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Protein

Disintegrin and metalloproteinase domain-containing protein 28

Gene

ADAM28

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000042980-MONOMER.

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

HGNCiHGNC:206. ADAM28.

Subcellular locationi

Topology

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi10863.
OpenTargetsiENSG00000042980.
PharmGKBiPA24523.

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...)Sequence analysis1
Glycosylationi275N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi315 ↔ 394By similarity
Disulfide bondi354 ↔ 378By similarity
Disulfide bondi356 ↔ 361By similarity
Disulfide bondi465 ↔ 485By similarity
Glycosylationi557N-linked (GlcNAc...)Sequence analysis1
Glycosylationi602N-linked (GlcNAc...)Sequence analysis1
Glycosylationi628N-linked (GlcNAc...)Sequence 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.

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.
CleanExiHS_ADAM23.
HS_ADAM28.
ExpressionAtlasiQ9UKQ2. baseline and differential.
GenevisibleiQ9UKQ2. HS.

Organism-specific databases

HPAiCAB000077.
CAB056155.

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.

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.
InParanoidiQ9UKQ2.
KOiK08614.
OMAiTSPQIMD.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9UKQ2.
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 (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

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

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 rs267601860dbSNPEnsembl.1
Natural variantiVAR_057067219R → M.Corresponds to variant rs9314282dbSNPEnsembl.1
Natural variantiVAR_057068226E → D.Corresponds to variant rs17736699dbSNPEnsembl.1
Natural variantiVAR_066319450G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs267601862dbSNPEnsembl.1
Natural variantiVAR_066320482S → F in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_057069493N → S.Corresponds to variant rs7001647dbSNPEnsembl.1
Natural variantiVAR_066321502G → D in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs267601864dbSNPEnsembl.1
Natural variantiVAR_057070593T → K.Corresponds to variant rs36041430dbSNPEnsembl.1
Natural variantiVAR_057071604T → P.Corresponds to variant rs35617826dbSNPEnsembl.1
Natural variantiVAR_057072684M → I.Corresponds to variant rs7829965dbSNPEnsembl.1
Natural variantiVAR_024596765V → M.4 PublicationsCorresponds to variant rs7814768dbSNPEnsembl.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

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.

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.

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.
GeneCardsiADAM28.
H-InvDBHIX0034262.
HGNCiHGNC:206. ADAM28.
HPAiCAB000077.
CAB056155.
MIMi606188. gene.
neXtProtiNX_Q9UKQ2.
OpenTargetsiENSG00000042980.
PharmGKBiPA24523.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9UKQ2.
KOiK08614.
OMAiTSPQIMD.
OrthoDBiEOG091G01NX.
PhylomeDBiQ9UKQ2.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000042980-MONOMER.

Miscellaneous databases

ChiTaRSiADAM28. human.
GeneWikiiADAM28.
GenomeRNAii10863.
PROiQ9UKQ2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000042980.
CleanExiHS_ADAM23.
HS_ADAM28.
ExpressionAtlasiQ9UKQ2. baseline and differential.
GenevisibleiQ9UKQ2. 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 nameiADA28_HUMAN
AccessioniPrimary (citable) accession number: Q9UKQ2
Secondary accession number(s): B2RMV5, Q9Y339, Q9Y3S0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 159 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.