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Q9UKJ8

- ADA21_HUMAN

UniProt

Q9UKJ8 - ADA21_HUMAN

Protein

Disintegrin and metalloproteinase domain-containing protein 21

Gene

ADAM21

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    Functioni

    May be involved in sperm maturation and/or fertilization. May also be involved in epithelia functions associated with establishing and maintaining gradients of ions or nutrients.

    Cofactori

    Binds 1 zinc ion per subunit.Curated

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi173 – 1731Zinc; in inhibited formBy similarity
    Metal bindingi341 – 3411Zinc; catalyticSequence Analysis
    Active sitei342 – 3421PROSITE-ProRule annotation
    Metal bindingi345 – 3451Zinc; catalyticSequence Analysis
    Metal bindingi351 – 3511Zinc; catalyticSequence Analysis

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: InterPro
    2. metallopeptidase activity Source: ProtInc
    3. zinc ion binding Source: InterPro

    GO - Biological processi

    1. binding of sperm to zona pellucida Source: Reactome
    2. multicellular organism reproduction Source: Reactome
    3. single fertilization Source: Reactome

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_163933. Interaction With The Zona Pellucida.

    Protein family/group databases

    MEROPSiM12.234.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 21 (EC:3.4.24.-)
    Short name:
    ADAM 21
    Gene namesi
    Name:ADAM21
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:200. ADAM21.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA24517.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3131Sequence AnalysisAdd
    BLAST
    Propeptidei32 – 196165Sequence AnalysisPRO_0000029108Add
    BLAST
    Chaini197 – 722526Disintegrin and metalloproteinase domain-containing protein 21PRO_0000029109Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi164 – 1641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi227 – 2271N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi316 ↔ 393By similarity
    Disulfide bondi356 ↔ 378By similarity
    Disulfide bondi358 ↔ 363By similarity
    Glycosylationi377 – 3771N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi464 ↔ 484By similarity
    Glycosylationi478 – 4781N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi546 – 5461N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi600 – 6001N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi634 ↔ 645By similarity
    Disulfide bondi639 ↔ 651By similarity
    Disulfide bondi653 ↔ 662By similarity

    Post-translational modificationi

    Has no obvious cleavage site for furin endopeptidase, suggesting that the proteolytic processing is regulated.

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiQ9UKJ8.
    PRIDEiQ9UKJ8.

    PTM databases

    PhosphoSiteiQ9UKJ8.

    Expressioni

    Gene expression databases

    BgeeiQ9UKJ8.
    CleanExiHS_ADAM21.
    GenevestigatoriQ9UKJ8.

    Organism-specific databases

    HPAiHPA059016.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000267499.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UKJ8.
    SMRiQ9UKJ8. Positions 209-628.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini197 – 681485ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini703 – 72220CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei682 – 70221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini208 – 398191Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini406 – 49287DisintegrinPROSITE-ProRule annotationAdd
    BLAST
    Domaini634 – 66330EGF-likeAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi171 – 1788Cysteine switchBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi213 – 2164Poly-Val
    Compositional biasi493 – 633141Cys-richAdd
    BLAST

    Domaini

    A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.
    The cysteine-rich domain encodes putative cell-fusion peptides, which could be involved in sperm-egg fusion.
    The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

    Sequence similaritiesi

    Contains 1 disintegrin domain.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.Curated
    Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG246189.
    HOGENOMiHOG000230883.
    HOVERGENiHBG006978.
    InParanoidiQ9UKJ8.
    KOiK08610.
    OMAiHSATFEH.
    OrthoDBiEOG7KWSGW.
    PhylomeDBiQ9UKJ8.
    TreeFamiTF314733.

    Family and domain databases

    Gene3Di3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProiIPR006586. ADAM_Cys-rich.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR018358. Disintegrin_CS.
    IPR013032. EGF-like_CS.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view]
    PfamiPF08516. ADAM_CR. 1 hit.
    PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    [Graphical view]
    PRINTSiPR00289. DISINTEGRIN.
    SMARTiSM00608. ACR. 1 hit.
    SM00050. DISIN. 1 hit.
    [Graphical view]
    SUPFAMiSSF57552. SSF57552. 1 hit.
    PROSITEiPS50215. ADAM_MEPRO. 1 hit.
    PS00427. DISINTEGRIN_1. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9UKJ8-1 [UniParc]FASTAAdd to Basket

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    MAVDGTLVYI RVTLLLLWLG VFLSISGYCQ AGPSQHFTSP EVVIPLKVIS    50
    RGRSAKAPGW LSYSLRFGGQ KHVVHMRVKK LLVSRHLPVF TYTDDRALLE 100
    DQLFIPDDCY YHGYVEAAPE SLVVFSACFG GFRGVLKISG LTYEIEPIRH 150
    SATFEHLVYK INSNETQFPA MRCGLTEKEV ARQQLEFEEA ENSALEPKSA 200
    GDWWTHAWFL ELVVVVNHDF FIYSQSNISK VQEDVFLVVN IVDSMYKQLG 250
    TYIILIGIEI WNQGNVFPMT SIEQVLNDFS QWKQISLSQL QHDAAHMFIK 300
    NSLISILGLA YVAGICRPPI DCGVDNFQGD TWSLFANTVA HELGHTLGMQ 350
    HDEEFCFCGE RGCIMNTFRV PAEKFTNCSY ADFMKTTLNQ GSCLHNPPRL 400
    GEIFMLKRCG NGVVEREEQC DCGSVQQCEQ DACCLLNCTL RPGAACAFGL 450
    CCKDCKFMPS GELCRQEVNE CDLPEWCNGT SHQCPEDRYV QDGIPCSDSA 500
    YCYQKRCNNH DQHCREIFGK DAKSASQNCY KEINSQGNRF GHCGINGTTY 550
    LKCHISDVFC GRVQCENVRD IPLLQDHFTL QHTHINGVTC WGIDYHLRMN 600
    ISDIGEVKDG TVCGPGKICI HKKCVSLSVL SHVCLPETCN MKGICNNKHH 650
    CHCGYGWSPP YCQHRGYGGS IDSGPASAKR GVFLPLIVIP SLSVLTFLFT 700
    VGLLMYLRQC SGPKETKAHS SG 722
    Length:722
    Mass (Da):80,834
    Last modified:May 18, 2010 - v2
    Checksum:i4D18503812A6C02F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti95 – 951D → E in AAD55255. (PubMed:10524237)Curated
    Sequence conflicti95 – 951D → E in AAI09025. (PubMed:15489334)Curated
    Sequence conflicti95 – 951D → E in AAI09026. (PubMed:15489334)Curated
    Sequence conflicti117 – 1171A → G in AAD55255. (PubMed:10524237)Curated
    Sequence conflicti117 – 1171A → G in AAI09025. (PubMed:15489334)Curated
    Sequence conflicti117 – 1171A → G in AAI09026. (PubMed:15489334)Curated
    Sequence conflicti161 – 1611I → V in AAD55255. (PubMed:10524237)Curated
    Sequence conflicti161 – 1611I → V in AAI09025. (PubMed:15489334)Curated
    Sequence conflicti161 – 1611I → V in AAI09026. (PubMed:15489334)Curated
    Sequence conflicti181 – 1811A → G in AAC52042. (PubMed:15489334)Curated
    Sequence conflicti247 – 2471K → Q in AAD55255. (PubMed:10524237)Curated
    Sequence conflicti247 – 2471K → Q in AAI09025. (PubMed:15489334)Curated
    Sequence conflicti247 – 2471K → Q in AAI09026. (PubMed:15489334)Curated
    Sequence conflicti345 – 3451H → Y in AAC52042. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF158644 Genomic DNA. Translation: AAD55255.1.
    AL357153 Genomic DNA. No translation available.
    AL391223 Genomic DNA. No translation available.
    BC109024 mRNA. Translation: AAI09025.1.
    BC109025 mRNA. Translation: AAI09026.1.
    AF029900 mRNA. Translation: AAC52042.1.
    CCDSiCCDS9804.1.
    RefSeqiNP_003804.2. NM_003813.3.
    UniGeneiHs.178748.

    Genome annotation databases

    EnsembliENST00000603540; ENSP00000474385; ENSG00000139985.
    GeneIDi8747.
    KEGGihsa:8747.
    UCSCiuc001xmd.3. human.

    Polymorphism databases

    DMDMi296434388.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF158644 Genomic DNA. Translation: AAD55255.1 .
    AL357153 Genomic DNA. No translation available.
    AL391223 Genomic DNA. No translation available.
    BC109024 mRNA. Translation: AAI09025.1 .
    BC109025 mRNA. Translation: AAI09026.1 .
    AF029900 mRNA. Translation: AAC52042.1 .
    CCDSi CCDS9804.1.
    RefSeqi NP_003804.2. NM_003813.3.
    UniGenei Hs.178748.

    3D structure databases

    ProteinModelPortali Q9UKJ8.
    SMRi Q9UKJ8. Positions 209-628.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000267499.

    Protein family/group databases

    MEROPSi M12.234.

    PTM databases

    PhosphoSitei Q9UKJ8.

    Polymorphism databases

    DMDMi 296434388.

    Proteomic databases

    PaxDbi Q9UKJ8.
    PRIDEi Q9UKJ8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000603540 ; ENSP00000474385 ; ENSG00000139985 .
    GeneIDi 8747.
    KEGGi hsa:8747.
    UCSCi uc001xmd.3. human.

    Organism-specific databases

    CTDi 8747.
    GeneCardsi GC14P070924.
    H-InvDB HIX0037649.
    HGNCi HGNC:200. ADAM21.
    HPAi HPA059016.
    MIMi 603713. gene.
    neXtProti NX_Q9UKJ8.
    PharmGKBi PA24517.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG246189.
    HOGENOMi HOG000230883.
    HOVERGENi HBG006978.
    InParanoidi Q9UKJ8.
    KOi K08610.
    OMAi HSATFEH.
    OrthoDBi EOG7KWSGW.
    PhylomeDBi Q9UKJ8.
    TreeFami TF314733.

    Enzyme and pathway databases

    Reactomei REACT_163933. Interaction With The Zona Pellucida.

    Miscellaneous databases

    GenomeRNAii 8747.
    NextBioi 32817.
    PROi Q9UKJ8.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9UKJ8.
    CleanExi HS_ADAM21.
    Genevestigatori Q9UKJ8.

    Family and domain databases

    Gene3Di 3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProi IPR006586. ADAM_Cys-rich.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR018358. Disintegrin_CS.
    IPR013032. EGF-like_CS.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view ]
    Pfami PF08516. ADAM_CR. 1 hit.
    PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    PF01421. Reprolysin. 1 hit.
    [Graphical view ]
    PRINTSi PR00289. DISINTEGRIN.
    SMARTi SM00608. ACR. 1 hit.
    SM00050. DISIN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57552. SSF57552. 1 hit.
    PROSITEi PS50215. ADAM_MEPRO. 1 hit.
    PS00427. DISINTEGRIN_1. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries."
      Poindexter K., Nelson N., DuBose R.F., Black R.A., Cerretti D.P.
      Gene 237:61-70(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    4. "ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha."
      Hooft van Huijsduijnen R.
      Gene 206:273-282(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 181-722.
      Tissue: Testis.

    Entry informationi

    Entry nameiADA21_HUMAN
    AccessioniPrimary (citable) accession number: Q9UKJ8
    Secondary accession number(s): O43507, Q2VPC6, Q32MR0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 2001
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 135 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    May be the functional equivalent of ADAM 1/fertilin alpha which is a pseudogene in human.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3