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Protein

Disintegrin and metalloproteinase domain-containing protein 21

Gene

ADAM21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Zn2+CuratedNote: 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
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 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:200. ADAM21.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini197 – 681485ExtracellularSequence AnalysisAdd
BLAST
Transmembranei682 – 70221HelicalSequence AnalysisAdd
BLAST
Topological domaini703 – 72220CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. neuronal cell body Source: Ensembl
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24517.

Polymorphism and mutation databases

BioMutaiADAM21.
DMDMi296434388.

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...

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.
GeneTreeiENSGT00760000118888.
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

        10         20         30         40         50
MAVDGTLVYI RVTLLLLWLG VFLSISGYCQ AGPSQHFTSP EVVIPLKVIS
60 70 80 90 100
RGRSAKAPGW LSYSLRFGGQ KHVVHMRVKK LLVSRHLPVF TYTDDRALLE
110 120 130 140 150
DQLFIPDDCY YHGYVEAAPE SLVVFSACFG GFRGVLKISG LTYEIEPIRH
160 170 180 190 200
SATFEHLVYK INSNETQFPA MRCGLTEKEV ARQQLEFEEA ENSALEPKSA
210 220 230 240 250
GDWWTHAWFL ELVVVVNHDF FIYSQSNISK VQEDVFLVVN IVDSMYKQLG
260 270 280 290 300
TYIILIGIEI WNQGNVFPMT SIEQVLNDFS QWKQISLSQL QHDAAHMFIK
310 320 330 340 350
NSLISILGLA YVAGICRPPI DCGVDNFQGD TWSLFANTVA HELGHTLGMQ
360 370 380 390 400
HDEEFCFCGE RGCIMNTFRV PAEKFTNCSY ADFMKTTLNQ GSCLHNPPRL
410 420 430 440 450
GEIFMLKRCG NGVVEREEQC DCGSVQQCEQ DACCLLNCTL RPGAACAFGL
460 470 480 490 500
CCKDCKFMPS GELCRQEVNE CDLPEWCNGT SHQCPEDRYV QDGIPCSDSA
510 520 530 540 550
YCYQKRCNNH DQHCREIFGK DAKSASQNCY KEINSQGNRF GHCGINGTTY
560 570 580 590 600
LKCHISDVFC GRVQCENVRD IPLLQDHFTL QHTHINGVTC WGIDYHLRMN
610 620 630 640 650
ISDIGEVKDG TVCGPGKICI HKKCVSLSVL SHVCLPETCN MKGICNNKHH
660 670 680 690 700
CHCGYGWSPP YCQHRGYGGS IDSGPASAKR GVFLPLIVIP SLSVLTFLFT
710 720
VGLLMYLRQC SGPKETKAHS SG
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:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiADAM21.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

STRINGi9606.ENSP00000267499.

Protein family/group databases

MEROPSiM12.234.

PTM databases

PhosphoSiteiQ9UKJ8.

Polymorphism and mutation databases

BioMutaiADAM21.
DMDMi296434388.

Proteomic databases

PaxDbiQ9UKJ8.
PRIDEiQ9UKJ8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8747.
GeneCardsiGC14P070924.
H-InvDBHIX0037649.
HGNCiHGNC:200. ADAM21.
HPAiHPA059016.
MIMi603713. gene.
neXtProtiNX_Q9UKJ8.
PharmGKBiPA24517.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG246189.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ9UKJ8.
KOiK08610.
OMAiHSATFEH.
OrthoDBiEOG7KWSGW.
PhylomeDBiQ9UKJ8.
TreeFamiTF314733.

Enzyme and pathway databases

ReactomeiREACT_163933. Interaction With The Zona Pellucida.

Miscellaneous databases

GenomeRNAii8747.
NextBioi32817.
PROiQ9UKJ8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UKJ8.
CleanExiHS_ADAM21.
GenevestigatoriQ9UKJ8.

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]
ProtoNetiSearch...

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: April 29, 2015
This is version 139 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.