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Q9UKJ8

- ADA21_HUMAN

UniProt

Q9UKJ8 - ADA21_HUMAN

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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

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 Reviewed prediction.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi173 – 1731Zinc; in inhibited form By similarity
Metal bindingi341 – 3411Zinc; catalytic Reviewed prediction
Active sitei342 – 3421 Reviewed prediction
Metal bindingi345 – 3451Zinc; catalytic Reviewed prediction
Metal bindingi351 – 3511Zinc; catalytic Reviewed prediction

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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini197 – 681485Extracellular Reviewed predictionAdd
BLAST
Transmembranei682 – 70221Helical; Reviewed predictionAdd
BLAST
Topological domaini703 – 72220Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24517.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131 Reviewed predictionAdd
BLAST
Propeptidei32 – 196165 Reviewed predictionPRO_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...) Reviewed prediction
Glycosylationi227 – 2271N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi316 ↔ 393 By similarity
Disulfide bondi356 ↔ 378 By similarity
Disulfide bondi358 ↔ 363 By similarity
Glycosylationi377 – 3771N-linked (GlcNAc...) Reviewed prediction
Glycosylationi437 – 4371N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi464 ↔ 484 By similarity
Glycosylationi478 – 4781N-linked (GlcNAc...) Reviewed prediction
Glycosylationi546 – 5461N-linked (GlcNAc...) Reviewed prediction
Glycosylationi600 – 6001N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi634 ↔ 645 By similarity
Disulfide bondi639 ↔ 651 By similarity
Disulfide bondi653 ↔ 662 By 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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini208 – 398191Peptidase M12BAdd
BLAST
Domaini406 – 49287DisintegrinAdd
BLAST
Domaini634 – 66330EGF-likeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi171 – 1788Cysteine switch By 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.
Contains 1 EGF-like domain.

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

« Hide

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti95 – 951D → E in AAD55255. 1 Publication
Sequence conflicti95 – 951D → E in AAI09025. 1 Publication
Sequence conflicti95 – 951D → E in AAI09026. 1 Publication
Sequence conflicti117 – 1171A → G in AAD55255. 1 Publication
Sequence conflicti117 – 1171A → G in AAI09025. 1 Publication
Sequence conflicti117 – 1171A → G in AAI09026. 1 Publication
Sequence conflicti161 – 1611I → V in AAD55255. 1 Publication
Sequence conflicti161 – 1611I → V in AAI09025. 1 Publication
Sequence conflicti161 – 1611I → V in AAI09026. 1 Publication
Sequence conflicti181 – 1811A → G in AAC52042. 1 Publication
Sequence conflicti247 – 2471K → Q in AAD55255. 1 Publication
Sequence conflicti247 – 2471K → Q in AAI09025. 1 Publication
Sequence conflicti247 – 2471K → Q in AAI09026. 1 Publication
Sequence conflicti345 – 3451H → Y in AAC52042. 1 Publication

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

EnsembliENST00000267499; ENSP00000267499; ENSG00000139985.
ENST00000603540; 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 ENST00000267499 ; ENSP00000267499 ; ENSG00000139985 .
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 134 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

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