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Protein

Disintegrin and metalloproteinase domain-containing protein 18

Gene

ADAM18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • cell differentiation Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • spermatogenesis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Spermatogenesis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000074251-MONOMER.
ZFISH:ENSG00000168619-MONOMER.

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

HGNCiHGNC:196. ADAM18.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8749.
OpenTargetsiENSG00000168619.
ENSG00000278548.
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...)Sequence analysis1
Glycosylationi76N-linked (GlcNAc...)Sequence analysis1
Glycosylationi122N-linked (GlcNAc...)Sequence analysis1
Glycosylationi149N-linked (GlcNAc...)Sequence analysis1
Glycosylationi156N-linked (GlcNAc...)Sequence analysis1
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi293 ↔ 376By similarity
Glycosylationi294N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi335 ↔ 360By similarity
Disulfide bondi337 ↔ 342By similarity
Glycosylationi359N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi450 ↔ 471By similarity
Glycosylationi465N-linked (GlcNAc...)Sequence analysis1
Glycosylationi561N-linked (GlcNAc...)Sequence analysis1
Glycosylationi611N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi624 ↔ 636By similarity
Glycosylationi625N-linked (GlcNAc...)Sequence 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.

PTM databases

iPTMnetiQ9Y3Q7.
PhosphoSitePlusiQ9Y3Q7.

Expressioni

Tissue specificityi

Expressed specifically in testis.

Gene expression databases

BgeeiENSG00000168619.
CleanExiHS_ADAM18.
ExpressionAtlasiQ9Y3Q7. baseline and differential.
GenevisibleiQ9Y3Q7. HS.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000265707.

Structurei

3D structure databases

ProteinModelPortaliQ9Y3Q7.
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

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

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00800000124044.
HOGENOMiHOG000142479.
HOVERGENiHBG103628.
InParanoidiQ9Y3Q7.
KOiK16909.
OMAiYMGSEMM.
OrthoDBiEOG091G02F0.
PhylomeDBiQ9Y3Q7.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
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]
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.
[Graphical view]

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

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066312170P → S in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs267601916dbSNPEnsembl.1
Natural variantiVAR_051588212V → F.Corresponds to variant rs10093794dbSNPEnsembl.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 rs267601918dbSNPEnsembl.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

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000265707.

Protein family/group databases

MEROPSiM12.957.

PTM databases

iPTMnetiQ9Y3Q7.
PhosphoSitePlusiQ9Y3Q7.

Polymorphism and mutation databases

BioMutaiADAM18.
DMDMi20137582.

Proteomic databases

PaxDbiQ9Y3Q7.
PeptideAtlasiQ9Y3Q7.
PRIDEiQ9Y3Q7.

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.
GeneCardsiADAM18.
HGNCiHGNC:196. ADAM18.
neXtProtiNX_Q9Y3Q7.
OpenTargetsiENSG00000168619.
ENSG00000278548.
PharmGKBiPA24513.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00800000124044.
HOGENOMiHOG000142479.
HOVERGENiHBG103628.
InParanoidiQ9Y3Q7.
KOiK16909.
OMAiYMGSEMM.
OrthoDBiEOG091G02F0.
PhylomeDBiQ9Y3Q7.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000074251-MONOMER.
ZFISH:ENSG00000168619-MONOMER.

Miscellaneous databases

ChiTaRSiADAM18. human.
GeneWikiiADAM18.
GenomeRNAii8749.
PROiQ9Y3Q7.

Gene expression databases

BgeeiENSG00000168619.
CleanExiHS_ADAM18.
ExpressionAtlasiQ9Y3Q7. baseline and differential.
GenevisibleiQ9Y3Q7. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
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]
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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADA18_HUMAN
AccessioniPrimary (citable) accession number: Q9Y3Q7
Secondary accession number(s): B2R9Y0
, Q0VAI4, Q6IRW9, Q6UXJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 1, 1999
Last modified: November 2, 2016
This is version 144 of the entry and version 1 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

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
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.