MUC4_HUMAN » Mucin-4

MUC4_HUMAN » Mucin-4
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
MUC4_HUMAN » Mucin-4 » MUC-4; Pancreatic adenocarcinoma mucin;Testis mucin;Ascites sialoglycoprotein;ASGP; Tracheobronchial mucin;
Hydrophobic Thickness 35.2 ± 2.0 Å
Tilt Angle 1 ± 0°
ΔGtransfer -52.2 kcal/mol
ΔGfold -16.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 2126-2153 (2125-2154)
Pathways none
PDB none
OPM none
Complexes none
Interactions

ERBB2, Complex: MUC4:ERBB2, PubMed

GLT11, Complex: GLT11:MUC4, PubMed

Domains

AA: 1224-1308, Nidogen-like

AA: 1439-1611, von Willebrand factor type D domain

UniProt annotation for MUC4_HUMAN » Mucin-4
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.

SUBUNIT: A heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain. Mucin- 4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3 (By similarity).

TISSUE SPECIFICITY: Expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands. Expressed in carcinomas arising from some of these epithelia, such as lung cancers, squamous cell carcinomas of the upper aerodigestive tract, mammary carcinomas, biliary tract, colon, and cervix cancers. Minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors and pancreatic tumor cell lines.

DEVELOPMENTAL STAGE: Expressed early in the primitive gut before respiratory and digestive epithelial cells have acquired their tissue and cell specificity. Expressed at the basal surface of the epithelium from week 14 to 26 weeks and then predominantly localized in only parietal cells. Immediately before birth, found in the cytoplasm of the mucous columnar epithelial cells. In the embryo expressed in skin, then disappears late in gestation.

MISCELLANEOUS: Expression is a very useful predictor of poor prognosis in patients with invasive ductal carcinoma and intrahepatic cholangiocarcinoma, mass forming type (IDC,ICC-MF). Patients with IDC or ICC-MF who have high MUC4 expression had a worse survival rate than those with low MUC4 expression.

UniProt features for MUC4_HUMAN » Mucin-4
SIGNAL 1 28 Potential.
CHAIN 29 2169 Mucin-4.
CHAIN 29 1444 Mucin-4 alpha chain.
CHAIN 1445 2169 Mucin-4 beta chain.
DOMAIN 1154 1309 NIDO.
DOMAIN 1310 1425 AMOP.
DOMAIN 1438 1673 VWFD.
DOMAIN 1875 1914 EGF-like 1.
DOMAIN 2078 2117 EGF-like 2.
REGION 1002 1038 Repeat.
SITE 1444 1445 Cleavage.
DISULFID 1879 1890 By similarity.
DISULFID 1884 1902 By similarity.
DISULFID 1904 1913 By similarity.
DISULFID 2081 2092 By similarity.
DISULFID 2086 2101 By similarity.
DISULFID 2103 2116 By similarity.
Amino Acid Sequence for MUC4_HUMAN » Mucin-4
MKGARWRRVP WVSLSCLCLC LLPHVVPGTT EDTLITGSKT PAPVTSTGST TATLEGQSTA ASSRTSNQDI SASSQNHQTK STETTSKAQT DTLTQMMTST LFSSPSVHNV METVTQETAP PDEMTTSFPS SVTNTLMMTS KTITMTTSTD STLGNTEETS TAGTESSTPV TSAVSITAGQ EGQSRTTSWR TSIQDTSASS QNHWTRSTQT TRESQTSTLT HRTTSTPSFS PSVHNVTGTV SQKTSPSGET ATSSLCSVTN TSMMTSEKIT VTTSTGSTLG NPGETSSVPV TGSLMPVTSA ALVTVDPEGQ SPATFSRTST QDTTAFSKNH QTQSVETTRV SQINTLNTLT PVTTSTVLSS PSGFNPSGTV SQETFPSGET TISSPSSVSN TFLVTSKVFR MPISRDSTLG NTEETSLSVS GTISAITSKV STIWWSDTLS TALSPSSLPP KISTAFHTQQ SEGAETTGRP HERSSFSPGV SQEIFTLHET TTWPSSFSSK GHTTWSQTEL PSTSTGAATR LVTGNPSTRA AGTIPRVPSK VSAIGEPGEP TTYSSHSTTL PKTTGAGAQT QWTQETGTTG EALLSSPSYS VIQMIKTATS PSSSPMLDRH TSQQITTAPS TNHSTIHSTS TSPQESPAVS QRGHTRAPQT TQESQTTRSV SPMTDTKTVT TPGSSFTASG HSPSEIVPQD APTISAATTF APAPTGNGHT TQAPTTALQA APSSHDATLG PSGGTSLSKT GALTLANSVV STPGGPEGQW TSASASTSPD TAAAMTHTHQ AESTEASGQT QTSEPASSGS RTTSAGTATP SSSGASGTTP SGSEGISTSG ETTRFSSNPS RDSHTTQSTT ELLSASASHG AIPVSTGMAS SIVPGTFHPT LSEASTAGRP TGQSSPTSPS ASPQETAAIS RMAQTQRTGT SRGSDTISLA SQATDTFSTV PPTPPSITSS GLTSPQTQTH TLSPSGSGKT FTTALISNAT PLPVTSTSSA STGHATPLAV SSATSASTVS SDSPLKMETS GMTTPSLKTD GGRRTATSPP PTTSQTIIST IPSTAMHTRS TAAPIPILPE RGVSLFPYGA DAGDLEFVRR TVDFTSPLFK PATGFPLGSS LRDSLYFTDN GQIIFPESDY QIFSYPNPLP TGFTGRDPVA LVAPFWDDAD FSTGRGTTFY QEYETFYGEH SLLVQQAESW IRKITNNGGY KARWALKVTW VNAHAYPAQW TLGSNTYQAI LSTDGSRSYA LFLYQSGGMQ WDVAQRSGNP VLMGFSSGDG YFENSPLMSQ PVWERYRPDR FLNSNSGLQG LQFYRLHREE RPNYRLECLQ WLKSQPRWPS WGWNQVSCPC SWQQGRRDLR FQPVSIGRWG LGSRQLCSFT SWRGGVCCSY GPWGEFREGW HVQRPWQLAQ ELEPQSWCCR WNDKPYLCAL YQQRRPHVGC ATYRPPQPAW MFGDPHITTL DGVSYTFNGL GDFLLVGAQD GNSSFLLQGR TAQTGSAQAT NFIAFAAQYR SSSLGPVTVQ WLLEPHDAIR VLLDNQTVTF QPDHEDGGGQ ETFNATGVLL SRNGSEVSAS FDGWATVSVI ALSNILHASA SLPPEYQNRT EGLLGVWNNN PEDDFRMPNG STIPPGSPEE MLFHFGMTWQ INGTGLLGKR NDQLPSNFTP VFYSQLQKNS SWAEHLISNC DGDSSCIYDT LALRNASIGL HTREVSKNYE QANATLNQYP PSINGGRVIE AYKGQTTLIQ YTSNAEDANF TLRDSCTDLE LFENGTLLWT PKSLEPFTLE ILARSAKIGL ASALQPRTVV CHCNAESQCL YNQTSRVGNS SLEVAGCKCD GGTFGRYCEG SEDACEEPCF PSVHCVPGKG CEACPPNLTG DGRHCAALGS SFLCQNQSCP VNYCYNQGHC YISQTLGCQP MCTCPPAFTD SRCFLAGNNF SPTVNLELPL RVIQLLLSEE ENASMAEVNA SVAYRLGTLD MRAFLRNSQV ERIDSAAPAS GSPIQHWMVI SEFQYRPRGP VIDFLNNQLL AAVVEAFLYH VPRRSEEPRN DVVFQPISGE DVRDVTALNV STLKAYFRCD GYKGYDLVYS PQSGFTCVSP CSRGYCDHGG QCQHLPSGPR CSCVSFSIYT AWGEHCEHLS MKLDAFFGIF FGALGGLLLL GVGTFVVLRF WGCSGARFSY FLNSAEALP