ID   ADAM2_HUMAN             Reviewed;         735 AA.
AC   Q99965; P78326; Q9UQQ8;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-2003, sequence version 2.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Disintegrin and metalloproteinase domain-containing protein 2;
DE            Short=ADAM 2;
DE   AltName: Full=Cancer/testis antigen 15;
DE            Short=CT15;
DE   AltName: Full=Fertilin subunit beta;
DE   AltName: Full=PH-30;
DE            Short=PH30;
DE   AltName: Full=PH30-beta;
DE   Flags: Precursor;
GN   Name=ADAM2; Synonyms=FTNB;
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;
RX   PubMed=9041139;
RX   DOI=10.1002/(sici)1098-2795(199703)46:3<363::aid-mrd15>3.0.co;2-#;
RA   Vidaeus C.M., von Kap-Herr C., Golden W.L., Eddy R.L., Shows T.B.,
RA   Herr J.C.;
RT   "Human fertilin beta: identification, characterization, and chromosomal
RT   mapping of an ADAM gene family member.";
RL   Mol. Reprod. Dev. 46:363-369(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=8702389; DOI=10.1006/bbrc.1996.1027;
RA   Gupta S.K., Alves K., Palladino L.O., Mark G.E., Hollis G.F.;
RT   "Molecular cloning of the human fertilin beta subunit.";
RL   Biochem. Biophys. Res. Commun. 224:318-326(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=9070941; DOI=10.1006/geno.1996.4531;
RA   Burkin H.R., Burkin D.J., Davey P.M., Griffin D.K., Affara N.A.;
RT   "Mapping, sequence, and expression analysis of the human fertilin beta gene
RT   (FTNB).";
RL   Genomics 40:190-192(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RA   Hall L., Frayne J.;
RT   "Nucleotide sequence of the human fertilin beta transcript.";
RL   Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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).
CC   -!- FUNCTION: Sperm surface membrane protein that may be involved in sperm-
CC       egg plasma membrane adhesion and fusion during fertilization. Could
CC       have a direct role in sperm-zona binding or migration of sperm from the
CC       uterus into the oviduct. Interactions with egg membrane could be
CC       mediated via binding between its disintegrin-like domain to one or more
CC       integrins receptors on the egg. This is a non catalytic
CC       metalloprotease-like protein.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q99965-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q99965-2; Sequence=VSP_005471;
CC   -!- TISSUE SPECIFICITY: Expressed specifically in spermatogenic cells in
CC       the seminiferous cells. Not detected in fetal tissues.
CC   -!- DOMAIN: A tripeptide motif (FEE) within disintegrin-like domain could
CC       be involved in the binding to egg integrin receptor and thus could
CC       mediate sperm/egg binding.
CC   -!- PTM: The prodomain and the metalloprotease domain are cleaved during
CC       the epididymal maturation of the spermatozoa.
CC   -!- MISCELLANEOUS: In mammals, exists as a heterodimer composed of an alpha
CC       and beta subunits. In human, fertilin subunit alpha is a pseudogene.
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DR   EMBL; U52370; AAC51110.1; -; mRNA.
DR   EMBL; U38805; AAD04206.1; -; mRNA.
DR   EMBL; X99374; CAA67753.1; -; mRNA.
DR   EMBL; AJ133005; CAB40813.1; -; mRNA.
DR   EMBL; BC034957; AAH34957.1; -; mRNA.
DR   CCDS; CCDS34884.1; -. [Q99965-1]
DR   CCDS; CCDS64882.1; -. [Q99965-2]
DR   PIR; JC4861; JC4861.
DR   RefSeq; NP_001265042.1; NM_001278113.1. [Q99965-2]
DR   RefSeq; NP_001265043.1; NM_001278114.1.
DR   RefSeq; NP_001455.3; NM_001464.4. [Q99965-1]
DR   AlphaFoldDB; Q99965; -.
DR   SMR; Q99965; -.
DR   BioGRID; 108791; 12.
DR   IntAct; Q99965; 7.
DR   STRING; 9606.ENSP00000265708; -.
DR   MEROPS; M12.950; -.
DR   GlyCosmos; Q99965; 5 sites, No reported glycans.
DR   GlyGen; Q99965; 5 sites.
DR   iPTMnet; Q99965; -.
DR   PhosphoSitePlus; Q99965; -.
DR   BioMuta; ADAM2; -.
DR   DMDM; 28202251; -.
DR   REPRODUCTION-2DPAGE; Q99965; -.
DR   MassIVE; Q99965; -.
DR   PaxDb; 9606-ENSP00000265708; -.
DR   PeptideAtlas; Q99965; -.
DR   ProteomicsDB; 78551; -. [Q99965-1]
DR   ProteomicsDB; 78552; -. [Q99965-2]
DR   Antibodypedia; 11200; 241 antibodies from 31 providers.
DR   DNASU; 2515; -.
DR   Ensembl; ENST00000265708.9; ENSP00000265708.4; ENSG00000104755.16. [Q99965-1]
DR   Ensembl; ENST00000347580.8; ENSP00000343854.4; ENSG00000104755.16. [Q99965-2]
DR   Ensembl; ENST00000613160.4; ENSP00000484999.1; ENSG00000276286.4. [Q99965-2]
DR   Ensembl; ENST00000620181.4; ENSP00000482337.1; ENSG00000276286.4. [Q99965-1]
DR   GeneID; 2515; -.
DR   KEGG; hsa:2515; -.
DR   MANE-Select; ENST00000265708.9; ENSP00000265708.4; NM_001464.5; NP_001455.3.
DR   UCSC; uc003xnj.5; human. [Q99965-1]
DR   AGR; HGNC:198; -.
DR   CTD; 2515; -.
DR   DisGeNET; 2515; -.
DR   GeneCards; ADAM2; -.
DR   HGNC; HGNC:198; ADAM2.
DR   HPA; ENSG00000104755; Tissue enriched (testis).
DR   MIM; 601533; gene.
DR   neXtProt; NX_Q99965; -.
DR   OpenTargets; ENSG00000104755; -.
DR   PharmGKB; PA24515; -.
DR   VEuPathDB; HostDB:ENSG00000104755; -.
DR   eggNOG; KOG3607; Eukaryota.
DR   GeneTree; ENSGT00940000161961; -.
DR   InParanoid; Q99965; -.
DR   OMA; FCYYQGH; -.
DR   OrthoDB; 5406290at2759; -.
DR   PhylomeDB; Q99965; -.
DR   TreeFam; TF314733; -.
DR   PathwayCommons; Q99965; -.
DR   Reactome; R-HSA-2534343; Interaction With Cumulus Cells And The Zona Pellucida.
DR   SignaLink; Q99965; -.
DR   BioGRID-ORCS; 2515; 19 hits in 1144 CRISPR screens.
DR   ChiTaRS; ADAM2; human.
DR   GeneWiki; ADAM2; -.
DR   GenomeRNAi; 2515; -.
DR   Pharos; Q99965; Tbio.
DR   PRO; PR:Q99965; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q99965; Protein.
DR   Bgee; ENSG00000104755; Expressed in testis and 28 other cell types or tissues.
DR   ExpressionAtlas; Q99965; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR   GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0030534; P:adult behavior; IEA:Ensembl.
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:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; TAS:ProtInc.
DR   GO; GO:0008584; P:male gonad development; IBA:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR   CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 4.10.70.10; Disintegrin domain; 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   PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1.
DR   PANTHER; PTHR11905:SF108; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 2; 1.
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; Blood coagulation inhibitor (disintegrin); 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS00427; DISINTEGRIN_1; 1.
DR   PROSITE; PS50214; DISINTEGRIN_2; 1.
DR   Genevisible; Q99965; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell adhesion; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   PROPEP          17..174
FT                   /id="PRO_0000029042"
FT   CHAIN           175..735
FT                   /note="Disintegrin and metalloproteinase domain-containing
FT                   protein 2"
FT                   /id="PRO_0000029043"
FT   TOPO_DOM        175..686
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        687..707
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        708..735
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          178..375
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          384..473
FT                   /note="Disintegrin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DOMAIN          612..645
FT                   /note="EGF-like"
FT   MOD_RES         729
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60718"
FT   CARBOHYD        122
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        220
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        459
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        566
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        287..370
FT                   /evidence="ECO:0000250"
FT   DISULFID        329..354
FT                   /evidence="ECO:0000250"
FT   DISULFID        331..336
FT                   /evidence="ECO:0000250"
FT   DISULFID        445..465
FT                   /evidence="ECO:0000250"
FT   DISULFID        616..627
FT                   /evidence="ECO:0000250"
FT   DISULFID        621..633
FT                   /evidence="ECO:0000250"
FT   DISULFID        635..644
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         172..190
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_005471"
FT   VARIANT         10
FT                   /note="G -> W (in dbSNP:rs34800519)"
FT                   /id="VAR_035217"
FT   CONFLICT        3
FT                   /note="Missing (in Ref. 2; AAD04206)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        21
FT                   /note="D -> H (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        99
FT                   /note="E -> D (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        106
FT                   /note="V -> G (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        170
FT                   /note="V -> A (in Ref. 2; AAD04206)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        288
FT                   /note="D -> H (in Ref. 1; AAC51110)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        321
FT                   /note="I -> T (in Ref. 1; AAC51110)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        388
FT                   /note="G -> S (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        396..398
FT                   /note="EEC -> DEF (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        501
FT                   /note="G -> S (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        529
FT                   /note="D -> Y (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        579
FT                   /note="S -> G (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        588
FT                   /note="W -> L (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        603
FT                   /note="N -> D (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        629..630
FT                   /note="NK -> KQ (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        638
FT                   /note="S -> F (in Ref. 3; CAA67753)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   735 AA;  82457 MW;  92867B5340BEE01F CRC64;
     MWRVLFLLSG LGGLRMDSNF DSLPVQITVP EKIRSIIKEG IESQASYKIV IEGKPYTVNL
     MQKNFLPHNF RVYSYSGTGI MKPLDQDFQN FCHYQGYIEG YPKSVVMVST CTGLRGVLQF
     ENVSYGIEPL ESSVGFEHVI YQVKHKKADV SLYNEKDIES RDLSFKLQSV EPQQDFAKYI
     EMHVIVEKQL YNHMGSDTTV VAQKVFQLIG LTNAIFVSFN ITIILSSLEL WIDENKIATT
     GEANELLHTF LRWKTSYLVL RPHDVAFLLV YREKSNYVGA TFQGKMCDAN YAGGVVLHPR
     TISLESLAVI LAQLLSLSMG ITYDDINKCQ CSGAVCIMNP EAIHFSGVKI FSNCSFEDFA
     HFISKQKSQC LHNQPRLDPF FKQQAVCGNA KLEAGEECDC GTEQDCALIG ETCCDIATCR
     FKAGSNCAEG PCCENCLFMS KERMCRPSFE ECDLPEYCNG SSASCPENHY VQTGHPCGLN
     QWICIDGVCM SGDKQCTDTF GKEVEFGPSE CYSHLNSKTD VSGNCGISDS GYTQCEADNL
     QCGKLICKYV GKFLLQIPRA TIIYANISGH LCIAVEFASD HADSQKMWIK DGTSCGSNKV
     CRNQRCVSSS YLGYDCTTDK CNDRGVCNNK KHCHCSASYL PPDCSVQSDL WPGGSIDSGN
     FPPVAIPARL PERRYIENIY HSKPMRWPFF LFIPFFIIFC VLIAIMVKVN FQRKKWRTED
     YSSDEQPESE SEPKG
//