Q9Y3Q7 (ADA18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ADAM18
Synonyms:	TMDC3
ORF Names:	UNQ858/PRO1867

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	739 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed specifically in testis.
Domain	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.
Post-translational modification	The prodomain and the metalloprotease-like domain are cleaved during the epididymal maturation of the spermatozoa By similarity.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Differentiation Spermatogenesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro spermatogenesis Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Traceable author statement. Source: ProtInc
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y3Q7-1)

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.

Isoform 2 (identifier: Q9Y3Q7-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Potential
	Propeptide	17 – 184	168	Potential		PRO_0000029096
	Chain	185 – 739	555	Disintegrin and metalloproteinase domain-containing protein 18		PRO_0000029097
Regions
	Topological domain	177 – 687	511	Extracellular Potential
	Transmembrane	688 – 708	21	Helical; Potential
	Topological domain	709 – 739	31	Cytoplasmic Potential
	Domain	184 – 381	198	Peptidase M12B
	Domain	390 – 479	90	Disintegrin
	Domain	620 – 654	35	EGF-like
	Compositional bias	480 – 622	143	Cys-rich
Amino acid modifications
	Glycosylation	36	1	N-linked (GlcNAc...) Potential
	Glycosylation	76	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	149	1	N-linked (GlcNAc...) Potential
	Glycosylation	156	1	N-linked (GlcNAc...) Potential
	Glycosylation	177	1	N-linked (GlcNAc...) Potential
	Glycosylation	294	1	N-linked (GlcNAc...) Potential
	Glycosylation	359	1	N-linked (GlcNAc...) Potential
	Glycosylation	465	1	N-linked (GlcNAc...) Potential
	Glycosylation	561	1	N-linked (GlcNAc...) Potential
	Glycosylation	611	1	N-linked (GlcNAc...) Potential
	Glycosylation	625	1	N-linked (GlcNAc...) Potential
	Disulfide bond	293 ↔ 376		By similarity
	Disulfide bond	335 ↔ 360		By similarity
	Disulfide bond	337 ↔ 342		By similarity
	Disulfide bond	450 ↔ 471		By similarity
	Disulfide bond	624 ↔ 636		By similarity
	Disulfide bond	630 ↔ 642		By similarity
	Disulfide bond	644 ↔ 653		By similarity
Natural variations
	Alternative sequence	197 – 220	24	Missing in isoform 2.		VSP_012033
	Natural variant	170	1	P → S in a cutaneous metastatic melanoma sample; somatic mutation. Ref.5		VAR_066312
	Natural variant	212	1	V → F. Corresponds to variant rs10093794 [ dbSNP | Ensembl ].		VAR_051588
	Natural variant	284	1	V → G in a cutaneous metastatic melanoma sample; somatic mutation. Ref.5		VAR_066313
	Natural variant	344	1	M → I in a cutaneous metastatic melanoma sample; somatic mutation. Ref.5		VAR_066314
	Natural variant	362	1	M → K in a cutaneous metastatic melanoma sample; somatic mutation. Ref.5		VAR_066315
	Natural variant	536	1	S → L in a cutaneous metastatic melanoma sample; somatic mutation. Ref.5		VAR_066316

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2D8BE9A975072CDD	FASTA	739	82,856
	10 20 30 40 50 60 MFLLLALLTE LGRLQAHEGS EGIFLHVTVP RKIKSNDSEV SERKMIYIIT IDGQPYTLHL 70 80 90 100 110 120 GKQSFLPQNF LVYTYNETGS LHSVSPYFMM HCHYQGYAAE FPNSFVTLSI CSGLRGFLQF 130 140 150 160 170 180 ENISYGIEPV ESSARFEHII YQMKNNDPNV SILAVNYSHI WQKDQPYKVP LNSQIKNLSK 190 200 210 220 230 240 LLPQYLEIYI IVEKALYDYM GSEMMAVTQK IVQVIGLVNT MFTQFKLTVI LSSLELWSNE 250 260 270 280 290 300 NQISTSGDAD DILQRFLAWK RDYLILRPHD IAYLLVYRKH PKYVGATFPG TVCNKSYDAG 310 320 330 340 350 360 IAMYPDAIGL EGFSVIIAQL LGLNVGLTYD DITQCFCLRA TCIMNHEAVS ASGRKIFSNC 370 380 390 400 410 420 SMHDYRYFVS KFETKCLQKL SNLQPLHQNQ PVCGNGILES NEECDCGNKN ECQFKKCCDY 430 440 450 460 470 480 NTCKLKGSVK CGSGPCCTSK CELSIAGTPC RKSIDPECDF TEYCNGTSSN CVPDTYALNG 490 500 510 520 530 540 RLCKLGTAYC YNGQCQTTDN QCAKIFGKGA QGAPFACFKE VNSLHERSEN CGFKNSQPLP 550 560 570 580 590 600 CERKDVLCGK LACVQPHKNA NKSDAQSTVY SYIQDHVCVS IATGSSMRSD GTDNAYVADG 610 620 630 640 650 660 TMCGPEMYCV NKTCRKVHLM GYNCNATTKC KGKGICNNFG NCQCFPGHRP PDCKFQFGSP 670 680 690 700 710 720 GGSIDDGNFQ KSGDFYTEKG YNTHWNNWFI LSFCIFLPFF IVFTTVIFKR NEISKSCNRE 730 NAEYNRNSSV VSESDDVGH
	Isoform 2 [UniParc]. Checksum: EF8EB71EBA6AB9DB	FASTA	715	80,183
	10 20 30 40 50 60 MFLLLALLTE LGRLQAHEGS EGIFLHVTVP RKIKSNDSEV SERKMIYIIT IDGQPYTLHL 70 80 90 100 110 120 GKQSFLPQNF LVYTYNETGS LHSVSPYFMM HCHYQGYAAE FPNSFVTLSI CSGLRGFLQF 130 140 150 160 170 180 ENISYGIEPV ESSARFEHII YQMKNNDPNV SILAVNYSHI WQKDQPYKVP LNSQIKNLSK 190 200 210 220 230 240 LLPQYLEIYI IVEKALMFTQ FKLTVILSSL ELWSNENQIS TSGDADDILQ RFLAWKRDYL 250 260 270 280 290 300 ILRPHDIAYL LVYRKHPKYV GATFPGTVCN KSYDAGIAMY PDAIGLEGFS VIIAQLLGLN 310 320 330 340 350 360 VGLTYDDITQ CFCLRATCIM NHEAVSASGR KIFSNCSMHD YRYFVSKFET KCLQKLSNLQ 370 380 390 400 410 420 PLHQNQPVCG NGILESNEEC DCGNKNECQF KKCCDYNTCK LKGSVKCGSG PCCTSKCELS 430 440 450 460 470 480 IAGTPCRKSI DPECDFTEYC NGTSSNCVPD TYALNGRLCK LGTAYCYNGQ CQTTDNQCAK 490 500 510 520 530 540 IFGKGAQGAP FACFKEVNSL HERSENCGFK NSQPLPCERK DVLCGKLACV QPHKNANKSD 550 560 570 580 590 600 AQSTVYSYIQ DHVCVSIATG SSMRSDGTDN AYVADGTMCG PEMYCVNKTC RKVHLMGYNC 610 620 630 640 650 660 NATTKCKGKG ICNNFGNCQC FPGHRPPDCK FQFGSPGGSI DDGNFQKSGD FYTEKGYNTH 670 680 690 700 710 WNNWFILSFC IFLPFFIVFT TVIFKRNEIS KSCNRENAEY NRNSSVVSES DDVGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the human tMDC III sperm surface protein transcript." Hall L., Frayne J., Dimsey E.A. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Testis.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma." Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., Rudloff U., Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y. Hum. Mutat. 32:E2148-E2175(2011) [PubMed: 21618342] [Abstract] Cited for: VARIANTS SER-170; GLY-284; ILE-344; LYS-362 AND LEU-536.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ133004 mRNA. Translation: CAB40812.1. AY358321 mRNA. Translation: AAQ88687.1. AK313961 mRNA. Translation: BAG36677.1. BC121045 mRNA. Translation: AAI21046.1.
IPI	IPI00003365. IPI00479446.
RefSeq	NP_055052.1. NM_014237.2.
UniGene	Hs.127930.
3D structure databases
ProteinModelPortal	Q9Y3Q7.
SMR	Q9Y3Q7. Positions 179-661.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y3Q7.
Protein family/group databases
MEROPS	M12.957.
PTM databases
PhosphoSite	Q9Y3Q7.
Polymorphism databases
DMDM	20137582.
Proteomic databases
PRIDE	Q9Y3Q7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265707; ENSP00000265707; ENSG00000168619.
GeneID	8749.
KEGG	hsa:8749.
UCSC	uc003xni.1. human. uc010lwx.1. human.
Organism-specific databases
CTD	8749.
GeneCards	GC08P039459.
H-InvDB	HIX0034291.
HGNC	HGNC:196. ADAM18.
HPA	HPA027605.
neXtProt	NX_Q9Y3Q7.
PharmGKB	PA24513.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13297.
GeneTree	ENSGT00590000082741.
HOGENOM	HBG507118.
HOVERGEN	HBG103628.
InParanoid	Q9Y3Q7.
OMA	GTAYCYN.
OrthoDB	EOG4P8FHF.
PhylomeDB	Q9Y3Q7.
Gene expression databases
ArrayExpress	Q9Y3Q7.
Bgee	Q9Y3Q7.
CleanEx	HS_ADAM18.
Genevestigator	Q9Y3Q7.
GermOnline	ENSG00000168619. Homo sapiens.
Family and domain databases
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR024079. MetalloPept_cat_dom. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Gene3D	G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit. G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.
Pfam	PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view]
SMART	SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. [Graphical view]
SUPFAM	SSF57552. Disintegrin. 1 hit.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	32825.

Entry information

Entry name

ADA18_HUMAN

Accession

Primary (citable) accession number: Q9Y3Q7
Secondary accession number(s): B2R9Y0, Q0VAI4, Q6UXJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	November 1, 1999
Last modified:	January 25, 2012
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.