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Protein

Disintegrin and metalloproteinase domain-containing protein 33

Gene

ADAM33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi133Zinc; in inhibited formBy similarity1
Metal bindingi345Zinc; catalytic1 Publication1
Active sitei346PROSITE-ProRule annotation1
Metal bindingi349Zinc; catalytic1 Publication1
Metal bindingi355Zinc; catalytic1 Publication1

GO - Molecular functioni

  • metalloendopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149451-MONOMER.

Protein family/group databases

MEROPSiM12.244.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 33 (EC:3.4.24.-)
Short name:
ADAM 33
Gene namesi
Name:ADAM33
Synonyms:C20orf153
ORF Names:UNQ873/PRO1891
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:15478. ADAM33.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 701ExtracellularSequence analysisAdd BLAST672
Transmembranei702 – 722HelicalSequence analysisAdd BLAST21
Topological domaini723 – 813CytoplasmicSequence analysisAdd BLAST91

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Asthma (ASTHMA)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionThe 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 wheezing due to spasmodic contraction of the bronchi.
See also OMIM:600807

Keywords - Diseasei

Asthma

Organism-specific databases

DisGeNETi80332.
MIMi600807. phenotype.
OpenTargetsiENSG00000149451.
PharmGKBiPA24526.

Chemistry databases

ChEMBLiCHEMBL6121.
GuidetoPHARMACOLOGYi1673.

Polymorphism and mutation databases

BioMutaiADAM33.
DMDMi20137458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
PropeptideiPRO_000002914230 – 203By similarityAdd BLAST174
ChainiPRO_0000029143204 – 813Disintegrin and metalloproteinase domain-containing protein 33Add BLAST610

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi109N-linked (GlcNAc...)Sequence analysis1
Glycosylationi145N-linked (GlcNAc...)Sequence analysis1
Glycosylationi231N-linked (GlcNAc...)1
Glycosylationi276N-linked (GlcNAc...)1
Disulfide bondi320 ↔ 4041 Publication
Disulfide bondi360 ↔ 3881 Publication
Disulfide bondi361 ↔ 3711 Publication
Glycosylationi448N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi475 ↔ 495By similarity
Disulfide bondi653 ↔ 663By similarity
Disulfide bondi657 ↔ 669By similarity
Disulfide bondi671 ↔ 680By similarity

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ9BZ11.
PeptideAtlasiQ9BZ11.
PRIDEiQ9BZ11.

PTM databases

iPTMnetiQ9BZ11.
PhosphoSitePlusiQ9BZ11.

Expressioni

Tissue specificityi

Expressed in all tissues, except liver, with high expression in placenta, lung, spleen and veins.1 Publication

Gene expression databases

BgeeiENSG00000149451.
CleanExiHS_ADAM33.
ExpressionAtlasiQ9BZ11. baseline and differential.
GenevisibleiQ9BZ11. HS.

Organism-specific databases

HPAiHPA067152.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CLEC7AQ9BXN23EBI-10303054,EBI-3939278
SLC30A2Q9BRI33EBI-10303054,EBI-8644112

Protein-protein interaction databases

BioGridi123243. 40 interactors.
IntActiQ9BZ11. 4 interactors.
MINTiMINT-2876745.
STRINGi9606.ENSP00000348912.

Chemistry databases

BindingDBiQ9BZ11.

Structurei

Secondary structure

1813
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi210 – 218Combined sources9
Helixi220 – 225Combined sources6
Turni226 – 228Combined sources3
Helixi230 – 248Combined sources19
Helixi249 – 251Combined sources3
Beta strandi253 – 262Combined sources10
Beta strandi264 – 266Combined sources3
Helixi275 – 292Combined sources18
Beta strandi296 – 303Combined sources8
Helixi307 – 309Combined sources3
Turni322 – 324Combined sources3
Beta strandi326 – 330Combined sources5
Beta strandi333 – 335Combined sources3
Helixi336 – 350Combined sources15
Helixi366 – 368Combined sources3
Helixi387 – 398Combined sources12
Turni399 – 402Combined sources4
Helixi403 – 406Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R54X-ray1.85A204-409[»]
1R55X-ray1.58A204-409[»]
ProteinModelPortaliQ9BZ11.
SMRiQ9BZ11.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BZ11.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini210 – 409Peptidase M12BPROSITE-ProRule annotationAdd BLAST200
Domaini417 – 503DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini649 – 681EGF-likePROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi131 – 138Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi503 – 648Cys-richAdd BLAST146

Domaini

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.

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9BZ11.
KOiK08616.
OMAiHFLPCAG.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9BZ11.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BZ11-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGWRPRRARG TPLLLLLLLL LLWPVPGAGV LQGHIPGQPV TPHWVLDGQP
60 70 80 90 100
WRTVSLEEPV SKPDMGLVAL EAEGQELLLE LEKNHRLLAP GYIETHYGPD
110 120 130 140 150
GQPVVLAPNH TDHCHYQGRV RGFPDSWVVL CTCSGMSGLI TLSRNASYYL
160 170 180 190 200
RPWPPRGSKD FSTHEIFRME QLLTWKGTCG HRDPGNKAGM TSLPGGPQSR
210 220 230 240 250
GRREARRTRK YLELYIVADH TLFLTRHRNL NHTKQRLLEV ANYVDQLLRT
260 270 280 290 300
LDIQVALTGL EVWTERDRSR VTQDANATLW AFLQWRRGLW AQRPHDSAQL
310 320 330 340 350
LTGRAFQGAT VGLAPVEGMC RAESSGGVST DHSELPIGAA ATMAHEIGHS
360 370 380 390 400
LGLSHDPDGC CVEAAAESGG CVMAAATGHP FPRVFSACSR RQLRAFFRKG
410 420 430 440 450
GGACLSNAPD PGLPVPPALC GNGFVEAGEE CDCGPGQECR DLCCFAHNCS
460 470 480 490 500
LRPGAQCAHG DCCVRCLLKP AGALCRQAMG DCDLPEFCTG TSSHCPPDVY
510 520 530 540 550
LLDGSPCARG SGYCWDGACP TLEQQCQQLW GPGSHPAPEA CFQVVNSAGD
560 570 580 590 600
AHGNCGQDSE GHFLPCAGRD ALCGKLQCQG GKPSLLAPHM VPVDSTVHLD
610 620 630 640 650
GQEVTCRGAL ALPSAQLDLL GLGLVEPGTQ CGPRMVCQSR RCRKNAFQEL
660 670 680 690 700
QRCLTACHSH GVCNSNHNCH CAPGWAPPFC DKPGFGGSMD SGPVQAENHD
710 720 730 740 750
TFLLAMLLSV LLPLLPGAGL AWCCYRLPGA HLQRCSWGCR RDPACSGPKD
760 770 780 790 800
GPHRDHPLGG VHPMELGPTA TGQPWPLDPE NSHEPSSHPE KPLPAVSPDP
810
QADQVQMPRS CLW
Length:813
Mass (Da):87,739
Last modified:March 27, 2002 - v2
Checksum:i90713A99668D5569
GO
Isoform 2 (identifier: Q9BZ11-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     636-661: Missing.

Show »
Length:787
Mass (Da):84,724
Checksum:iCBAF1B08B263A890
GO
Isoform 3 (identifier: Q9BZ11-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:309
Mass (Da):32,554
Checksum:iA60AC04E056CF264
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti802Missing in AAM80482 (PubMed:12110844).Curated1
Sequence conflicti802Missing in AAM80483 (PubMed:12110844).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030512109N → S.1 PublicationCorresponds to variant rs41467948dbSNPEnsembl.1
Natural variantiVAR_029143178T → A.1 PublicationCorresponds to variant rs3918392dbSNPEnsembl.1
Natural variantiVAR_030513272T → M.1 PublicationCorresponds to variant rs41534847dbSNPEnsembl.1
Natural variantiVAR_066337305A → V in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030514316V → I.1 PublicationCorresponds to variant rs41459049dbSNPEnsembl.1
Natural variantiVAR_030515336P → S.1 PublicationCorresponds to variant rs41483049dbSNPEnsembl.1
Natural variantiVAR_030516365A → S.1 PublicationCorresponds to variant rs41419248dbSNPEnsembl.1
Natural variantiVAR_030517441D → E.1 PublicationCorresponds to variant rs41382144dbSNPEnsembl.1
Natural variantiVAR_030518515W → R.1 PublicationCorresponds to variant rs615436dbSNPEnsembl.1
Natural variantiVAR_030519612L → H.1 PublicationCorresponds to variant rs41453444dbSNPEnsembl.1
Natural variantiVAR_030520710V → I.1 PublicationCorresponds to variant rs3918396dbSNPEnsembl.1
Natural variantiVAR_030521739C → G.1 PublicationCorresponds to variant rs41434648dbSNPEnsembl.1
Natural variantiVAR_030522742D → Y.1 PublicationCorresponds to variant rs41462450dbSNPEnsembl.1
Natural variantiVAR_021847764M → T.1 PublicationCorresponds to variant rs2280091dbSNPEnsembl.1
Natural variantiVAR_029144774P → S.1 PublicationCorresponds to variant rs2280090dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0154211 – 478Missing in isoform 3. CuratedAdd BLAST478
Alternative sequenceiVSP_005495636 – 661Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13058.1. [Q9BZ11-1]
RefSeqiNP_001269376.1. NM_001282447.2.
NP_079496.1. NM_025220.4. [Q9BZ11-1]
NP_694882.1. NM_153202.3. [Q9BZ11-2]
UniGeneiHs.173716.

Genome annotation databases

EnsembliENST00000350009; ENSP00000322550; ENSG00000149451. [Q9BZ11-2]
ENST00000356518; ENSP00000348912; ENSG00000149451. [Q9BZ11-1]
GeneIDi80332.
KEGGihsa:80332.
UCSCiuc002wit.5. human. [Q9BZ11-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13058.1. [Q9BZ11-1]
RefSeqiNP_001269376.1. NM_001282447.2.
NP_079496.1. NM_025220.4. [Q9BZ11-1]
NP_694882.1. NM_153202.3. [Q9BZ11-2]
UniGeneiHs.173716.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R54X-ray1.85A204-409[»]
1R55X-ray1.58A204-409[»]
ProteinModelPortaliQ9BZ11.
SMRiQ9BZ11.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123243. 40 interactors.
IntActiQ9BZ11. 4 interactors.
MINTiMINT-2876745.
STRINGi9606.ENSP00000348912.

Chemistry databases

BindingDBiQ9BZ11.
ChEMBLiCHEMBL6121.
GuidetoPHARMACOLOGYi1673.

Protein family/group databases

MEROPSiM12.244.

PTM databases

iPTMnetiQ9BZ11.
PhosphoSitePlusiQ9BZ11.

Polymorphism and mutation databases

BioMutaiADAM33.
DMDMi20137458.

Proteomic databases

PaxDbiQ9BZ11.
PeptideAtlasiQ9BZ11.
PRIDEiQ9BZ11.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000350009; ENSP00000322550; ENSG00000149451. [Q9BZ11-2]
ENST00000356518; ENSP00000348912; ENSG00000149451. [Q9BZ11-1]
GeneIDi80332.
KEGGihsa:80332.
UCSCiuc002wit.5. human. [Q9BZ11-1]

Organism-specific databases

CTDi80332.
DisGeNETi80332.
GeneCardsiADAM33.
HGNCiHGNC:15478. ADAM33.
HPAiHPA067152.
MIMi600807. phenotype.
607114. gene.
neXtProtiNX_Q9BZ11.
OpenTargetsiENSG00000149451.
PharmGKBiPA24526.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9BZ11.
KOiK08616.
OMAiHFLPCAG.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9BZ11.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000149451-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ9BZ11.
GeneWikiiADAM33.
GenomeRNAii80332.
PROiQ9BZ11.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149451.
CleanExiHS_ADAM33.
ExpressionAtlasiQ9BZ11. baseline and differential.
GenevisibleiQ9BZ11. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADA33_HUMAN
AccessioniPrimary (citable) accession number: Q9BZ11
Secondary accession number(s): A0A1K6
, Q5JT75, Q5JT76, Q8N0W6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 27, 2002
Last modified: November 2, 2016
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.