Full text data of MUC2
MUC2
(SMUC)
[Confidence: low (only semi-automatic identification from reviews)]
Mucin-2; MUC-2 (Intestinal mucin-2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Mucin-2; MUC-2 (Intestinal mucin-2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q02817
ID MUC2_HUMAN Reviewed; 5179 AA.
AC Q02817; Q14878;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Mucin-2;
DE Short=MUC-2;
DE AltName: Full=Intestinal mucin-2;
DE Flags: Precursor;
GN Name=MUC2; Synonyms=SMUC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RX PubMed=8300571;
RA Gum J.R. Jr., Hicks J.W., Toribara N.W., Siddiki B., Kim Y.S.;
RT "Molecular cloning of human intestinal mucin (MUC2) cDNA.
RT Identification of the amino terminus and overall sequence similarity
RT to prepro-von Willebrand factor.";
RL J. Biol. Chem. 269:2440-2446(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 626-1895 AND 4196-5179.
RC TISSUE=Colon;
RX PubMed=1400449;
RA Gum J.R. Jr., Hicks J.W., Toribara N.W., Rothe E.-M., Lagace R.E.,
RA Kim Y.S.;
RT "The human MUC2 intestinal mucin has cysteine-rich subdomains located
RT both upstream and downstream of its central repetitive region.";
RL J. Biol. Chem. 267:21375-21383(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1343-1895 AND 4176-4195.
RX PubMed=1885763; DOI=10.1172/JCI115360;
RA Toribara N.W., Gum J.R. Jr., Culhane P.J., Lagace R.E., Hicks J.W.,
RA Petersen G.M., Kim Y.S.;
RT "MUC-2 human small intestinal mucin gene structure. Repeated arrays
RT and polymorphism.";
RL J. Clin. Invest. 88:1005-1013(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4075-4352.
RX PubMed=2703501;
RA Gum J.R. Jr., Byrd J.C., Hicks J.W., Toribara N.W., Lamport D.T.A.,
RA Kim Y.S.;
RT "Molecular cloning of human intestinal mucin cDNAs. Sequence analysis
RT and evidence for genetic polymorphism.";
RL J. Biol. Chem. 264:6480-6487(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4487-4627.
RX PubMed=1550588; DOI=10.1016/0006-291X(92)90557-2;
RA Xu G., Huan L., Khatri I., Sajjan U.S., McCool D., Wang D., Jones C.,
RA Forstner G., Forstner J.;
RT "Human intestinal mucin-like protein (MLP) is homologous with rat MLP
RT in the C-terminal region, and is encoded by a gene on chromosome 11 p
RT 15.5.";
RL Biochem. Biophys. Res. Commun. 183:821-828(1992).
RN [6]
RP STRUCTURE OF O-LINKED CARBOHYDRATES.
RX PubMed=11445551; DOI=10.1093/glycob/11.6.459;
RA Silverman H.S., Parry S., Sutton-Smith M., Burdick M.D., McDermott K.,
RA Reid C.J., Batra S.K., Morris H.R., Hollingsworth M.A., Dell A.,
RA Harris A.;
RT "In vivo glycosylation of mucin tandem repeats.";
RL Glycobiology 11:459-471(2001).
RN [7]
RP SUBUNIT.
RX PubMed=12374796; DOI=10.1074/jbc.M208483200;
RA Godl K., Johansson M.E.V., Lidell M.E., Moergelin M., Karlsson H.,
RA Olson F.J., Gum J.R. Jr., Kim Y.S., Hansson G.C.;
RT "The N terminus of the MUC2 mucin forms trimers that are held together
RT within a trypsin-resistant core fragment.";
RL J. Biol. Chem. 277:47248-47256(2002).
RN [8]
RP AUTOCATALYTIC CLEAVAGE.
RX PubMed=12582180; DOI=10.1074/jbc.M210069200;
RA Lidell M.E., Johansson M.E.V., Hansson G.C.;
RT "An autocatalytic cleavage in the C terminus of the human MUC2 mucin
RT occurs at the low pH of the late secretory pathway.";
RL J. Biol. Chem. 278:13944-13951(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH AGR2.
RX PubMed=19359471; DOI=10.1073/pnas.0808722106;
RA Park S.-W., Zhen G., Verhaeghe C., Nakagami Y., Nguyenvu L.T.,
RA Barczak A.J., Killeen N., Erle D.J.;
RT "The protein disulfide isomerase AGR2 is essential for production of
RT intestinal mucus.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6950-6955(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH
RP FCGBP.
RX PubMed=19432394; DOI=10.1021/pr9002504;
RA Johansson M.E.V., Thomsson K.A., Hansson G.C.;
RT "Proteomic analyses of the two mucus layers of the colon barrier
RT reveal that their main component, the Muc2 mucin, is strongly bound to
RT the Fcgbp protein.";
RL J. Proteome Res. 8:3549-3557(2009).
CC -!- FUNCTION: Coats the epithelia of the intestines, airways, and
CC other mucus membrane-containing organs. Thought to provide a
CC protective, lubricating barrier against particles and infectious
CC agents at mucosal surfaces. Major constituent of both the inner
CC and outer mucus layers of the colon and may play a role in
CC excluding bacteria from the inner mucus layer.
CC -!- SUBUNIT: Homotrimer; disulfide-linked. Dimerizes in the
CC endoplasmic reticulum via its C-terminal region and polymerizes
CC via its N-terminal region by disulfide-linked trimerization.
CC Interacts with FCGBP. Interacts with AGR2; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=In the intestine, secreted
CC into the inner and outer mucus layers (By similarity).
CC -!- TISSUE SPECIFICITY: Colon, small intestine, colonic tumors,
CC bronchus, cervix and gall bladder.
CC -!- PTM: O-glycosylated.
CC -!- PTM: May undergo proteolytic cleavage in the outer mucus layer of
CC the colon, contributing to the expanded volume and loose nature of
CC this layer which allows for bacterial colonization in contrast to
CC the inner mucus layer which is dense and devoid of bacteria (By
CC similarity).
CC -!- PTM: At low pH of 6 and under, undergoes autocatalytic cleavage in
CC vitro in the N-terminal region of the fourth VWD domain. It is
CC likely that this also occurs in vivo and is triggered by the low
CC pH of the late secretory pathway.
CC -!- POLYMORPHISM: The number of repeats is highly polymorphic and
CC varies among different alleles.
CC -!- SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain.
CC -!- SIMILARITY: Contains 1 TIL (trypsin inhibitory-like) domain.
CC -!- SIMILARITY: Contains 2 VWFC domains.
CC -!- SIMILARITY: Contains 4 VWFD domains.
CC -!- WEB RESOURCE: Name=Mucin database;
CC URL="http://www.medkem.gu.se/mucinbiology/databases/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MUC2ID41457ch11p15.html";
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DR EMBL; L21998; AAB95295.1; -; mRNA.
DR EMBL; M74027; AAA59875.1; -; Genomic_DNA.
DR EMBL; M94131; AAA59163.1; -; mRNA.
DR EMBL; M94132; AAA59164.1; -; mRNA.
DR PIR; A49963; A43932.
DR RefSeq; NP_002448.3; NM_002457.3.
DR UniGene; Hs.315; -.
DR ProteinModelPortal; Q02817; -.
DR DIP; DIP-48824N; -.
DR IntAct; Q02817; 2.
DR STRING; 9606.ENSP00000415183; -.
DR DrugBank; DB01411; Pranlukast.
DR PhosphoSite; Q02817; -.
DR UniCarbKB; Q02817; -.
DR DMDM; 2506877; -.
DR PaxDb; Q02817; -.
DR PRIDE; Q02817; -.
DR Ensembl; ENST00000359061; ENSP00000351956; ENSG00000198788.
DR GeneID; 4583; -.
DR KEGG; hsa:4583; -.
DR UCSC; uc001lsx.1; human.
DR CTD; 4583; -.
DR GeneCards; GC11P001064; -.
DR HGNC; HGNC:7512; MUC2.
DR HPA; CAB005317; -.
DR HPA; CAB016275; -.
DR HPA; HPA006197; -.
DR MIM; 158370; gene.
DR neXtProt; NX_Q02817; -.
DR PharmGKB; PA31316; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000168234; -.
DR HOVERGEN; HBG004380; -.
DR InParanoid; Q02817; -.
DR KO; K10955; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; MUC2; human.
DR GeneWiki; MUC2; -.
DR GenomeRNAi; 4583; -.
DR NextBio; 17613; -.
DR PRO; PR:Q02817; -.
DR ArrayExpress; Q02817; -.
DR Bgee; Q02817; -.
DR CleanEx; HS_MUC2; -.
DR Genevestigator; Q02817; -.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0070702; C:inner mucus layer; ISS:UniProtKB.
DR GO; GO:0070703; C:outer mucus layer; ISS:UniProtKB.
DR GO; GO:0016266; P:O-glycan processing; TAS:Reactome.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR028580; MUC2.
DR InterPro; IPR002919; TIL_dom.
DR InterPro; IPR014853; Unchr_dom_Cys-rich.
DR InterPro; IPR006552; VWC_out.
DR InterPro; IPR001007; VWF_C.
DR InterPro; IPR001846; VWF_type-D.
DR InterPro; IPR025155; WxxW_domain.
DR PANTHER; PTHR11339:SF141; PTHR11339:SF141; 1.
DR Pfam; PF08742; C8; 4.
DR Pfam; PF13330; Mucin2_WxxW; 2.
DR Pfam; PF01826; TIL; 1.
DR Pfam; PF00094; VWD; 4.
DR SMART; SM00832; C8; 4.
DR SMART; SM00041; CT; 1.
DR SMART; SM00214; VWC; 2.
DR SMART; SM00215; VWC_out; 1.
DR SMART; SM00216; VWD; 4.
DR SUPFAM; SSF57567; SSF57567; 4.
DR PROSITE; PS01185; CTCK_1; 1.
DR PROSITE; PS01225; CTCK_2; 1.
DR PROSITE; PS01208; VWFC_1; 2.
DR PROSITE; PS50184; VWFC_2; 2.
DR PROSITE; PS51233; VWFD; 4.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Complete proteome; Disulfide bond;
KW Glycoprotein; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 5179 Mucin-2.
FT /FTId=PRO_0000019281.
FT DOMAIN 36 240 VWFD 1.
FT DOMAIN 295 351 TIL.
FT DOMAIN 390 604 VWFD 2.
FT DOMAIN 859 1065 VWFD 3.
FT REPEAT 1401 1416 1.
FT REPEAT 1417 1432 2.
FT REPEAT 1433 1448 3.
FT REPEAT 1449 1464 4.
FT REPEAT 1465 1471 5.
FT REPEAT 1472 1478 6.
FT REPEAT 1479 1494 7A.
FT REPEAT 1495 1517 7B.
FT REPEAT 1518 1533 8A.
FT REPEAT 1534 1556 8B.
FT REPEAT 1557 1572 9A.
FT REPEAT 1573 1596 9B.
FT REPEAT 1597 1612 10A.
FT REPEAT 1613 1635 10B.
FT REPEAT 1636 1651 11A.
FT REPEAT 1652 1675 11B.
FT REPEAT 1676 1683 12.
FT REPEAT 1684 1699 13.
FT REPEAT 1700 1715 14.
FT REPEAT 1716 1731 15.
FT REPEAT 1732 1747 16.
FT DOMAIN 4480 4690 VWFD 4.
FT DOMAIN 4815 4886 VWFC 1.
FT DOMAIN 4924 4991 VWFC 2.
FT DOMAIN 5075 5160 CTCK.
FT REGION 1401 1747 Approximate repeats.
FT SITE 4486 4487 Cleavage; by autolysis; in vitro.
FT MOD_RES 21 21 Phosphoserine.
FT CARBOHYD 163 163 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 423 423 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 670 670 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 770 770 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 894 894 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1139 1139 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1154 1154 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1215 1215 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1230 1230 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1246 1246 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1787 1787 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1820 1820 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4339 4339 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4351 4351 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4362 4362 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4373 4373 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4422 4422 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4438 4438 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4502 4502 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4616 4616 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4627 4627 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4752 4752 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4787 4787 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4881 4881 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4888 4888 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4955 4955 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4970 4970 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5019 5019 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5038 5038 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5069 5069 N-linked (GlcNAc...) (Potential).
FT DISULFID 59 67 By similarity.
FT DISULFID 5075 5122 By similarity.
FT DISULFID 5089 5136 By similarity.
FT DISULFID 5098 5152 By similarity.
FT DISULFID 5102 5154 By similarity.
FT DISULFID ? 5159 By similarity.
FT VARIANT 58 58 L -> P (in dbSNP:rs2856111).
FT /FTId=VAR_056582.
FT VARIANT 116 116 V -> M (in dbSNP:rs11825977).
FT /FTId=VAR_056583.
FT VARIANT 832 832 G -> S (in dbSNP:rs11245936).
FT /FTId=VAR_056584.
FT VARIANT 1619 1619 S -> R (in dbSNP:rs11245947).
FT /FTId=VAR_059531.
FT VARIANT 1689 1689 P -> L (in dbSNP:rs11245949).
FT /FTId=VAR_059532.
FT VARIANT 1768 1768 P -> H (in dbSNP:rs34493663).
FT /FTId=VAR_061487.
FT VARIANT 2154 2154 I -> T (in dbSNP:rs6421972).
FT /FTId=VAR_059533.
FT VARIANT 2524 2524 T -> P (in dbSNP:rs7480563).
FT /FTId=VAR_059534.
FT VARIANT 2524 2524 T -> S (in dbSNP:rs7480563).
FT /FTId=VAR_059535.
FT VARIANT 2653 2653 Q -> L (in dbSNP:rs7126405).
FT /FTId=VAR_059536.
FT VARIANT 2653 2653 Q -> P (in dbSNP:rs7126405).
FT /FTId=VAR_059537.
FT CONFLICT 1351 1351 H -> L (in Ref. 3; AAA59875).
FT CONFLICT 1412 1412 T -> S (in Ref. 3; AAA59875).
FT CONFLICT 1449 1449 L -> P (in Ref. 3; AAA59875).
FT CONFLICT 1504 1504 M -> T (in Ref. 3; AAA59875).
FT CONFLICT 4076 4083 TGTQTPTT -> NGLQAPTP (in Ref. 4).
FT CONFLICT 4087 4087 T -> S (in Ref. 4).
FT CONFLICT 4130 4131 TP -> VL (in Ref. 4).
FT CONFLICT 4138 4138 V -> M (in Ref. 4).
FT CONFLICT 4146 4152 GTQTPTT -> STKSTTV (in Ref. 4).
FT CONFLICT 4163 4163 P -> A (in Ref. 4).
FT CONFLICT 4175 4176 TT -> MI (in Ref. 4).
FT CONFLICT 4179 4179 T -> S (in Ref. 4).
FT CONFLICT 4192 4194 GTQ -> TGS (in Ref. 4).
SQ SEQUENCE 5179 AA; 540300 MW; 85CD7571FB9A5663 CRC64;
MGLPLARLAA VCLALSLAGG SELQTEGRTR YHGRNVCSTW GNFHYKTFDG DVFRFPGLCD
YNFASDCRGS YKEFAVHLKR GPGQAEAPAG VESILLTIKD DTIYLTRHLA VLNGAVVSTP
HYSPGLLIEK SDAYTKVYSR AGLTLMWNRE DALMLELDTK FRNHTCGLCG DYNGLQSYSE
FLSDGVLFSP LEFGNMQKIN QPDVVCEDPE EEVAPASCSE HRAECERLLT AEAFADCQDL
VPLEPYLRAC QQDRCRCPGG DTCVCSTVAE FSRQCSHAGG RPGNWRTATL CPKTCPGNLV
YLESGSPCMD TCSHLEVSSL CEEHRMDGCF CPEGTVYDDI GDSGCVPVSQ CHCRLHGHLY
TPGQEITNDC EQCVCNAGRW VCKDLPCPGT CALEGGSHIT TFDGKTYTFH GDCYYVLAKG
DHNDSYALLG ELAPCGSTDK QTCLKTVVLL ADKKKNAVVF KSDGSVLLNQ LQVNLPHVTA
SFSVFRPSSY HIMVSMAIGV RLQVQLAPVM QLFVTLDQAS QGQVQGLCGN FNGLEGDDFK
TASGLVEATG AGFANTWKAQ STCHDKLDWL DDPCSLNIES ANYAEHWCSL LKKTETPFGR
CHSAVDPAEY YKRCKYDTCN CQNNEDCLCA ALSSYARACT AKGVMLWGWR EHVCNKDVGS
CPNSQVFLYN LTTCQQTCRS LSEADSHCLE GFAPVDGCGC PDHTFLDEKG RCVPLAKCSC
YHRGLYLEAG DVVVRQEERC VCRDGRLHCR QIRLIGQSCT APKIHMDCSN LTALATSKPR
ALSCQTLAAG YYHTECVSGC VCPDGLMDDG RGGCVVEKEC PCVHNNDLYS SGAKIKVDCN
TCTCKRGRWV CTQAVCHGTC SIYGSGHYIT FDGKYYDFDG HCSYVAVQDY CGQNSSLGSF
SIITENVPCG TTGVTCSKAI KIFMGRTELK LEDKHRVVIQ RDEGHHVAYT TREVGQYLVV
ESSTGIIVIW DKRTTVFIKL APSYKGTVCG LCGNFDHRSN NDFTTRDHMV VSSELDFGNS
WKEAPTCPDV STNPEPCSLN PHRRSWAEKQ CSILKSSVFS ICHSKVDPKP FYEACVHDSC
SCDTGGDCEC FCSAVASYAQ ECTKEGACVF WRTPDLCPIF CDYYNPPHEC EWHYEPCGNR
SFETCRTING IHSNISVSYL EGCYPRCPKD RPIYEEDLKK CVTADKCGCY VEDTHYPPGA
SVPTEETCKS CVCTNSSQVV CRPEEGKILN QTQDGAFCYW EICGPNGTVE KHFNICSITT
RPSTLTTFTT ITLPTTPTSF TTTTTTTTPT SSTVLSTTPK LCCLWSDWIN EDHPSSGSDD
GDREPFDGVC GAPEDIECRS VKDPHLSLEQ HGQKVQCDVS VGFICKNEDQ FGNGPFGLCY
DYKIRVNCCW PMDKCITTPS PPTTTPSPPP TTTTTLPPTT TPSPPTTTTT TPPPTTTPSP
PITTTTTPLP TTTPSPPIST TTTPPPTTTP SPPTTTPSPP TTTPSPPTTT TTTPPPTTTP
SPPMTTPITP PASTTTLPPT TTPSPPTTTT TTPPPTTTPS PPTTTPITPP TSTTTLPPTT
TPSPPPTTTT TPPPTTTPSP PTTTTPSPPT ITTTTPPPTT TPSPPTTTTT TPPPTTTPSP
PTTTPITPPT STTTLPPTTT PSPPPTTTTT PPPTTTPSPP TTTTPSPPIT TTTTPPPTTT
PSSPITTTPS PPTTTMTTPS PTTTPSSPIT TTTTPSSTTT PSPPPTTMTT PSPTTTPSPP
TTTMTTLPPT TTSSPLTTTP LPPSITPPTF SPFSTTTPTT PCVPLCNWTG WLDSGKPNFH
KPGGDTELIG DVCGPGWAAN ISCRATMYPD VPIGQLGQTV VCDVSVGLIC KNEDQKPGGV
IPMAFCLNYE INVQCCECVT QPTTMTTTTT ENPTPPTTTP ITTTTTVTPT PTPTGTQTPT
TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP
TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT
TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT
QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV
TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT
TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT
PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT
TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ
TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT
PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT
PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP
TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT
TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT
PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP
TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP
ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT
GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT
TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP
TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT
PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI
TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG
TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT
VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT
TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP
TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT
TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT
QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV
TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT
TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT
PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT
TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ
TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT
PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT
PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP
TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT
TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT
PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP
TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTGPPTH
TSTAPIAELT TSNPPPESST PQTSRSTSSP LTESTTLLST LPPAIEMTST APPSTPTAPT
TTSGGHTLSP PPSTTTSPPG TPTRGTTTGS SSAPTPSTVQ TTTTSAWTPT PTPLSTPSII
RTTGLRPYPS SVLICCVLND TYYAPGEEVY NGTYGDTCYF VNCSLSCTLE FYNWSCPSTP
SPTPTPSKST PTPSKPSSTP SKPTPGTKPP ECPDFDPPRQ ENETWWLCDC FMATCKYNNT
VEIVKVECEP PPMPTCSNGL QPVRVEDPDG CCWHWECDCY CTGWGDPHYV TFDGLYYSYQ
GNCTYVLVEE ISPSVDNFGV YIDNYHCDPN DKVSCPRTLI VRHETQEVLI KTVHMMPMQV
QVQVNRQAVA LPYKKYGLEV YQSGINYVVD IPELGVLVSY NGLSFSVRLP YHRFGNNTKG
QCGTCTNTTS DDCILPSGEI VSNCEAAADQ WLVNDPSKPH CPHSSSTTKR PAVTVPGGGK
TTPHKDCTPS PLCQLIKDSL FAQCHALVPP QHYYDACVFD SCFMPGSSLE CASLQAYAAL
CAQQNICLDW RNHTHGACLV ECPSHREYQA CGPAEEPTCK SSSSQQNNTV LVEGCFCPEG
TMNYAPGFDV CVKTCGCVGP DNVPREFGEH FEFDCKNCVC LEGGSGIICQ PKRCSQKPVT
HCVEDGTYLA TEVNPADTCC NITVCKCNTS LCKEKPSVCP LGFEVKSKMV PGRCCPFYWC
ESKGVCVHGN AEYQPGSPVY SSKCQDCVCT DKVDNNTLLN VIACTHVPCN TSCSPGFELM
EAPGECCKKC EQTHCIIKRP DNQHVILKPG DFKSDPKNNC TFFSCVKIHN QLISSVSNIT
CPNFDASICI PGSITFMPNG CCKTCTPRNE TRVPCSTVPV TTEVSYAGCT KTVLMNHCSG
SCGTFVMYSA KAQALDHSCS CCKEEKTSQR EVVLSCPNGG SLTHTYTHIE SCQCQDTVCG
LPTGTSRRAR RSPRHLGSG
//
ID MUC2_HUMAN Reviewed; 5179 AA.
AC Q02817; Q14878;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Mucin-2;
DE Short=MUC-2;
DE AltName: Full=Intestinal mucin-2;
DE Flags: Precursor;
GN Name=MUC2; Synonyms=SMUC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RX PubMed=8300571;
RA Gum J.R. Jr., Hicks J.W., Toribara N.W., Siddiki B., Kim Y.S.;
RT "Molecular cloning of human intestinal mucin (MUC2) cDNA.
RT Identification of the amino terminus and overall sequence similarity
RT to prepro-von Willebrand factor.";
RL J. Biol. Chem. 269:2440-2446(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 626-1895 AND 4196-5179.
RC TISSUE=Colon;
RX PubMed=1400449;
RA Gum J.R. Jr., Hicks J.W., Toribara N.W., Rothe E.-M., Lagace R.E.,
RA Kim Y.S.;
RT "The human MUC2 intestinal mucin has cysteine-rich subdomains located
RT both upstream and downstream of its central repetitive region.";
RL J. Biol. Chem. 267:21375-21383(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1343-1895 AND 4176-4195.
RX PubMed=1885763; DOI=10.1172/JCI115360;
RA Toribara N.W., Gum J.R. Jr., Culhane P.J., Lagace R.E., Hicks J.W.,
RA Petersen G.M., Kim Y.S.;
RT "MUC-2 human small intestinal mucin gene structure. Repeated arrays
RT and polymorphism.";
RL J. Clin. Invest. 88:1005-1013(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4075-4352.
RX PubMed=2703501;
RA Gum J.R. Jr., Byrd J.C., Hicks J.W., Toribara N.W., Lamport D.T.A.,
RA Kim Y.S.;
RT "Molecular cloning of human intestinal mucin cDNAs. Sequence analysis
RT and evidence for genetic polymorphism.";
RL J. Biol. Chem. 264:6480-6487(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4487-4627.
RX PubMed=1550588; DOI=10.1016/0006-291X(92)90557-2;
RA Xu G., Huan L., Khatri I., Sajjan U.S., McCool D., Wang D., Jones C.,
RA Forstner G., Forstner J.;
RT "Human intestinal mucin-like protein (MLP) is homologous with rat MLP
RT in the C-terminal region, and is encoded by a gene on chromosome 11 p
RT 15.5.";
RL Biochem. Biophys. Res. Commun. 183:821-828(1992).
RN [6]
RP STRUCTURE OF O-LINKED CARBOHYDRATES.
RX PubMed=11445551; DOI=10.1093/glycob/11.6.459;
RA Silverman H.S., Parry S., Sutton-Smith M., Burdick M.D., McDermott K.,
RA Reid C.J., Batra S.K., Morris H.R., Hollingsworth M.A., Dell A.,
RA Harris A.;
RT "In vivo glycosylation of mucin tandem repeats.";
RL Glycobiology 11:459-471(2001).
RN [7]
RP SUBUNIT.
RX PubMed=12374796; DOI=10.1074/jbc.M208483200;
RA Godl K., Johansson M.E.V., Lidell M.E., Moergelin M., Karlsson H.,
RA Olson F.J., Gum J.R. Jr., Kim Y.S., Hansson G.C.;
RT "The N terminus of the MUC2 mucin forms trimers that are held together
RT within a trypsin-resistant core fragment.";
RL J. Biol. Chem. 277:47248-47256(2002).
RN [8]
RP AUTOCATALYTIC CLEAVAGE.
RX PubMed=12582180; DOI=10.1074/jbc.M210069200;
RA Lidell M.E., Johansson M.E.V., Hansson G.C.;
RT "An autocatalytic cleavage in the C terminus of the human MUC2 mucin
RT occurs at the low pH of the late secretory pathway.";
RL J. Biol. Chem. 278:13944-13951(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP INTERACTION WITH AGR2.
RX PubMed=19359471; DOI=10.1073/pnas.0808722106;
RA Park S.-W., Zhen G., Verhaeghe C., Nakagami Y., Nguyenvu L.T.,
RA Barczak A.J., Killeen N., Erle D.J.;
RT "The protein disulfide isomerase AGR2 is essential for production of
RT intestinal mucus.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6950-6955(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH
RP FCGBP.
RX PubMed=19432394; DOI=10.1021/pr9002504;
RA Johansson M.E.V., Thomsson K.A., Hansson G.C.;
RT "Proteomic analyses of the two mucus layers of the colon barrier
RT reveal that their main component, the Muc2 mucin, is strongly bound to
RT the Fcgbp protein.";
RL J. Proteome Res. 8:3549-3557(2009).
CC -!- FUNCTION: Coats the epithelia of the intestines, airways, and
CC other mucus membrane-containing organs. Thought to provide a
CC protective, lubricating barrier against particles and infectious
CC agents at mucosal surfaces. Major constituent of both the inner
CC and outer mucus layers of the colon and may play a role in
CC excluding bacteria from the inner mucus layer.
CC -!- SUBUNIT: Homotrimer; disulfide-linked. Dimerizes in the
CC endoplasmic reticulum via its C-terminal region and polymerizes
CC via its N-terminal region by disulfide-linked trimerization.
CC Interacts with FCGBP. Interacts with AGR2; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=In the intestine, secreted
CC into the inner and outer mucus layers (By similarity).
CC -!- TISSUE SPECIFICITY: Colon, small intestine, colonic tumors,
CC bronchus, cervix and gall bladder.
CC -!- PTM: O-glycosylated.
CC -!- PTM: May undergo proteolytic cleavage in the outer mucus layer of
CC the colon, contributing to the expanded volume and loose nature of
CC this layer which allows for bacterial colonization in contrast to
CC the inner mucus layer which is dense and devoid of bacteria (By
CC similarity).
CC -!- PTM: At low pH of 6 and under, undergoes autocatalytic cleavage in
CC vitro in the N-terminal region of the fourth VWD domain. It is
CC likely that this also occurs in vivo and is triggered by the low
CC pH of the late secretory pathway.
CC -!- POLYMORPHISM: The number of repeats is highly polymorphic and
CC varies among different alleles.
CC -!- SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain.
CC -!- SIMILARITY: Contains 1 TIL (trypsin inhibitory-like) domain.
CC -!- SIMILARITY: Contains 2 VWFC domains.
CC -!- SIMILARITY: Contains 4 VWFD domains.
CC -!- WEB RESOURCE: Name=Mucin database;
CC URL="http://www.medkem.gu.se/mucinbiology/databases/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MUC2ID41457ch11p15.html";
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DR EMBL; L21998; AAB95295.1; -; mRNA.
DR EMBL; M74027; AAA59875.1; -; Genomic_DNA.
DR EMBL; M94131; AAA59163.1; -; mRNA.
DR EMBL; M94132; AAA59164.1; -; mRNA.
DR PIR; A49963; A43932.
DR RefSeq; NP_002448.3; NM_002457.3.
DR UniGene; Hs.315; -.
DR ProteinModelPortal; Q02817; -.
DR DIP; DIP-48824N; -.
DR IntAct; Q02817; 2.
DR STRING; 9606.ENSP00000415183; -.
DR DrugBank; DB01411; Pranlukast.
DR PhosphoSite; Q02817; -.
DR UniCarbKB; Q02817; -.
DR DMDM; 2506877; -.
DR PaxDb; Q02817; -.
DR PRIDE; Q02817; -.
DR Ensembl; ENST00000359061; ENSP00000351956; ENSG00000198788.
DR GeneID; 4583; -.
DR KEGG; hsa:4583; -.
DR UCSC; uc001lsx.1; human.
DR CTD; 4583; -.
DR GeneCards; GC11P001064; -.
DR HGNC; HGNC:7512; MUC2.
DR HPA; CAB005317; -.
DR HPA; CAB016275; -.
DR HPA; HPA006197; -.
DR MIM; 158370; gene.
DR neXtProt; NX_Q02817; -.
DR PharmGKB; PA31316; -.
DR eggNOG; NOG12793; -.
DR HOGENOM; HOG000168234; -.
DR HOVERGEN; HBG004380; -.
DR InParanoid; Q02817; -.
DR KO; K10955; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; MUC2; human.
DR GeneWiki; MUC2; -.
DR GenomeRNAi; 4583; -.
DR NextBio; 17613; -.
DR PRO; PR:Q02817; -.
DR ArrayExpress; Q02817; -.
DR Bgee; Q02817; -.
DR CleanEx; HS_MUC2; -.
DR Genevestigator; Q02817; -.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0070702; C:inner mucus layer; ISS:UniProtKB.
DR GO; GO:0070703; C:outer mucus layer; ISS:UniProtKB.
DR GO; GO:0016266; P:O-glycan processing; TAS:Reactome.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR028580; MUC2.
DR InterPro; IPR002919; TIL_dom.
DR InterPro; IPR014853; Unchr_dom_Cys-rich.
DR InterPro; IPR006552; VWC_out.
DR InterPro; IPR001007; VWF_C.
DR InterPro; IPR001846; VWF_type-D.
DR InterPro; IPR025155; WxxW_domain.
DR PANTHER; PTHR11339:SF141; PTHR11339:SF141; 1.
DR Pfam; PF08742; C8; 4.
DR Pfam; PF13330; Mucin2_WxxW; 2.
DR Pfam; PF01826; TIL; 1.
DR Pfam; PF00094; VWD; 4.
DR SMART; SM00832; C8; 4.
DR SMART; SM00041; CT; 1.
DR SMART; SM00214; VWC; 2.
DR SMART; SM00215; VWC_out; 1.
DR SMART; SM00216; VWD; 4.
DR SUPFAM; SSF57567; SSF57567; 4.
DR PROSITE; PS01185; CTCK_1; 1.
DR PROSITE; PS01225; CTCK_2; 1.
DR PROSITE; PS01208; VWFC_1; 2.
DR PROSITE; PS50184; VWFC_2; 2.
DR PROSITE; PS51233; VWFD; 4.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Complete proteome; Disulfide bond;
KW Glycoprotein; Phosphoprotein; Polymorphism; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1 20 Potential.
FT CHAIN 21 5179 Mucin-2.
FT /FTId=PRO_0000019281.
FT DOMAIN 36 240 VWFD 1.
FT DOMAIN 295 351 TIL.
FT DOMAIN 390 604 VWFD 2.
FT DOMAIN 859 1065 VWFD 3.
FT REPEAT 1401 1416 1.
FT REPEAT 1417 1432 2.
FT REPEAT 1433 1448 3.
FT REPEAT 1449 1464 4.
FT REPEAT 1465 1471 5.
FT REPEAT 1472 1478 6.
FT REPEAT 1479 1494 7A.
FT REPEAT 1495 1517 7B.
FT REPEAT 1518 1533 8A.
FT REPEAT 1534 1556 8B.
FT REPEAT 1557 1572 9A.
FT REPEAT 1573 1596 9B.
FT REPEAT 1597 1612 10A.
FT REPEAT 1613 1635 10B.
FT REPEAT 1636 1651 11A.
FT REPEAT 1652 1675 11B.
FT REPEAT 1676 1683 12.
FT REPEAT 1684 1699 13.
FT REPEAT 1700 1715 14.
FT REPEAT 1716 1731 15.
FT REPEAT 1732 1747 16.
FT DOMAIN 4480 4690 VWFD 4.
FT DOMAIN 4815 4886 VWFC 1.
FT DOMAIN 4924 4991 VWFC 2.
FT DOMAIN 5075 5160 CTCK.
FT REGION 1401 1747 Approximate repeats.
FT SITE 4486 4487 Cleavage; by autolysis; in vitro.
FT MOD_RES 21 21 Phosphoserine.
FT CARBOHYD 163 163 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 423 423 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 670 670 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 770 770 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 894 894 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1139 1139 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1154 1154 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1215 1215 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1230 1230 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1246 1246 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1787 1787 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 1820 1820 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4339 4339 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4351 4351 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4362 4362 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4373 4373 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4422 4422 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4438 4438 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4502 4502 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4616 4616 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4627 4627 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4752 4752 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4787 4787 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4881 4881 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4888 4888 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4955 4955 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 4970 4970 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5019 5019 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5038 5038 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 5069 5069 N-linked (GlcNAc...) (Potential).
FT DISULFID 59 67 By similarity.
FT DISULFID 5075 5122 By similarity.
FT DISULFID 5089 5136 By similarity.
FT DISULFID 5098 5152 By similarity.
FT DISULFID 5102 5154 By similarity.
FT DISULFID ? 5159 By similarity.
FT VARIANT 58 58 L -> P (in dbSNP:rs2856111).
FT /FTId=VAR_056582.
FT VARIANT 116 116 V -> M (in dbSNP:rs11825977).
FT /FTId=VAR_056583.
FT VARIANT 832 832 G -> S (in dbSNP:rs11245936).
FT /FTId=VAR_056584.
FT VARIANT 1619 1619 S -> R (in dbSNP:rs11245947).
FT /FTId=VAR_059531.
FT VARIANT 1689 1689 P -> L (in dbSNP:rs11245949).
FT /FTId=VAR_059532.
FT VARIANT 1768 1768 P -> H (in dbSNP:rs34493663).
FT /FTId=VAR_061487.
FT VARIANT 2154 2154 I -> T (in dbSNP:rs6421972).
FT /FTId=VAR_059533.
FT VARIANT 2524 2524 T -> P (in dbSNP:rs7480563).
FT /FTId=VAR_059534.
FT VARIANT 2524 2524 T -> S (in dbSNP:rs7480563).
FT /FTId=VAR_059535.
FT VARIANT 2653 2653 Q -> L (in dbSNP:rs7126405).
FT /FTId=VAR_059536.
FT VARIANT 2653 2653 Q -> P (in dbSNP:rs7126405).
FT /FTId=VAR_059537.
FT CONFLICT 1351 1351 H -> L (in Ref. 3; AAA59875).
FT CONFLICT 1412 1412 T -> S (in Ref. 3; AAA59875).
FT CONFLICT 1449 1449 L -> P (in Ref. 3; AAA59875).
FT CONFLICT 1504 1504 M -> T (in Ref. 3; AAA59875).
FT CONFLICT 4076 4083 TGTQTPTT -> NGLQAPTP (in Ref. 4).
FT CONFLICT 4087 4087 T -> S (in Ref. 4).
FT CONFLICT 4130 4131 TP -> VL (in Ref. 4).
FT CONFLICT 4138 4138 V -> M (in Ref. 4).
FT CONFLICT 4146 4152 GTQTPTT -> STKSTTV (in Ref. 4).
FT CONFLICT 4163 4163 P -> A (in Ref. 4).
FT CONFLICT 4175 4176 TT -> MI (in Ref. 4).
FT CONFLICT 4179 4179 T -> S (in Ref. 4).
FT CONFLICT 4192 4194 GTQ -> TGS (in Ref. 4).
SQ SEQUENCE 5179 AA; 540300 MW; 85CD7571FB9A5663 CRC64;
MGLPLARLAA VCLALSLAGG SELQTEGRTR YHGRNVCSTW GNFHYKTFDG DVFRFPGLCD
YNFASDCRGS YKEFAVHLKR GPGQAEAPAG VESILLTIKD DTIYLTRHLA VLNGAVVSTP
HYSPGLLIEK SDAYTKVYSR AGLTLMWNRE DALMLELDTK FRNHTCGLCG DYNGLQSYSE
FLSDGVLFSP LEFGNMQKIN QPDVVCEDPE EEVAPASCSE HRAECERLLT AEAFADCQDL
VPLEPYLRAC QQDRCRCPGG DTCVCSTVAE FSRQCSHAGG RPGNWRTATL CPKTCPGNLV
YLESGSPCMD TCSHLEVSSL CEEHRMDGCF CPEGTVYDDI GDSGCVPVSQ CHCRLHGHLY
TPGQEITNDC EQCVCNAGRW VCKDLPCPGT CALEGGSHIT TFDGKTYTFH GDCYYVLAKG
DHNDSYALLG ELAPCGSTDK QTCLKTVVLL ADKKKNAVVF KSDGSVLLNQ LQVNLPHVTA
SFSVFRPSSY HIMVSMAIGV RLQVQLAPVM QLFVTLDQAS QGQVQGLCGN FNGLEGDDFK
TASGLVEATG AGFANTWKAQ STCHDKLDWL DDPCSLNIES ANYAEHWCSL LKKTETPFGR
CHSAVDPAEY YKRCKYDTCN CQNNEDCLCA ALSSYARACT AKGVMLWGWR EHVCNKDVGS
CPNSQVFLYN LTTCQQTCRS LSEADSHCLE GFAPVDGCGC PDHTFLDEKG RCVPLAKCSC
YHRGLYLEAG DVVVRQEERC VCRDGRLHCR QIRLIGQSCT APKIHMDCSN LTALATSKPR
ALSCQTLAAG YYHTECVSGC VCPDGLMDDG RGGCVVEKEC PCVHNNDLYS SGAKIKVDCN
TCTCKRGRWV CTQAVCHGTC SIYGSGHYIT FDGKYYDFDG HCSYVAVQDY CGQNSSLGSF
SIITENVPCG TTGVTCSKAI KIFMGRTELK LEDKHRVVIQ RDEGHHVAYT TREVGQYLVV
ESSTGIIVIW DKRTTVFIKL APSYKGTVCG LCGNFDHRSN NDFTTRDHMV VSSELDFGNS
WKEAPTCPDV STNPEPCSLN PHRRSWAEKQ CSILKSSVFS ICHSKVDPKP FYEACVHDSC
SCDTGGDCEC FCSAVASYAQ ECTKEGACVF WRTPDLCPIF CDYYNPPHEC EWHYEPCGNR
SFETCRTING IHSNISVSYL EGCYPRCPKD RPIYEEDLKK CVTADKCGCY VEDTHYPPGA
SVPTEETCKS CVCTNSSQVV CRPEEGKILN QTQDGAFCYW EICGPNGTVE KHFNICSITT
RPSTLTTFTT ITLPTTPTSF TTTTTTTTPT SSTVLSTTPK LCCLWSDWIN EDHPSSGSDD
GDREPFDGVC GAPEDIECRS VKDPHLSLEQ HGQKVQCDVS VGFICKNEDQ FGNGPFGLCY
DYKIRVNCCW PMDKCITTPS PPTTTPSPPP TTTTTLPPTT TPSPPTTTTT TPPPTTTPSP
PITTTTTPLP TTTPSPPIST TTTPPPTTTP SPPTTTPSPP TTTPSPPTTT TTTPPPTTTP
SPPMTTPITP PASTTTLPPT TTPSPPTTTT TTPPPTTTPS PPTTTPITPP TSTTTLPPTT
TPSPPPTTTT TPPPTTTPSP PTTTTPSPPT ITTTTPPPTT TPSPPTTTTT TPPPTTTPSP
PTTTPITPPT STTTLPPTTT PSPPPTTTTT PPPTTTPSPP TTTTPSPPIT TTTTPPPTTT
PSSPITTTPS PPTTTMTTPS PTTTPSSPIT TTTTPSSTTT PSPPPTTMTT PSPTTTPSPP
TTTMTTLPPT TTSSPLTTTP LPPSITPPTF SPFSTTTPTT PCVPLCNWTG WLDSGKPNFH
KPGGDTELIG DVCGPGWAAN ISCRATMYPD VPIGQLGQTV VCDVSVGLIC KNEDQKPGGV
IPMAFCLNYE INVQCCECVT QPTTMTTTTT ENPTPPTTTP ITTTTTVTPT PTPTGTQTPT
TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP
TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT
TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT
QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV
TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT
TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT
PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT
TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ
TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT
PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT
PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP
TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT
TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT
PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP
TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP
ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT
GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT
TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP
TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT
PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI
TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG
TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT
VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT
TTPITTTTTV TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP
TPTGTQTPTT TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT
TTTTVTPTPT PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT
QTPTTTPITT TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV
TPTPTPTGTQ TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT
TPITTTTTVT PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT
PTGTQTPTTT PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT
TTTVTPTPTP TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ
TPTTTPITTT TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT
PTPTPTGTQT PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT
PITTTTTVTP TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP
TGTQTPTTTP ITTTTTVTPT PTPTGTQTPT TTPITTTTTV TPTPTPTGTQ TPTTTPITTT
TTVTPTPTPT GTQTPTTTPI TTTTTVTPTP TPTGTQTPTT TPITTTTTVT PTPTPTGTQT
PTTTPITTTT TVTPTPTPTG TQTPTTTPIT TTTTVTPTPT PTGTQTPTTT PITTTTTVTP
TPTPTGTQTP TTTPITTTTT VTPTPTPTGT QTPTTTPITT TTTVTPTPTP TGTQTGPPTH
TSTAPIAELT TSNPPPESST PQTSRSTSSP LTESTTLLST LPPAIEMTST APPSTPTAPT
TTSGGHTLSP PPSTTTSPPG TPTRGTTTGS SSAPTPSTVQ TTTTSAWTPT PTPLSTPSII
RTTGLRPYPS SVLICCVLND TYYAPGEEVY NGTYGDTCYF VNCSLSCTLE FYNWSCPSTP
SPTPTPSKST PTPSKPSSTP SKPTPGTKPP ECPDFDPPRQ ENETWWLCDC FMATCKYNNT
VEIVKVECEP PPMPTCSNGL QPVRVEDPDG CCWHWECDCY CTGWGDPHYV TFDGLYYSYQ
GNCTYVLVEE ISPSVDNFGV YIDNYHCDPN DKVSCPRTLI VRHETQEVLI KTVHMMPMQV
QVQVNRQAVA LPYKKYGLEV YQSGINYVVD IPELGVLVSY NGLSFSVRLP YHRFGNNTKG
QCGTCTNTTS DDCILPSGEI VSNCEAAADQ WLVNDPSKPH CPHSSSTTKR PAVTVPGGGK
TTPHKDCTPS PLCQLIKDSL FAQCHALVPP QHYYDACVFD SCFMPGSSLE CASLQAYAAL
CAQQNICLDW RNHTHGACLV ECPSHREYQA CGPAEEPTCK SSSSQQNNTV LVEGCFCPEG
TMNYAPGFDV CVKTCGCVGP DNVPREFGEH FEFDCKNCVC LEGGSGIICQ PKRCSQKPVT
HCVEDGTYLA TEVNPADTCC NITVCKCNTS LCKEKPSVCP LGFEVKSKMV PGRCCPFYWC
ESKGVCVHGN AEYQPGSPVY SSKCQDCVCT DKVDNNTLLN VIACTHVPCN TSCSPGFELM
EAPGECCKKC EQTHCIIKRP DNQHVILKPG DFKSDPKNNC TFFSCVKIHN QLISSVSNIT
CPNFDASICI PGSITFMPNG CCKTCTPRNE TRVPCSTVPV TTEVSYAGCT KTVLMNHCSG
SCGTFVMYSA KAQALDHSCS CCKEEKTSQR EVVLSCPNGG SLTHTYTHIE SCQCQDTVCG
LPTGTSRRAR RSPRHLGSG
//
MIM
158370
*RECORD*
*FIELD* NO
158370
*FIELD* TI
*158370 MUCIN 2, INTESTINAL; MUC2
*FIELD* TX
CLONING
Many epithelial tissues including those of trachea, submaxillary gland,
read moremammary gland, pancreas, stomach, cervix, and intestine produce high
molecular weight, complex glycoconjugates known as mucins. These consist
of a polypeptide core (apomucin) covered almost entirely by O-linked
carbohydrate chains which may constitute up to 80% of the total
molecular weight. Because of their heavy glycosylation, the apomucins
were difficult to analyze by conventional peptide sequencing methods. It
has been easier to isolate cDNAs and deduce the structure of the
proteins therefrom. Gum et al. (1989) cloned a cDNA for human intestinal
mucin and by in vitro translation of a polyadenylated RNA from human
small intestine, colon, and colon cancer cells, produced a 162-kD
peptide that was immunoprecipitated with antibodies to deglycosylated
mucin. Griffiths et al., 1990 stated that MUC2 resembles the gene for
the urinary mucin PUM (MUC1; 158340) in showing high level of
polymorphism, some of which appears to be due to variation in allele
length, as observed for PUM. Jany et al. (1991) concluded that the same
mucin gene is expressed in both intestine and bronchus and is homologous
to a gene or genes expressed in the gallbladder, cervix, and mammary
gland.
Allen et al. (1998) indicated that a total of 9 human MUC genes had been
identified to date. Like the others, MUC2 is characterized by tandem and
irregular repeat sequences rich in threonine and serine, the potential
sites of attachment of the oligosaccharide chains. The MUC2 gene product
has more than 5,100 amino acids in its commonest allelic form. The MUC2
product is polymerized end to end through disulfide bridges to form
large secreted polymeric gel-forming mucins.
Rousseau et al. (2004) described the domain structure of human MUC2.
MUC2 contains an N-terminal signal peptide, followed by several Von
Willebrand factor (VWF; 193400)-like domains, a cysteine-rich domain, a
small invariant tandem repeat domain, a second cysteine-rich domain, the
main tandem repeat domain, a second group of VWF-like domains, and a
C-terminal cystine knot domain.
Using real-time RT-PCR, Moehle et al. (2006) found that MUC2 was highly
expressed in adult small intestine and colon. Expression was lower in
fetal lung and adult trachea and stomach, with weak expression in
skeletal muscle, testis, and prostate. No expression was detected in
other tissues examined.
GENE STRUCTURE
As the first intestinal mucin gene to be described, MUC2 has become
important as a prototype for secreted mucins in several organ systems.
Toribara et al. (1991) showed that MUC2 contains 2 distinct regions
which have with a high degree of internal homology but no significant
homology to each other. Region 1 consists mostly of 48-bp repeats which
are interrupted in places by 21 to 24 bp segments. Region 2 is composed
of 69-bp tandem repeats arranged in an uninterrupted array of up to 115
individual units. Southern analysis of genomic DNA samples using TaqI
and HinfI revealed both length and sequence polymorphisms occurring in
region 2. The sequence polymorphisms had different ethnic distributions
while the length polymorphisms were attributable to variable numbers of
tandem repeats (VNTRs).
Rousseau et al. (2004) determined that the MUC2 gene contains
twenty-nine 5-prime exons, 1 large central exon containing the tandem
repeat sequences, and nineteen 3-prime exons.
MAPPING
Using the clone isolated by Gum et al. (1989) in the study of somatic
cell hybrids, Griffiths et al. (1989) showed that the MUC2 gene is
located on chromosome 11. By in situ hybridization, Griffiths et al.
(1990) assigned the gene to 11p15. Analysis of the CEPH (Centre d'Etude
du Polymorphisme Humain) families showed that MUC2 is part of the tight
linkage group on 11p15 that contains HRAS (190020), INS (176730), TH
(191290), and HBB (141900).
Rousseau et al. (2004) determined that the MUC2 and MUC6 (158374) genes
are located 38.5 kb apart in a head-to-head orientation within a gene
complex on chromosome 11p15.5.
GENE FAMILY
Tracheobronchial mucin (MUC5AC; 158373), which was also mapped to 11p15,
was thought to be distinct from MUC2. However, Shankar et al. (1995)
presented evidence that they may be identical. MUC2 is a protein of
greater than 500 amino acids that can be divided into 3 major structural
domains. MUC transcripts in the intestine and trachea showed sequence
identity in 3 areas: the region of imperfect repeats; the sequence
immediately upstream of the 69-bp tandem repeats; and the extreme C
terminus. Shankar et al. (1995) granted that differences may exist in
the extreme N terminus of the MUC2 gene transcripts in the intestine and
trachea, possibly due to alternative splicing.
Three of the 4 distinct mucin genes that map to 11p15.5 show a high
level of genetically determined polymorphism: MUC2, MUC5AC, and MUC6.
Pigny et al. (1996) performed linkage analysis of these 3 genes in the
CEPH families and demonstrated that all 3 genes are clustered on 11p15.5
between HRAS and IGF2 (147470). Pulsed-field gel electrophoresis was
used to make a detailed physical map of the MUC cluster and to integrate
the physical and genetic maps. The gene order was determined to be
tel-HRAS--MUC6--MUC2--MUC5AC--MUC5B--IGF2--cen. The MUC genes span a
region of some 400 kb. Pigny et al. (1996) noted that the order of the
MUC genes on the map corresponds to the relative order of their
expression along the anterior-posterior axis of the body, suggesting a
possible functional significance to the gene order.
GENE FUNCTION
Allen et al. (1998) stated that the primary function of the MUC2 gene
product is to provide a protective barrier between the epithelial
surfaces and the gut lumen. There is decreased expression of MUC2 in
colonic cancer and defective polymerization of secreted mucin in
ulcerative colitis (see 266600).
Mucus is especially thick in the colon and helps protect the colonic
epithelium from enteric pathogens, such as Entamoeba histolytica (Eh),
which adheres to mucin oligosaccharides via a 170-kD lectin. In a small
percentage of cases, Eh overcomes the mucus barrier and invades the
epithelium by means of cysteine proteases. Lidell et al. (2006) found
that Eh cysteine proteases digested recombinant C-terminal, but not
N-terminal, cysteine-rich regions of MUC2, as well as mucins from an
MUC2-producing cell line. The major cleavage site was predicted to
disrupt MUC2 polymers, thereby disrupting the mucus gel. Lidell et al.
(2006) proposed that Eh cysteine proteases use this mechanism in the
pathogenesis of invasive amoebiasis.
By microarray analysis, Moehle et al. (2006) found coordinated
downregulation of mucins, including MUC2, in ileum and colon of Crohn
disease and ulcerative colitis (see 266600) patients compared with
controls. They identified an NF-kappa-B (see 164011)-binding site in the
MUC2 promoter and showed that activation of the NF-kappa-B signaling
pathway by inflammatory cytokines TNF-alpha (TNF; 191160) and TGF-beta
(TGFB1; 190180) upregulated MUC2 mRNA expression nearly 6-fold and
3-fold, respectively.
Shan et al. (2013) showed that the small intestine has a porous mucus
layer, which permitted the uptake of MUC2 by antigen-sampling dendritic
cells. Glycans associated with MUC2 imprinted dendritic cells with
antiinflammatory properties by assembling a galectin-3 (153619)-dectin-1
(606264)-Fc-gamma-RIIB (604590) receptor complex that activated
beta-catenin (116806). This transcription factor interfered with
dendritic cell expression of inflammatory but not tolerogenic cytokines
by inhibiting gene transcription through NF-kappa-B. MUC2 induced
additional conditioning signals in intestinal epithelial cells. Shan et
al. (2013) concluded that mucus does not merely form a nonspecific
physical barrier, but also constrains the immunogenicity of gut antigens
by delivering tolerogenic signals.
MOLECULAR GENETICS
To test the hypothesis that short MUC2 alleles predispose to ulcerative
colitis (see 266600), Swallow et al. (1999) analyzed DNA from 125
unrelated individuals with inflammatory bowel disease. They found no
evidence of an association between MUC2 allele length and ulcerative
colitis.
ANIMAL MODEL
Velcich et al. (2002) generated mice deficient in MUC2, the most
abundant secreted gastrointestinal mucin. Heterozygous mice were
indistinguishable from wildtype mice, and homozygous mutant mice were
born at the expected mendelian frequency. Muc2 -/- mice showed absence
of recognizable goblet cells along the entire length of the intestine
upon alcian blue staining. However, expression of intestinal trefoil
factor (600633), another product of fully differentiated goblet cells,
was detectable, suggesting that at least some aspects of the
differentiation program of the goblet cell lineage persist in Muc2 -/-
mice. Muc2 -/- mice had increased proliferation, decreased apoptosis,
and increased migration of intestinal epithelial cells. Muc2 -/- mice
frequently developed adenomas in the small intestine that progressed to
invasive adenocarcinoma, as well as rectal tumors, with up to 68% of
mice manifesting with gastrointestinal tumors at 1 year of age.
*FIELD* SA
Nguyen et al. (1990)
*FIELD* RF
1. Allen, A.; Hutton, D. A.; Pearson, J. P.: The MUC2 gene product:
a human intestinal mucin. Int. J. Biochem. Cell Biol. 30: 797-801,
1998.
2. Griffiths, B.; Gum, J.; West, L. F.; Povey, S.; Swallow, D. M.;
Kim, Y. S.: Mapping of the gene coding for intestinal mucin to chromosome
11p15. (Abstract) Cytogenet. Cell Genet. 51: 1008 only, 1989.
3. Griffiths, B.; Matthews, D. J.; West, L.; Attwood, J.; Povey, S.;
Swallow, D. M.; Gum, J. R.; Kim, Y. S.: Assignment of the polymorphic
intestinal mucin gene (MUC2) to chromosome 11p15. Ann. Hum. Genet. 54:
277-285, 1990.
4. Gum, J. R.; Byrd, J. C.; Hicks, J. W.; Toribara, N. W.; Lamport,
D. T. A.; Kim, Y. S.: Molecular cloning of human intestinal mucin
cDNAs: sequence analysis and evidence for genetic polymorphism. J.
Biol. Chem. 264: 6480-6487, 1989.
5. Jany, B. H.; Gallup, M. W.; Yan, P.-S.; Gum, J. R.; Kim, Y. S.;
Basbaum, C. B.: Human bronchus and intestine express the same mucin
gene. J. Clin. Invest. 87: 77-82, 1991.
6. Lidell, M. E.; Moncada, D. M.; Chadee, K.; Hansson, G. C.: Entamoeba
histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal
domain and dissolve the protective colonic mucus gel. Proc. Nat.
Acad. Sci. 103: 9298-9303, 2006.
7. Moehle, C.; Ackermann, N.; Langmann, T.; Aslanidis, C.; Kel, A.;
Kel-Margoulis, O.; Schmitz-Madry, A.; Zahn, A.; Stremmel, W.; Schmitz,
G.: Aberrant intestinal expression and allelic variants of mucin
genes associated with inflammatory bowel disease. J. Molec. Med. 84:
1055-1066, 2006.
8. Nguyen, V. C.; Aubert, J. P.; Gross, M. S.; Porchet, N.; Degand,
P.; Frezal, J.: Assignment of human tracheobronchial mucin gene(s)
to 11p15 and a tracheobronchial mucin-related sequence to chromosome
13. Hum. Genet. 86: 167-172, 1990.
9. Pigny, P.; Guyonnet-Duperat, V.; Hill, A. S.; Pratt, W. S.; Galiegue-Zouitina,
S.; Collyn d'Hooge, M.; Laine, A.; Van-Seuningen, I.; Degand, P.;
Gum, J. R.; Kim, Y. S.; Swallow, D. M.; Aubert, J.-P.; Porchet, N.
: Human mucin genes assigned to 11p15.5: identification and organization
of a cluster of genes. Genomics 38: 340-352, 1996.
10. Rousseau, K.; Byrne, C.; Kim, Y. S.; Gum, J. R.; Swallow, D. M.;
Toribara, N. W.: The complete genomic organization of the human MUC6
and MUC2 mucin genes. Genomics 83: 936-939, 2004.
11. Shan, M.; Gentile, M.; Yeiser, J. R.; Walland, A. C.; Bornstein,
V. U.; Chen, K.; He, B.; Cassis, L.; Bigas, A.; Cols, M.; Comerma,
L.; Huang, B.; Blander, J. M.; Xiong, H.; Mayer, L.; Berin, C.; Augenlicht,
L. H.; Velcich, A.; Cerutti, A. Mucus enhances gut homeostasis
and oral tolerance by delivering immunoregulatory signals. Science 342:
447-453, 2013.
12. Shankar, V.; Gilmore, M. S.; Sachdev, G. P.: Further evidence
that the human MUC2 gene transcripts in the intestine and trachea
are identical. (Letter) Biochem. J 306: 311-312, 1995.
13. Swallow, D. M.; Vinall, L. E.; Gum, J. R.; Kim, Y. S.; Yang, H.;
Rotter, J. I.; Mirza, M.; Lee, J. C. W.; Lennard-Jones, J. E.: Ulcerative
colitis is not associated with differences in MUC2 mucin allele length.
(Letter) J. Med. Genet. 36: 859-860, 1999.
14. Toribara, N. W.; Gum, J. R., Jr.; Culhane, P. J.; Lagace, R. E.;
Hicks, J. W.; Petersen, G. M.; Kim, Y. S.: MUC-2 human small intestinal
mucin gene structure: repeated arrays and polymorphism. J. Clin.
Invest. 88: 1005-1013, 1991.
15. Velcich, A.; Yang, W.; Heyer, J.; Fragale, A.; Nicholas, C.; Viani,
S.; Kucherlapati, R.; Lipkin, M.; Yang, K.; Augenlicht, L.: Colorectal
cancer in mice genetically deficient in the mucin Muc2. Science 295:
1726-1729, 2002.
*FIELD* CN
Ada Hamosh - updated: 02/03/2014
Patricia A. Hartz - updated: 7/23/2008
Paul J. Converse - updated: 7/28/2006
Patricia A. Hartz - updated: 5/13/2004
Ada Hamosh - updated: 3/6/2002
Victor A. McKusick - updated: 3/11/1999
Victor A. McKusick - updated: 2/4/1997
*FIELD* CD
Victor A. McKusick: 6/1/1989
*FIELD* ED
alopez: 02/03/2014
carol: 10/24/2008
carol: 8/14/2008
wwang: 7/25/2008
terry: 7/23/2008
terry: 7/27/2007
mgross: 9/25/2006
terry: 7/28/2006
terry: 3/16/2005
mgross: 5/20/2004
terry: 5/13/2004
alopez: 3/6/2002
terry: 3/6/2002
carol: 3/29/1999
terry: 3/11/1999
jenny: 2/4/1997
terry: 1/21/1997
mark: 9/12/1995
terry: 4/19/1995
supermim: 3/16/1992
carol: 3/3/1992
carol: 3/2/1992
carol: 10/4/1991
*RECORD*
*FIELD* NO
158370
*FIELD* TI
*158370 MUCIN 2, INTESTINAL; MUC2
*FIELD* TX
CLONING
Many epithelial tissues including those of trachea, submaxillary gland,
read moremammary gland, pancreas, stomach, cervix, and intestine produce high
molecular weight, complex glycoconjugates known as mucins. These consist
of a polypeptide core (apomucin) covered almost entirely by O-linked
carbohydrate chains which may constitute up to 80% of the total
molecular weight. Because of their heavy glycosylation, the apomucins
were difficult to analyze by conventional peptide sequencing methods. It
has been easier to isolate cDNAs and deduce the structure of the
proteins therefrom. Gum et al. (1989) cloned a cDNA for human intestinal
mucin and by in vitro translation of a polyadenylated RNA from human
small intestine, colon, and colon cancer cells, produced a 162-kD
peptide that was immunoprecipitated with antibodies to deglycosylated
mucin. Griffiths et al., 1990 stated that MUC2 resembles the gene for
the urinary mucin PUM (MUC1; 158340) in showing high level of
polymorphism, some of which appears to be due to variation in allele
length, as observed for PUM. Jany et al. (1991) concluded that the same
mucin gene is expressed in both intestine and bronchus and is homologous
to a gene or genes expressed in the gallbladder, cervix, and mammary
gland.
Allen et al. (1998) indicated that a total of 9 human MUC genes had been
identified to date. Like the others, MUC2 is characterized by tandem and
irregular repeat sequences rich in threonine and serine, the potential
sites of attachment of the oligosaccharide chains. The MUC2 gene product
has more than 5,100 amino acids in its commonest allelic form. The MUC2
product is polymerized end to end through disulfide bridges to form
large secreted polymeric gel-forming mucins.
Rousseau et al. (2004) described the domain structure of human MUC2.
MUC2 contains an N-terminal signal peptide, followed by several Von
Willebrand factor (VWF; 193400)-like domains, a cysteine-rich domain, a
small invariant tandem repeat domain, a second cysteine-rich domain, the
main tandem repeat domain, a second group of VWF-like domains, and a
C-terminal cystine knot domain.
Using real-time RT-PCR, Moehle et al. (2006) found that MUC2 was highly
expressed in adult small intestine and colon. Expression was lower in
fetal lung and adult trachea and stomach, with weak expression in
skeletal muscle, testis, and prostate. No expression was detected in
other tissues examined.
GENE STRUCTURE
As the first intestinal mucin gene to be described, MUC2 has become
important as a prototype for secreted mucins in several organ systems.
Toribara et al. (1991) showed that MUC2 contains 2 distinct regions
which have with a high degree of internal homology but no significant
homology to each other. Region 1 consists mostly of 48-bp repeats which
are interrupted in places by 21 to 24 bp segments. Region 2 is composed
of 69-bp tandem repeats arranged in an uninterrupted array of up to 115
individual units. Southern analysis of genomic DNA samples using TaqI
and HinfI revealed both length and sequence polymorphisms occurring in
region 2. The sequence polymorphisms had different ethnic distributions
while the length polymorphisms were attributable to variable numbers of
tandem repeats (VNTRs).
Rousseau et al. (2004) determined that the MUC2 gene contains
twenty-nine 5-prime exons, 1 large central exon containing the tandem
repeat sequences, and nineteen 3-prime exons.
MAPPING
Using the clone isolated by Gum et al. (1989) in the study of somatic
cell hybrids, Griffiths et al. (1989) showed that the MUC2 gene is
located on chromosome 11. By in situ hybridization, Griffiths et al.
(1990) assigned the gene to 11p15. Analysis of the CEPH (Centre d'Etude
du Polymorphisme Humain) families showed that MUC2 is part of the tight
linkage group on 11p15 that contains HRAS (190020), INS (176730), TH
(191290), and HBB (141900).
Rousseau et al. (2004) determined that the MUC2 and MUC6 (158374) genes
are located 38.5 kb apart in a head-to-head orientation within a gene
complex on chromosome 11p15.5.
GENE FAMILY
Tracheobronchial mucin (MUC5AC; 158373), which was also mapped to 11p15,
was thought to be distinct from MUC2. However, Shankar et al. (1995)
presented evidence that they may be identical. MUC2 is a protein of
greater than 500 amino acids that can be divided into 3 major structural
domains. MUC transcripts in the intestine and trachea showed sequence
identity in 3 areas: the region of imperfect repeats; the sequence
immediately upstream of the 69-bp tandem repeats; and the extreme C
terminus. Shankar et al. (1995) granted that differences may exist in
the extreme N terminus of the MUC2 gene transcripts in the intestine and
trachea, possibly due to alternative splicing.
Three of the 4 distinct mucin genes that map to 11p15.5 show a high
level of genetically determined polymorphism: MUC2, MUC5AC, and MUC6.
Pigny et al. (1996) performed linkage analysis of these 3 genes in the
CEPH families and demonstrated that all 3 genes are clustered on 11p15.5
between HRAS and IGF2 (147470). Pulsed-field gel electrophoresis was
used to make a detailed physical map of the MUC cluster and to integrate
the physical and genetic maps. The gene order was determined to be
tel-HRAS--MUC6--MUC2--MUC5AC--MUC5B--IGF2--cen. The MUC genes span a
region of some 400 kb. Pigny et al. (1996) noted that the order of the
MUC genes on the map corresponds to the relative order of their
expression along the anterior-posterior axis of the body, suggesting a
possible functional significance to the gene order.
GENE FUNCTION
Allen et al. (1998) stated that the primary function of the MUC2 gene
product is to provide a protective barrier between the epithelial
surfaces and the gut lumen. There is decreased expression of MUC2 in
colonic cancer and defective polymerization of secreted mucin in
ulcerative colitis (see 266600).
Mucus is especially thick in the colon and helps protect the colonic
epithelium from enteric pathogens, such as Entamoeba histolytica (Eh),
which adheres to mucin oligosaccharides via a 170-kD lectin. In a small
percentage of cases, Eh overcomes the mucus barrier and invades the
epithelium by means of cysteine proteases. Lidell et al. (2006) found
that Eh cysteine proteases digested recombinant C-terminal, but not
N-terminal, cysteine-rich regions of MUC2, as well as mucins from an
MUC2-producing cell line. The major cleavage site was predicted to
disrupt MUC2 polymers, thereby disrupting the mucus gel. Lidell et al.
(2006) proposed that Eh cysteine proteases use this mechanism in the
pathogenesis of invasive amoebiasis.
By microarray analysis, Moehle et al. (2006) found coordinated
downregulation of mucins, including MUC2, in ileum and colon of Crohn
disease and ulcerative colitis (see 266600) patients compared with
controls. They identified an NF-kappa-B (see 164011)-binding site in the
MUC2 promoter and showed that activation of the NF-kappa-B signaling
pathway by inflammatory cytokines TNF-alpha (TNF; 191160) and TGF-beta
(TGFB1; 190180) upregulated MUC2 mRNA expression nearly 6-fold and
3-fold, respectively.
Shan et al. (2013) showed that the small intestine has a porous mucus
layer, which permitted the uptake of MUC2 by antigen-sampling dendritic
cells. Glycans associated with MUC2 imprinted dendritic cells with
antiinflammatory properties by assembling a galectin-3 (153619)-dectin-1
(606264)-Fc-gamma-RIIB (604590) receptor complex that activated
beta-catenin (116806). This transcription factor interfered with
dendritic cell expression of inflammatory but not tolerogenic cytokines
by inhibiting gene transcription through NF-kappa-B. MUC2 induced
additional conditioning signals in intestinal epithelial cells. Shan et
al. (2013) concluded that mucus does not merely form a nonspecific
physical barrier, but also constrains the immunogenicity of gut antigens
by delivering tolerogenic signals.
MOLECULAR GENETICS
To test the hypothesis that short MUC2 alleles predispose to ulcerative
colitis (see 266600), Swallow et al. (1999) analyzed DNA from 125
unrelated individuals with inflammatory bowel disease. They found no
evidence of an association between MUC2 allele length and ulcerative
colitis.
ANIMAL MODEL
Velcich et al. (2002) generated mice deficient in MUC2, the most
abundant secreted gastrointestinal mucin. Heterozygous mice were
indistinguishable from wildtype mice, and homozygous mutant mice were
born at the expected mendelian frequency. Muc2 -/- mice showed absence
of recognizable goblet cells along the entire length of the intestine
upon alcian blue staining. However, expression of intestinal trefoil
factor (600633), another product of fully differentiated goblet cells,
was detectable, suggesting that at least some aspects of the
differentiation program of the goblet cell lineage persist in Muc2 -/-
mice. Muc2 -/- mice had increased proliferation, decreased apoptosis,
and increased migration of intestinal epithelial cells. Muc2 -/- mice
frequently developed adenomas in the small intestine that progressed to
invasive adenocarcinoma, as well as rectal tumors, with up to 68% of
mice manifesting with gastrointestinal tumors at 1 year of age.
*FIELD* SA
Nguyen et al. (1990)
*FIELD* RF
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histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal
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Gum, J. R.; Kim, Y. S.; Swallow, D. M.; Aubert, J.-P.; Porchet, N.
: Human mucin genes assigned to 11p15.5: identification and organization
of a cluster of genes. Genomics 38: 340-352, 1996.
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Toribara, N. W.: The complete genomic organization of the human MUC6
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are identical. (Letter) Biochem. J 306: 311-312, 1995.
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colitis is not associated with differences in MUC2 mucin allele length.
(Letter) J. Med. Genet. 36: 859-860, 1999.
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*FIELD* CN
Ada Hamosh - updated: 02/03/2014
Patricia A. Hartz - updated: 7/23/2008
Paul J. Converse - updated: 7/28/2006
Patricia A. Hartz - updated: 5/13/2004
Ada Hamosh - updated: 3/6/2002
Victor A. McKusick - updated: 3/11/1999
Victor A. McKusick - updated: 2/4/1997
*FIELD* CD
Victor A. McKusick: 6/1/1989
*FIELD* ED
alopez: 02/03/2014
carol: 10/24/2008
carol: 8/14/2008
wwang: 7/25/2008
terry: 7/23/2008
terry: 7/27/2007
mgross: 9/25/2006
terry: 7/28/2006
terry: 3/16/2005
mgross: 5/20/2004
terry: 5/13/2004
alopez: 3/6/2002
terry: 3/6/2002
carol: 3/29/1999
terry: 3/11/1999
jenny: 2/4/1997
terry: 1/21/1997
mark: 9/12/1995
terry: 4/19/1995
supermim: 3/16/1992
carol: 3/3/1992
carol: 3/2/1992
carol: 10/4/1991