Skip Header

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

Reviewed, UniProtKB/Swiss-Prot Q9P0K1 (ADA22_HUMAN)

Last modified July 7, 2009. Version 84. 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 · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein namesRecommended name:
    Disintegrin and metalloproteinase domain-containing protein 22
      Short name=ADAM 22
Alternative name(s):
    Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2
    Metalloproteinase-disintegrin ADAM22-3
Gene names
Name: ADAM22
Synonyms: MDC2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length906 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

Hide | Top

General annotation (Comments)

Function

Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation. Ref.5 Ref.7 Ref.8

Subunit structure

Interacts through its C-terminal region with YWHAB/14-3-3 beta and YWHAZ/14-3-3 zeta but not with YWHAE/14-3-3 epsilon or YWHAH/14-3-3 eta. Ref.5 Ref.7

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Highly expressed in the brain and in some high-grade but not low-grade gliomas. Detected slightly or not at all in other tissues. Ref.8

Post-translational modification

The precursor is cleaved by a furin endopeptidase By similarity.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 EGF-like domain.

Contains 1 peptidase M12B domain.

Hide | Top

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9P0K1-1)

Also known as: Epsilon;

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: Q9P0K1-2)

Also known as: Delta;

The sequence of this isoform differs from the canonical sequence as follows:
     768-803: Missing.
     859-859: E → EYLNPWFKRDYNVAKWVEDVNKNTEEPYFR
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: Q9P0K1-3)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     860-906: Missing.
Isoform 4 (identifier: Q9P0K1-4)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     768-803: Missing.
     860-906: Missing.
Isoform 5 (identifier: Q9P0K1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     768-803: Missing.

Hide | Top

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 222197 By similarity
PRO_0000029112
Chain223 – 906684Disintegrin and metalloproteinase domain-containing protein 22
PRO_0000029113

Regions

Topological domain223 – 736514Extracellular Potential
Transmembrane737 – 75721 Potential
Topological domain758 – 906149Cytoplasmic Potential
Domain239 – 438200Peptidase M12B
Domain444 – 53188Disintegrin
Domain675 – 71238EGF-like
Compositional bias532 – 678147Cys-rich

Amino acid modifications

Modified residue8341Phosphoserine By similarity
Modified residue8661Phosphoserine By similarity
Modified residue8681Phosphoserine By similarity
Glycosylation1751N-linked (GlcNAc...) Potential
Glycosylation5191N-linked (GlcNAc...) Potential
Glycosylation6341N-linked (GlcNAc...) Potential
Glycosylation6751N-linked (GlcNAc...) Potential
Disulfide bond349 ↔ 433 By similarity
Disulfide bond392 ↔ 417 By similarity
Disulfide bond394 ↔ 401 By similarity
Disulfide bond503 ↔ 523 By similarity
Disulfide bond679 ↔ 694 By similarity
Disulfide bond688 ↔ 700 By similarity
Disulfide bond702 ↔ 711 By similarity

Natural variations

Alternative sequence768 – 80336Missing in isoform 2, isoform 4 and isoform 5.
VSP_005482
Alternative sequence8591E → EYLNPWFKRDYNVAKWVEDV NKNTEEPYFR in isoform 2.
VSP_005484
Alternative sequence860 – 90647Missing in isoform 3 and isoform 4.
VSP_005483
Natural variant811P → R: dbSNP rs2279542. Ref.3 Ref.4
VAR_020057
Natural variant1191H → Y: dbSNP rs4728730.
VAR_051589
Natural variant2071V → I: dbSNP rs17255978.
VAR_051590

Experimental info

Mutagenesis8341S → A: Abolishes interactions with YWHAB and YWHAZ; when associated with A-857. Ref.5 Ref.7
Mutagenesis8571S → A: Abolishes interactions with YWHAB and YWHAZ; when associated with A-834. Ref.5 Ref.7

Hide | Top

Sequences

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

Last modified October 1, 2000. Version 1.
Checksum: 265ECCD0FA6C088B

FASTA906100,433
        10         20         30         40         50         60 
MQAAVAVSVP FLLLCVLGTC PPARCGQAGD ASLMELEKRK ENRFVERQSI VPLRLIYRSG 

        70         80         90        100        110        120 
GEDESRHDAL DTRVRGDLGG PQLTHVDQAS FQVDAFGTSF ILDVVLNHDL LSSEYIERHI 

       130        140        150        160        170        180 
EHGGKTVEVK GGEHCYYQGH IRGNPDSFVA LSTCHGLHGM FYDGNHTYLI EPEENDTTQE 

       190        200        210        220        230        240 
DFHFHSVYKS RLFEFSLDDL PSEFQQVNIT PSKFILKPRP KRSKRQLRRY PRNVEEETKY 

       250        260        270        280        290        300 
IELMIVNDHL MFKKHRLSVV HTNTYAKSVV NMADLIYKDQ LKTRIVLVAM ETWATDNKFA 

       310        320        330        340        350        360 
ISENPLITLR EFMKYRRDFI KEKSDAVHLF SGSQFESSRS GAAYIGGICS LLKGGGVNEF 

       370        380        390        400        410        420 
GKTDLMAVTL AQSLAHNIGI ISDKRKLASG ECKCEDTWSG CIMGDTGYYL PKKFTQCNIE 

       430        440        450        460        470        480 
EYHDFLNSGG GACLFNKPSK LLDPPECGNG FIETGEECDC GTPAECVLEG AECCKKCTLT 

       490        500        510        520        530        540 
QDSQCSDGLC CKKCKFQPMG TVCREAVNDC DIRETCSGNS SQCAPNIHKM DGYSCDGVQG 

       550        560        570        580        590        600 
ICFGGRCKTR DRQCKYIWGQ KVTASDKYCY EKLNIEGTEK GNCGKDKDTW IQCNKRDVLC 

       610        620        630        640        650        660 
GYLLCTNIGN IPRLGELDGE ITSTLVVQQG RTLNCSGGHV KLEEDVDLGY VEDGTPCGPQ 

       670        680        690        700        710        720 
MMCLEHRCLP VASFNFSTCL SSKEGTICSG NGVCSNELKC VCNRHWIGSD CNTYFPHNDD 

       730        740        750        760        770        780 
AKTGITLSGN GVAGTNIIIG IIAGTILVLA LILGITAWGY KNYREQRQLP QGDYVKKPGD 

       790        800        810        820        830        840 
GDSFYSDIPP GVSTNSASSS KKRSNGLSHS WSERIPDTKH ISDICENGRP RSNSWQGNLG 

       850        860        870        880        890        900 
GNKKKIRGKR FRPRSNSTET LSPAKSPSSS TGSIASSRKY PYPMPPLPDE DKKVNRQSAR 


LWETSI

« Hide

Isoform 2 (Delta).

Checksum: 5AB89C260378DFD6
Show »

FASTA899100,341
Isoform 3 (Alpha).

Checksum: 6105B681A1331D55
Show »

FASTA85995,288
Isoform 4 (Beta).

Checksum: E9FD1A9BA99DE0DB
Show »

FASTA82391,492
Isoform 5.

Checksum: C236086AD0BCCA2F
Show »

FASTA87096,637

Hide | Top

References

[1]"Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain."
Sagane K., Ohya Y., Hasegawa Y., Tanaka I.
Biochem. J. 334:93-98(1998) [PubMed: 9693107] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
Tissue: Brain.
[2]"The specific expression of three novel splice variant forms of human metalloprotease-like disintegrin-like cysteine-rich protein 2 gene in brain tissues and gliomas."
Harada T., Nishie A., Torigoe K., Ikezaki K., Shono T., Maehara Y., Kuwano M., Wada M.
Jpn. J. Cancer Res. 91:1001-1006(2000) [PubMed: 11050470] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]"Isolation and tissue specific expression of novel ADAM family from 7q21.1 region."
Wada M., Torigoe K., Harada T., Kuwano M.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), VARIANT ARG-81.
Tissue: Brain.
[4]"The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries."
Poindexter K., Nelson N., DuBose R.F., Black R.A., Cerretti D.P.
Gene 237:61-70(1999) [PubMed: 10524237] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 40-906 (ISOFORM 1), VARIANT ARG-81.
Tissue: Cerebellum.
[5]"The interaction between ADAM 22 and 14-3-3zeta: regulation of cell adhesion and spreading."
Zhu P., Sun Y., Xu R., Sang Y., Zhao J., Liu G., Cai L., Li C., Zhao S.
Biochem. Biophys. Res. Commun. 301:991-999(2003) [PubMed: 12589811] [Abstract]
Cited for: FUNCTION, INTERACTION WITH YWHAZ, MUTAGENESIS OF SER-834 AND SER-857.
[6]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[7]"ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3."
Zhu P., Sang Y., Xu H., Zhao J., Xu R., Sun Y., Xu T., Wang X., Chen L., Feng H., Li C., Zhao S.
Biochem. Biophys. Res. Commun. 331:938-946(2005) [PubMed: 15882968] [Abstract]
Cited for: FUNCTION, INTERACTION WITH YWHAB, MUTAGENESIS OF SER-834 AND SER-857.
[8]"ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain."
D'Abaco G.M., Ng K., Paradiso L., Godde N.J., Kaye A., Novak U.
Neurosurgery 58:179-186(2006) [PubMed: 16385342] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases

AB009671 mRNA. Translation: BAA32349.1.
AB009671 mRNA. Translation: BAA32350.1.
AF155381 mRNA. Translation: AAF73288.1.
AF155382 mRNA. Translation: AAF73289.1.
AF073291 mRNA. Translation: AAF22476.2.
AF158637 mRNA. Translation: AAD55251.1.
IPIIPI00000779.
IPI00220631.
IPI00220632.
IPI00220634.
IPI00220635.
RefSeqNP_057435.2.
NP_068368.2.
NP_068369.1.
UniGeneHs.592282

3D structure databases

HSSPHSSP built from PDB template 1FVL based on UniProtKB P18619.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9P0K1. 9 interactions.

Protein family/group databases

MEROPSM12.978.

PTM databases

PhosphoSiteQ9P0K1.

Proteomic databases

PRIDEQ9P0K1.

Genome annotation databases

EnsemblENSG00000008277. Homo sapiens. [Contig view]
GeneID53616.
UCSCuc003ujk.1. human.
uc003ujl.1. human.
uc003ujn.1. human.
uc003ujo.1. human.

Organism-specific databases

GeneCardsGC07P087401.
H-InvDBHIX0025260.
HIX0039022.
HGNCHGNC:201. ADAM22.
MIM603709. gene.
PharmGKBPA24518.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ9P0K1.
HOVERGENQ9P0K1.

Gene expression databases

ArrayExpressQ9P0K1.
BgeeQ9P0K1.
CleanExHS_ADAM22.
GermOnlineENSG00000008277. 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.
IPR013111. EGF_extracell.
IPR006025. Pept_M_Zn_BS.
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.
PF07974. EGF_2. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSPR00289. DISINTEGRIN.
ProDomPD000664. Disintegrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
SM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. False negative.
PS50026. EGF_3. False negative.
PS00142. ZINC_PROTEASE. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio56096.
SOURCESearch...

Hide | Top

Entry information

Entry nameADA22_HUMAN
AccessionPrimary (citable) accession number: Q9P0K1
Secondary accession number(s): O75075 expand/collapse secondary AC list , O75076, Q9P0K2, Q9UIA1, Q9UKK2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: October 1, 2000
Last modified: July 7, 2009
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Hide | Top

Relevant documents

Human chromosome 7

Human chromosome 7: 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

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 · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents