Q02817 (MUC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 110.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Mucin-2 Short name=MUC-2 Alternative name(s): Intestinal mucin-2 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 5179 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Coats the epithelia of the intestines, airways, and other mucus membrane-containing organs. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. Major constituent of both the inner and outer mucus layers of the colon and may play a role in excluding bacteria from the inner mucus layer. Ref.11 |
| Subunit structure | Homotrimer; disulfide-linked. Dimerizes in the endoplasmic reticulum via its C-terminal region and polymerizes via its N-terminal region by disulfide-linked trimerization. Interacts with FCGBP. Interacts with AGR2; disulfide-linked. Ref.7 Ref.10 Ref.11 |
| Subcellular location | Secreted. Note: In the intestine, secreted into the inner and outer mucus layers By similarity. |
| Tissue specificity | Colon, small intestine, colonic tumors, bronchus, cervix and gall bladder. |
| Post-translational modification | O-glycosylated. Ref.6 May undergo proteolytic cleavage in the outer mucus layer of the colon, contributing to the expanded volume and loose nature of this layer which allows for bacterial colonization in contrast to the inner mucus layer which is dense and devoid of bacteria By similarity. At low pH of 6 and under, undergoes autocatalytic cleavage in vitro in the N-terminal region of the fourth VWD domain. It is likely that this also occurs in vivo and is triggered by the low pH of the late secretory pathway. |
| Polymorphism | The number of repeats is highly polymorphic and varies among different alleles. |
| Sequence similarities | Contains 1 CTCK (C-terminal cystine knot-like) domain. Contains 1 TIL (trypsin inhibitory-like) domain. Contains 2 VWFC domains. Contains 4 VWFD domains. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Secreted |
| Coding sequence diversity | Polymorphism |
| Domain | Repeat Signal |
| PTM | Autocatalytic cleavage Disulfide bond Glycoprotein Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Cellular component | inner mucus layer Inferred from sequence or structural similarity. Source: UniProtKB outer mucus layerInferred from sequence or structural similarity. Source: UniProtKB |
| Molecular function | protein binding Inferred from physical interaction Ref.10Ref.11. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 20 | 20 | Potential | ||||||||
| Chain | 21 – 5179 | 5159 | Mucin-2 | PRO_0000019281 | |||||||
Regions | |||||||||||
| Domain | 36 – 240 | 205 | VWFD 1 | ||||||||
| Domain | 295 – 351 | 57 | TIL | ||||||||
| Domain | 390 – 604 | 215 | VWFD 2 | ||||||||
| Domain | 859 – 1065 | 207 | VWFD 3 | ||||||||
| Repeat | 1401 – 1416 | 16 | 1 | ||||||||
| Repeat | 1417 – 1432 | 16 | 2 | ||||||||
| Repeat | 1433 – 1448 | 16 | 3 | ||||||||
| Repeat | 1449 – 1464 | 16 | 4 | ||||||||
| Repeat | 1465 – 1471 | 7 | 5 | ||||||||
| Repeat | 1472 – 1478 | 7 | 6 | ||||||||
| Repeat | 1479 – 1494 | 16 | 7A | ||||||||
| Repeat | 1495 – 1517 | 23 | 7B | ||||||||
| Repeat | 1518 – 1533 | 16 | 8A | ||||||||
| Repeat | 1534 – 1556 | 23 | 8B | ||||||||
| Repeat | 1557 – 1572 | 16 | 9A | ||||||||
| Repeat | 1573 – 1596 | 24 | 9B | ||||||||
| Repeat | 1597 – 1612 | 16 | 10A | ||||||||
| Repeat | 1613 – 1635 | 23 | 10B | ||||||||
| Repeat | 1636 – 1651 | 16 | 11A | ||||||||
| Repeat | 1652 – 1675 | 24 | 11B | ||||||||
| Repeat | 1676 – 1683 | 8 | 12 | ||||||||
| Repeat | 1684 – 1699 | 16 | 13 | ||||||||
| Repeat | 1700 – 1715 | 16 | 14 | ||||||||
| Repeat | 1716 – 1731 | 16 | 15 | ||||||||
| Repeat | 1732 – 1747 | 16 | 16 | ||||||||
| Domain | 4480 – 4690 | 211 | VWFD 4 | ||||||||
| Domain | 4815 – 4886 | 72 | VWFC 1 | ||||||||
| Domain | 4924 – 4991 | 68 | VWFC 2 | ||||||||
| Domain | 5075 – 5160 | 86 | CTCK | ||||||||
| Region | 1401 – 1747 | 347 | Approximate repeats | ||||||||
Sites | |||||||||||
| Site | 4486 – 4487 | 2 | Cleavage; by autolysis; in vitro | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 16 | 1 | Phosphoserine Ref.9 | ||||||||
| Modified residue | 21 | 1 | Phosphoserine Ref.9 | ||||||||
| Modified residue | 25 | 1 | Phosphothreonine Ref.9 | ||||||||
| Glycosylation | 163 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 423 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 670 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 770 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 894 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1139 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1154 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1215 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1230 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1246 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1787 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1820 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4339 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4351 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4362 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4373 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4422 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4438 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4502 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4616 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4627 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4752 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4787 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4881 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4888 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4955 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 4970 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 5019 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 5038 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 5069 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 59 ↔ 67 | By similarity | |||||||||
| Disulfide bond | 5075 ↔ 5122 | By similarity | |||||||||
| Disulfide bond | 5089 ↔ 5136 | By similarity | |||||||||
| Disulfide bond | 5098 ↔ 5152 | By similarity | |||||||||
| Disulfide bond | 5102 ↔ 5154 | By similarity | |||||||||
| Disulfide bond | ? ↔ 5159 | By similarity | |||||||||
Natural variations | |||||||||||
| Natural variant | 58 | 1 | L → P. Corresponds to variant rs2856111 [ dbSNP | Ensembl ]. | VAR_056582 | |||||||
| Natural variant | 116 | 1 | V → M. Corresponds to variant rs11825977 [ dbSNP | Ensembl ]. | VAR_056583 | |||||||
| Natural variant | 832 | 1 | G → S. Corresponds to variant rs11245936 [ dbSNP | Ensembl ]. | VAR_056584 | |||||||
| Natural variant | 1619 | 1 | S → R. Corresponds to variant rs11245947 [ dbSNP | Ensembl ]. | VAR_059531 | |||||||
| Natural variant | 1689 | 1 | P → L. Corresponds to variant rs11245949 [ dbSNP | Ensembl ]. | VAR_059532 | |||||||
| Natural variant | 1768 | 1 | P → H. Corresponds to variant rs34493663 [ dbSNP | Ensembl ]. | VAR_061487 | |||||||
| Natural variant | 2154 | 1 | I → T. Corresponds to variant rs6421972 [ dbSNP | Ensembl ]. | VAR_059533 | |||||||
| Natural variant | 2524 | 1 | T → P. Corresponds to variant rs7480563 [ dbSNP | Ensembl ]. | VAR_059534 | |||||||
| Natural variant | 2524 | 1 | T → S. Corresponds to variant rs7480563 [ dbSNP | Ensembl ]. | VAR_059535 | |||||||
| Natural variant | 2653 | 1 | Q → L. Corresponds to variant rs7126405 [ dbSNP | Ensembl ]. | VAR_059536 | |||||||
| Natural variant | 2653 | 1 | Q → P. Corresponds to variant rs7126405 [ dbSNP | Ensembl ]. | VAR_059537 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 1351 | 1 | H → L in AAA59875. Ref.3 | ||||||||
| Sequence conflict | 1412 | 1 | T → S in AAA59875. Ref.3 | ||||||||
| Sequence conflict | 1449 | 1 | L → P in AAA59875. Ref.3 | ||||||||
| Sequence conflict | 1504 | 1 | M → T in AAA59875. Ref.3 | ||||||||
| Sequence conflict | 4076 – 4083 | 8 | TGTQTPTT → NGLQAPTP Ref.4 | ||||||||
| Sequence conflict | 4087 | 1 | T → S Ref.4 | ||||||||
| Sequence conflict | 4130 – 4131 | 2 | TP → VL Ref.4 | ||||||||
| Sequence conflict | 4138 | 1 | V → M Ref.4 | ||||||||
| Sequence conflict | 4146 – 4152 | 7 | GTQTPTT → STKSTTV Ref.4 | ||||||||
| Sequence conflict | 4163 | 1 | P → A Ref.4 | ||||||||
| Sequence conflict | 4175 – 4176 | 2 | TT → MI Ref.4 | ||||||||
| Sequence conflict | 4179 | 1 | T → S Ref.4 | ||||||||
| Sequence conflict | 4192 – 4194 | 3 | GTQ → TGS Ref.4 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor." Gum J.R. Jr., Hicks J.W., Toribara N.W., Siddiki B., Kim Y.S. J. Biol. Chem. 269:2440-2446(1994) [PubMed: 8300571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Intestine. |
| [2] | "The human MUC2 intestinal mucin has cysteine-rich subdomains located both upstream and downstream of its central repetitive region." Gum J.R. Jr., Hicks J.W., Toribara N.W., Rothe E.-M., Lagace R.E., Kim Y.S. J. Biol. Chem. 267:21375-21383(1992) [PubMed: 1400449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 626-1895 AND 4196-5179. Tissue: Colon. |
| [3] | "MUC-2 human small intestinal mucin gene structure. Repeated arrays and polymorphism." Toribara N.W., Gum J.R. Jr., Culhane P.J., Lagace R.E., Hicks J.W., Petersen G.M., Kim Y.S. J. Clin. Invest. 88:1005-1013(1991) [PubMed: 1885763] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1343-1895 AND 4176-4195. |
| [4] | "Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism." Gum J.R. Jr., Byrd J.C., Hicks J.W., Toribara N.W., Lamport D.T.A., Kim Y.S. J. Biol. Chem. 264:6480-6487(1989) [PubMed: 2703501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4075-4352. |
| [5] | "Human intestinal mucin-like protein (MLP) is homologous with rat MLP in the C-terminal region, and is encoded by a gene on chromosome 11 p 15.5." Xu G., Huan L., Khatri I., Sajjan U.S., McCool D., Wang D., Jones C., Forstner G., Forstner J. Biochem. Biophys. Res. Commun. 183:821-828(1992) [PubMed: 1550588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4487-4627. |
| [6] | "In vivo glycosylation of mucin tandem repeats." Silverman H.S., Parry S., Sutton-Smith M., Burdick M.D., McDermott K., Reid C.J., Batra S.K., Morris H.R., Hollingsworth M.A., Dell A., Harris A. Glycobiology 11:459-471(2001) [PubMed: 11445551] [Abstract] Cited for: STRUCTURE OF O-LINKED CARBOHYDRATES. |
| [7] | "The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment." Godl K., Johansson M.E.V., Lidell M.E., Moergelin M., Karlsson H., Olson F.J., Gum J.R. Jr., Kim Y.S., Hansson G.C. J. Biol. Chem. 277:47248-47256(2002) [PubMed: 12374796] [Abstract] Cited for: SUBUNIT. |
| [8] | "An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway." Lidell M.E., Johansson M.E.V., Hansson G.C. J. Biol. Chem. 278:13944-13951(2003) [PubMed: 12582180] [Abstract] Cited for: AUTOCATALYTIC CLEAVAGE. |
| [9] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-21 AND THR-25, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [10] | "The protein disulfide isomerase AGR2 is essential for production of intestinal mucus." Park S.-W., Zhen G., Verhaeghe C., Nakagami Y., Nguyenvu L.T., Barczak A.J., Killeen N., Erle D.J. Proc. Natl. Acad. Sci. U.S.A. 106:6950-6955(2009) [PubMed: 19359471] [Abstract] Cited for: INTERACTION WITH AGR2. |
| [11] | "Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein." Johansson M.E.V., Thomsson K.A., Hansson G.C. J. Proteome Res. 8:3549-3557(2009) [PubMed: 19432394] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH FCGBP. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | L21998 mRNA. Translation: AAB95295.1. M74027 Genomic DNA. Translation: AAA59875.1. M94131 mRNA. Translation: AAA59163.1. M94132 mRNA. Translation: AAA59164.1. |
| IPI | IPI00027201. |
| PIR | A43932. A49963. |
| RefSeq | NP_002448.2. NM_002457.2. |
| UniGene | Hs.315. |
3D structure databases | |
| ProteinModelPortal | Q02817. |
| SMR | Q02817. Positions 292-362, 4759-4814. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-48824N. |
| IntAct | Q02817. 2 interactions. |
| STRING | Q02817. |
PTM databases | |
| GlycoSuiteDB | Q02817. |
| PhosphoSite | Q02817. |
Polymorphism databases | |
| DMDM | 2506877. |
Proteomic databases | |
| PRIDE | Q02817. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000359061; ENSP00000351956; ENSG00000198788. |
| GeneID | 4583. |
| KEGG | hsa:4583. |
Organism-specific databases | |
| CTD | 4583. |
| GeneCards | GC11P001064. |
| HGNC | HGNC:7512. MUC2. |
| HPA | CAB005317. CAB016275. HPA006197. |
| MIM | 158370. gene. |
| neXtProt | NX_Q02817. |
| PharmGKB | PA31316. |
| GenAtlas | Search... |
Phylogenomic databases | |
| GeneTree | ENSGT00600000084117. |
| HOVERGEN | HBG004380. |
| InParanoid | Q02817. |
Gene expression databases | |
| ArrayExpress | Q02817. |
| Bgee | Q02817. |
| CleanEx | HS_MUC2. |
| Genevestigator | Q02817. |
| GermOnline | ENSG00000198788. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006207. Cys_knot_C. IPR002919. Prot_Inh_CR_TIL. IPR014853. Unchr_dom_Cys-rich. IPR006552. VWC_out. IPR001007. VWF_C. IPR001846. VWF_type-D. [Graphical view] |
| KO | K10955. |
| Pfam | PF08742. C8. 4 hits. PF01826. TIL. 1 hit. PF00094. VWD. 4 hits. [Graphical view] |
| SMART | SM00832. C8. 4 hits. SM00041. CT. 1 hit. SM00214. VWC. 2 hits. SM00215. VWC_out. 1 hit. SM00216. VWD. 4 hits. [Graphical view] |
| SUPFAM | SSF57567. Cysrich_TIL. 5 hits. |
| PROSITE | PS01185. CTCK_1. 1 hit. PS01225. CTCK_2. 1 hit. PS01208. VWFC_1. 2 hits. PS50184. VWFC_2. 2 hits. PS51233. VWFD. 4 hits. [Graphical view] |
| ProtoNet | Search... |
Other | |
| DrugBank | DB01411. Pranlukast. |
| NextBio | 17613. |
| SOURCE | Search... |
Entry information
| Entry name | MUC2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q02817 Secondary accession number(s): Q14878 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with