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Q9P0K1 (ADA22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 22

Short name=ADAM 22
Alternative name(s):
Metalloproteinase-disintegrin ADAM22-3
Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2
Gene names
Name:ADAM22
Synonyms:MDC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

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. Neuronal receptor for LGI1. Ref.6 Ref.8 Ref.9

Subunit structure

Interacts with LGI1 and can bind to LGI4 By similarity. 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.6 Ref.8

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.9

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.

Binary interactions

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 → EYLNPWFKRDYNVAKWVEDVNKNTEGPYFR
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.

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

Amino acid modifications

Modified residue8341Phosphoserine Ref.10
Glycosylation1751N-linked (GlcNAc...) Potential
Glycosylation5191N-linked (GlcNAc...) Ref.11
Glycosylation6341N-linked (GlcNAc...) Ref.11
Glycosylation6751N-linked (GlcNAc...) Ref.11
Disulfide bond349 ↔ 433 Ref.11
Disulfide bond392 ↔ 417 Ref.11
Disulfide bond394 ↔ 401 Ref.11
Disulfide bond447 ↔ 477 Ref.11
Disulfide bond458 ↔ 474 Ref.11
Disulfide bond460 ↔ 466 Ref.11
Disulfide bond473 ↔ 494 Ref.11
Disulfide bond485 ↔ 491 Ref.11
Disulfide bond490 ↔ 516 Ref.11
Disulfide bond503 ↔ 523 Ref.11
Disulfide bond510 ↔ 542 Ref.11
Disulfide bond535 ↔ 547 Ref.11
Disulfide bond554 ↔ 605 Ref.11
Disulfide bond569 ↔ 635 Ref.11
Disulfide bond583 ↔ 593 Ref.11
Disulfide bond600 ↔ 663 Ref.11
Disulfide bond657 ↔ 668 Ref.11
Disulfide bond679 ↔ 694 Ref.11
Disulfide bond688 ↔ 700 Ref.11
Disulfide bond702 ↔ 711 Ref.11

Natural variations

Alternative sequence768 – 80336Missing in isoform 2, isoform 4 and isoform 5.
VSP_005482
Alternative sequence8591E → EYLNPWFKRDYNVAKWVEDV NKNTEGPYFR in isoform 2.
VSP_005484
Alternative sequence860 – 90647Missing in isoform 3 and isoform 4.
VSP_005483
Natural variant811P → R. Ref.3 Ref.5
Corresponds to variant rs2279542 [ dbSNP | Ensembl ].
VAR_020057
Natural variant1191H → Y.
Corresponds to variant rs4728730 [ dbSNP | Ensembl ].
VAR_051589
Natural variant2071V → I.
Corresponds to variant rs17255978 [ dbSNP | Ensembl ].
VAR_051590

Experimental info

Mutagenesis8341S → A: Abolishes interactions with YWHAB and YWHAZ; when associated with A-857. Ref.6 Ref.8
Mutagenesis8571S → A: Abolishes interactions with YWHAB and YWHAZ; when associated with A-834. Ref.6 Ref.8
Isoform 2:
Sequence conflict8481G → E in AAF73288. Ref.2

Secondary structure

................................................................................ 906
Helix Strand Turn

Details...

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) [UniParc].

Checksum: 5AB89C258ECE0736
Show »

FASTA899100,269
Isoform 3 (Alpha) [UniParc].

Checksum: 6105B681A1331D55
Show »

FASTA85995,288
Isoform 4 (Beta) [UniParc].

Checksum: E9FD1A9BA99DE0DB
Show »

FASTA82391,492
Isoform 5 [UniParc].

Checksum: C236086AD0BCCA2F
Show »

FASTA87096,637

References

« Hide 'large scale' 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] [Europe PMC] [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] [Europe PMC] [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 DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 40-906 (ISOFORM 1), VARIANT ARG-81.
Tissue: Cerebellum.
[6]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH YWHAZ, MUTAGENESIS OF SER-834 AND SER-857.
[7]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH YWHAB, MUTAGENESIS OF SER-834 AND SER-857.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-834, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase: insights on ADAM function."
Liu H., Shim A.H., He X.
J. Biol. Chem. 284:29077-29086(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 233-736, GLYCOSYLATION AT ASN-519; ASN-634 AND ASN-675, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
AC005075 Genomic DNA. No translation available.
AF158637 mRNA. Translation: AAD55251.1.
RefSeqNP_004185.1. NM_004194.3.
NP_068367.1. NM_021721.3.
NP_068368.2. NM_021722.4.
NP_068369.1. NM_021723.3.
UniGeneHs.256398.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3G5CX-ray2.36A/B233-736[»]
ProteinModelPortalQ9P0K1.
SMRQ9P0K1. Positions 233-718.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119789. 6 interactions.
IntActQ9P0K1. 11 interactions.
MINTMINT-252818.
STRING9606.ENSP00000265727.

Protein family/group databases

MEROPSM12.978.

PTM databases

PhosphoSiteQ9P0K1.

Polymorphism databases

DMDM14423634.

Proteomic databases

PaxDbQ9P0K1.
PRIDEQ9P0K1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265727; ENSP00000265727; ENSG00000008277. [Q9P0K1-1]
ENST00000398201; ENSP00000381260; ENSG00000008277. [Q9P0K1-3]
ENST00000398204; ENSP00000381262; ENSG00000008277. [Q9P0K1-5]
ENST00000398209; ENSP00000381267; ENSG00000008277. [Q9P0K1-2]
GeneID53616.
KEGGhsa:53616.
UCSCuc003ujk.2. human. [Q9P0K1-1]
uc003ujl.2. human. [Q9P0K1-4]
uc003ujm.3. human. [Q9P0K1-2]
uc003ujo.3. human. [Q9P0K1-5]

Organism-specific databases

CTD53616.
GeneCardsGC07P087563.
HGNCHGNC:201. ADAM22.
HPAHPA045282.
MIM603709. gene.
neXtProtNX_Q9P0K1.
PharmGKBPA24518.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG256419.
HOGENOMHOG000231962.
HOVERGENHBG050456.
InParanoidQ9P0K1.
KOK16068.
OMAFSGSQFE.
OrthoDBEOG7B31M6.
PhylomeDBQ9P0K1.
TreeFamTF314733.

Gene expression databases

ArrayExpressQ9P0K1.
BgeeQ9P0K1.
CleanExHS_ADAM22.
GenevestigatorQ9P0K1.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProIPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
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]
SUPFAMSSF57552. SSF57552. 1 hit.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00022. EGF_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAM22. human.
EvolutionaryTraceQ9P0K1.
GeneWikiADAM22.
GenomeRNAi53616.
NextBio56096.
PROQ9P0K1.
SOURCESearch...

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: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM