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Reviewed, UniProtKB/Swiss-Prot P58335 (ANTR2_HUMAN)

Last modified March 2, 2010. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
Anthrax toxin receptor 2
Alternative name(s):
Capillary morphogenesis gene 2 protein
Short name=CMG-2
Gene names
Name:ANTXR2
Synonyms:CMG2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length489 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Necessary for cellular interactions with laminin and the extracellular matrix. Ref.1 Ref.14

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. Ref.13

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. Ref.14 Ref.13

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. Ref.14 Ref.13

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.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

LRP6O755811EBI-456840,EBI-910915
pagAP134234EBI-456840,EBI-456868From a different organism.

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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.
Note: 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.
Note: 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.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 4 (identifier: P58335-4)

The sequence of this isoform differs from the canonical sequence as follows:
     477-489: VCIWECIEKELTA → GRCINFSRVPSQ

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 489456Anthrax toxin receptor 2
PRO_0000002694

Regions

Topological domain34 – 318285Extracellular Potential
Transmembrane319 – 34123 Potential
Topological domain342 – 489148Cytoplasmic Potential
Domain44 – 213170VWFA
Compositional bias352 – 3609Poly-Pro
Compositional bias362 – 3665Poly-Glu

Sites

Metal binding521Divalent metal cation
Metal binding541Divalent metal cation
Metal binding1181Divalent metal cation

Amino acid modifications

Modified residue1471Phosphothreonine Ref.9
Glycosylation2501N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...) Potential
Disulfide bond39 ↔ 218

Natural variations

Alternative sequence213 – 315103Missing in isoform 2.
VSP_008343
Alternative sequence290 – 32233TLDVS…GIAAI → WGLTVTQAGVKWHDLTHCTF GLSGSGDPPTSAS in isoform 3.
VSP_008344
Alternative sequence323 – 489167Missing in isoform 3.
VSP_008345
Alternative sequence477 – 48913VCIWE…KELTA → GRCINFSRVPSQ in isoform 4.
VSP_008346
Natural variant451L → P in ISH. Ref.13
VAR_022687
Natural variant1051G → D in JHF. Ref.14
VAR_022688
Natural variant1891I → T in ISH. Ref.14 Ref.13
VAR_022689
Natural variant2181C → R in ISH. Ref.13
VAR_022690
Natural variant2931V → VQ in JHF. Ref.13
VAR_022691
Natural variant3291L → R in JHF. Ref.14
VAR_022692
Natural variant3571P → A: dbSNP rs12647691. Ref.13 Ref.3 Ref.5
VAR_022693
Natural variant3811Y → C in JHF. Ref.13
VAR_022694

Secondary structure

1 ......................... 489
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 4.
Checksum: B9F679DB75B6E2B7

FASTA48953,692
        10         20         30         40         50         60 
MVAERSPARS PGSWLFPGLW LLVLSGPGGL LRAQEQPSCR RAFDLYFVLD KSGSVANNWI 

        70         80         90        100        110        120 
EIYNFVQQLA ERFVSPEMRL SFIVFSSQAT IILPLTGDRG KISKGLEDLK RVSPVGETYI 

       130        140        150        160        170        180 
HEGLKLANEQ IQKAGGLKTS SIIIALTDGK LDGLVPSYAE KEAKISRSLG ASVYCVGVLD 

       190        200        210        220        230        240 
FEQAQLERIA DSKEQVFPVK GGFQALKGII NSILAQSCTE ILELQPSSVC VGEEFQIVLS 

       250        260        270        280        290        300 
GRGFMLGSRN GSVLCTYTVN ETYTTSVKPV SVQLNSMLCP APILNKAGET LDVSVSFNGG 

       310        320        330        340        350        360 
KSVISGSLIV TATECSNGIA AIIVILVLLL LLGIGLMWWF WPLCCKVVIK DPPPPPPPAP 

       370        380        390        400        410        420 
KEEEEEPLPT KKWPTVDASY YGGRGVGGIK RMEVRWGDKG STEEGARLEK AKNAVVKIPE 

       430        440        450        460        470        480 
ETEEPIRPRP PRPKPTHQPP QTKWYTPIKG RLDALWALLR RQYDRVSLMR PQEGDEVCIW 


ECIEKELTA

« Hide

Isoform 2.

Checksum: 0F9B2D6688EAB17A
Show »

FASTA38642,919
Isoform 3.

Checksum: 19D061AAFBE6CFF8
Show »

FASTA32234,763
Isoform 4.

Checksum: 1FF5E0144CE750F6
Show »

FASTA48853,519

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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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., 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 R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Aortic endothelium.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
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]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-147, MASS SPECTROMETRY.
Tissue: T-cell.
[10]"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.
[11]"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.
[12]"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.
[13]"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. expand/collapse author list , Superti-Furga A., Futreal P.A., 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 ALA-357, TISSUE SPECIFICITY.
[14]"Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis."
Dowling O., Difeo A., Ramirez M.C., Tukel T., Narla G., Bonafe L., Kayserili H., Yuksel-Apak M., Paller A.S., Norton K., Teebi A.S., Grum-Tokars V., Martin G.S., Davis G.E., Glucksman M.J., Martignetti J.A.
Am. J. Hum. Genet. 73:957-966(2003) [PubMed: 12973667] [Abstract]
Cited for: VARIANT ISH THR-189, VARIANTS JHF ASP-105 AND ARG-329, FUNCTION.
[15]"Capillary morphogenesis gene-2 mutation in infantile systemic hyalinosis: ultrastructural study and mutation analysis in a Taiwanese infant."
Lee J.Y.-Y., Tsai Y.-M., Chao S.-C., Tu Y.-F.
Clin. Exp. Dermatol. 30:176-179(2005) [PubMed: 15725249] [Abstract]
Cited for: INVOLVEMENT IN INFANTILE SYSTEMIC HYALINOSIS.
+Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AY040326 mRNA. Translation: AAK77222.1.
AY233452 mRNA. Translation: AAP04016.1.
AK055636 mRNA. Translation: BAB70976.1. Different initiation.
AK091721 mRNA. Translation: BAC03731.1.
AB209913 mRNA. Translation: BAD93150.1. Different initiation.
AL832851 mRNA. Translation: CAI46157.2.
BC034001 mRNA. Translation: AAH34001.1. Different initiation.
IPIIPI00036552.
IPI00375552.
IPI00375555.
IPI00375556.
RefSeqNP_001139266.1.
NP_477520.2.
UniGeneHs.162963

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SHTX-ray1.81X38-217[»]
1SHUX-ray1.50X38-218[»]
1T6BX-ray2.50Y40-212[»]
1TZNX-ray4.30a/b/c/d/e/f/g/h/i/j/k/l/m/o38-218[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP58335. 3 interactions.
STRINGP58335.

Proteomic databases

PRIDEP58335.

Genome annotation databases

EnsemblENST00000307333; ENSP00000306185; ENSG00000163297; Homo sapiens. [Genome view]
GeneID118429.
KEGGhsa:118429.
UCSCuc003hly.2. human.
uc003hlz.2. human.
uc010ijn.1. human.

Organism-specific databases

CTD118429.
GeneCardsGC04M081045.
HGNCHGNC:21732. ANTXR2.
MIM228600. phenotype.
236490. phenotype.
608041. gene.
Orphanet2028. Hyaline fibromatosis, juvenile.
2176. Hyalinosis, infantile systemic.
PharmGKBPA128394752.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG050514.
InParanoidP58335.

Enzyme and pathway databases

Pathway_Interaction_DBanthraxpathway. Cellular roles of Anthrax toxin.

Gene expression databases

ArrayExpressP58335.
BgeeP58335.
CleanExHS_ANTXR2.
GenevestigatorP58335.
GermOnlineENSG00000163297. Homo sapiens.

Family and domain databases

InterProIPR017360. Anthrax_toxin_rcpt_2.
IPR008399. Anthrax_toxin_rcpt_C.
IPR008400. Anthrax_toxin_rcpt_extracel.
IPR002035. VWF_A.
[Graphical view]
PfamPF05586. Ant_C. 1 hit.
PF05587. Anth_Ig. 1 hit.
PF00092. VWA. 1 hit.
[Graphical view]
PIRSFPIRSF038023. Anthrax_toxin_receptor_2. 1 hit.
ProDomPD377005. Anthrax_toxin_rcpt_C. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00327. VWA. 1 hit.
[Graphical view]
PROSITEPS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

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Entry information

Entry nameANTR2_HUMAN
AccessionPrimary (citable) accession number: P58335
Secondary accession number(s): Q59E98 expand/collapse secondary AC list , Q5JPE9, Q86UI1, Q8N4J8, Q8NB13, Q96NC7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: February 20, 2007
Last modified: March 2, 2010
This is version 94 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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SIMILARITY comments

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents