ADA18_HUMAN
ID ADA18_HUMAN Reviewed; 739 AA.
AC Q9Y3Q7; B2R9Y0; Q0VAI4; Q6IRW9; Q6UXJ9;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 18;
DE Short=ADAM 18;
DE AltName: Full=Transmembrane metalloproteinase-like, disintegrin-like, and cysteine-rich protein III;
DE Short=tMDC III;
DE Flags: Precursor;
GN Name=ADAM18; Synonyms=TMDC3; ORFNames=UNQ858/PRO1867;
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] (ISOFORM 1).
RC TISSUE=Testis;
RA Hall L., Frayne J., Dimsey E.A.;
RT "Nucleotide sequence of the human tMDC III sperm surface protein
RT transcript.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Testis;
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 SER-170; GLY-284; ILE-344; LYS-362 AND LEU-536.
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: Sperm surface membrane protein that may be involved in
CC spermatogenesis and fertilization. This is a non catalytic
CC metalloprotease-like protein (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y3Q7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3Q7-2; Sequence=VSP_012033;
CC Name=3;
CC IsoId=Q9Y3Q7-3; Sequence=VSP_043285, VSP_043286;
CC -!- TISSUE SPECIFICITY: Expressed specifically in testis.
CC -!- DOMAIN: A tripeptide motif (ECD) within disintegrin-like domain could
CC be involved in the binding to egg integrin receptor and thus could
CC mediate sperm/egg binding. {ECO:0000250}.
CC -!- PTM: The prodomain and the metalloprotease-like domain are cleaved
CC during the epididymal maturation of the spermatozoa. {ECO:0000250}.
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DR EMBL; AJ133004; CAB40812.1; -; mRNA.
DR EMBL; AY358321; AAQ88687.1; -; mRNA.
DR EMBL; AK313961; BAG36677.1; -; mRNA.
DR EMBL; AC109633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136365; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034624; AAH34624.1; -; mRNA.
DR EMBL; BC070279; AAH70279.1; -; mRNA.
DR EMBL; BC121045; AAI21046.1; -; mRNA.
DR CCDS; CCDS55225.1; -. [Q9Y3Q7-3]
DR CCDS; CCDS6113.1; -. [Q9Y3Q7-1]
DR CCDS; CCDS83287.1; -. [Q9Y3Q7-2]
DR RefSeq; NP_001177885.1; NM_001190956.1. [Q9Y3Q7-3]
DR RefSeq; NP_001307242.1; NM_001320313.1. [Q9Y3Q7-2]
DR RefSeq; NP_055052.1; NM_014237.2. [Q9Y3Q7-1]
DR AlphaFoldDB; Q9Y3Q7; -.
DR SMR; Q9Y3Q7; -.
DR BioGRID; 114285; 28.
DR STRING; 9606.ENSP00000265707; -.
DR MEROPS; M12.957; -.
DR GlyGen; Q9Y3Q7; 12 sites.
DR iPTMnet; Q9Y3Q7; -.
DR PhosphoSitePlus; Q9Y3Q7; -.
DR BioMuta; ADAM18; -.
DR DMDM; 20137582; -.
DR MassIVE; Q9Y3Q7; -.
DR PaxDb; Q9Y3Q7; -.
DR PeptideAtlas; Q9Y3Q7; -.
DR PRIDE; Q9Y3Q7; -.
DR ProteomicsDB; 86061; -. [Q9Y3Q7-1]
DR ProteomicsDB; 86062; -. [Q9Y3Q7-2]
DR Antibodypedia; 23870; 40 antibodies from 8 providers.
DR DNASU; 8749; -.
DR Ensembl; ENST00000265707.10; ENSP00000265707.5; ENSG00000168619.16. [Q9Y3Q7-1]
DR Ensembl; ENST00000379866.5; ENSP00000369195.1; ENSG00000168619.16. [Q9Y3Q7-2]
DR Ensembl; ENST00000520772.5; ENSP00000429908.1; ENSG00000168619.16. [Q9Y3Q7-3]
DR Ensembl; ENST00000613609.4; ENSP00000482348.1; ENSG00000278548.4. [Q9Y3Q7-1]
DR Ensembl; ENST00000633688.1; ENSP00000488128.1; ENSG00000278548.4. [Q9Y3Q7-3]
DR Ensembl; ENST00000633768.1; ENSP00000488176.1; ENSG00000278548.4. [Q9Y3Q7-2]
DR GeneID; 8749; -.
DR KEGG; hsa:8749; -.
DR MANE-Select; ENST00000265707.10; ENSP00000265707.5; NM_014237.3; NP_055052.1.
DR UCSC; uc003xnh.4; human. [Q9Y3Q7-1]
DR CTD; 8749; -.
DR DisGeNET; 8749; -.
DR GeneCards; ADAM18; -.
DR HGNC; HGNC:196; ADAM18.
DR HPA; ENSG00000168619; Tissue enriched (testis).
DR MIM; 619495; gene.
DR neXtProt; NX_Q9Y3Q7; -.
DR OpenTargets; ENSG00000168619; -.
DR PharmGKB; PA24513; -.
DR VEuPathDB; HostDB:ENSG00000168619; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000162281; -.
DR HOGENOM; CLU_012714_4_3_1; -.
DR InParanoid; Q9Y3Q7; -.
DR OMA; GPQMYCV; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; Q9Y3Q7; -.
DR TreeFam; TF314733; -.
DR PathwayCommons; Q9Y3Q7; -.
DR BioGRID-ORCS; 8749; 11 hits in 1066 CRISPR screens.
DR ChiTaRS; ADAM18; human.
DR GeneWiki; ADAM18; -.
DR GenomeRNAi; 8749; -.
DR Pharos; Q9Y3Q7; Tdark.
DR PRO; PR:Q9Y3Q7; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9Y3Q7; protein.
DR Bgee; ENSG00000168619; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; Q9Y3Q7; baseline and differential.
DR Genevisible; Q9Y3Q7; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
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; 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 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.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW Reference proteome; Signal; Spermatogenesis; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..184
FT /evidence="ECO:0000255"
FT /id="PRO_0000029096"
FT CHAIN 185..739
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 18"
FT /id="PRO_0000029097"
FT TOPO_DOM 177..687
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 688..708
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 709..739
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 184..381
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 390..479
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 620..654
FT /note="EGF-like"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 465
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 625
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 293..376
FT /evidence="ECO:0000250"
FT DISULFID 335..360
FT /evidence="ECO:0000250"
FT DISULFID 337..342
FT /evidence="ECO:0000250"
FT DISULFID 450..471
FT /evidence="ECO:0000250"
FT DISULFID 624..636
FT /evidence="ECO:0000250"
FT DISULFID 630..642
FT /evidence="ECO:0000250"
FT DISULFID 644..653
FT /evidence="ECO:0000250"
FT VAR_SEQ 175..182
FT /note="IKNLSKLL -> VTVIILML (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043285"
FT VAR_SEQ 183..739
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043286"
FT VAR_SEQ 197..220
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_012033"
FT VARIANT 170
FT /note="P -> S (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs267601916)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066312"
FT VARIANT 212
FT /note="V -> F (in dbSNP:rs10093794)"
FT /id="VAR_051588"
FT VARIANT 284
FT /note="V -> G (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066313"
FT VARIANT 344
FT /note="M -> I (in a cutaneous metastatic melanoma sample;
FT somatic mutation; dbSNP:rs267601918)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066314"
FT VARIANT 362
FT /note="M -> K (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066315"
FT VARIANT 536
FT /note="S -> L (in a cutaneous metastatic melanoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21618342"
FT /id="VAR_066316"
SQ SEQUENCE 739 AA; 82856 MW; 2D8BE9A975072CDD CRC64;
MFLLLALLTE LGRLQAHEGS EGIFLHVTVP RKIKSNDSEV SERKMIYIIT IDGQPYTLHL
GKQSFLPQNF LVYTYNETGS LHSVSPYFMM HCHYQGYAAE FPNSFVTLSI CSGLRGFLQF
ENISYGIEPV ESSARFEHII YQMKNNDPNV SILAVNYSHI WQKDQPYKVP LNSQIKNLSK
LLPQYLEIYI IVEKALYDYM GSEMMAVTQK IVQVIGLVNT MFTQFKLTVI LSSLELWSNE
NQISTSGDAD DILQRFLAWK RDYLILRPHD IAYLLVYRKH PKYVGATFPG TVCNKSYDAG
IAMYPDAIGL EGFSVIIAQL LGLNVGLTYD DITQCFCLRA TCIMNHEAVS ASGRKIFSNC
SMHDYRYFVS KFETKCLQKL SNLQPLHQNQ PVCGNGILES NEECDCGNKN ECQFKKCCDY
NTCKLKGSVK CGSGPCCTSK CELSIAGTPC RKSIDPECDF TEYCNGTSSN CVPDTYALNG
RLCKLGTAYC YNGQCQTTDN QCAKIFGKGA QGAPFACFKE VNSLHERSEN CGFKNSQPLP
CERKDVLCGK LACVQPHKNA NKSDAQSTVY SYIQDHVCVS IATGSSMRSD GTDNAYVADG
TMCGPEMYCV NKTCRKVHLM GYNCNATTKC KGKGICNNFG NCQCFPGHRP PDCKFQFGSP
GGSIDDGNFQ KSGDFYTEKG YNTHWNNWFI LSFCIFLPFF IVFTTVIFKR NEISKSCNRE
NAEYNRNSSV VSESDDVGH
