Reviewed, UniProtKB/Swiss-Prot O75078 (ADA11_HUMAN)

Names and origin

Protein names

Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 11
      Short name=ADAM 11
Alternative name(s):
    Metalloproteinase-like, disintegrin-like, and cysteine-rich protein
      Short name=MDC

Gene names

Name:	ADAM11
Synonyms:	MDC

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	769 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	Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein.
Subunit structure	Can bind to LGI1 and LGI4 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed predominantly in brain. Slightly detected or not at all in other tissues.
Domain	A conserved motif [AVN[ED]CD] within the disintegrin-like domain could be involved in the binding to the integrin receptor.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity.
Involvement in disease	Rearrangements occur in breast and ovarian cancers which involve multiple exons and disrupt the coding region.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	EGF-like domain Signal Transmembrane
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	integrin-mediated signaling pathway Ref.2 Traceable author statement. Source: ProtInc proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	integrin binding Ref.1 Traceable author statement. Source: ProtInc 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 Long (identifier: O75078-1)

Also known as: MDC-769;

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 Short (identifier: O75078-2)

Also known as: MDC-524;

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.
     100-104: DLELN → MCWLS
     595-623: DVLCGFLLCVNISGAPRLGDLVGDISSVT → PQQGRAVWLPPLCQHLWSSSARGPGGRHQ
     624-769: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Propeptide	24 – 225	202	By similarity		PRO_0000029074
	Chain	226 – 769	544	Disintegrin and metalloproteinase domain-containing protein 11		PRO_0000029075
Regions
	Topological domain	226 – 734	509	Extracellular Potential
	Transmembrane	735 – 755	21	Potential
	Topological domain	756 – 769	14	Cytoplasmic Potential
	Domain	239 – 438	200	Peptidase M12B
	Domain	444 – 531	88	Disintegrin
	Domain	677 – 709	33	EGF-like
	Compositional bias	532 – 676	145	Cys-rich
Amino acid modifications
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	163	1	N-linked (GlcNAc...) Potential
	Glycosylation	605	1	N-linked (GlcNAc...) Potential
	Glycosylation	673	1	N-linked (GlcNAc...) Potential
	Disulfide bond	349 ↔ 433		By similarity
	Disulfide bond	392 ↔ 417		By similarity
	Disulfide bond	394 ↔ 401		By similarity
	Disulfide bond	503 ↔ 523		By similarity
	Disulfide bond	677 ↔ 692		By similarity
	Disulfide bond	686 ↔ 698		By similarity
	Disulfide bond	700 ↔ 709		By similarity
Natural variations
	Alternative sequence	1 – 99	99	Missing in isoform Short.		VSP_005472
	Alternative sequence	100 – 104	5	DLELN → MCWLS in isoform Short.		VSP_005473
	Alternative sequence	595 – 623	29	DVLCG…ISSVT → PQQGRAVWLPPLCQHLWSSS ARGPGGRHQ in isoform Short.		VSP_005474
	Alternative sequence	624 – 769	146	Missing in isoform Short.		VSP_005475
Experimental info
	Sequence conflict	106	1	H → Q in BAA06670. Ref.2
	Sequence conflict	106	1	H → Q in BAA06671. Ref.3
	Sequence conflict	325	1	D → N in BAA04213. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long (MDC-769) [UniParc]. Last modified October 3, 2006. Version 3. Checksum: EEB091EB6730AC36	FASTA	769	83,418
	10 20 30 40 50 60 MRLLRRWAFA ALLLSLLPTP GLGTQGPAGA LRWGGLPQLG GPGAPEVTEP SRLVRESSGG 70 80 90 100 110 120 EVRKQQLDTR VRQEPPGGPP VHLAQVSFVI PAFNSNFTLD LELNHHLLSS QYVERHFSRE 130 140 150 160 170 180 GTTQHSTGAG DHCYYQGKLR GNPHSFAALS TCQGLHGVFS DGNLTYIVEP QEVAGPWGAP 190 200 210 220 230 240 QGPLPHLIYR TPLLPDPLGC REPGCLFAVP AQSAPPNRPR LRRKRQVRRG HPTVHSETKY 250 260 270 280 290 300 VELIVINDHQ LFEQMRQSVV LTSNFAKSVV NLADVIYKEQ LNTRIVLVAM ETWADGDKIQ 310 320 330 340 350 360 VQDDLLETLA RLMVYRREGL PEPSDATHLF SGRTFQSTSS GAAYVGGICS LSHGGGVNEY 370 380 390 400 410 420 GNMGAMAVTL AQTLGQNLGM MWNKHRSSAG DCKCPDIWLG CIMEDTGFYL PRKFSRCSID 430 440 450 460 470 480 EYNQFLQEGG GSCLFNKPLK LLDPPECGNG FVEAGEECDC GSVQECSRAG GNCCKKCTLT 490 500 510 520 530 540 HDAMCSDGLC CRRCKYEPRG VSCREAVNEC DIAETCTGDS SQCPPNLHKL DGYYCDHEQG 550 560 570 580 590 600 RCYGGRCKTR DRQCQVLWGH AAADRFCYEK LNVEGTERGS CGRKGSGWVQ CSKQDVLCGF 610 620 630 640 650 660 LLCVNISGAP RLGDLVGDIS SVTFYHQGKE LDCRGGHVQL ADGSDLSYVE DGTACGPNML 670 680 690 700 710 720 CLDHRCLPAS AFNFSTCPGS GERRICSHHG VCSNEGKCIC QPDWTGKDCS IHNPLPTSPP 730 740 750 760 TGETERYKGP SGTNIIIGSI AGAVLVAAIV LGGTGWGFKN IRRGRSGGA
	Isoform Short (MDC-524). Checksum: CC3756772F1EB346	FASTA	524	57,911
	10 20 30 40 50 60 MCWLSHHLLS SQYVERHFSR EGTTQHSTGA GDHCYYQGKL RGNPHSFAAL STCQGLHGVF 70 80 90 100 110 120 SDGNLTYIVE PQEVAGPWGA PQGPLPHLIY RTPLLPDPLG CREPGCLFAV PAQSAPPNRP 130 140 150 160 170 180 RLRRKRQVRR GHPTVHSETK YVELIVINDH QLFEQMRQSV VLTSNFAKSV VNLADVIYKE 190 200 210 220 230 240 QLNTRIVLVA METWADGDKI QVQDDLLETL ARLMVYRREG LPEPSDATHL FSGRTFQSTS 250 260 270 280 290 300 SGAAYVGGIC SLSHGGGVNE YGNMGAMAVT LAQTLGQNLG MMWNKHRSSA GDCKCPDIWL 310 320 330 340 350 360 GCIMEDTGFY LPRKFSRCSI DEYNQFLQEG GGSCLFNKPL KLLDPPECGN GFVEAGEECD 370 380 390 400 410 420 CGSVQECSRA GGNCCKKCTL THDAMCSDGL CCRRCKYEPR GVSCREAVNE CDIAETCTGD 430 440 450 460 470 480 SSQCPPNLHK LDGYYCDHEQ GRCYGGRCKT RDRQCQVLWG HAAADRFCYE KLNVEGTERG 490 500 510 520 SCGRKGSGWV QCSKQPQQGR AVWLPPLCQH LWSSSARGPG GRHQ

References

[1]	"Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain." Sagane K., Ohya Y., Hasegawa Y., Tanaka I. Biochem. J. 334:93-98(1998) [PubMed: 9693107] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Brain.
[2]	"A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers." Emi M., Katagiri T., Harada Y., Saito H., Inazawa J., Ito I., Kasumi F., Nakamura Y. Nat. Genet. 5:151-157(1993) [PubMed: 8252040] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Cerebellum.
[3]	"Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing." Katagiri T., Harada Y., Emi M., Nakamura Y. Cytogenet. Cell Genet. 68:39-44(1995) [PubMed: 7956356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 106-769 (ISOFORMS LONG AND SHORT). Tissue: Brain, Mammary gland, Ovary and Testis.
[4]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB009675 mRNA. Translation: BAA32352.1. D17390 mRNA. Translation: BAA04213.1. D31872 Genomic DNA. Translation: BAA06670.1. D31872 Genomic DNA. Translation: BAA06671.1.
IPI	IPI00299652. IPI00299653.
PIR	I65967. S38539.
RefSeq	NP_002381.2.
UniGene	Hs.6088
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O75078. 1 interaction.
STRING	O75078.
Proteomic databases
PRIDE	O75078.
Genome annotation databases
Ensembl	ENST00000200557; ENSP00000200557; ENSG00000073670; Homo sapiens. [Genome view]
GeneID	4185.
KEGG	hsa:4185.
UCSC	uc002ihh.1. human.
Organism-specific databases
CTD	4185.
GeneCards	GC17P040192.
HGNC	HGNC:189. ADAM11.
MIM	155120. gene.
PharmGKB	PA24506.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O75078.
HOVERGEN	O75078.
OMA	TGFYLPR
OrthoDB	EOG96DPNQ
Gene expression databases
ArrayExpress	O75078.
Bgee	O75078.
CleanEx	HS_ADAM11.
Genevestigator	O75078.
GermOnline	ENSG00000073670. Homo sapiens.
Family and domain databases
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR013111. EGF_extracell. 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. PF07974. EGF_2. 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]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. 1 hit. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16498.
SOURCE	Search...

Entry information

Entry name

ADA11_HUMAN

Accession

Primary (citable) accession number: O75078
Secondary accession number(s): Q14808, Q14809, Q14810

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	October 3, 2006
Last modified:	November 24, 2009
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.