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Protein

Disintegrin and metalloproteinase domain-containing protein 18

Gene

ADAM18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (By similarity).By similarity

GO - Molecular functioni

  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processDifferentiation, Spermatogenesis

Protein family/group databases

MEROPSiM12.957

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 18
Short name:
ADAM 18
Alternative name(s):
Transmembrane metalloproteinase-like, disintegrin-like, and cysteine-rich protein III
Short name:
tMDC III
Gene namesi
Name:ADAM18
Synonyms:TMDC3
ORF Names:UNQ858/PRO1867
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000168619.15
HGNCiHGNC:196 ADAM18
neXtProtiNX_Q9Y3Q7

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini177 – 687ExtracellularSequence analysisAdd BLAST511
Transmembranei688 – 708HelicalSequence analysisAdd BLAST21
Topological domaini709 – 739CytoplasmicSequence analysisAdd BLAST31

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8749
OpenTargetsiENSG00000168619
PharmGKBiPA24513

Polymorphism and mutation databases

BioMutaiADAM18
DMDMi20137582

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000002909617 – 184Sequence analysisAdd BLAST168
ChainiPRO_0000029097185 – 739Disintegrin and metalloproteinase domain-containing protein 18Add BLAST555

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi36N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi76N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi122N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi149N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi156N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi177N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi293 ↔ 376By similarity
Glycosylationi294N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi335 ↔ 360By similarity
Disulfide bondi337 ↔ 342By similarity
Glycosylationi359N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi450 ↔ 471By similarity
Glycosylationi465N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi561N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi611N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi624 ↔ 636By similarity
Glycosylationi625N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi630 ↔ 642By similarity
Disulfide bondi644 ↔ 653By similarity

Post-translational modificationi

The prodomain and the metalloprotease-like domain are cleaved during the epididymal maturation of the spermatozoa.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y3Q7
PeptideAtlasiQ9Y3Q7
PRIDEiQ9Y3Q7
ProteomicsDBi86061
86062 [Q9Y3Q7-2]
86063 [Q9Y3Q7-3]

PTM databases

iPTMnetiQ9Y3Q7
PhosphoSitePlusiQ9Y3Q7

Expressioni

Tissue specificityi

Expressed specifically in testis.

Gene expression databases

BgeeiENSG00000168619 Expressed in 29 organ(s), highest expression level in right testis
CleanExiHS_ADAM18
ExpressionAtlasiQ9Y3Q7 baseline and differential
GenevisibleiQ9Y3Q7 HS

Interactioni

Protein-protein interaction databases

BioGridi114285, 74 interactors
STRINGi9606.ENSP00000265707

Structurei

3D structure databases

ProteinModelPortaliQ9Y3Q7
SMRiQ9Y3Q7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini184 – 381Peptidase M12BPROSITE-ProRule annotationAdd BLAST198
Domaini390 – 479DisintegrinPROSITE-ProRule annotationAdd BLAST90
Domaini620 – 654EGF-likeAdd BLAST35

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi480 – 622Cys-richAdd BLAST143

Domaini

A tripeptide motif (ECD) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.By similarity

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144019
HOGENOMiHOG000230883
HOVERGENiHBG103628
InParanoidiQ9Y3Q7
KOiK16909
OMAiAGTPCRK
OrthoDBiEOG091G02F0
PhylomeDBiQ9Y3Q7
TreeFamiTF314733

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS00427 DISINTEGRIN_1, 1 hit
PS50214 DISINTEGRIN_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y3Q7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MFLLLALLTE LGRLQAHEGS EGIFLHVTVP RKIKSNDSEV SERKMIYIIT
60 70 80 90 100
IDGQPYTLHL GKQSFLPQNF LVYTYNETGS LHSVSPYFMM HCHYQGYAAE
110 120 130 140 150
FPNSFVTLSI CSGLRGFLQF ENISYGIEPV ESSARFEHII YQMKNNDPNV
160 170 180 190 200
SILAVNYSHI WQKDQPYKVP LNSQIKNLSK LLPQYLEIYI IVEKALYDYM
210 220 230 240 250
GSEMMAVTQK IVQVIGLVNT MFTQFKLTVI LSSLELWSNE NQISTSGDAD
260 270 280 290 300
DILQRFLAWK RDYLILRPHD IAYLLVYRKH PKYVGATFPG TVCNKSYDAG
310 320 330 340 350
IAMYPDAIGL EGFSVIIAQL LGLNVGLTYD DITQCFCLRA TCIMNHEAVS
360 370 380 390 400
ASGRKIFSNC SMHDYRYFVS KFETKCLQKL SNLQPLHQNQ PVCGNGILES
410 420 430 440 450
NEECDCGNKN ECQFKKCCDY NTCKLKGSVK CGSGPCCTSK CELSIAGTPC
460 470 480 490 500
RKSIDPECDF TEYCNGTSSN CVPDTYALNG RLCKLGTAYC YNGQCQTTDN
510 520 530 540 550
QCAKIFGKGA QGAPFACFKE VNSLHERSEN CGFKNSQPLP CERKDVLCGK
560 570 580 590 600
LACVQPHKNA NKSDAQSTVY SYIQDHVCVS IATGSSMRSD GTDNAYVADG
610 620 630 640 650
TMCGPEMYCV NKTCRKVHLM GYNCNATTKC KGKGICNNFG NCQCFPGHRP
660 670 680 690 700
PDCKFQFGSP GGSIDDGNFQ KSGDFYTEKG YNTHWNNWFI LSFCIFLPFF
710 720 730
IVFTTVIFKR NEISKSCNRE NAEYNRNSSV VSESDDVGH
Length:739
Mass (Da):82,856
Last modified:November 1, 1999 - v1
Checksum:i2D8BE9A975072CDD
GO
Isoform 2 (identifier: Q9Y3Q7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     197-220: Missing.

Show »
Length:715
Mass (Da):80,183
Checksum:iEF8EB71EBA6AB9DB
GO
Isoform 3 (identifier: Q9Y3Q7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     175-182: IKNLSKLL → VTVIILML
     183-739: Missing.

Note: No experimental confirmation available.
Show »
Length:182
Mass (Da):20,853
Checksum:i8B524D83BC944C8B
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RK96E5RK96_HUMAN
Disintegrin and metalloproteinase d...
ADAM18
115Annotation score:
E5RIP0E5RIP0_HUMAN
Disintegrin and metalloproteinase d...
ADAM18
62Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066312170P → S in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267601916Ensembl.1
Natural variantiVAR_051588212V → F. Corresponds to variant dbSNP:rs10093794Ensembl.1
Natural variantiVAR_066313284V → G in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_066314344M → I in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs267601918Ensembl.1
Natural variantiVAR_066315362M → K in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_066316536S → L in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043285175 – 182IKNLSKLL → VTVIILML in isoform 3. 1 Publication8
Alternative sequenceiVSP_043286183 – 739Missing in isoform 3. 1 PublicationAdd BLAST557
Alternative sequenceiVSP_012033197 – 220Missing in isoform 2. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ133004 mRNA Translation: CAB40812.1
AY358321 mRNA Translation: AAQ88687.1
AK313961 mRNA Translation: BAG36677.1
AC109633 Genomic DNA No translation available.
AC136365 Genomic DNA No translation available.
BC034624 mRNA Translation: AAH34624.1
BC070279 mRNA Translation: AAH70279.1
BC121045 mRNA Translation: AAI21046.1
CCDSiCCDS55225.1 [Q9Y3Q7-3]
CCDS6113.1 [Q9Y3Q7-1]
CCDS83287.1 [Q9Y3Q7-2]
RefSeqiNP_001177885.1, NM_001190956.1 [Q9Y3Q7-3]
NP_001307242.1, NM_001320313.1 [Q9Y3Q7-2]
NP_055052.1, NM_014237.2 [Q9Y3Q7-1]
UniGeneiHs.127930

Genome annotation databases

EnsembliENST00000265707; ENSP00000265707; ENSG00000168619 [Q9Y3Q7-1]
ENST00000379866; ENSP00000369195; ENSG00000168619 [Q9Y3Q7-2]
ENST00000520772; ENSP00000429908; ENSG00000168619 [Q9Y3Q7-3]
ENST00000613609; ENSP00000482348; ENSG00000278548 [Q9Y3Q7-1]
ENST00000633688; ENSP00000488128; ENSG00000278548 [Q9Y3Q7-3]
ENST00000633768; ENSP00000488176; ENSG00000278548 [Q9Y3Q7-2]
GeneIDi8749
KEGGihsa:8749
UCSCiuc003xnh.4 human [Q9Y3Q7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ133004 mRNA Translation: CAB40812.1
AY358321 mRNA Translation: AAQ88687.1
AK313961 mRNA Translation: BAG36677.1
AC109633 Genomic DNA No translation available.
AC136365 Genomic DNA No translation available.
BC034624 mRNA Translation: AAH34624.1
BC070279 mRNA Translation: AAH70279.1
BC121045 mRNA Translation: AAI21046.1
CCDSiCCDS55225.1 [Q9Y3Q7-3]
CCDS6113.1 [Q9Y3Q7-1]
CCDS83287.1 [Q9Y3Q7-2]
RefSeqiNP_001177885.1, NM_001190956.1 [Q9Y3Q7-3]
NP_001307242.1, NM_001320313.1 [Q9Y3Q7-2]
NP_055052.1, NM_014237.2 [Q9Y3Q7-1]
UniGeneiHs.127930

3D structure databases

ProteinModelPortaliQ9Y3Q7
SMRiQ9Y3Q7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114285, 74 interactors
STRINGi9606.ENSP00000265707

Protein family/group databases

MEROPSiM12.957

PTM databases

iPTMnetiQ9Y3Q7
PhosphoSitePlusiQ9Y3Q7

Polymorphism and mutation databases

BioMutaiADAM18
DMDMi20137582

Proteomic databases

PaxDbiQ9Y3Q7
PeptideAtlasiQ9Y3Q7
PRIDEiQ9Y3Q7
ProteomicsDBi86061
86062 [Q9Y3Q7-2]
86063 [Q9Y3Q7-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265707; ENSP00000265707; ENSG00000168619 [Q9Y3Q7-1]
ENST00000379866; ENSP00000369195; ENSG00000168619 [Q9Y3Q7-2]
ENST00000520772; ENSP00000429908; ENSG00000168619 [Q9Y3Q7-3]
ENST00000613609; ENSP00000482348; ENSG00000278548 [Q9Y3Q7-1]
ENST00000633688; ENSP00000488128; ENSG00000278548 [Q9Y3Q7-3]
ENST00000633768; ENSP00000488176; ENSG00000278548 [Q9Y3Q7-2]
GeneIDi8749
KEGGihsa:8749
UCSCiuc003xnh.4 human [Q9Y3Q7-1]

Organism-specific databases

CTDi8749
DisGeNETi8749
EuPathDBiHostDB:ENSG00000168619.15
GeneCardsiADAM18
HGNCiHGNC:196 ADAM18
neXtProtiNX_Q9Y3Q7
OpenTargetsiENSG00000168619
PharmGKBiPA24513
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144019
HOGENOMiHOG000230883
HOVERGENiHBG103628
InParanoidiQ9Y3Q7
KOiK16909
OMAiAGTPCRK
OrthoDBiEOG091G02F0
PhylomeDBiQ9Y3Q7
TreeFamiTF314733

Miscellaneous databases

ChiTaRSiADAM18 human
GeneWikiiADAM18
GenomeRNAii8749
PROiPR:Q9Y3Q7

Gene expression databases

BgeeiENSG00000168619 Expressed in 29 organ(s), highest expression level in right testis
CleanExiHS_ADAM18
ExpressionAtlasiQ9Y3Q7 baseline and differential
GenevisibleiQ9Y3Q7 HS

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS00427 DISINTEGRIN_1, 1 hit
PS50214 DISINTEGRIN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA18_HUMAN
AccessioniPrimary (citable) accession number: Q9Y3Q7
Secondary accession number(s): B2R9Y0
, Q0VAI4, Q6IRW9, Q6UXJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 1, 1999
Last modified: October 10, 2018
This is version 160 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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