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Q9UKQ2 (ADA28_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 28

Short name=ADAM 28
EC=3.4.24.-
Alternative name(s):
Epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II
Short name=eMDC II
Metalloproteinase-like, disintegrin-like, and cysteine-rich protein L
Short name=MDC-L
Gene names
Name:ADAM28
Synonyms:ADAM23, MDCL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length775 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

May play a role in the adhesive and proteolytic events that occur during lymphocyte emigration or may function in ectodomain shedding of lymphocyte surface target proteins, such as FASL and CD40L. May be involved in sperm maturation.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Tissue specificity

Expressed predominantly in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix and trachea. The lymphocyte population is responsible for expression of this protein in these tissues. Isoform 2 is expressed preferentially in spleen.

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

Pro-domain removal and maturation may be, at least in part, autocatalytic By similarity.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 EGF-like domain.

Contains 1 peptidase M12B domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKQ2-1)

Also known as: MDC-LM;

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: Q9UKQ2-2)

Also known as: MDC-LS;

The sequence of this isoform differs from the canonical sequence as follows:
     524-540: TEVADKSCYNRNEGGSK → RRTNPFPCACAKENHFR
     541-775: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Propeptide19 – 198180 By similarity
PRO_0000029128
Chain199 – 775577Disintegrin and metalloproteinase domain-containing protein 28
PRO_0000029129

Regions

Topological domain199 – 665467Extracellular Potential
Transmembrane666 – 68621Helical; Potential
Topological domain687 – 77589Cytoplasmic Potential
Domain204 – 399196Peptidase M12B
Domain407 – 49387Disintegrin
Domain625 – 65733EGF-like
Motif167 – 1748Cysteine switch By similarity
Compositional bias494 – 628135Cys-rich

Sites

Active site3401 By similarity
Metal binding1691Zinc; in inhibited form By similarity
Metal binding3391Zinc; catalytic By similarity
Metal binding3431Zinc; catalytic By similarity
Metal binding3491Zinc; catalytic By similarity

Amino acid modifications

Glycosylation2681N-linked (GlcNAc...) Potential
Glycosylation2751N-linked (GlcNAc...) Potential
Glycosylation5571N-linked (GlcNAc...) Potential
Glycosylation6021N-linked (GlcNAc...) Potential
Glycosylation6281N-linked (GlcNAc...) Potential
Disulfide bond315 ↔ 394 By similarity
Disulfide bond354 ↔ 378 By similarity
Disulfide bond356 ↔ 361 By similarity
Disulfide bond465 ↔ 485 By similarity
Disulfide bond629 ↔ 639 By similarity
Disulfide bond633 ↔ 645 By similarity
Disulfide bond647 ↔ 656 By similarity

Natural variations

Alternative sequence524 – 54017TEVAD…EGGSK → RRTNPFPCACAKENHFR in isoform 2.
VSP_005486
Alternative sequence541 – 775235Missing in isoform 2.
VSP_005487
Natural variant651G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6
VAR_066317
Natural variant1341G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6
VAR_066318
Natural variant2191R → M.
Corresponds to variant rs9314282 [ dbSNP | Ensembl ].
VAR_057067
Natural variant2261E → D.
Corresponds to variant rs17736699 [ dbSNP | Ensembl ].
VAR_057068
Natural variant4501G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6
VAR_066319
Natural variant4821S → F in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6
VAR_066320
Natural variant4931N → S.
Corresponds to variant rs7001647 [ dbSNP | Ensembl ].
VAR_057069
Natural variant5021G → D in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6
VAR_066321
Natural variant5931T → K.
Corresponds to variant rs36041430 [ dbSNP | Ensembl ].
VAR_057070
Natural variant6041T → P.
Corresponds to variant rs35617826 [ dbSNP | Ensembl ].
VAR_057071
Natural variant6841M → I.
Corresponds to variant rs7829965 [ dbSNP | Ensembl ].
VAR_057072
Natural variant7651V → M. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs7814768 [ dbSNP | Ensembl ].
VAR_024596

Experimental info

Sequence conflict5131Q → R in AAD25099. Ref.1
Sequence conflict5131Q → R in AAD25100. Ref.1
Sequence conflict7741K → E in AAD25099. Ref.1

Sequences

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

Last modified January 11, 2011. Version 3.
Checksum: 895E0985840F971C

FASTA77587,148
        10         20         30         40         50         60 
MLQGLLPVSL LLSVAVSAIK ELPGVKKYEV VYPIRLHPLH KREAKEPEQQ EQFETELKYK 

        70         80         90        100        110        120 
MTINGKIAVL YLKKNKNLLA PGYTETYYNS TGKEITTSPQ IMDDCYYQGH ILNEKVSDAS 

       130        140        150        160        170        180 
ISTCRGLRGY FSQGDQRYFI EPLSPIHRDG QEHALFKYNP DEKNYDSTCG MDGVLWAHDL 

       190        200        210        220        230        240 
QQNIALPATK LVKLKDRKVQ EHEKYIEYYL VLDNGEFKRY NENQDEIRKR VFEMANYVNM 

       250        260        270        280        290        300 
LYKKLNTHVA LVGMEIWTDK DKIKITPNAS FTLENFSKWR GSVLSRRKRH DIAQLITATE 

       310        320        330        340        350        360 
LAGTTVGLAF MSTMCSPYSV GVVQDHSDNL LRVAGTMAHE MGHNFGMFHD DYSCKCPSTI 

       370        380        390        400        410        420 
CVMDKALSFY IPTDFSSCSR LSYDKFFEDK LSNCLFNAPL PTDIISTPIC GNQLVEMGED 

       430        440        450        460        470        480 
CDCGTSEECT NICCDAKTCK IKATFQCALG ECCEKCQFKK AGMVCRPAKD ECDLPEMCNG 

       490        500        510        520        530        540 
KSGNCPDDRF QVNGFPCHHG KGHCLMGTCP TLQEQCTELW GPGTEVADKS CYNRNEGGSK 

       550        560        570        580        590        600 
YGYCRRVDDT LIPCKANDTM CGKLFCQGGS DNLPWKGRIV TFLTCKTFDP EDTSQEIGMV 

       610        620        630        640        650        660 
ANGTKCGDNK VCINAECVDI EKAYKSTNCS SKCKGHAVCD HELQCQCEEG WIPPDCDDSS 

       670        680        690        700        710        720 
VVFHFSIVVG VLFPMAVIFV VVAMVIRHQS SREKQKKDQR PLSTTGTRPH KQKRKPQMVK 

       730        740        750        760        770 
AVQPQEMSQM KPHVYDLPVE GNEPPASFHK DTNALPPTVF KDNPVSTPKD SNPKA 

« Hide

Isoform 2 (MDC-LS) [UniParc].

Checksum: 65F475E18650D227
Show »

FASTA54061,232

References

« Hide 'large scale' references
[1]"MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes."
Roberts C.M., Tani P.H., Bridges L.C., Laszik Z., Bowditch R.D.
J. Biol. Chem. 274:29251-29259(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT MET-765.
Tissue: Lymph node.
[2]"Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis."
Jury J.A., Perry A.C., Hall L.
Mol. Hum. Reprod. 5:1127-1134(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-765.
Tissue: Epididymis.
[3]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT MET-765.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-765.
Tissue: Brain.
[6]"Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma."
Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., Rudloff U., Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.
Hum. Mutat. 32:E2148-E2175(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLU-65; GLU-134; GLU-450; PHE-482 AND ASP-502.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF137334 mRNA. Translation: AAD25099.1.
AF137335 mRNA. Translation: AAD25100.1.
AJ242015 mRNA. Translation: CAB42085.1.
AC044891 Genomic DNA. No translation available.
AC120193 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63609.1.
BC136478 mRNA. Translation: AAI36479.1.
CCDSCCDS34865.1. [Q9UKQ2-1]
CCDS47830.1. [Q9UKQ2-2]
RefSeqNP_055080.2. NM_014265.4. [Q9UKQ2-1]
NP_068547.2. NM_021777.3. [Q9UKQ2-2]
UniGeneHs.174030.

3D structure databases

ProteinModelPortalQ9UKQ2.
SMRQ9UKQ2. Positions 199-658.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000265769.

Protein family/group databases

MEROPSM12.224.

PTM databases

PhosphoSiteQ9UKQ2.

Polymorphism databases

DMDM317373485.

Proteomic databases

PaxDbQ9UKQ2.
PRIDEQ9UKQ2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265769; ENSP00000265769; ENSG00000042980. [Q9UKQ2-1]
ENST00000437154; ENSP00000393699; ENSG00000042980. [Q9UKQ2-2]
GeneID10863.
KEGGhsa:10863.
UCSCuc003xdx.3. human. [Q9UKQ2-2]
uc003xdy.3. human. [Q9UKQ2-1]

Organism-specific databases

CTD10863.
GeneCardsGC08P024207.
H-InvDBHIX0034262.
HGNCHGNC:206. ADAM28.
MIM606188. gene.
neXtProtNX_Q9UKQ2.
PharmGKBPA24523.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG277164.
HOGENOMHOG000230883.
HOVERGENHBG006978.
InParanoidQ9UKQ2.
KOK08614.
OMATSPQIMD.
OrthoDBEOG7PGDQ7.
PhylomeDBQ9UKQ2.
TreeFamTF314733.

Gene expression databases

ArrayExpressQ9UKQ2.
BgeeQ9UKQ2.
CleanExHS_ADAM23.
HS_ADAM28.
GenevestigatorQ9UKQ2.

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.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiADAM28.
GenomeRNAi10863.
NextBio41241.
PROQ9UKQ2.
SOURCESearch...

Entry information

Entry nameADA28_HUMAN
AccessionPrimary (citable) accession number: Q9UKQ2
Secondary accession number(s): B2RMV5, Q9Y339, Q9Y3S0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 139 of the entry and version 3 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

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 8

Human chromosome 8: entries, gene names and cross-references to MIM