ADA21_MOUSE
ID ADA21_MOUSE Reviewed; 729 AA.
AC Q9JI76; A2RSL1;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 21;
DE Short=ADAM 21;
DE EC=3.4.24.-;
DE AltName: Full=Disintegrin and metalloproteinase domain-containing protein 31;
DE Short=ADAM 31;
DE Flags: Precursor;
GN Name=Adam21; Synonyms=Adam31;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Bone marrow;
RX PubMed=10830287; DOI=10.1210/endo.141.6.7497;
RA Liu L., Smith J.W.;
RT "Identification of ADAM 31: a protein expressed in Leydig cells and
RT specialized epithelia.";
RL Endocrinology 141:2033-2042(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
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 -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in Leydig cells. Expressed also in
CC cauda epididymidis, vas deferens, convoluted tubules, kidney and the
CC parietal cells of stomach. Not detected on developing spermatocytes or
CC mature sperm.
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. {ECO:0000250}.
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DR EMBL; AF251559; AAF74731.1; -; mRNA.
DR EMBL; AK014827; BAB29569.1; -; mRNA.
DR EMBL; BC132152; AAI32153.1; -; mRNA.
DR EMBL; BC132344; AAI32345.1; -; mRNA.
DR CCDS; CCDS26022.1; -.
DR RefSeq; NP_065063.1; NM_020330.5.
DR AlphaFoldDB; Q9JI76; -.
DR SMR; Q9JI76; -.
DR STRING; 10090.ENSMUSP00000008582; -.
DR MEROPS; M12.233; -.
DR GlyGen; Q9JI76; 5 sites.
DR iPTMnet; Q9JI76; -.
DR PhosphoSitePlus; Q9JI76; -.
DR PaxDb; Q9JI76; -.
DR PRIDE; Q9JI76; -.
DR ProteomicsDB; 285756; -.
DR Antibodypedia; 25130; 37 antibodies from 17 providers.
DR DNASU; 56622; -.
DR Ensembl; ENSMUST00000008582; ENSMUSP00000008582; ENSMUSG00000008438.
DR GeneID; 56622; -.
DR KEGG; mmu:56622; -.
DR UCSC; uc007ock.1; mouse.
DR CTD; 8747; -.
DR MGI; MGI:1861229; Adam21.
DR VEuPathDB; HostDB:ENSMUSG00000008438; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000162712; -.
DR HOGENOM; CLU_012714_4_0_1; -.
DR InParanoid; Q9JI76; -.
DR OMA; CIMNAIR; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9JI76; -.
DR TreeFam; TF314733; -.
DR Reactome; R-MMU-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR BioGRID-ORCS; 56622; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q9JI76; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9JI76; protein.
DR Bgee; ENSMUSG00000008438; Expressed in spermatid and 24 other tissues.
DR Genevisible; Q9JI76; MM.
DR GO; GO:0030424; C:axon; IDA:MGI.
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:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
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:0008584; P:male gonad development; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 2: Evidence at transcript 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..39
FT /evidence="ECO:0000255"
FT PROPEP 40..209
FT /evidence="ECO:0000255"
FT /id="PRO_0000029110"
FT CHAIN 210..729
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 21"
FT /id="PRO_0000029111"
FT TOPO_DOM 210..685
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 707..729
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 212..402
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 410..496
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 638..667
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT MOTIF 176..183
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 178
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 345
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 349
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT BINDING 355
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 482
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 320..397
FT /evidence="ECO:0000250"
FT DISULFID 360..382
FT /evidence="ECO:0000250"
FT DISULFID 362..367
FT /evidence="ECO:0000250"
FT DISULFID 468..488
FT /evidence="ECO:0000250"
FT DISULFID 638..649
FT /evidence="ECO:0000250"
FT DISULFID 643..655
FT /evidence="ECO:0000250"
FT DISULFID 657..666
FT /evidence="ECO:0000250"
SQ SEQUENCE 729 AA; 80850 MW; E70B79BC46B64549 CRC64;
MECFIMLGAD ARTLMRVTLL LLWLKALPSL IDLSQTGSTQ YLSSPEVVIP LKVTSRARGA
KNSEWLSYSL VFGGRRHVVH MRVKKLLVST HIPVLTYTEE HTPLSDYPFV PSDCYYHGYV
EGALESLVAF SACNGGLQGV LQMNGFSYEI EPIKHSSTFE HLVYTLNNNK TQFPPMLCSL
TEKRLLYQPF GVEEAKKSAM KQNYGKLWPH MWFLELAVVV DYGFFTNAQQ NLSKVRGDVV
LVVNMVDSMY KPLDTYVTLV GIEIWNRGNV LPMENIHQVL EDFSHWKQIS LSQVHHDAAH
IFIRSSLISV LGIAYIAGIC RPPLDCGVEN FQGDAWSLFA NTVAHELGHT FGMKHDEESC
SCGKSGCVMS TFRVPAERFT NCSYSDFMKT TLNQGTCLYN HPRPGAGFLV KRCGNGMVES
EEECDCGSVQ ECEQDPCCFL NCTLRPAAAC SFGLCCKDCK FMLLGELCRP KINECDLPEW
CNGTSHQCPE DGYVQDGVPC GAGAYCYQKQ CNNHDQQCRE IFGKGARSAS HNCYKEINLQ
GNRFGHCGTD GTVFLKCRMS DVFCGKVHCE NVEDIHHPQA PYVLQNIYAN GITCWSTGHC
LGMGVPDVGE VKDGTTCGVG KICLHKKCVS LSVLSNACLP ETCNRKGVCN NKHHCHCDYG
WSPPFCLHRG YGGSIDSGPT SQKRRVIITV LSITVPVLSI LICLLIAGLY RIYCKIPSGP
KETKASSPG
