 FDGWATVSVI ALSNILHASA SLPPEYQNRT EGLLGVWNNN PEDDFRMPNG STIPPGSPEE 1630 1640 1650 1660 1670 1680 MLFHFGMTWQ INGTGLLGKR NDQLPSNFTP VFYSQLQKNS SWAEHLISNC DGDSSCIYDT 1690 1700 1710 1720 1730 1740 LALRNASIGL HTREVSKNYE QANATLNQYP PSINGGRVIE AYKGQTTLIQ YTSNAEDANF 1750 1760 1770 1780 1790 1800 TLRDSCTDLE LFENGTLLWT PKSLEPFTLE ILARSAKIGL ASALQPRTVV CHCNAESQCL 1810 1820 1830 1840 1850 1860 YNQTSRVGNS SLEVAGCKCD GGTFGRYCEG SEDACEEPCF PSVHCVPGKG CEACPPNLTG 1870 1880 1890 1900 1910 1920 DGRHCAALGS SFLCQNQSCP VNYCYNQGHC YISQTLGCQP MCTCPPAFTD SRCFLAGNNF 1930 1940 1950 1960 1970 1980 SPTVNLELPL RVIQLLLSEE ENASMAEVNA SVAYRLGTLD MRAFLRNSQV ERIDSAAPAS 1990 2000 2010 2020 2030 2040 GSPIQHWMVI SEFQYRPRGP VIDFLNNQLL AAVVEAFLYH VPRRSEEPRN DVVFQPISGE 2050 2060 2070 2080 2090 2100 DVRDVTALNV STLKAYFRCD GYKGYDLVYS PQSGFTCVSP CSRGYCDHGG QCQHLPSGPR 2110 2120 2130 2140 2150 2160 CSCVSFSIYT AWGEHCEHLS MKLDAFFGIF FGALGGLLLL GVGTFVVLRF WGCSGARFSY FLNSAEALP

CATM prediction

The sequence of MUC4_HUMAN returned 10 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
         2130      2140      
  +    |    +    |    +    		 (Å) (°) (Å) (°)  
Model 1 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.5 -34.8° 3.8 53.0 -39.6
Model 2 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.5 -51.4° 6.0 45.2 -29.0
Model 3 LDAFFGIFFGALGGLLLLGVGTFVVLR 7.3 -18.0° 3.6 40.0 -27.5
Model 4 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.7 -49.0° 5.4 49.1 -27.2
Model 5 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.6 +52.1° 1.8 0.8 -23.2
Model 6 LDAFFGIFFGALGGLLLLGVGTFVVLR 7.1 -52.0° 0.6 48.2 -19.8
Model 7 LDAFFGIFFGALGGLLLLGVGTFVVLR 7.0 -30.0° 3.5 53.0 -18.2
Model 8 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.6 -53.9° 3.6 35.1 -16.6
Model 9 LDAFFGIFFGALGGLLLLGVGTFVVLR 6.9 -40.0° 5.1 44.0 -7.9
Model 10 LDAFFGIFFGALGGLLLLGVGTFVVLR 7.4 -40.9° 3.5 37.7 -4.4

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


Click on the image to enlarge

Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 2129, ILE, HA A, 2128, GLY, O 2.33Å
B, 2132, GLY, HA1 A, 2129, ILE, O 2.77Å
B, 2133, ALA, HA A, 2132, GLY, O 3.17Å
A, 2129, ILE, HA B, 2128, GLY, O 2.33Å
A, 2132, GLY, HA1 B, 2129, ILE, O 2.77Å
A, 2133, ALA, HA B, 2132, GLY, O 3.17Å