ADA21_HUMAN
ID ADA21_HUMAN Reviewed; 722 AA.
AC Q9UKJ8; O43507; Q2VPC6; Q32MR0;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 21;
DE Short=ADAM 21;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=ADAM21;
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 [GENOMIC DNA].
RX PubMed=10524237; DOI=10.1016/s0378-1119(99)00302-9;
RA Poindexter K., Nelson N., DuBose R.F., Black R.A., Cerretti D.P.;
RT "The identification of seven metalloproteinase-disintegrin (ADAM) genes
RT from genomic libraries.";
RL Gene 237:61-70(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 181-722.
RC TISSUE=Testis;
RX PubMed=9469942; DOI=10.1016/s0378-1119(97)00597-0;
RA Hooft van Huijsduijnen R.;
RT "ADAM 20 and 21; two novel human testis-specific membrane metalloproteases
RT with similarity to fertilin-alpha.";
RL Gene 206:273-282(1998).
CC -!- FUNCTION: May be involved in sperm maturation and/or fertilization. May
CC also be involved in epithelia functions associated with establishing
CC and maintaining gradients of ions or nutrients.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000305};
CC -!- INTERACTION:
CC Q9UKJ8; P34972: CNR2; NbExp=3; IntAct=EBI-12046857, EBI-2835940;
CC Q9UKJ8; O43765: SGTA; NbExp=3; IntAct=EBI-12046857, EBI-347996;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- DOMAIN: A tripeptide motif (VGE) within disintegrin-like domain could
CC be involved in the binding to egg integrin receptor and thus could
CC mediate sperm/egg binding.
CC -!- DOMAIN: The cysteine-rich domain encodes putative cell-fusion peptides,
CC which could be involved in sperm-egg fusion.
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: Has no obvious cleavage site for furin endopeptidase, suggesting
CC that the proteolytic processing is regulated.
CC -!- MISCELLANEOUS: May be the functional equivalent of ADAM 1/fertilin
CC alpha which is a pseudogene in human.
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DR EMBL; AF158644; AAD55255.1; -; Genomic_DNA.
DR EMBL; AL357153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109024; AAI09025.1; -; mRNA.
DR EMBL; BC109025; AAI09026.1; -; mRNA.
DR EMBL; AF029900; AAC52042.1; -; mRNA.
DR CCDS; CCDS9804.1; -.
DR RefSeq; NP_003804.2; NM_003813.3.
DR AlphaFoldDB; Q9UKJ8; -.
DR SMR; Q9UKJ8; -.
DR BioGRID; 114283; 112.
DR IntAct; Q9UKJ8; 28.
DR STRING; 9606.ENSP00000474385; -.
DR MEROPS; M12.234; -.
DR GlyGen; Q9UKJ8; 7 sites.
DR iPTMnet; Q9UKJ8; -.
DR PhosphoSitePlus; Q9UKJ8; -.
DR BioMuta; ADAM21; -.
DR DMDM; 296434388; -.
DR MassIVE; Q9UKJ8; -.
DR PaxDb; Q9UKJ8; -.
DR PeptideAtlas; Q9UKJ8; -.
DR PRIDE; Q9UKJ8; -.
DR ProteomicsDB; 84810; -.
DR Antibodypedia; 25130; 37 antibodies from 17 providers.
DR DNASU; 8747; -.
DR Ensembl; ENST00000603540.2; ENSP00000474385.1; ENSG00000139985.8.
DR Ensembl; ENST00000679631.1; ENSP00000506213.1; ENSG00000139985.8.
DR GeneID; 8747; -.
DR KEGG; hsa:8747; -.
DR MANE-Select; ENST00000603540.2; ENSP00000474385.1; NM_003813.4; NP_003804.2.
DR UCSC; uc001xmd.4; human.
DR CTD; 8747; -.
DR DisGeNET; 8747; -.
DR GeneCards; ADAM21; -.
DR HGNC; HGNC:200; ADAM21.
DR HPA; ENSG00000139985; Tissue enriched (testis).
DR MIM; 603713; gene.
DR neXtProt; NX_Q9UKJ8; -.
DR OpenTargets; ENSG00000139985; -.
DR PharmGKB; PA24517; -.
DR VEuPathDB; HostDB:ENSG00000139985; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000162712; -.
DR HOGENOM; CLU_012714_4_0_1; -.
DR InParanoid; Q9UKJ8; -.
DR OMA; CIMNAIR; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9UKJ8; -.
DR TreeFam; TF314733; -.
DR PathwayCommons; Q9UKJ8; -.
DR Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR SignaLink; Q9UKJ8; -.
DR BioGRID-ORCS; 8747; 34 hits in 1036 CRISPR screens.
DR GenomeRNAi; 8747; -.
DR Pharos; Q9UKJ8; Tdark.
DR PRO; PR:Q9UKJ8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9UKJ8; protein.
DR Bgee; ENSG00000139985; Expressed in sperm and 79 other tissues.
DR Genevisible; Q9UKJ8; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:1990913; C:sperm head plasma membrane; 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; TAS:ProtInc.
DR GO; GO:0008584; P:male gonad development; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0007338; P:single fertilization; 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; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT PROPEP 32..196
FT /evidence="ECO:0000255"
FT /id="PRO_0000029108"
FT CHAIN 197..722
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 21"
FT /id="PRO_0000029109"
FT TOPO_DOM 197..681
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 682..702
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 703..722
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 208..398
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 406..492
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 634..663
FT /note="EGF-like"
FT MOTIF 171..178
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 342
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 173
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 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 351
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 316..393
FT /evidence="ECO:0000250"
FT DISULFID 356..378
FT /evidence="ECO:0000250"
FT DISULFID 358..363
FT /evidence="ECO:0000250"
FT DISULFID 464..484
FT /evidence="ECO:0000250"
FT DISULFID 634..645
FT /evidence="ECO:0000250"
FT DISULFID 639..651
FT /evidence="ECO:0000250"
FT DISULFID 653..662
FT /evidence="ECO:0000250"
FT CONFLICT 95
FT /note="D -> E (in Ref. 1; AAD55255 and 3; AAI09025/
FT AAI09026)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="A -> G (in Ref. 1; AAD55255 and 3; AAI09025/
FT AAI09026)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="I -> V (in Ref. 1; AAD55255 and 3; AAI09025/
FT AAI09026)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="A -> G (in Ref. 3; AAC52042)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="K -> Q (in Ref. 1; AAD55255 and 3; AAI09025/
FT AAI09026)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="H -> Y (in Ref. 3; AAC52042)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 722 AA; 80834 MW; 4D18503812A6C02F CRC64;
MAVDGTLVYI RVTLLLLWLG VFLSISGYCQ AGPSQHFTSP EVVIPLKVIS RGRSAKAPGW
LSYSLRFGGQ KHVVHMRVKK LLVSRHLPVF TYTDDRALLE DQLFIPDDCY YHGYVEAAPE
SLVVFSACFG GFRGVLKISG LTYEIEPIRH SATFEHLVYK INSNETQFPA MRCGLTEKEV
ARQQLEFEEA ENSALEPKSA GDWWTHAWFL ELVVVVNHDF FIYSQSNISK VQEDVFLVVN
IVDSMYKQLG TYIILIGIEI WNQGNVFPMT SIEQVLNDFS QWKQISLSQL QHDAAHMFIK
NSLISILGLA YVAGICRPPI DCGVDNFQGD TWSLFANTVA HELGHTLGMQ HDEEFCFCGE
RGCIMNTFRV PAEKFTNCSY ADFMKTTLNQ GSCLHNPPRL GEIFMLKRCG NGVVEREEQC
DCGSVQQCEQ DACCLLNCTL RPGAACAFGL CCKDCKFMPS GELCRQEVNE CDLPEWCNGT
SHQCPEDRYV QDGIPCSDSA YCYQKRCNNH DQHCREIFGK DAKSASQNCY KEINSQGNRF
GHCGINGTTY LKCHISDVFC GRVQCENVRD IPLLQDHFTL QHTHINGVTC WGIDYHLRMN
ISDIGEVKDG TVCGPGKICI HKKCVSLSVL SHVCLPETCN MKGICNNKHH CHCGYGWSPP
YCQHRGYGGS IDSGPASAKR GVFLPLIVIP SLSVLTFLFT VGLLMYLRQC SGPKETKAHS
SG
