Reviewed, UniProtKB/Swiss-Prot Q9UKQ2 (ADA28_HUMAN)

Names and origin

Protein names

Recommended name:
    ADAM 28
    EC=3.4.24.-
Alternative name(s):
    A disintegrin and metalloproteinase domain 28
    Metalloproteinase-like, disintegrin-like, and cysteine-rich protein-L
      Short name=MDC-L
    eMDC II

Gene names

Name:	ADAM28
Synonyms:	ADAM23, MDCL

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	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
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	spermatogenesis Ref.2 Traceable author statement. Source: ProtInc
Molecular function	metallopeptidase activity Ref.2 Traceable author statement. Source: ProtInc
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
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Propeptide	19 – 198	180	By similarity
	Chain	199 – 775	577	ADAM 28
Regions
	Topological domain	199 – 665	467	Extracellular Potential
	Transmembrane	666 – 686	21	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.
	Alternative sequence	541 – 775	235	Missing in isoform 2.
	Natural variant	765	1	M → V: dbSNP rs7814768.
Experimental info
	Sequence conflict	513	1	Q → R in AAD25099 and AAD25100. Ref.1
	Sequence conflict	774	1	E → K in CAB42085. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MDC-LM) [UniParc]. Last modified November 13, 2007. Version 2. Checksum: 89563432840F971C	FASTA	775	87,181
	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 KDNPMSTPKD SNPEA
	Isoform 2 (MDC-LS) [UniParc]. Checksum: 65F475E18650D227		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

[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: 10506182] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). 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: 10587367] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Epididymis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF137334 mRNA. Translation: AAD25099.1. AF137335 mRNA. Translation: AAD25100.1. AJ242015 mRNA. Translation: CAB42085.1.
RefSeq	NP_055080.2. NP_068547.2.
UniGene	Hs.174030
3D structure databases
HSSP	HSSP built from PDB template 1FVL based on UniProtKB P18619.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UKQ2.
Protein family/group databases
MEROPS	M12.224.
Genome annotation databases
Ensembl	ENSG00000042980. Homo sapiens. [Contig view]
GeneID	10863.
KEGG	hsa:10863.
Organism-specific databases
H-InvDB	HIX0034262.
HGNC	HGNC:206. ADAM28.
MIM	606188. gene.
PharmGKB	PA24523.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q9UKQ2.
HOVERGEN	Q9UKQ2.
Gene expression databases
ArrayExpress	Q9UKQ2.
CleanEx	HS_ADAM23. HS_ADAM28.
GermOnline	ENSG00000042980. Homo sapiens.
Family and domain databases
InterPro	IPR006586. ADAM_cysteine. IPR001762. Blood-coag_inhib_Disintegrin. IPR006210. EGF. IPR000742. EGF_3. IPR013032. EGF_like_reg_CS. IPR001818. Pept_M10A_M12B. IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Gene3D	G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
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.
ProDom	PD000664. Disintegrin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. SM00181. EGF. 1 hit. [Graphical view]
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]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ADA28_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	November 13, 2007
Last modified:	September 2, 2008
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)