Reviewed, UniProtKB/Swiss-Prot Q13443 (ADAM9_HUMAN)

Names and origin

Protein names

Recommended name:
    ADAM 9
    EC=3.4.24.-
Alternative name(s):
    A disintegrin and metalloproteinase domain 9
    Metalloprotease/disintegrin/cysteine-rich protein 9
    Myeloma cell metalloproteinase
    Meltrin-gamma
    Cellular disintegrin-related protein

Gene names

Name:	ADAM9
Synonyms:	KIAA0021, MCMP, MDC9, MLTNG

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	819 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	Probable zinc protease. May mediate cell-cell or cell-matrix interactions. Isoform 2 displays alpha-secretase activity for APP.
Cofactor	Binds 1 zinc ion per subunit Probable.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted.
Tissue specificity	Widely expressed. Expressed in chondrocytes. Highest expression of isoform 2 found in liver and heart.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.
Caution	Has sometimes been referred to as ADAM-12.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein kinase cascade Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	SH3 domain binding Inferred from physical interaction. Source: UniProtKB integrin binding Ref.1 Traceable author statement. Source: ProtInc metallopeptidase activity Ref.1 Non-traceable author statement. Source: UniProtKB protein kinase binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAD2L2	Q9UI95	3	EBI-77903,EBI-77889
PACSIN3	Q9UKS6	1	EBI-77903,EBI-77926
SH3GL2	Q99962	1	EBI-77903,EBI-77938

Alternative products

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

Isoform 1 (identifier: Q13443-1)

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: Q13443-2)

The sequence of this isoform differs from the canonical sequence as follows:
     655-655: V → K
     656-819: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 819

791

ADAM 9

Regions

Topological domain

29 – 697

669

Extracellular Potential

Transmembrane

698 – 718

21

Potential

Topological domain

719 – 819

101

Cytoplasmic Potential

Domain

212 – 406

195

Peptidase M12B

Domain

414 – 501

88

Disintegrin

Domain

644 – 698

55

EGF-like

Compositional bias

505 – 634

130

Cys-rich

Compositional bias

790 – 795

6

Poly-Pro

Sites

Active site

348

1

By similarity

Metal binding

347

1

Zinc (catalytic) By similarity

Metal binding

351

1

Zinc (catalytic) By similarity

Metal binding

357

1

Zinc (catalytic) By similarity

Amino acid modifications

Modified residue

758

1

Phosphoserine

Modified residue

761

1

Phosphothreonine

Glycosylation

125

1

N-linked (GlcNAc...) Potential

Glycosylation

144

1

N-linked (GlcNAc...) Potential

Glycosylation

154

1

N-linked (GlcNAc...) Potential

Glycosylation

231

1

N-linked (GlcNAc...) Potential

Glycosylation

381

1

N-linked (GlcNAc...) Potential

Glycosylation

487

1

N-linked (GlcNAc...) Potential

Disulfide bond

322 ↔ 401

By similarity

Disulfide bond

363 ↔ 385

By similarity

Disulfide bond

365 ↔ 370

By similarity

Disulfide bond

473 ↔ 493

By similarity

Disulfide bond

644 ↔ 656

By similarity

Disulfide bond

650 ↔ 662

By similarity

Disulfide bond

664 ↔ 673

By similarity

Natural variations

Alternative sequence

655

1

V → K in isoform 2.

Alternative sequence

656 – 819

164

Missing in isoform 2.

Experimental info

Sequence conflict

1 – 118

118

Missing Ref.2

Sequence conflict

117

1

R → Q in BAA03499. Ref.4

Sequence conflict

119 – 135

17

YVEGV…SDCFG → MWREFIIHPLLLATVLD Ref.2

Sequence conflict

154

1

N → M Ref.2

Sequence conflict

566

1

G → GLSLKFHAPFLSTMLQEAVR QTGTYLGGSVCCMKSDCRIV TLVK Ref.2

Sequence conflict

713 – 735

23

AIFIF…KRSQT → DYFYLHQEGSTVEKLLQKEE ITN Ref.2

Sequence conflict

736 – 819

84

Missing Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

819

Helix Strand Turn

Details...

Beta strand

212 – 220

9

Helix

222 – 227

6

Turn

228 – 230

3

Helix

232 – 250

19

Helix

251 – 253

3

Beta strand

255 – 264

10

Helix

277 – 290

14

Turn

291 – 295

5

Beta strand

299 – 305

7

Beta strand

311 – 316

6

Beta strand

327 – 331

5

Turn

337 – 339

3

Helix

340 – 352

13

Beta strand

369 – 374

6

Helix

384 – 397

14

Helix

400 – 402

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: BC186641833137FF	FASTA	819	90,556
	10 20 30 40 50 60 MGSGARFPSG TLRVRWLLLL GLVGPVLGAA RPGFQQTSHL SSYEIITPWR LTRERREAPR 70 80 90 100 110 120 PYSKQVSYVI QAEGKEHIIH LERNKDLLPE DFVVYTYNKE GTLITDHPNI QNHCHYRGYV 130 140 150 160 170 180 EGVHNSSIAL SDCFGLRGLL HLENASYGIE PLQNSSHFEH IIYRMDDVYK EPLKCGVSNK 190 200 210 220 230 240 DIEKETAKDE EEEPPSMTQL LRRRRAVLPQ TRYVELFIVV DKERYDMMGR NQTAVREEMI 250 260 270 280 290 300 LLANYLDSMY IMLNIRIVLV GLEIWTNGNL INIVGGAGDV LGNFVQWREK FLITRRRHDS 310 320 330 340 350 360 AQLVLKKGFG GTAGMAFVGT VCSRSHAGGI NVFGQITVET FASIVAHELG HNLGMNHDDG 370 380 390 400 410 420 RDCSCGAKSC IMNSGASGSR NFSSCSAEDF EKLTLNKGGN CLLNIPKPDE AYSAPSCGNK 430 440 450 460 470 480 LVDAGEECDC GTPKECELDP CCEGSTCKLK SFAECAYGDC CKDCRFLPGG TLCRGKTSEC 490 500 510 520 530 540 DVPEYCNGSS QFCQPDVFIQ NGYPCQNNKA YCYNGMCQYY DAQCQVIFGS KAKAAPKDCF 550 560 570 580 590 600 IEVNSKGDRF GNCGFSGNEY KKCATGNALC GKLQCENVQE IPVFGIVPAI IQTPSRGTKC 610 620 630 640 650 660 WGVDFQLGSD VPDPGMVNEG TKCGAGKICR NFQCVDASVL NYDCDVQKKC HGHGVCNSNK 670 680 690 700 710 720 NCHCENGWAP PNCETKGYGG SVDSGPTYNE MNTALRDGLL VFFFLIVPLI VCAIFIFIKR 730 740 750 760 770 780 DQLWRSYFRK KRSQTYESDG KNQANPSRQP GSVPRHVSPV TPPREVPIYA NRFAVPTYAA 790 800 810 KQPQQFPSRP PPPQPKVSSQ GNLIPARPAP APPLYSSLT
	Isoform 2 [UniParc]. Checksum: 1E99DD3A056B90B7		655	72,359
	10 20 30 40 50 60 MGSGARFPSG TLRVRWLLLL GLVGPVLGAA RPGFQQTSHL SSYEIITPWR LTRERREAPR 70 80 90 100 110 120 PYSKQVSYVI QAEGKEHIIH LERNKDLLPE DFVVYTYNKE GTLITDHPNI QNHCHYRGYV 130 140 150 160 170 180 EGVHNSSIAL SDCFGLRGLL HLENASYGIE PLQNSSHFEH IIYRMDDVYK EPLKCGVSNK 190 200 210 220 230 240 DIEKETAKDE EEEPPSMTQL LRRRRAVLPQ TRYVELFIVV DKERYDMMGR NQTAVREEMI 250 260 270 280 290 300 LLANYLDSMY IMLNIRIVLV GLEIWTNGNL INIVGGAGDV LGNFVQWREK FLITRRRHDS 310 320 330 340 350 360 AQLVLKKGFG GTAGMAFVGT VCSRSHAGGI NVFGQITVET FASIVAHELG HNLGMNHDDG 370 380 390 400 410 420 RDCSCGAKSC IMNSGASGSR NFSSCSAEDF EKLTLNKGGN CLLNIPKPDE AYSAPSCGNK 430 440 450 460 470 480 LVDAGEECDC GTPKECELDP CCEGSTCKLK SFAECAYGDC CKDCRFLPGG TLCRGKTSEC 490 500 510 520 530 540 DVPEYCNGSS QFCQPDVFIQ NGYPCQNNKA YCYNGMCQYY DAQCQVIFGS KAKAAPKDCF 550 560 570 580 590 600 IEVNSKGDRF GNCGFSGNEY KKCATGNALC GKLQCENVQE IPVFGIVPAI IQTPSRGTKC 610 620 630 640 650 WGVDFQLGSD VPDPGMVNEG TKCGAGKICR NFQCVDASVL NYDCDVQKKC HGHGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains." Weskamp G., Kraetzschmar J., Reid M.S., Blobel C.P. J. Cell Biol. 132:717-726(1996) [PubMed: 8647900] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Mammary carcinoma.
[2]	"Cloning of a novel membrane-linked metalloproteinase from human myeloma cells." McKie N., Dallas D.J., Edwards T., Apperley J.F., Russell R.G.G., Croucher P.I. Biochem. J. 318:459-462(1996) [PubMed: 8809033] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[3]	"A secreted form of human ADAM9 has an alpha-secretase activity for APP." Hotoda N., Koike H., Sasagawa N., Ishiura S. Biochem. Biophys. Res. Commun. 293:800-805(2002) [PubMed: 12054541] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed: 7584026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Bone marrow.
[5]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[6]	"Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes." McKie N., Edwards T., Dallas D.J., Houghton A., Stringer B., Graham R., Russell G., Croucher P.I. Biochem. Biophys. Res. Commun. 230:335-339(1997) [PubMed: 9016778] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-758 AND THR-761, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Exploring the substrate affinities of MMP-3, ADAM-9 and ADAM-10 using molecular modelling and dynamics simulations." Manzetti S., McCulloch D.R., Herington A.C. Submitted (JUN-2002) to the PDB data bank Cited for: 3D-STRUCTURE MODELING OF 208-404.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U41766 mRNA. Translation: AAC50403.1.
AF495383 mRNA. Translation: AAM49575.1.
D14665 mRNA. Translation: BAA03499.2.

PIR

JC7850.
S71949.

RefSeq

NP_001005845.1.
NP_003807.1.

UniGene

Hs.591852

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M1V	model	-	A	208-404	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13443.

Protein family/group databases

MEROPS

M12.209.

PTM databases

PhosphoSite

Q13443.

Genome annotation databases

Ensembl

ENSG00000168615. Homo sapiens. [Contig view]

GeneID

8754.

KEGG

hsa:8754.

Organism-specific databases

H-InvDB

HIX0021419.

HGNC

HGNC:216. ADAM9.

HPA

HPA004000.

MIM

602713. gene.

PharmGKB

PA24534.

HUGE

Search...

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOVERGEN

Q13443.

Gene expression databases

ArrayExpress

Q13443.

CleanEx

HS_ADAM9.

Family and domain databases

InterPro

IPR006586. ADAM_cysteine.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR006210. EGF.
IPR000742. EGF_3.
IPR013111. EGF_extracell.
IPR013032. EGF_like_reg_CS.
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