P51512 (MMP16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-16
Short name=MMP-16
EC=3.4.24.-

Alternative name(s):
MMP-X2
Membrane-type matrix metalloproteinase 3
Short name=MT-MMP 3
Short name=MTMMP3
Membrane-type-3 matrix metalloproteinase
Short name=MT3-MMP
Short name=MT3MMP

Gene names

Name:	MMP16
Synonyms:	MMPX2

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	607 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	Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. Isoform short cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells. Ref.9
Cofactor	Binds 1 zinc ion per subunit By similarity. Calcium By similarity.
Enzyme regulation	TIMP-2 shows little inhibitory activity compared to TIMP-1. TIMP-1 seems to have less binding affinity than TIMP-2 for the short isoform.
Subunit structure	Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Ref.9
Subcellular location	Isoform Long: Cell membrane; Single-pass type I membrane protein; Extracellular side Potential. Note: Localized at the cell surface of melanoma cells. Ref.9 Isoform Short: Secreted › extracellular space › extracellular matrix. Cell surface. Note: Localized at the cell surface of melanoma cells. Ref.9
Tissue specificity	Expressed in heart, brain, placenta, ovary and small intestine. Isoform Short is found in the ovary.
Developmental stage	Expressed in tissues undergoing reconstruction. Present in fetal tissues, especially in brain. Expression seems to decline with advanced development.
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	The precursor is cleaved by a furin endopeptidase By similarity.
Sequence similarities	Belongs to the peptidase M10A family. Contains 4 hemopexin-like domains.

Ontologies

Keywords
Biological process	Collagen degradation
Cellular component	Cell membrane Extracellular matrix Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW extracellular matrix disassembly Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome cell surface Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro enzyme activator activity Traceable author statement Ref.1. Source: ProtInc metalloendopeptidase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: P51512-1)

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 Short (identifier: P51512-2)

Also known as: SM3;

The sequence of this isoform differs from the canonical sequence as follows:
     408-457: GNKYWVFKDT...VGKTYFFKGD → VKGDTLSVIQ...TYEELSSITY
     458-607: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Potential

Propeptide

32 – 119

88

By similarity

PRO_0000028812

Chain

120 – 607

488

Matrix metalloproteinase-16

PRO_0000028813

Regions

Topological domain

120 – 564

445

Extracellular Potential

Transmembrane

565 – 585

21

Helical; Potential

Topological domain

586 – 607

22

Cytoplasmic Potential

Domain

347 – 390

44

Hemopexin-like 1

Domain

392 – 436

45

Hemopexin-like 2

Domain

439 – 485

47

Hemopexin-like 3

Domain

487 – 532

46

Hemopexin-like 4

Motif

99 – 106

8

Cysteine switch By similarity

Sites

Active site

247

1

Metal binding

101

1

Zinc 1; in inhibited form By similarity

Metal binding

183

1

Calcium 1; via carbonyl oxygen

Metal binding

193

1

Zinc 1

Metal binding

195

1

Zinc 1

Metal binding

200

1

Calcium 2

Metal binding

201

1

Calcium 2; via carbonyl oxygen

Metal binding

203

1

Calcium 2; via carbonyl oxygen

Metal binding

205

1

Calcium 2; via carbonyl oxygen

Metal binding

215

1

Calcium 1; via carbonyl oxygen

Metal binding

217

1

Calcium 1; via carbonyl oxygen

Metal binding

219

1

Calcium 1

Metal binding

223

1

Calcium 2

Metal binding

226

1

Calcium 2

Metal binding

246

1

Zinc 2; catalytic

Metal binding

250

1

Zinc 2; catalytic

Metal binding

256

1

Zinc 2; catalytic

Amino acid modifications

Glycosylation

83

1

N-linked (GlcNAc...) Potential

Disulfide bond

343 ↔ 532

By similarity

Natural variations

Alternative sequence

408 – 457

50

GNKYW…FFKGD → VKGDTLSVIQDGWLYKYHWK WILEQRQSVPVLSRQTEKHK TYEELSSITY in isoform Short.

VSP_005453

Alternative sequence

458 – 607

150

Missing in isoform Short.

VSP_005454

Experimental info

Sequence conflict

521

1

Y → H in BAA23742. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

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.

.

.

.

.

.

607

Helix Strand Turn

Details...

Beta strand

128 – 136

9

Turn

141 – 143

3

Helix

145 – 160

16

Beta strand

166 – 169

4

Beta strand

177 – 179

3

Beta strand

183 – 191

9

Beta strand

194 – 196

3

Beta strand

201 – 204

4

Beta strand

207 – 209

3

Turn

215 – 218

4

Beta strand

220 – 223

4

Beta strand

228 – 231

4

Beta strand

234 – 239

6

Helix

240 – 251

12

Beta strand

265 – 267

3

Helix

280 – 290

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 30D6247D9CB21663	FASTA	607	69,521
	10 20 30 40 50 60 MILLTFSTGR RLDFVHHSGV FFLQTLLWIL CATVCGTEQY FNVEVWLQKY GYLPPTDPRM 70 80 90 100 110 120 SVLRSAETMQ SALAAMQQFY GINMTGKVDR NTIDWMKKPR CGVPDQTRGS SKFHIRRKRY 130 140 150 160 170 180 ALTGQKWQHK HITYSIKNVT PKVGDPETRK AIRRAFDVWQ NVTPLTFEEV PYSELENGKR 190 200 210 220 230 240 DVDITIIFAS GFHGDSSPFD GEGGFLAHAY FPGPGIGGDT HFDSDEPWTL GNPNHDGNDL 250 260 270 280 290 300 FLVAVHELGH ALGLEHSNDP TAIMAPFYQY METDNFKLPN DDLQGIQKIY GPPDKIPPPT 310 320 330 340 350 360 RPLPTVPPHR SIPPADPRKN DRPKPPRPPT GRPSYPGAKP NICDGNFNTL AILRREMFVF 370 380 390 400 410 420 KDQWFWRVRN NRVMDGYPMQ ITYFWRGLPP SIDAVYENSD GNFVFFKGNK YWVFKDTTLQ 430 440 450 460 470 480 PGYPHDLITL GSGIPPHGID SAIWWEDVGK TYFFKGDRYW RYSEEMKTMD PGYPKPITVW 490 500 510 520 530 540 KGIPESPQGA FVHKENGFTY FYKGKEYWKF NNQILKVEPG YPRSILKDFM GCDGPTDRVK 550 560 570 580 590 600 EGHSPPDDVD IVIKLDNTAS TVKAIAIVIP CILALCLLVL VYTVFQFKRK GTPRHILYCK RSMQEWV
	Isoform Short (SM3) [UniParc]. Checksum: 94184CDA9F76C5EB	FASTA	457	52,515
	10 20 30 40 50 60 MILLTFSTGR RLDFVHHSGV FFLQTLLWIL CATVCGTEQY FNVEVWLQKY GYLPPTDPRM 70 80 90 100 110 120 SVLRSAETMQ SALAAMQQFY GINMTGKVDR NTIDWMKKPR CGVPDQTRGS SKFHIRRKRY 130 140 150 160 170 180 ALTGQKWQHK HITYSIKNVT PKVGDPETRK AIRRAFDVWQ NVTPLTFEEV PYSELENGKR 190 200 210 220 230 240 DVDITIIFAS GFHGDSSPFD GEGGFLAHAY FPGPGIGGDT HFDSDEPWTL GNPNHDGNDL 250 260 270 280 290 300 FLVAVHELGH ALGLEHSNDP TAIMAPFYQY METDNFKLPN DDLQGIQKIY GPPDKIPPPT 310 320 330 340 350 360 RPLPTVPPHR SIPPADPRKN DRPKPPRPPT GRPSYPGAKP NICDGNFNTL AILRREMFVF 370 380 390 400 410 420 KDQWFWRVRN NRVMDGYPMQ ITYFWRGLPP SIDAVYENSD GNFVFFKVKG DTLSVIQDGW 430 440 450 LYKYHWKWIL EQRQSVPVLS RQTEKHKTYE ELSSITY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family." Takino T., Sato H., Shinagawa A., Seiki M. J. Biol. Chem. 270:23013-23020(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Placenta.
[2]	Seiki M. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternatively spliced mRNA." Matsumoto S., Katoh M., Saito S., Watanabe T., Masuho Y. Biochim. Biophys. Acta 1354:159-170(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Tissue: Ovary.
[4]	"Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain." Shofuda K., Yasumitsu H., Nishihashi A., Miki K., Miyazaki K. J. Biol. Chem. 272:9749-9754(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Fetal brain.
[5]	NIEHS SNPs program Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[7]	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].
[8]	"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] (ISOFORM LONG). Tissue: Brain.
[9]	"Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen." Iida J., Pei D., Kang T., Simpson M.A., Herlyn M., Furcht L.T., McCarthy J.B. J. Biol. Chem. 276:18786-18794(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CSPG4, SUBCELLULAR LOCATION, FUNCTION.
[10]	"Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features." Lang R., Braun M., Sounni N.E., Noel A., Frankenne F., Foidart J.M., Bode W., Maskos K. J. Mol. Biol. 336:213-225(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 124-292 IN COMPLEX WITH INHIBITOR, ZINC-BINDING SITES, CALCIUM-BINDING SITES.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB009303 mRNA. Translation: BAA23742.1.
D83646 mRNA. Translation: BAA12022.1.
D83647 mRNA. Translation: BAA12023.1.
D85511 mRNA. Translation: BAA22226.1.
DQ003082 Genomic DNA. Translation: AAX84515.1.
AK314274 mRNA. Translation: BAG36934.1.
CH471060 Genomic DNA. Translation: EAW91651.1.
BC069500 mRNA. Translation: AAH69500.1.
BC075004 mRNA. Translation: AAH75004.1.
BC075005 mRNA. Translation: AAH75005.1.

IPI

IPI00019243.
IPI00221078.

RefSeq

NP_005932.2. NM_005941.4.

UniGene

Hs.492187.
Hs.546267.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RM8	X-ray	1.80	A	124-292	[»]

ProteinModelPortal

P51512.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000286614.

Protein family/group databases

MEROPS

M10.016.

PTM databases

PhosphoSite

P51512.

Polymorphism databases

DMDM

3041669.

Proteomic databases

PaxDb

P51512.

PRIDE

P51512.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000286614; ENSP00000286614; ENSG00000156103.

GeneID

4325.

KEGG

hsa:4325.

UCSC

uc003yeb.4. human.

Organism-specific databases

CTD

4325.

GeneCards

GC08M089044.

HGNC

HGNC:7162. MMP16.

HPA

HPA023693.

MIM

602262. gene.

neXtProt

NX_P51512.

PharmGKB

PA30874.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG295915.

HOGENOM

HOG000217928.

HOVERGEN

HBG052484.

InParanoid

P51512.

KO

K07996.

OMA

GPTDRDK.

OrthoDB

EOG4R5029.

PhylomeDB

P51512.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpress

P51512.

Bgee

P51512.

CleanEx

HS_MMP16.

Genevestigator

P51512.

GermOnline

ENSG00000156103. Homo sapiens.

Family and domain databases

Gene3D

2.110.10.10. 1 hit.
3.40.390.10. 1 hit.

InterPro

IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_Metazoans.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]

Pfam

PF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]

PIRSF

PIRSF001191. Peptidase_M10A_matrix. 1 hit.

PRINTS

PR00138. MATRIXIN.

SMART

SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]

SUPFAM

SSF50923. Hemopexin. 1 hit.
SSF47090. PGBD_like. 1 hit.

PROSITE

PS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P51512.

ChEMBL

CHEMBL2200.

EvolutionaryTrace

P51512.

GenomeRNAi

4325.

NextBio

17017.

PMAP-CutDB

P51512.

SOURCE

Search...

Entry information

Entry name

MMP16_HUMAN

Accession

Primary (citable) accession number: P51512
Secondary accession number(s): B2RAN7, Q14824, Q52H48

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 137 of the entry and version 2 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.