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Protein

Disintegrin and metalloproteinase domain-containing protein 28

Gene

ADAM28

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi169Zinc; in inhibited formBy similarity1
Metal bindingi339Zinc; catalyticBy similarity1
Active sitei340PROSITE-ProRule annotation1
Metal bindingi343Zinc; catalyticBy similarity1
Metal bindingi349Zinc; catalyticBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: BHF-UCL

GO - Biological processi

  • spermatogenesis Source: ProtInc

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Protein family/group databases

MEROPSiM12.224
TCDBi8.A.77.1.3 the sheddase (sheddase) family

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 28 (EC:3.4.24.-)
Short name:
ADAM 28
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 namesi
Name:ADAM28
Synonyms:ADAM23, MDCL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000042980.12
HGNCiHGNC:206 ADAM28
MIMi606188 gene
neXtProtiNX_Q9UKQ2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini199 – 665ExtracellularSequence analysisAdd BLAST467
Transmembranei666 – 686HelicalSequence analysisAdd BLAST21
Topological domaini687 – 775CytoplasmicSequence analysisAdd BLAST89

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi10863
OpenTargetsiENSG00000042980
PharmGKBiPA24523

Chemistry databases

DrugBankiDB02996 2-(Thiomethylene)-4-Methylpentanoic Acid
DB03880 Batimastat
DB02215 Furoyl-Leucine
DB02255 GM6001
DB02046 N-[(Furan-2-Yl)Carbonyl]-(S)-Leucyl-(R)-[1-Amino-2(1h-Indol-3-Yl)Ethyl]-Phosphonic Acid
DB03088 Pyroglutamic Acid

Polymorphism and mutation databases

BioMutaiADAM28
DMDMi317373485

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000002912819 – 198By similarityAdd BLAST180
ChainiPRO_0000029129199 – 775Disintegrin and metalloproteinase domain-containing protein 28Add BLAST577

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi268N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi275N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi315 ↔ 394By similarity
Disulfide bondi354 ↔ 378By similarity
Disulfide bondi356 ↔ 361By similarity
Disulfide bondi465 ↔ 485By similarity
Glycosylationi557N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi602N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi628N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi629 ↔ 639By similarity
Disulfide bondi633 ↔ 645By similarity
Disulfide bondi647 ↔ 656By similarity

Post-translational modificationi

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

Keywords - PTMi

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

Proteomic databases

PaxDbiQ9UKQ2
PeptideAtlasiQ9UKQ2
PRIDEiQ9UKQ2
ProteomicsDBi84834
84835 [Q9UKQ2-2]

PTM databases

iPTMnetiQ9UKQ2
PhosphoSitePlusiQ9UKQ2

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000042980 Expressed in 181 organ(s), highest expression level in caput epididymis
CleanExiHS_ADAM23
HS_ADAM28
ExpressionAtlasiQ9UKQ2 baseline and differential
GenevisibleiQ9UKQ2 HS

Organism-specific databases

HPAiHPA074034

Interactioni

Protein-protein interaction databases

BioGridi116072, 1 interactor
IntActiQ9UKQ2, 1 interactor
STRINGi9606.ENSP00000265769

Structurei

3D structure databases

ProteinModelPortaliQ9UKQ2
SMRiQ9UKQ2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini204 – 399Peptidase M12BPROSITE-ProRule annotationAdd BLAST196
Domaini407 – 493DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini625 – 657EGF-likePROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi167 – 174Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi494 – 628Cys-richAdd BLAST135

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.

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144014
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiQ9UKQ2
KOiK08614
OMAiTSPQIMD
OrthoDBiEOG091G01NX
PhylomeDBiQ9UKQ2
TreeFamiTF314733

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UKQ2-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MLQGLLPVSL LLSVAVSAIK ELPGVKKYEV VYPIRLHPLH KREAKEPEQQ
60 70 80 90 100
EQFETELKYK MTINGKIAVL YLKKNKNLLA PGYTETYYNS TGKEITTSPQ
110 120 130 140 150
IMDDCYYQGH ILNEKVSDAS ISTCRGLRGY FSQGDQRYFI EPLSPIHRDG
160 170 180 190 200
QEHALFKYNP DEKNYDSTCG MDGVLWAHDL QQNIALPATK LVKLKDRKVQ
210 220 230 240 250
EHEKYIEYYL VLDNGEFKRY NENQDEIRKR VFEMANYVNM LYKKLNTHVA
260 270 280 290 300
LVGMEIWTDK DKIKITPNAS FTLENFSKWR GSVLSRRKRH DIAQLITATE
310 320 330 340 350
LAGTTVGLAF MSTMCSPYSV GVVQDHSDNL LRVAGTMAHE MGHNFGMFHD
360 370 380 390 400
DYSCKCPSTI CVMDKALSFY IPTDFSSCSR LSYDKFFEDK LSNCLFNAPL
410 420 430 440 450
PTDIISTPIC GNQLVEMGED CDCGTSEECT NICCDAKTCK IKATFQCALG
460 470 480 490 500
ECCEKCQFKK AGMVCRPAKD ECDLPEMCNG KSGNCPDDRF QVNGFPCHHG
510 520 530 540 550
KGHCLMGTCP TLQEQCTELW GPGTEVADKS CYNRNEGGSK YGYCRRVDDT
560 570 580 590 600
LIPCKANDTM CGKLFCQGGS DNLPWKGRIV TFLTCKTFDP EDTSQEIGMV
610 620 630 640 650
ANGTKCGDNK VCINAECVDI EKAYKSTNCS SKCKGHAVCD HELQCQCEEG
660 670 680 690 700
WIPPDCDDSS VVFHFSIVVG VLFPMAVIFV VVAMVIRHQS SREKQKKDQR
710 720 730 740 750
PLSTTGTRPH KQKRKPQMVK AVQPQEMSQM KPHVYDLPVE GNEPPASFHK
760 770
DTNALPPTVF KDNPVSTPKD SNPKA
Length:775
Mass (Da):87,148
Last modified:January 11, 2011 - v3
Checksum:i895E0985840F971C
GO
Isoform 2 (identifier: Q9UKQ2-2) [UniParc]FASTAAdd to basket
Also known as: MDC-LS

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

Show »
Length:540
Mass (Da):61,232
Checksum:i65F475E18650D227
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YBG8H0YBG8_HUMAN
Disintegrin and metalloproteinase d...
ADAM28
387Annotation score:
H0YBQ8H0YBQ8_HUMAN
Disintegrin and metalloproteinase d...
ADAM28
174Annotation score:
E5RGY1E5RGY1_HUMAN
Disintegrin and metalloproteinase d...
ADAM28
217Annotation score:
E5RJQ1E5RJQ1_HUMAN
Disintegrin and metalloproteinase d...
ADAM28
58Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti513Q → R in AAD25099 (PubMed:10506182).Curated1
Sequence conflicti513Q → R in AAD25100 (PubMed:10506182).Curated1
Sequence conflicti774K → E in AAD25099 (PubMed:10506182).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06631765G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_066318134G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267601860Ensembl.1
Natural variantiVAR_057067219R → M. Corresponds to variant dbSNP:rs9314282Ensembl.1
Natural variantiVAR_057068226E → D. Corresponds to variant dbSNP:rs17736699Ensembl.1
Natural variantiVAR_066319450G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267601862Ensembl.1
Natural variantiVAR_066320482S → F in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_057069493N → S. Corresponds to variant dbSNP:rs7001647Ensembl.1
Natural variantiVAR_066321502G → D in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267601864Ensembl.1
Natural variantiVAR_057070593T → K. Corresponds to variant dbSNP:rs36041430Ensembl.1
Natural variantiVAR_057071604T → P. Corresponds to variant dbSNP:rs35617826Ensembl.1
Natural variantiVAR_057072684M → I. Corresponds to variant dbSNP:rs7829965Ensembl.1
Natural variantiVAR_024596765V → M4 PublicationsCorresponds to variant dbSNP:rs7814768Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005486524 – 540TEVAD…EGGSK → RRTNPFPCACAKENHFR in isoform 2. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_005487541 – 775Missing in isoform 2. 1 PublicationAdd BLAST235

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34865.1 [Q9UKQ2-1]
CCDS47830.1 [Q9UKQ2-2]
RefSeqiNP_001291280.1, NM_001304351.1
NP_055080.2, NM_014265.5 [Q9UKQ2-1]
NP_068547.2, NM_021777.4 [Q9UKQ2-2]
UniGeneiHs.174030
Hs.388903

Genome annotation databases

EnsembliENST00000265769; ENSP00000265769; ENSG00000042980 [Q9UKQ2-1]
ENST00000437154; ENSP00000393699; ENSG00000042980 [Q9UKQ2-2]
GeneIDi10863
KEGGihsa:10863
UCSCiuc003xdx.4 human [Q9UKQ2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34865.1 [Q9UKQ2-1]
CCDS47830.1 [Q9UKQ2-2]
RefSeqiNP_001291280.1, NM_001304351.1
NP_055080.2, NM_014265.5 [Q9UKQ2-1]
NP_068547.2, NM_021777.4 [Q9UKQ2-2]
UniGeneiHs.174030
Hs.388903

3D structure databases

ProteinModelPortaliQ9UKQ2
SMRiQ9UKQ2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116072, 1 interactor
IntActiQ9UKQ2, 1 interactor
STRINGi9606.ENSP00000265769

Chemistry databases

DrugBankiDB02996 2-(Thiomethylene)-4-Methylpentanoic Acid
DB03880 Batimastat
DB02215 Furoyl-Leucine
DB02255 GM6001
DB02046 N-[(Furan-2-Yl)Carbonyl]-(S)-Leucyl-(R)-[1-Amino-2(1h-Indol-3-Yl)Ethyl]-Phosphonic Acid
DB03088 Pyroglutamic Acid

Protein family/group databases

MEROPSiM12.224
TCDBi8.A.77.1.3 the sheddase (sheddase) family

PTM databases

iPTMnetiQ9UKQ2
PhosphoSitePlusiQ9UKQ2

Polymorphism and mutation databases

BioMutaiADAM28
DMDMi317373485

Proteomic databases

PaxDbiQ9UKQ2
PeptideAtlasiQ9UKQ2
PRIDEiQ9UKQ2
ProteomicsDBi84834
84835 [Q9UKQ2-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265769; ENSP00000265769; ENSG00000042980 [Q9UKQ2-1]
ENST00000437154; ENSP00000393699; ENSG00000042980 [Q9UKQ2-2]
GeneIDi10863
KEGGihsa:10863
UCSCiuc003xdx.4 human [Q9UKQ2-1]

Organism-specific databases

CTDi10863
DisGeNETi10863
EuPathDBiHostDB:ENSG00000042980.12
GeneCardsiADAM28
H-InvDBiHIX0034262
HGNCiHGNC:206 ADAM28
HPAiHPA074034
MIMi606188 gene
neXtProtiNX_Q9UKQ2
OpenTargetsiENSG00000042980
PharmGKBiPA24523
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144014
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiQ9UKQ2
KOiK08614
OMAiTSPQIMD
OrthoDBiEOG091G01NX
PhylomeDBiQ9UKQ2
TreeFamiTF314733

Miscellaneous databases

ChiTaRSiADAM28 human
GeneWikiiADAM28
GenomeRNAii10863
PROiPR:Q9UKQ2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000042980 Expressed in 181 organ(s), highest expression level in caput epididymis
CleanExiHS_ADAM23
HS_ADAM28
ExpressionAtlasiQ9UKQ2 baseline and differential
GenevisibleiQ9UKQ2 HS

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 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
ProtoNetiSearch...

Entry informationi

Entry nameiADA28_HUMAN
AccessioniPrimary (citable) accession number: Q9UKQ2
Secondary accession number(s): B2RMV5, Q9Y339, Q9Y3S0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: January 11, 2011
Last modified: September 12, 2018
This is version 170 of the entry and version 3 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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