Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q9BZ11 (ADA33_HUMAN)

Last modified January 19, 2010. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Disintegrin and metalloproteinase domain-containing protein 33
      Short name=ADAM 33
    EC=3.4.24.-
Gene names
Name: ADAM33
ORF Names: UNQ873/PRO1891
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length813 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

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 componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAsthma
   DomainEGF-like domain
Signal
Transmembrane
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processproteolysis Ref.1

Non-traceable author statement. Source: UniProtKB

   Cellular componentintegral to membrane Ref.1

Non-traceable author statement. Source: UniProtKB

   Molecular functionmetalloendopeptidase activity Ref.1

Non-traceable author statement. Source: UniProtKB

zinc ion binding Ref.1

Non-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Propeptide30 – 203174 By similarity
PRO_0000029142
Chain204 – 813610Disintegrin and metalloproteinase domain-containing protein 33
PRO_0000029143

Regions

Topological domain30 – 701672Extracellular Potential
Transmembrane702 – 72221 Potential
Topological domain723 – 81391Cytoplasmic Potential
Domain210 – 409200Peptidase M12B
Domain417 – 50387Disintegrin
Domain649 – 68133EGF-like
Motif131 – 1388Cysteine switch By similarity
Compositional bias503 – 648146Cys-rich

Sites

Active site3461 By similarity
Metal binding1331Zinc; in inhibited form By similarity
Metal binding3451Zinc; catalytic
Metal binding3491Zinc; catalytic
Metal binding3551Zinc; catalytic

Amino acid modifications

Modified residue2691Phosphoserine Ref.6
Glycosylation1091N-linked (GlcNAc...) Potential
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation2311N-linked (GlcNAc...)
Glycosylation2761N-linked (GlcNAc...)
Glycosylation4481N-linked (GlcNAc...) Potential
Disulfide bond320 ↔ 404
Disulfide bond360 ↔ 388
Disulfide bond361 ↔ 371
Disulfide bond475 ↔ 495 By similarity
Disulfide bond653 ↔ 663 By similarity
Disulfide bond657 ↔ 669 By similarity
Disulfide bond671 ↔ 680 By similarity

Natural variations

Alternative sequence1 – 478478Missing in isoform 3.
VSP_015421
Alternative sequence636 – 66126Missing in isoform 2 and isoform 3.
VSP_005495
Natural variant1091N → S: dbSNP rs41467948. Ref.4
VAR_030512
Natural variant1781T → A: dbSNP rs3918392. Ref.4
VAR_029143
Natural variant2721T → M: dbSNP rs41534847. Ref.4
VAR_030513
Natural variant3161V → I: dbSNP rs41459049. Ref.4
VAR_030514
Natural variant3361P → S: dbSNP rs41483049. Ref.4
VAR_030515
Natural variant3651A → S: dbSNP rs41419248. Ref.4
VAR_030516
Natural variant4411D → E: dbSNP rs41382144. Ref.4
VAR_030517
Natural variant5151W → R: dbSNP rs615436. Ref.4
VAR_030518
Natural variant6121L → H: dbSNP rs41453444. Ref.4
VAR_030519
Natural variant7101V → I: dbSNP rs3918396. Ref.4
VAR_030520
Natural variant7391C → G: dbSNP rs41434648. Ref.4
VAR_030521
Natural variant7421D → Y: dbSNP rs41462450. Ref.4
VAR_030522
Natural variant7641M → T: dbSNP rs2280091. Ref.4
VAR_021847
Natural variant7741P → S: dbSNP rs2280090. Ref.4
VAR_029144

Experimental info

Sequence conflict8021Missing in AAM80482. Ref.2
Sequence conflict8021Missing in AAM80483. Ref.2

Secondary structure

............................. 813
Helix Strand Turn

Details...

Sequences

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

Last modified March 27, 2002. Version 2.
Checksum: 90713A99668D5569

FASTA81387,739
        10         20         30         40         50         60 
MGWRPRRARG TPLLLLLLLL LLWPVPGAGV LQGHIPGQPV TPHWVLDGQP WRTVSLEEPV 

        70         80         90        100        110        120 
SKPDMGLVAL EAEGQELLLE LEKNHRLLAP GYIETHYGPD GQPVVLAPNH TDHCHYQGRV 

       130        140        150        160        170        180 
RGFPDSWVVL CTCSGMSGLI TLSRNASYYL RPWPPRGSKD FSTHEIFRME QLLTWKGTCG 

       190        200        210        220        230        240 
HRDPGNKAGM TSLPGGPQSR GRREARRTRK YLELYIVADH TLFLTRHRNL NHTKQRLLEV 

       250        260        270        280        290        300 
ANYVDQLLRT LDIQVALTGL EVWTERDRSR VTQDANATLW AFLQWRRGLW AQRPHDSAQL 

       310        320        330        340        350        360 
LTGRAFQGAT VGLAPVEGMC RAESSGGVST DHSELPIGAA ATMAHEIGHS LGLSHDPDGC 

       370        380        390        400        410        420 
CVEAAAESGG CVMAAATGHP FPRVFSACSR RQLRAFFRKG GGACLSNAPD PGLPVPPALC 

       430        440        450        460        470        480 
GNGFVEAGEE CDCGPGQECR DLCCFAHNCS LRPGAQCAHG DCCVRCLLKP AGALCRQAMG 

       490        500        510        520        530        540 
DCDLPEFCTG TSSHCPPDVY LLDGSPCARG SGYCWDGACP TLEQQCQQLW GPGSHPAPEA 

       550        560        570        580        590        600 
CFQVVNSAGD AHGNCGQDSE GHFLPCAGRD ALCGKLQCQG GKPSLLAPHM VPVDSTVHLD 

       610        620        630        640        650        660 
GQEVTCRGAL ALPSAQLDLL GLGLVEPGTQ CGPRMVCQSR RCRKNAFQEL QRCLTACHSH 

       670        680        690        700        710        720 
GVCNSNHNCH CAPGWAPPFC DKPGFGGSMD SGPVQAENHD TFLLAMLLSV LLPLLPGAGL 

       730        740        750        760        770        780 
AWCCYRLPGA HLQRCSWGCR RDPACSGPKD GPHRDHPLGG VHPMELGPTA TGQPWPLDPE 

       790        800        810 
NSHEPSSHPE KPLPAVSPDP QADQVQMPRS CLW 

« Hide

Isoform 2.

Checksum: CBAF1B08B263A890
Show »

FASTA78784,724
Isoform 3.

Checksum: A60AC04E056CF264
Show »

FASTA30932,554

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. expand/collapse author list , Benchekroun Y., Capparell N., Wang M., Adair R., Feng Y., Dubois J., FitzGerald M.G., Huang H., Gibson R., Allen K.M., Pedan A., Danzig M.R., Umland S.P., Egan R.W., Cuss F.M., Rorke S., Clough J.B., Holloway J.W., Holgate S.T., 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. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., 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. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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.

Web resources

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.
IPIIPI00079482.
IPI00218715.
IPI00642419.
RefSeqNP_079496.1.
NP_694882.1.
UniGeneHs.173716

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R54X-ray1.85A204-409[»]
1R55X-ray1.58A204-409[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ9BZ11. 1 interaction.
STRINGQ9BZ11.

Protein family/group databases

MEROPSM12.244.

PTM databases

PhosphoSiteQ9BZ11.

Proteomic databases

PRIDEQ9BZ11.

Genome annotation databases

EnsemblENST00000356518; ENSP00000348912; ENSG00000149451; Homo sapiens. [Genome view]
GeneID80332.
KEGGhsa:80332.
UCSCuc002wis.1. human.
uc002wit.1. human.
uc002wiu.1. human.

Organism-specific databases

CTD80332.
GeneCardsGC20M003596.
H-InvDBHIX0015597.
HGNCHGNC:15478. ADAM33.
MIM600807. phenotype.
607114. gene.
PharmGKBPA24526.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17963.
HOGENOMHBG507118.
HOVERGENQ9BZ11.
InParanoidQ9BZ11.
OMAGGACLSN.
OrthoDBEOG91NX68.
PhylomeDBQ9BZ11.

Gene expression databases

ArrayExpressQ9BZ11.
BgeeQ9BZ11.
CleanExHS_ADAM33.
GenevestigatorQ9BZ11.
GermOnlineENSG00000149451. Homo sapiens.

Family and domain databases

InterProIPR006586. 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]
Gene3DG3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
PfamPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSPR00289. DISINTEGRIN.
SMARTSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
SM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS50215. 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]
ProtoNetSearch...

Other Resources

NextBio70880.
SOURCESearch...

Entry information

Entry nameADA33_HUMAN
AccessionPrimary (citable) accession number: Q9BZ11
Secondary accession number(s): A0A1K6 expand/collapse secondary AC list , Q5JT75, Q5JT76, Q8N0W6
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 27, 2002
Last modified: January 19, 2010
This is version 99 of the entry and version 2 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.

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

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