ADA28_HUMAN
ID ADA28_HUMAN Reviewed; 775 AA.
AC Q9UKQ2; B2RMV5; Q9Y339; Q9Y3S0;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 28;
DE Short=ADAM 28;
DE EC=3.4.24.-;
DE AltName: Full=Epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II;
DE Short=eMDC II;
DE AltName: Full=Metalloproteinase-like, disintegrin-like, and cysteine-rich protein L;
DE Short=MDC-L;
DE Flags: Precursor;
GN Name=ADAM28; Synonyms=ADAM23, MDCL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT MET-765.
RC TISSUE=Lymph node;
RX PubMed=10506182; DOI=10.1074/jbc.274.41.29251;
RA Roberts C.M., Tani P.H., Bridges L.C., Laszik Z., Bowditch R.D.;
RT "MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family
RT member expressed by human lymphocytes.";
RL J. Biol. Chem. 274:29251-29259(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-765.
RC TISSUE=Epididymis;
RX PubMed=10587367; DOI=10.1093/molehr/5.12.1127;
RA Jury J.A., Perry A.C., Hall L.;
RT "Identification, sequence analysis and expression of transcripts encoding a
RT putative metalloproteinase, eMDC II, in human and macaque epididymis.";
RL Mol. Hum. Reprod. 5:1127-1134(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-765.
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-765.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP VARIANTS GLU-65; GLU-134; GLU-450; PHE-482 AND ASP-502.
RX PubMed=21618342; DOI=10.1002/humu.21477;
RA Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., Rudloff U.,
RA Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.;
RT "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and
RT ADAM7 are often mutated in melanoma.";
RL Hum. Mutat. 32:E2148-E2175(2011).
CC -!- FUNCTION: May play a role in the adhesive and proteolytic events that
CC occur during lymphocyte emigration or may function in ectodomain
CC shedding of lymphocyte surface target proteins, such as FASL and CD40L.
CC May be involved in sperm maturation.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- INTERACTION:
CC Q9UKQ2; P00749: PLAU; NbExp=3; IntAct=EBI-1384181, EBI-3905042;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=MDC-LM;
CC IsoId=Q9UKQ2-1; Sequence=Displayed;
CC Name=2; Synonyms=MDC-LS;
CC IsoId=Q9UKQ2-2; Sequence=VSP_005486, VSP_005487;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in secondary lymphoid
CC tissues, such as lymph node, spleen, small intestine, stomach, colon,
CC appendix and trachea. The lymphocyte population is responsible for
CC expression of this protein in these tissues. Isoform 2 is expressed
CC preferentially in spleen.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme.
CC -!- PTM: Pro-domain removal and maturation may be, at least in part,
CC autocatalytic. {ECO:0000250}.
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DR EMBL; AF137334; AAD25099.1; -; mRNA.
DR EMBL; AF137335; AAD25100.1; -; mRNA.
DR EMBL; AJ242015; CAB42085.1; -; mRNA.
DR EMBL; AC044891; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC120193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63609.1; -; Genomic_DNA.
DR EMBL; BC136478; AAI36479.1; -; mRNA.
DR CCDS; CCDS34865.1; -. [Q9UKQ2-1]
DR CCDS; CCDS47830.1; -. [Q9UKQ2-2]
DR RefSeq; NP_001291280.1; NM_001304351.1.
DR RefSeq; NP_055080.2; NM_014265.5. [Q9UKQ2-1]
DR RefSeq; NP_068547.2; NM_021777.4. [Q9UKQ2-2]
DR AlphaFoldDB; Q9UKQ2; -.
DR SMR; Q9UKQ2; -.
DR BioGRID; 116072; 4.
DR IntAct; Q9UKQ2; 1.
DR STRING; 9606.ENSP00000265769; -.
DR DrugBank; DB08733; (2R,3R)-N^1^-[(1S)-2,2-DIMETHYL-1-(METHYLCARBAMOYL)PROPYL]-N^4^-HYDROXY-2-(2-METHYLPROPYL)-3-{[(1,3-THIAZOL-2-YLCARBONYL)AMINO]METHYL}BUTANEDIAMIDE.
DR DrugBank; DB02996; 2-(Thiomethylene)-4-Methylpentanoic Acid.
DR DrugBank; DB03880; Batimastat.
DR DrugBank; DB02215; Furoyl-Leucine.
DR DrugBank; DB02255; Ilomastat.
DR DrugBank; DB02046; N-[(Furan-2-Yl)Carbonyl]-(S)-Leucyl-(R)-[1-Amino-2(1h-Indol-3-Yl)Ethyl]-Phosphonic Acid.
DR DrugBank; DB03088; Pidolic acid.
DR MEROPS; M12.224; -.
DR TCDB; 8.A.77.1.3; the sheddase (sheddase) family.
DR GlyGen; Q9UKQ2; 6 sites.
DR iPTMnet; Q9UKQ2; -.
DR PhosphoSitePlus; Q9UKQ2; -.
DR BioMuta; ADAM28; -.
DR DMDM; 317373485; -.
DR jPOST; Q9UKQ2; -.
DR MassIVE; Q9UKQ2; -.
DR PaxDb; Q9UKQ2; -.
DR PeptideAtlas; Q9UKQ2; -.
DR PRIDE; Q9UKQ2; -.
DR ProteomicsDB; 84834; -. [Q9UKQ2-1]
DR ProteomicsDB; 84835; -. [Q9UKQ2-2]
DR Antibodypedia; 58742; 202 antibodies from 24 providers.
DR DNASU; 10863; -.
DR Ensembl; ENST00000265769.9; ENSP00000265769.4; ENSG00000042980.13. [Q9UKQ2-1]
DR Ensembl; ENST00000437154.6; ENSP00000393699.2; ENSG00000042980.13. [Q9UKQ2-2]
DR GeneID; 10863; -.
DR KEGG; hsa:10863; -.
DR MANE-Select; ENST00000265769.9; ENSP00000265769.4; NM_014265.6; NP_055080.2.
DR UCSC; uc003xdx.4; human. [Q9UKQ2-1]
DR CTD; 10863; -.
DR DisGeNET; 10863; -.
DR GeneCards; ADAM28; -.
DR HGNC; HGNC:206; ADAM28.
DR HPA; ENSG00000042980; Group enriched (epididymis, stomach).
DR MIM; 606188; gene.
DR neXtProt; NX_Q9UKQ2; -.
DR OpenTargets; ENSG00000042980; -.
DR PharmGKB; PA24523; -.
DR VEuPathDB; HostDB:ENSG00000042980; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000156716; -.
DR HOGENOM; CLU_012714_7_1_1; -.
DR InParanoid; Q9UKQ2; -.
DR OMA; ICVMDRA; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9UKQ2; -.
DR TreeFam; TF314733; -.
DR PathwayCommons; Q9UKQ2; -.
DR SignaLink; Q9UKQ2; -.
DR BioGRID-ORCS; 10863; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; ADAM28; human.
DR GeneWiki; ADAM28; -.
DR GenomeRNAi; 10863; -.
DR Pharos; Q9UKQ2; Tbio.
DR PRO; PR:Q9UKQ2; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9UKQ2; protein.
DR Bgee; ENSG00000042980; Expressed in corpus epididymis and 169 other tissues.
DR ExpressionAtlas; Q9UKQ2; baseline and differential.
DR Genevisible; Q9UKQ2; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
DR InterPro; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR034027; Reprolysin_adamalysin.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00427; DISINTEGRIN_1; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Secreted;
KW Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..198
FT /evidence="ECO:0000250"
FT /id="PRO_0000029128"
FT CHAIN 199..775
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 28"
FT /id="PRO_0000029129"
FT TOPO_DOM 199..665
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 666..686
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 687..775
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 204..399
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 407..493
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 625..657
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 690..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 167..174
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT COMPBIAS 690..704
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 315..394
FT /evidence="ECO:0000250"
FT DISULFID 354..378
FT /evidence="ECO:0000250"
FT DISULFID 356..361
FT /evidence="ECO:0000250"
FT DISULFID 465..485
FT /evidence="ECO:0000250"
FT DISULFID 629..639
FT /evidence="ECO:0000250"
FT DISULFID 633..645
FT /evidence="ECO:0000250"
FT DISULFID 647..656
FT /evidence="ECO:0000250"
FT VAR_SEQ 524..540
FT /note="TEVADKSCYNRNEGGSK -> RRTNPFPCACAKENHFR (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:10506182"
FT /id="VSP_005486"
FT VAR_SEQ 541..775
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10506182"
FT /id="VSP_005487"
FT VARIANT 65
FT /note="G -> E (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066317"
FT VARIANT 134
FT /note="G -> E (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs267601860)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066318"
FT VARIANT 219
FT /note="R -> M (in dbSNP:rs9314282)"
FT /id="VAR_057067"
FT VARIANT 226
FT /note="E -> D (in dbSNP:rs17736699)"
FT /id="VAR_057068"
FT VARIANT 450
FT /note="G -> E (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs267601862)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066319"
FT VARIANT 482
FT /note="S -> F (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066320"
FT VARIANT 493
FT /note="N -> S (in dbSNP:rs7001647)"
FT /id="VAR_057069"
FT VARIANT 502
FT /note="G -> D (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs267601864)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066321"
FT VARIANT 593
FT /note="T -> K (in dbSNP:rs36041430)"
FT /id="VAR_057070"
FT VARIANT 604
FT /note="T -> P (in dbSNP:rs35617826)"
FT /id="VAR_057071"
FT VARIANT 684
FT /note="M -> I (in dbSNP:rs7829965)"
FT /id="VAR_057072"
FT VARIANT 765
FT /note="V -> M (in dbSNP:rs7814768)"
FT /evidence="ECO:0000269|PubMed:10506182,
FT ECO:0000269|PubMed:10587367, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.4"
FT /id="VAR_024596"
FT CONFLICT 513
FT /note="Q -> R (in Ref. 1; AAD25099/AAD25100)"
FT /evidence="ECO:0000305"
FT CONFLICT 774
FT /note="K -> E (in Ref. 1; AAD25099)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 775 AA; 87148 MW; 895E0985840F971C CRC64;
MLQGLLPVSL LLSVAVSAIK ELPGVKKYEV VYPIRLHPLH KREAKEPEQQ EQFETELKYK
MTINGKIAVL YLKKNKNLLA PGYTETYYNS TGKEITTSPQ IMDDCYYQGH ILNEKVSDAS
ISTCRGLRGY FSQGDQRYFI EPLSPIHRDG QEHALFKYNP DEKNYDSTCG MDGVLWAHDL
QQNIALPATK LVKLKDRKVQ EHEKYIEYYL VLDNGEFKRY NENQDEIRKR VFEMANYVNM
LYKKLNTHVA LVGMEIWTDK DKIKITPNAS FTLENFSKWR GSVLSRRKRH DIAQLITATE
LAGTTVGLAF MSTMCSPYSV GVVQDHSDNL LRVAGTMAHE MGHNFGMFHD DYSCKCPSTI
CVMDKALSFY IPTDFSSCSR LSYDKFFEDK LSNCLFNAPL PTDIISTPIC GNQLVEMGED
CDCGTSEECT NICCDAKTCK IKATFQCALG ECCEKCQFKK AGMVCRPAKD ECDLPEMCNG
KSGNCPDDRF QVNGFPCHHG KGHCLMGTCP TLQEQCTELW GPGTEVADKS CYNRNEGGSK
YGYCRRVDDT LIPCKANDTM CGKLFCQGGS DNLPWKGRIV TFLTCKTFDP EDTSQEIGMV
ANGTKCGDNK VCINAECVDI EKAYKSTNCS SKCKGHAVCD HELQCQCEEG WIPPDCDDSS
VVFHFSIVVG VLFPMAVIFV VVAMVIRHQS SREKQKKDQR PLSTTGTRPH KQKRKPQMVK
AVQPQEMSQM KPHVYDLPVE GNEPPASFHK DTNALPPTVF KDNPVSTPKD SNPKA
