Reviewed,
UniProtKB/Swiss-Prot P58335 (ANTR2_HUMAN)
Last modified
November 25, 2008.
Version 78.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Anthrax toxin receptor 2 Alternative name(s): Capillary morphogenesis gene 2 protein Short name=CMG-2 | ||||
| Gene names |
| ||||
| 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 | 489 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 | Necessary for cellular interactions with laminin and the extracellular matrix. |
| Subunit structure | Binds laminin, and possibly also collagen type IV. Binds to the protective antigen (PA) of Bacillus anthracis in a divalent cation-dependent manner, with the following preference: calcium > manganese > magnesium > zinc. Binding of PA leads to heptamerization of the receptor-PA complex. |
| Subcellular location | Isoform 1: Cell membrane; Single-pass type I membrane protein. Note= Expressed at the cell surface. Isoform 2: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Note= Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane. Isoform 3: Secreted. |
| Tissue specificity | Expressed in prostate, thymus, ovary, testis, pancreas, colon, heart, kidney, lung, liver, peripheral blood leukocytes, placenta, skeletal muscle, small intestine and spleen. |
| Domain | Binding to PA seems to be effected through the VWA domain. |
| Involvement in disease | Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures. Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility. |
| Miscellaneous | Upon binding of the protective antigen (PA) of Bacillus anthracis the complex moves to glycosphingolipid-rich lipid rafts, where it is internalized via a clathrin-dependent pathway. |
| Sequence similarities | Belongs to the ATR family. Contains 1 VWFA domain. |
Ontologies
Keywords | |
|---|---|
| Cellular component | Cell membrane Endoplasmic reticulum Membrane Secreted |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| Domain | Signal Transmembrane |
| Ligand | Metal-binding |
| Molecular function | Receptor |
| PTM | Glycoprotein |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Cellular component | endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular regionInferred from electronic annotation. Source: UniProtKB-KW integral to membraneInferred from electronic annotation. Source: InterPro plasma membraneInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein bindingInferred from physical interaction. Source: IntAct receptor activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| LRP6 | O75581 | 1 | EBI-456840,EBI-910915 | |
| pagA | P13423 | 4 | EBI-456840,EBI-456868 | From a different organism. |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P58335-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Notes: Expressed at the cell surface. | ||||||
| Isoform 2 (identifier: P58335-2) The sequence of this isoform differs from the canonical sequence as follows: 213-315: Missing. | ||||||
| Notes: Expressed predominantly within the endoplasmic reticulum and not at the plasma membrane. | ||||||
| Isoform 3 (identifier: P58335-3) The sequence of this isoform differs from the canonical sequence as follows: 290-322: TLDVSVSFNGGKSVISGSLIVTATECSNGIAAI → WGLTVTQAGVKWHDLTHCTFGLSGSGDPPTSAS 323-489: Missing. | ||||||
| Notes: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: P58335-4) The sequence of this isoform differs from the canonical sequence as follows: 477-489: VCIWECIEKELTA → GRCINFSRVPSQ | ||||||
| Notes: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 33 | 33 | Potential | ||||||||||||||||||||||||||||||
| Chain | 34 – 489 | 456 | Anthrax toxin receptor 2 | PRO_0000002694 | |||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||
| Topological domain | 34 – 318 | 285 | Extracellular Potential | ||||||||||||||||||||||||||||||
| Transmembrane | 319 – 341 | 23 | Potential | ||||||||||||||||||||||||||||||
| Topological domain | 342 – 489 | 148 | Cytoplasmic Potential | ||||||||||||||||||||||||||||||
| Domain | 44 – 213 | 170 | VWFA | ||||||||||||||||||||||||||||||
| Compositional bias | 352 – 360 | 9 | Poly-Pro | ||||||||||||||||||||||||||||||
| Compositional bias | 362 – 366 | 5 | Poly-Glu | ||||||||||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||||||||
| Metal binding | 52 | 1 | Divalent metal cation | ||||||||||||||||||||||||||||||
| Metal binding | 54 | 1 | Divalent metal cation | ||||||||||||||||||||||||||||||
| Metal binding | 118 | 1 | Divalent metal cation | ||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||
| Glycosylation | 250 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||
| Glycosylation | 260 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||
| Disulfide bond | 39 ↔ 218 | ||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||
| Alternative sequence | 213 – 315 | 103 | Missing in isoform 2. | VSP_008343 | |||||||||||||||||||||||||||||
| Alternative sequence | 290 – 322 | 33 | TLDVS…GIAAI → WGLTVTQAGVKWHDLTHCTF GLSGSGDPPTSAS in isoform 3. | VSP_008344 | |||||||||||||||||||||||||||||
| Alternative sequence | 323 – 489 | 167 | Missing in isoform 3. | VSP_008345 | |||||||||||||||||||||||||||||
| Alternative sequence | 477 – 489 | 13 | VCIWE…KELTA → GRCINFSRVPSQ in isoform 4. | VSP_008346 | |||||||||||||||||||||||||||||
| Natural variant | 45 | 1 | L → P in ISH. | VAR_022687 | |||||||||||||||||||||||||||||
| Natural variant | 105 | 1 | G → D in JHF. | VAR_022688 | |||||||||||||||||||||||||||||
| Natural variant | 189 | 1 | I → T in ISH. | VAR_022689 | |||||||||||||||||||||||||||||
| Natural variant | 218 | 1 | C → R in ISH. | VAR_022690 | |||||||||||||||||||||||||||||
| Natural variant | 293 | 1 | V → VQ in JHF. | VAR_022691 | |||||||||||||||||||||||||||||
| Natural variant | 329 | 1 | L → R in JHF. | VAR_022692 | |||||||||||||||||||||||||||||
| Natural variant | 357 | 1 | P → A: dbSNP rs12647691. | VAR_022693 | |||||||||||||||||||||||||||||
| Natural variant | 381 | 1 | Y → C in JHF. | VAR_022694 | |||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||
| Beta strand | 43 – 50 | 8 | |||||||||||||||||||||||||||||||
| Helix | 53 – 58 | 6 | |||||||||||||||||||||||||||||||
| Helix | 59 – 72 | 14 | |||||||||||||||||||||||||||||||
| Beta strand | 79 – 96 | 18 | |||||||||||||||||||||||||||||||
| Helix | 99 – 110 | 12 | |||||||||||||||||||||||||||||||
| Helix | 120 – 134 | 15 | |||||||||||||||||||||||||||||||
| Helix | 136 – 138 | 3 | |||||||||||||||||||||||||||||||
| Beta strand | 139 – 147 | 9 | |||||||||||||||||||||||||||||||
| Helix | 155 – 168 | 14 | |||||||||||||||||||||||||||||||
| Beta strand | 172 – 177 | 6 | |||||||||||||||||||||||||||||||
| Helix | 183 – 189 | 7 | |||||||||||||||||||||||||||||||
| Beta strand | 190 – 192 | 3 | |||||||||||||||||||||||||||||||
| Helix | 193 – 195 | 3 | |||||||||||||||||||||||||||||||
| Beta strand | 196 – 204 | 9 | |||||||||||||||||||||||||||||||
| Helix | 205 – 214 | 10 | |||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling." Bell S.E., Mavila A., Salazar R., Bayless K.J., Kanagala S., Maxwell S.A., Davis G.E. J. Cell Sci. 114:2755-2773(2001) [PubMed: 11683410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION. |
| [2] | "Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor." Scobie H.M., Rainey G.J.A., Bradley K.A., Young J.A.T. Proc. Natl. Acad. Sci. U.S.A. 100:5170-5174(2003) [PubMed: 12700348] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH ANTHRAX TOXIN. Tissue: Placenta. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 78-489 (ISOFORM 3), VARIANT ALA-357. Tissue: Synovial cell. |
| [4] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Aortic endothelium. |
| [5] | The German cDNA consortium Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 137-489 (ISOFORM 4), VARIANT ALA-357. Tissue: Lymph node. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 248-489 (ISOFORM 4). Tissue: Brain. |
| [7] | "Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process." Abrami L., Liu S., Cosson P., Leppla S.H., van der Goot F.G. J. Cell Biol. 160:321-328(2003) [PubMed: 12551953] [Abstract] Cited for: INTERACTION WITH ANTHRAX TOXIN, CLATHRIN-DEPENDENT INTERNALIZATION. |
| [8] | "Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway." Abrami L., Lindsay M., Parton R.G., Leppla S.H., van der Goot F.G. J. Cell Biol. 166:645-651(2004) [PubMed: 15337774] [Abstract] Cited for: INTERNALIZATION. |
| [9] | "Crystal structure of a complex between anthrax toxin and its host cell receptor." Santelli E., Bankston L.A., Leppla S.H., Liddington R.C. Nature 430:905-908(2004) [PubMed: 15243628] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-212 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS. |
| [10] | "Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor." Lacy D.B., Wigelsworth D.J., Scobie H.M., Young J.A.T., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 101:6367-6372(2004) [PubMed: 15079089] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 38-217. |
| [11] | "Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation." Lacy D.B., Wigelsworth D.J., Melnyk R.A., Harrison S.C., Collier R.J. Proc. Natl. Acad. Sci. U.S.A. 101:13147-13151(2004) [PubMed: 15326297] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 38-218 OF COMPLEX WITH THE PROTECTIVE ANTIGEN OF BACILLUS ANTHRACIS. |
| [12] | "Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis." Hanks S., Adams S., Douglas J., Arbour L., Atherton D.J., Balci S., Bode H., Campbell M.E., Feingold M., Keser G., Kleijer W., Mancini G., McGrath J.A., Muntoni F., Nanda A., Teare M.D., Warman M., Pope F.M. Rahman N.Am. J. Hum. Genet. 73:791-800(2003) [PubMed: 14508707] [Abstract] Cited for: VARIANTS ISH PRO-45; THR-189 AND ARG-218, VARIANTS JHF GLN-293 INS AND CYS-381, VARIANT |

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