Q9UKQ2 (ADA28_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disintegrin and metalloproteinase domain-containing protein 28
Short name=ADAM 28
EC=3.4.24.-

Alternative name(s):
Epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II
Short name=eMDC II
Metalloproteinase-like, disintegrin-like, and cysteine-rich protein L
Short name=MDC-L

Gene names

Name:	ADAM28
Synonyms:	ADAM23, MDCL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	775 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	May play a role in the adhesive and proteolytic events that occur during lymphocyte emigration or may function in ectodomain shedding of lymphocyte surface target proteins, such as FASL and CD40L. May be involved in sperm maturation.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted.
Tissue specificity	Expressed predominantly in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix and trachea. The lymphocyte population is responsible for expression of this protein in these tissues. Isoform 2 is expressed preferentially in spleen.
Domain	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.
Post-translational modification	Pro-domain removal and maturation may be, at least in part, autocatalytic By similarity.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Traceable author statement Ref.2. Source: ProtInc
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro metallopeptidase activity Inferred from direct assay PubMed 12777399. Source: BHF-UCL 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: Q9UKQ2-1)

Also known as: MDC-LM;

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: Q9UKQ2-2)

Also known as: MDC-LS;

The sequence of this isoform differs from the canonical sequence as follows:
     524-540: TEVADKSCYNRNEGGSK → RRTNPFPCACAKENHFR
     541-775: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Propeptide	19 – 198	180	By similarity		PRO_0000029128
	Chain	199 – 775	577	Disintegrin and metalloproteinase domain-containing protein 28		PRO_0000029129
Regions
	Topological domain	199 – 665	467	Extracellular Potential
	Transmembrane	666 – 686	21	Helical; Potential
	Topological domain	687 – 775	89	Cytoplasmic Potential
	Domain	204 – 399	196	Peptidase M12B
	Domain	407 – 493	87	Disintegrin
	Domain	625 – 657	33	EGF-like
	Motif	167 – 174	8	Cysteine switch By similarity
	Compositional bias	494 – 628	135	Cys-rich
Sites
	Active site	340	1	By similarity
	Metal binding	169	1	Zinc; in inhibited form By similarity
	Metal binding	339	1	Zinc; catalytic By similarity
	Metal binding	343	1	Zinc; catalytic By similarity
	Metal binding	349	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	268	1	N-linked (GlcNAc...) Potential
	Glycosylation	275	1	N-linked (GlcNAc...) Potential
	Glycosylation	557	1	N-linked (GlcNAc...) Potential
	Glycosylation	602	1	N-linked (GlcNAc...) Potential
	Glycosylation	628	1	N-linked (GlcNAc...) Potential
	Disulfide bond	315 ↔ 394		By similarity
	Disulfide bond	354 ↔ 378		By similarity
	Disulfide bond	356 ↔ 361		By similarity
	Disulfide bond	465 ↔ 485		By similarity
	Disulfide bond	629 ↔ 639		By similarity
	Disulfide bond	633 ↔ 645		By similarity
	Disulfide bond	647 ↔ 656		By similarity
Natural variations
	Alternative sequence	524 – 540	17	TEVAD…EGGSK → RRTNPFPCACAKENHFR in isoform 2.		VSP_005486
	Alternative sequence	541 – 775	235	Missing in isoform 2.		VSP_005487
	Natural variant	65	1	G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6		VAR_066317
	Natural variant	134	1	G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6		VAR_066318
	Natural variant	219	1	R → M. Corresponds to variant rs9314282 [ dbSNP | Ensembl ].		VAR_057067
	Natural variant	226	1	E → D. Corresponds to variant rs17736699 [ dbSNP | Ensembl ].		VAR_057068
	Natural variant	450	1	G → E in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6		VAR_066319
	Natural variant	482	1	S → F in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6		VAR_066320
	Natural variant	493	1	N → S. Corresponds to variant rs7001647 [ dbSNP | Ensembl ].		VAR_057069
	Natural variant	502	1	G → D in a cutaneous metastatic melanoma sample; somatic mutation. Ref.6		VAR_066321
	Natural variant	593	1	T → K. Corresponds to variant rs36041430 [ dbSNP | Ensembl ].		VAR_057070
	Natural variant	604	1	T → P. Corresponds to variant rs35617826 [ dbSNP | Ensembl ].		VAR_057071
	Natural variant	684	1	M → I. Corresponds to variant rs7829965 [ dbSNP | Ensembl ].		VAR_057072
	Natural variant	765	1	V → M. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs7814768 [ dbSNP | Ensembl ].		VAR_024596
Experimental info
	Sequence conflict	513	1	Q → R in AAD25099. Ref.1
	Sequence conflict	513	1	Q → R in AAD25100. Ref.1
	Sequence conflict	774	1	K → E in AAD25099. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MDC-LM) [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 895E0985840F971C	FASTA	775	87,148
	10 20 30 40 50 60 MLQGLLPVSL LLSVAVSAIK ELPGVKKYEV VYPIRLHPLH KREAKEPEQQ EQFETELKYK 70 80 90 100 110 120 MTINGKIAVL YLKKNKNLLA PGYTETYYNS TGKEITTSPQ IMDDCYYQGH ILNEKVSDAS 130 140 150 160 170 180 ISTCRGLRGY FSQGDQRYFI EPLSPIHRDG QEHALFKYNP DEKNYDSTCG MDGVLWAHDL 190 200 210 220 230 240 QQNIALPATK LVKLKDRKVQ EHEKYIEYYL VLDNGEFKRY NENQDEIRKR VFEMANYVNM 250 260 270 280 290 300 LYKKLNTHVA LVGMEIWTDK DKIKITPNAS FTLENFSKWR GSVLSRRKRH DIAQLITATE 310 320 330 340 350 360 LAGTTVGLAF MSTMCSPYSV GVVQDHSDNL LRVAGTMAHE MGHNFGMFHD DYSCKCPSTI 370 380 390 400 410 420 CVMDKALSFY IPTDFSSCSR LSYDKFFEDK LSNCLFNAPL PTDIISTPIC GNQLVEMGED 430 440 450 460 470 480 CDCGTSEECT NICCDAKTCK IKATFQCALG ECCEKCQFKK AGMVCRPAKD ECDLPEMCNG 490 500 510 520 530 540 KSGNCPDDRF QVNGFPCHHG KGHCLMGTCP TLQEQCTELW GPGTEVADKS CYNRNEGGSK 550 560 570 580 590 600 YGYCRRVDDT LIPCKANDTM CGKLFCQGGS DNLPWKGRIV TFLTCKTFDP EDTSQEIGMV 610 620 630 640 650 660 ANGTKCGDNK VCINAECVDI EKAYKSTNCS SKCKGHAVCD HELQCQCEEG WIPPDCDDSS 670 680 690 700 710 720 VVFHFSIVVG VLFPMAVIFV VVAMVIRHQS SREKQKKDQR PLSTTGTRPH KQKRKPQMVK 730 740 750 760 770 AVQPQEMSQM KPHVYDLPVE GNEPPASFHK DTNALPPTVF KDNPVSTPKD SNPKA
	Isoform 2 (MDC-LS) [UniParc]. Checksum: 65F475E18650D227	FASTA	540	61,232
	10 20 30 40 50 60 MLQGLLPVSL LLSVAVSAIK ELPGVKKYEV VYPIRLHPLH KREAKEPEQQ EQFETELKYK 70 80 90 100 110 120 MTINGKIAVL YLKKNKNLLA PGYTETYYNS TGKEITTSPQ IMDDCYYQGH ILNEKVSDAS 130 140 150 160 170 180 ISTCRGLRGY FSQGDQRYFI EPLSPIHRDG QEHALFKYNP DEKNYDSTCG MDGVLWAHDL 190 200 210 220 230 240 QQNIALPATK LVKLKDRKVQ EHEKYIEYYL VLDNGEFKRY NENQDEIRKR VFEMANYVNM 250 260 270 280 290 300 LYKKLNTHVA LVGMEIWTDK DKIKITPNAS FTLENFSKWR GSVLSRRKRH DIAQLITATE 310 320 330 340 350 360 LAGTTVGLAF MSTMCSPYSV GVVQDHSDNL LRVAGTMAHE MGHNFGMFHD DYSCKCPSTI 370 380 390 400 410 420 CVMDKALSFY IPTDFSSCSR LSYDKFFEDK LSNCLFNAPL PTDIISTPIC GNQLVEMGED 430 440 450 460 470 480 CDCGTSEECT NICCDAKTCK IKATFQCALG ECCEKCQFKK AGMVCRPAKD ECDLPEMCNG 490 500 510 520 530 540 KSGNCPDDRF QVNGFPCHHG KGHCLMGTCP TLQEQCTELW GPGRRTNPFP CACAKENHFR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes." Roberts C.M., Tani P.H., Bridges L.C., Laszik Z., Bowditch R.D. J. Biol. Chem. 274:29251-29259(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT MET-765. Tissue: Lymph node.
[2]	"Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis." Jury J.A., Perry A.C., Hall L. Mol. Hum. Reprod. 5:1127-1134(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-765. Tissue: Epididymis.
[3]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT MET-765.
[5]	"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], VARIANT MET-765. Tissue: Brain.
[6]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS GLU-65; GLU-134; GLU-450; PHE-482 AND ASP-502.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF137334 mRNA. Translation: AAD25099.1. AF137335 mRNA. Translation: AAD25100.1. AJ242015 mRNA. Translation: CAB42085.1. AC044891 Genomic DNA. No translation available. AC120193 Genomic DNA. No translation available. CH471080 Genomic DNA. Translation: EAW63609.1. BC136478 mRNA. Translation: AAI36479.1.
IPI	IPI00007709. IPI00029097.
RefSeq	NP_055080.2. NM_014265.4. NP_068547.2. NM_021777.3.
UniGene	Hs.174030.
3D structure databases
ProteinModelPortal	Q9UKQ2.
SMR	Q9UKQ2. Positions 199-657.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000265769.
Protein family/group databases
MEROPS	M12.224.
PTM databases
PhosphoSite	Q9UKQ2.
Polymorphism databases
DMDM	160332334.
Proteomic databases
PaxDb	Q9UKQ2.
PRIDE	Q9UKQ2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265769; ENSP00000265769; ENSG00000042980. ENST00000437154; ENSP00000393699; ENSG00000042980.
GeneID	10863.
KEGG	hsa:10863.
UCSC	uc003xdx.3. human. uc003xdy.3. human.
Organism-specific databases
CTD	10863.
GeneCards	GC08P024207.
H-InvDB	HIX0034262.
HGNC	HGNC:206. ADAM28.
MIM	606188. gene.
neXtProt	NX_Q9UKQ2.
PharmGKB	PA24523.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG277164.
HOGENOM	HOG000230883.
HOVERGEN	HBG006978.
InParanoid	Q9UKQ2.
KO	K08614.
OMA	TSPQIMD.
OrthoDB	EOG4PC9RW.
PhylomeDB	Q9UKQ2.
Gene expression databases
ArrayExpress	Q9UKQ2.
Bgee	Q9UKQ2.
CleanEx	HS_ADAM23. HS_ADAM28.
Genevestigator	Q9UKQ2.
GermOnline	ENSG00000042980. Homo sapiens.
Family and domain databases
Gene3D	3.40.390.10. 1 hit. 4.10.70.10. 1 hit.
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR024079. MetalloPept_cat_dom. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Pfam	PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view]
PRINTS	PR00289. DISINTEGRIN.
SMART	SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. SM00181. EGF. 1 hit. [Graphical view]
SUPFAM	SSF57552. Disintegrin. 1 hit.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10863.
NextBio	41241.
SOURCE	Search...

Entry information

Entry name

ADA28_HUMAN

Accession

Primary (citable) accession number: Q9UKQ2
Secondary accession number(s): B2RMV5, Q9Y339, Q9Y3S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 129 of the entry and version 3 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.