Reviewed,
UniProtKB/Swiss-Prot Q9BZ11 (ADA33_HUMAN)
Last modified
January 19, 2010.
Version 99.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended name: Disintegrin and metalloproteinase domain-containing protein 33 Short name=ADAM 33 EC=3.4.24.- | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 813 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)
| Cofactor | Binds 1 zinc ion per subunit By similarity. |
| Subcellular location | |
| Tissue specificity | Expressed in all tissues, except liver, with high expression in placenta, lung, spleen and veins. Ref.1 |
| Domain | The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme. |
| Post-translational modification | The precursor is cleaved by a furin endopeptidase By similarity. |
| Involvement in disease | Genetic variations in ADAM33 are associated with susceptibility to asthma (ASTHMA) [MIM:600807]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi. |
| Sequence similarities | Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Asthma |
| Domain | EGF-like domain Signal Transmembrane |
| Ligand | Metal-binding Zinc |
| Molecular function | Hydrolase Metalloprotease Protease |
| PTM | Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Zymogen |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | proteolysis Ref.1 Non-traceable author statement. Source: UniProtKB |
| Cellular component | integral to membrane Ref.1 Non-traceable author statement. Source: UniProtKB |
| Molecular function | metalloendopeptidase activity Ref.1 Non-traceable author statement. Source: UniProtKB zinc ion binding Ref.1Non-traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9BZ11-1) 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. | ||||||
| Isoform 2 (identifier: Q9BZ11-2) The sequence of this isoform differs from the canonical sequence as follows: 636-661: Missing. | ||||||
| Note: Described in Ref.1. | ||||||
| Isoform 3 (identifier: Q9BZ11-3) The sequence of this isoform differs from the canonical sequence as follows: 1-478: Missing. 636-661: Missing. | ||||||
| Note: No experimental confirmation available. By similarity with mouse isoform. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 29 | 29 | Potential | ||||||||||||||||||||||||||||||||||
| Propeptide | 30 – 203 | 174 | By similarity | PRO_0000029142 | |||||||||||||||||||||||||||||||||
| Chain | 204 – 813 | 610 | Disintegrin and metalloproteinase domain-containing protein 33 | PRO_0000029143 | |||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||
| Topological domain | 30 – 701 | 672 | Extracellular Potential | ||||||||||||||||||||||||||||||||||
| Transmembrane | 702 – 722 | 21 | Potential | ||||||||||||||||||||||||||||||||||
| Topological domain | 723 – 813 | 91 | Cytoplasmic Potential | ||||||||||||||||||||||||||||||||||
| Domain | 210 – 409 | 200 | Peptidase M12B | ||||||||||||||||||||||||||||||||||
| Domain | 417 – 503 | 87 | Disintegrin | ||||||||||||||||||||||||||||||||||
| Domain | 649 – 681 | 33 | EGF-like | ||||||||||||||||||||||||||||||||||
| Motif | 131 – 138 | 8 | Cysteine switch By similarity | ||||||||||||||||||||||||||||||||||
| Compositional bias | 503 – 648 | 146 | Cys-rich | ||||||||||||||||||||||||||||||||||
Sites | |||||||||||||||||||||||||||||||||||||
| Active site | 346 | 1 | By similarity | ||||||||||||||||||||||||||||||||||
| Metal binding | 133 | 1 | Zinc; in inhibited form By similarity | ||||||||||||||||||||||||||||||||||
| Metal binding | 345 | 1 | Zinc; catalytic | ||||||||||||||||||||||||||||||||||
| Metal binding | 349 | 1 | Zinc; catalytic | ||||||||||||||||||||||||||||||||||
| Metal binding | 355 | 1 | Zinc; catalytic | ||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||
| Modified residue | 269 | 1 | Phosphoserine Ref.6 | ||||||||||||||||||||||||||||||||||
| Glycosylation | 109 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||||||
| Glycosylation | 145 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||||||
| Glycosylation | 231 | 1 | N-linked (GlcNAc...) | ||||||||||||||||||||||||||||||||||
| Glycosylation | 276 | 1 | N-linked (GlcNAc...) | ||||||||||||||||||||||||||||||||||
| Glycosylation | 448 | 1 | N-linked (GlcNAc...) Potential | ||||||||||||||||||||||||||||||||||
| Disulfide bond | 320 ↔ 404 | ||||||||||||||||||||||||||||||||||||
| Disulfide bond | 360 ↔ 388 | ||||||||||||||||||||||||||||||||||||
| Disulfide bond | 361 ↔ 371 | ||||||||||||||||||||||||||||||||||||
| Disulfide bond | 475 ↔ 495 | By similarity | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 653 ↔ 663 | By similarity | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 657 ↔ 669 | By similarity | |||||||||||||||||||||||||||||||||||
| Disulfide bond | 671 ↔ 680 | By similarity | |||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 478 | 478 | Missing in isoform 3. | VSP_015421 | |||||||||||||||||||||||||||||||||
| Alternative sequence | 636 – 661 | 26 | Missing in isoform 2 and isoform 3. | VSP_005495 | |||||||||||||||||||||||||||||||||
| Natural variant | 109 | 1 | N → S: dbSNP rs41467948. Ref.4 | VAR_030512 | |||||||||||||||||||||||||||||||||
| Natural variant | 178 | 1 | T → A: dbSNP rs3918392. Ref.4 | VAR_029143 | |||||||||||||||||||||||||||||||||
| Natural variant | 272 | 1 | T → M: dbSNP rs41534847. Ref.4 | VAR_030513 | |||||||||||||||||||||||||||||||||
| Natural variant | 316 | 1 | V → I: dbSNP rs41459049. Ref.4 | VAR_030514 | |||||||||||||||||||||||||||||||||
| Natural variant | 336 | 1 | P → S: dbSNP rs41483049. Ref.4 | VAR_030515 | |||||||||||||||||||||||||||||||||
| Natural variant | 365 | 1 | A → S: dbSNP rs41419248. Ref.4 | VAR_030516 | |||||||||||||||||||||||||||||||||
| Natural variant | 441 | 1 | D → E: dbSNP rs41382144. Ref.4 | VAR_030517 | |||||||||||||||||||||||||||||||||
| Natural variant | 515 | 1 | W → R: dbSNP rs615436. Ref.4 | VAR_030518 | |||||||||||||||||||||||||||||||||
| Natural variant | 612 | 1 | L → H: dbSNP rs41453444. Ref.4 | VAR_030519 | |||||||||||||||||||||||||||||||||
| Natural variant | 710 | 1 | V → I: dbSNP rs3918396. Ref.4 | VAR_030520 | |||||||||||||||||||||||||||||||||
| Natural variant | 739 | 1 | C → G: dbSNP rs41434648. Ref.4 | VAR_030521 | |||||||||||||||||||||||||||||||||
| Natural variant | 742 | 1 | D → Y: dbSNP rs41462450. Ref.4 | VAR_030522 | |||||||||||||||||||||||||||||||||
| Natural variant | 764 | 1 | M → T: dbSNP rs2280091. Ref.4 | VAR_021847 | |||||||||||||||||||||||||||||||||
| Natural variant | 774 | 1 | P → S: dbSNP rs2280090. Ref.4 | VAR_029144 | |||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||
| Sequence conflict | 802 | 1 | Missing in AAM80482. Ref.2 | ||||||||||||||||||||||||||||||||||
| Sequence conflict | 802 | 1 | Missing in AAM80483. Ref.2 | ||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||
| Beta strand | 210 – 218 | 9 | |||||||||||||||||||||||||||||||||||
| Helix | 220 – 225 | 6 | |||||||||||||||||||||||||||||||||||
| Turn | 226 – 228 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 230 – 249 | 20 | |||||||||||||||||||||||||||||||||||
| Turn | 250 – 252 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 253 – 262 | 10 | |||||||||||||||||||||||||||||||||||
| Beta strand | 264 – 266 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 275 – 292 | 18 | |||||||||||||||||||||||||||||||||||
| Beta strand | 296 – 304 | 9 | |||||||||||||||||||||||||||||||||||
| Turn | 322 – 324 | 3 | |||||||||||||||||||||||||||||||||||
| Beta strand | 326 – 330 | 5 | |||||||||||||||||||||||||||||||||||
| Beta strand | 333 – 335 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 336 – 350 | 15 | |||||||||||||||||||||||||||||||||||
| Helix | 366 – 368 | 3 | |||||||||||||||||||||||||||||||||||
| Helix | 387 – 398 | 12 | |||||||||||||||||||||||||||||||||||
| Turn | 399 – 402 | 4 | |||||||||||||||||||||||||||||||||||
| Helix | 403 – 405 | 3 | |||||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity." Yoshinaka T., Nishii K., Yamada K., Sawada H., Nishiwaki E., Smith K., Yoshino K., Ishiguro H., Higashiyama S. Gene 282:227-236(2002) [PubMed: 11814695] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Testis. |
| [2] | "Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness." Van Eerdewegh P., Little R.D., Dupuis J., Del Mastro R.G., Falls K., Simon J., Torrey D., Pandit S., McKenny J., Braunschweiger K., Walsh A., Liu Z., Hayward B., Folz C., Manning S.P., Bawa A., Saracino L., Thackston M. Keith T.P.Nature 418:426-430(2002) [PubMed: 12110844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), INVOLVEMENT IN ASTHMA. Tissue: Uterus. |
| [3] | "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M.Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [4] | NIEHS SNPs program Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-109; ALA-178; MET-272; ILE-316; SER-336; SER-365; GLU-441; ARG-515; HIS-612; ILE-710; GLY-739; TYR-742; THR-764 AND SER-774. |
| [5] | "The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. Rogers J.Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, MASS SPECTROMETRY. Tissue: Epithelium. |
| [7] | "ADAM33 haplotypes are associated with asthma in a large Australian population." Kedda M.A., Duffy D.L., Bradley B., O'Hehir R.E., Thompson P.J. Eur. J. Hum. Genet. 14:1027-1036(2006) [PubMed: 16773130] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA. |
| [8] | "Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort." Blakey J.D., Sayers I., Ring S.M., Strachan D.P., Hall I.P. Thorax 64:381-387(2009) [PubMed: 19237393] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA. |
| [9] | "Crystal structure of the catalytic domain of human ADAM33." Orth P., Reichert P., Wang W., Prosise W.W., Yarosh-Tomaine T., Hammond G., Ingram R.N., Xiao L., Mirza U.A., Zou J., Strickland C., Taremi S.S., Le H.V., Madison V. J. Mol. Biol. 335:129-137(2004) [PubMed: 14659745] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 204-410 IN COMPLEX WITH METALLOPROTEASE INHIBITOR MARIMASTAT, X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 204-410. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AB055891 mRNA. Translation: BAB83092.1. AF466287 mRNA. Translation: AAM80482.1. AF466288 Genomic DNA. Translation: AAM80483.1. AY358314 mRNA. Translation: AAQ88680.1. DQ995342 Genomic DNA. Translation: ABI97387.1. AL109804, AL356755 Genomic DNA. Translation: CAI18840.1. | ||||||||||||||||||
| IPI | IPI00079482. IPI00218715. IPI00642419. | ||||||||||||||||||
| RefSeq | NP_079496.1. NP_694882.1. | ||||||||||||||||||
| UniGene | Hs.173716 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| IntAct | Q9BZ11. 1 interaction. | ||||||||||||||||||
| STRING | Q9BZ11. | ||||||||||||||||||
Protein family/group databases | |||||||||||||||||||
| MEROPS | M12.244. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | Q9BZ11. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PRIDE | Q9BZ11. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000356518; ENSP00000348912; ENSG00000149451; Homo sapiens. [Genome view] | ||||||||||||||||||
| GeneID | 80332. | ||||||||||||||||||
| KEGG | hsa:80332. | ||||||||||||||||||
| UCSC | uc002wis.1. human. uc002wit.1. human. uc002wiu.1. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 80332. | ||||||||||||||||||
| GeneCards | GC20M003596. | ||||||||||||||||||
| H-InvDB | HIX0015597. | ||||||||||||||||||
| HGNC | HGNC:15478. ADAM33. | ||||||||||||||||||
| MIM | 600807. phenotype. 607114. gene. | ||||||||||||||||||
| PharmGKB | PA24526. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | prNOG17963. | ||||||||||||||||||
| HOGENOM | HBG507118. | ||||||||||||||||||
| HOVERGEN | Q9BZ11. | ||||||||||||||||||
| InParanoid | Q9BZ11. | ||||||||||||||||||
| OMA | GGACLSN. | ||||||||||||||||||
| OrthoDB | EOG91NX68. | ||||||||||||||||||
| PhylomeDB | Q9BZ11. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q9BZ11. | ||||||||||||||||||
| Bgee | Q9BZ11. | ||||||||||||||||||
| CleanEx | HS_ADAM33. | ||||||||||||||||||
| Genevestigator | Q9BZ11. | ||||||||||||||||||
| GermOnline | ENSG00000149451. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view] | ||||||||||||||||||
| Gene3D | G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit. | ||||||||||||||||||
| Pfam | PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view] | ||||||||||||||||||
| PRINTS | PR00289. DISINTEGRIN. | ||||||||||||||||||
| SMART | SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. SM00181. EGF. 1 hit. [Graphical view] | ||||||||||||||||||
| PROSITE | PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view] | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| NextBio | 70880. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | ADA33_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9BZ11 Secondary accession number(s): A0A1K6 Q8N0W6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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 20 Human chromosome 20: 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 |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


