O75077 (ADA23_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disintegrin and metalloproteinase domain-containing protein 23
Short name=ADAM 23

Alternative name(s):
Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 3
Short name=MDC-3

Gene names

Name:	ADAM23
Synonyms:	MDC3

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

General annotation (Comments)

Function	May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein.
Subunit structure	Can bind to LGI1 and LGI4 By similarity. Ligand for integrin alpha-V/beta-3.
Subcellular location	Cell membrane; Single-pass type I membrane protein Potential. Isoform Gamma: Secreted.
Tissue specificity	Highly expressed in the brain and weakly expressed in the heart. In the brain, expressed prominently in the amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital pole. Ref.3
Developmental stage	Highly expressed in the fetal brain.
Domain	A conserved motif AVN[ED]CD within the disintegrin-like domain could be involved in the binding to the integrin receptor.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW central nervous system development Traceable author statement. Source: ProtInc proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	integrin binding 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 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: O75077-1)

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 Beta (identifier: O75077-2)

The sequence of this isoform differs from the canonical sequence as follows:
     787-817: GPSATNLIIGSIAGAILVAAIVLGGTGWGFK → VNMATSRLIGAVAGTLLALGVIFGGTGWGIE

Isoform Gamma (identifier: O75077-3)

The sequence of this isoform differs from the canonical sequence as follows:
     787-832: GPSATNLIIG...RFDPTQQGPI → EMSRREGSIL...AAVLLELLSL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 59	59	Potential
	Propeptide	60 – 286	227	Potential		PRO_0000029118
	Chain	287 – 832	546	Disintegrin and metalloproteinase domain-containing protein 23		PRO_0000029119
Regions
	Topological domain	287 – 792	506	Extracellular Potential
	Transmembrane	793 – 813	21	Helical; Potential
	Topological domain	814 – 832	19	Cytoplasmic Potential
	Domain	299 – 496	198	Peptidase M12B
	Domain	502 – 588	87	Disintegrin
	Domain	732 – 769	38	EGF-like
	Region	563 – 568	6	May bind the integrin receptor
	Compositional bias	589 – 611	23	Cys-rich
Amino acid modifications
	Modified residue	707	1	Phosphotyrosine Ref.6
	Glycosylation	76	1	N-linked (GlcNAc...) Potential
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	100	1	N-linked (GlcNAc...) Potential
	Glycosylation	263	1	N-linked (GlcNAc...) Potential
	Glycosylation	547	1	N-linked (GlcNAc...) Potential
	Glycosylation	548	1	N-linked (GlcNAc...) Potential
	Glycosylation	664	1	N-linked (GlcNAc...) Potential
	Glycosylation	732	1	N-linked (GlcNAc...) Potential
	Disulfide bond	408 ↔ 491		By similarity
	Disulfide bond	450 ↔ 475		By similarity
	Disulfide bond	452 ↔ 459		By similarity
	Disulfide bond	560 ↔ 580		By similarity
	Disulfide bond	736 ↔ 751		By similarity
	Disulfide bond	745 ↔ 757		By similarity
	Disulfide bond	759 ↔ 768		By similarity
Natural variations
	Alternative sequence	787 – 832	46	GPSAT…QQGPI → EMSRREGSILLSKAPSESAA LDGHRLALLDSGYDILAAVL LELLSL in isoform Gamma.		VSP_012045
	Alternative sequence	787 – 817	31	GPSAT…GWGFK → VNMATSRLIGAVAGTLLALG VIFGGTGWGIE in isoform Beta.		VSP_012046
Experimental info
	Mutagenesis	566	1	E → A: Significantly lower of adhesion-promoting activity. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 7841A9670E1C24EF	FASTA	832	91,926
	10 20 30 40 50 60 MKPPGSSSRQ PPLAGCSLAG ASCGPQRGPA GSVPASAPAR TPPCRLLLVL LLLPPLAASS 70 80 90 100 110 120 RPRAWGAAAP SAPHWNETAE KNLGVLADED NTLQQNSSSN ISYSNAMQKE ITLPSRLIYY 130 140 150 160 170 180 INQDSESPYH VLDTKARHQQ KHNKAVHLAQ ASFQIEAFGS KFILDLILNN GLLSSDYVEI 190 200 210 220 230 240 HYENGKPQYS KGGEHCYYHG SIRGVKDSKV ALSTCNGLHG MFEDDTFVYM IEPLELVHDE 250 260 270 280 290 300 KSTGRPHIIQ KTLAGQYSKQ MKNLTMERGD QWPFLSELQW LKRRKRAVNP SRGIFEEMKY 310 320 330 340 350 360 LELMIVNDHK TYKKHRSSHA HTNNFAKSVV NLVDSIYKEQ LNTRVVLVAV ETWTEKDQID 370 380 390 400 410 420 ITTNPVQMLH EFSKYRQRIK QHADAVHLIS RVTFHYKRSS LSYFGGVCSR TRGVGVNEYG 430 440 450 460 470 480 LPMAVAQVLS QSLAQNLGIQ WEPSSRKPKC DCTESWGGCI MEETGVSHSR KFSKCSILEY 490 500 510 520 530 540 RDFLQRGGGA CLFNRPTKLF EPTECGNGYV EAGEECDCGF HVECYGLCCK KCSLSNGAHC 550 560 570 580 590 600 SDGPCCNNTS CLFQPRGYEC RDAVNECDIT EYCTGDSGQC PPNLHKQDGY ACNQNQGRCY 610 620 630 640 650 660 NGECKTRDNQ CQYIWGTKAA GSDKFCYEKL NTEGTEKGNC GKDGDRWIQC SKHDVFCGFL 670 680 690 700 710 720 LCTNLTRAPR IGQLQGEIIP TSFYHQGRVI DCSGAHVVLD DDTDVGYVED GTPCGPSMMC 730 740 750 760 770 780 LDRKCLQIQA LNMSSCPLDS KGKVCSGHGV CSNEATCICD FTWAGTDCSI RDPVRNLHPP 790 800 810 820 830 KDEGPKGPSA TNLIIGSIAG AILVAAIVLG GTGWGFKNVK KRRFDPTQQG PI
	Isoform Beta [UniParc]. Checksum: E388ACE51334052C	FASTA	832	92,046
	10 20 30 40 50 60 MKPPGSSSRQ PPLAGCSLAG ASCGPQRGPA GSVPASAPAR TPPCRLLLVL LLLPPLAASS 70 80 90 100 110 120 RPRAWGAAAP SAPHWNETAE KNLGVLADED NTLQQNSSSN ISYSNAMQKE ITLPSRLIYY 130 140 150 160 170 180 INQDSESPYH VLDTKARHQQ KHNKAVHLAQ ASFQIEAFGS KFILDLILNN GLLSSDYVEI 190 200 210 220 230 240 HYENGKPQYS KGGEHCYYHG SIRGVKDSKV ALSTCNGLHG MFEDDTFVYM IEPLELVHDE 250 260 270 280 290 300 KSTGRPHIIQ KTLAGQYSKQ MKNLTMERGD QWPFLSELQW LKRRKRAVNP SRGIFEEMKY 310 320 330 340 350 360 LELMIVNDHK TYKKHRSSHA HTNNFAKSVV NLVDSIYKEQ LNTRVVLVAV ETWTEKDQID 370 380 390 400 410 420 ITTNPVQMLH EFSKYRQRIK QHADAVHLIS RVTFHYKRSS LSYFGGVCSR TRGVGVNEYG 430 440 450 460 470 480 LPMAVAQVLS QSLAQNLGIQ WEPSSRKPKC DCTESWGGCI MEETGVSHSR KFSKCSILEY 490 500 510 520 530 540 RDFLQRGGGA CLFNRPTKLF EPTECGNGYV EAGEECDCGF HVECYGLCCK KCSLSNGAHC 550 560 570 580 590 600 SDGPCCNNTS CLFQPRGYEC RDAVNECDIT EYCTGDSGQC PPNLHKQDGY ACNQNQGRCY 610 620 630 640 650 660 NGECKTRDNQ CQYIWGTKAA GSDKFCYEKL NTEGTEKGNC GKDGDRWIQC SKHDVFCGFL 670 680 690 700 710 720 LCTNLTRAPR IGQLQGEIIP TSFYHQGRVI DCSGAHVVLD DDTDVGYVED GTPCGPSMMC 730 740 750 760 770 780 LDRKCLQIQA LNMSSCPLDS KGKVCSGHGV CSNEATCICD FTWAGTDCSI RDPVRNLHPP 790 800 810 820 830 KDEGPKVNMA TSRLIGAVAG TLLALGVIFG GTGWGIENVK KRRFDPTQQG PI
	Isoform Gamma [UniParc]. Checksum: 7F54A1805FA2EC58	FASTA	832	92,130
	10 20 30 40 50 60 MKPPGSSSRQ PPLAGCSLAG ASCGPQRGPA GSVPASAPAR TPPCRLLLVL LLLPPLAASS 70 80 90 100 110 120 RPRAWGAAAP SAPHWNETAE KNLGVLADED NTLQQNSSSN ISYSNAMQKE ITLPSRLIYY 130 140 150 160 170 180 INQDSESPYH VLDTKARHQQ KHNKAVHLAQ ASFQIEAFGS KFILDLILNN GLLSSDYVEI 190 200 210 220 230 240 HYENGKPQYS KGGEHCYYHG SIRGVKDSKV ALSTCNGLHG MFEDDTFVYM IEPLELVHDE 250 260 270 280 290 300 KSTGRPHIIQ KTLAGQYSKQ MKNLTMERGD QWPFLSELQW LKRRKRAVNP SRGIFEEMKY 310 320 330 340 350 360 LELMIVNDHK TYKKHRSSHA HTNNFAKSVV NLVDSIYKEQ LNTRVVLVAV ETWTEKDQID 370 380 390 400 410 420 ITTNPVQMLH EFSKYRQRIK QHADAVHLIS RVTFHYKRSS LSYFGGVCSR TRGVGVNEYG 430 440 450 460 470 480 LPMAVAQVLS QSLAQNLGIQ WEPSSRKPKC DCTESWGGCI MEETGVSHSR KFSKCSILEY 490 500 510 520 530 540 RDFLQRGGGA CLFNRPTKLF EPTECGNGYV EAGEECDCGF HVECYGLCCK KCSLSNGAHC 550 560 570 580 590 600 SDGPCCNNTS CLFQPRGYEC RDAVNECDIT EYCTGDSGQC PPNLHKQDGY ACNQNQGRCY 610 620 630 640 650 660 NGECKTRDNQ CQYIWGTKAA GSDKFCYEKL NTEGTEKGNC GKDGDRWIQC SKHDVFCGFL 670 680 690 700 710 720 LCTNLTRAPR IGQLQGEIIP TSFYHQGRVI DCSGAHVVLD DDTDVGYVED GTPCGPSMMC 730 740 750 760 770 780 LDRKCLQIQA LNMSSCPLDS KGKVCSGHGV CSNEATCICD FTWAGTDCSI RDPVRNLHPP 790 800 810 820 830 KDEGPKEMSR REGSILLSKA PSESAALDGH RLALLDSGYD ILAAVLLELL SL

References

	« Hide 'large scale' referencesShow 'large scale' 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 ALPHA). Tissue: Brain.
[2]	"ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alpha v beta 3 integrin through an RGD-independent mechanism." Cal S., Freije J.M.P., Lopez J.M., Takada Y., Lopez-Otin C. Mol. Biol. Cell 11:1457-1469(2000) [PubMed: 10749942] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), INTERACTION WITH INTEGRIN ALPHA-V/BETA-3, MUTAGENESIS OF GLU-566. Tissue: Brain.
[3]	"Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains." Sun Y.P., Deng K.J., Wang F., Zhang J., Huang X., Qiao S., Zhao S. Gene 325:171-178(2004) [PubMed: 14697522] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA), TISSUE SPECIFICITY. Tissue: Fetal brain.
[4]	Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). Tissue: Brain.
[6]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-707, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB009672 mRNA. Translation: BAA32351.1. AJ005580 mRNA. Translation: CAC20565.1. CH471063 Genomic DNA. Translation: EAW70386.1. BC132763 mRNA. Translation: AAI32764.1. BC132765 mRNA. Translation: AAI32766.1.
IPI	IPI00021903. IPI00477723. IPI00478084.
RefSeq	NP_003803.1. NM_003812.2.
UniGene	Hs.591643.
3D structure databases
ProteinModelPortal	O75077.
SMR	O75077. Positions 293-774.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-257697.
STRING	O75077.
Protein family/group databases
MEROPS	M12.979.
PTM databases
PhosphoSite	O75077.
Proteomic databases
PRIDE	O75077.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264377; ENSP00000264377; ENSG00000114948.
GeneID	8745.
KEGG	hsa:8745.
UCSC	uc002vbq.1. human.
Organism-specific databases
CTD	8745.
GeneCards	GC02P207272.
H-InvDB	HIX0002773.
HGNC	HGNC:202. ADAM23.
HPA	CAB033276. HPA012130.
MIM	603710. gene.
neXtProt	NX_O75077.
PharmGKB	PA24519.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG050456.
OMA	SCLFQPR.
OrthoDB	EOG4HX50C.
PhylomeDB	O75077.
Gene expression databases
ArrayExpress	O75077.
Bgee	O75077.
CleanEx	HS_ADAM23.
Genevestigator	O75077.
GermOnline	ENSG00000114948. Homo sapiens.
Family and domain databases
InterPro	IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. 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.
KO	K06837.
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. SM00181. EGF. 1 hit. [Graphical view]
SUPFAM	SSF57552. Disintegrin. 1 hit.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. 1 hit. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	32813.
SOURCE	Search...

Entry information

Entry name

ADA23_HUMAN

Accession

Primary (citable) accession number: O75077
Secondary accession number(s): A2RU59

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 87 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.