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Protein

Matrix metalloproteinase-17

Gene

MMP17

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin.

Catalytic activityi

Cleaves pro-TNF-alpha at the 74-Ala-|-Gln-75 site.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi110 – 1101Zinc; in inhibited formBy similarity
Metal bindingi248 – 2481Zinc; catalyticPROSITE-ProRule annotation
Active sitei249 – 2491PROSITE-ProRule annotation
Metal bindingi252 – 2521Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi258 – 2581Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. enzyme activator activity Source: ProtInc
  3. metalloendopeptidase activity Source: ProtInc
  4. zinc ion binding Source: ProtInc

GO - Biological processi

  1. positive regulation of catalytic activity Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_118682. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.017.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-17 (EC:3.4.24.-)
Short name:
MMP-17
Alternative name(s):
Membrane-type matrix metalloproteinase 4
Short name:
MT-MMP 4
Short name:
MTMMP4
Membrane-type-4 matrix metalloproteinase
Short name:
MT4-MMP
Short name:
MT4MMP
Gene namesi
Name:MMP17
Synonyms:MT4MMP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:7163. MMP17.

Subcellular locationi

GO - Cellular componenti

  1. anchored component of membrane Source: UniProtKB-KW
  2. integral component of plasma membrane Source: ProtInc
  3. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30875.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3535Sequence AnalysisAdd
BLAST
Propeptidei36 – 12590By similarityPRO_0000028818Add
BLAST
Chaini126 – 565440Matrix metalloproteinase-17PRO_0000028819Add
BLAST
Propeptidei566 – 60338Removed in mature formSequence AnalysisPRO_0000028820Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi137 – 1371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi332 ↔ 523By similarity
Lipidationi565 – 5651GPI-anchor amidated serineSequence Analysis

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Zymogen

Proteomic databases

PaxDbiQ9ULZ9.
PRIDEiQ9ULZ9.

PTM databases

PhosphoSiteiQ9ULZ9.

Expressioni

Tissue specificityi

Expressed in brain, leukocytes, colon, ovary testis and breast cancer. Expressed also in many transformed and non-transformed cell types.

Gene expression databases

BgeeiQ9ULZ9.
CleanExiHS_MMP17.
ExpressionAtlasiQ9ULZ9. baseline and differential.
GenevestigatoriQ9ULZ9.

Interactioni

Protein-protein interaction databases

BioGridi110469. 1 interaction.
STRINGi9606.ENSP00000353767.

Structurei

3D structure databases

ProteinModelPortaliQ9ULZ9.
SMRiQ9ULZ9. Positions 39-523.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati333 – 37846Hemopexin 1Add
BLAST
Repeati382 – 42746Hemopexin 2Add
BLAST
Repeati428 – 47548Hemopexin 3Add
BLAST
Repeati476 – 52348Hemopexin 4Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi108 – 1158Cysteine switchBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi122 – 1254Poly-Arg

Domaini

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.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG295915.
GeneTreeiENSGT00760000118870.
HOVERGENiHBG052484.
InParanoidiQ9ULZ9.
KOiK07997.
OMAiAHNDRTY.
OrthoDBiEOG7XPZ57.
PhylomeDBiQ9ULZ9.
TreeFamiTF315428.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR028726. MMP17.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF118. PTHR10201:SF118. 1 hit.
PfamiPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q9ULZ9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRRRAARGPG PPPPGPGLSR LPLPLLLLLA LGTRGGCAAP APAPRAEDLS
60 70 80 90 100
LGVEWLSRFG YLPPADPTTG QLQTQEELSK AITAMQQFGG LEATGILDEA
110 120 130 140 150
TLALMKTPRC SLPDLPVLTQ ARRRRQAPAP TKWNKRNLSW RVRTFPRDSP
160 170 180 190 200
LGHDTVRALM YYALKVWSDI APLNFHEVAG SAADIQIDFS KADHNDGYPF
210 220 230 240 250
DGPGGTVAHA FFPGHHHTAG DTHFDDDEAW TFRSSDAHGM DLFAVAVHEF
260 270 280 290 300
GHAIGLSHVA AAHSIMRPYY QGPVGDPLRY GLPYEDKVRV WQLYGVRESV
310 320 330 340 350
SPTAQPEEPP LLPEPPDNRS SAPPRKDVPH RCSTHFDAVA QIRGEAFFFK
360 370 380 390 400
GKYFWRLTRD RHLVSLQPAQ MHRFWRGLPL HLDSVDAVYE RTSDHKIVFF
410 420 430 440 450
KGDRYWVFKD NNVEEGYPRP VSDFSLPPGG IDAAFSWAHN DRTYFFKDQL
460 470 480 490 500
YWRYDDHTRH MDPGYPAQSP LWRGVPSTLD DAMRWSDGAS YFFRGQEYWK
510 520 530 540 550
VLDGELEVAP GYPQSTARDW LVCGDSQADG SVAAGVDAAE GPRAPPGQHD
560 570 580 590 600
QSRSEDGYEV CSCTSGASSP PGAPGPLVAA TMLLLLPPLS PGALWTAAQA

LTL
Length:603
Mass (Da):66,653
Last modified:May 18, 2010 - v4
Checksum:iBB297B21973C7A0B
GO
Isoform Short (identifier: Q9ULZ9-2) [UniParc]FASTAAdd to basket

Also known as: Puente

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Show »
Length:519
Mass (Da):57,938
Checksum:iEB74B32E8A7619C3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 231L → LLPL in BAA82707 (PubMed:10471807).Curated
Sequence conflicti23 – 231L → LLPL in CAA61753 (Ref. 2) Curated
Sequence conflicti182 – 1821A → T in BAA82707 (PubMed:10471807).Curated
Sequence conflicti182 – 1821A → T in CAA61753 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8484Missing in isoform Short. 1 PublicationVSP_005456Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021225 mRNA. Translation: BAA82707.2.
X89576 mRNA. Translation: CAA61753.1.
AC131009 Genomic DNA. No translation available.
CCDSiCCDS31927.1. [Q9ULZ9-1]
RefSeqiNP_057239.4. NM_016155.4. [Q9ULZ9-1]
UniGeneiHs.709245.

Genome annotation databases

EnsembliENST00000360564; ENSP00000353767; ENSG00000198598. [Q9ULZ9-1]
ENST00000535291; ENSP00000441106; ENSG00000198598. [Q9ULZ9-2]
GeneIDi4326.
KEGGihsa:4326.
UCSCiuc001ujc.1. human. [Q9ULZ9-1]

Polymorphism databases

DMDMi296439485.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB021225 mRNA. Translation: BAA82707.2.
X89576 mRNA. Translation: CAA61753.1.
AC131009 Genomic DNA. No translation available.
CCDSiCCDS31927.1. [Q9ULZ9-1]
RefSeqiNP_057239.4. NM_016155.4. [Q9ULZ9-1]
UniGeneiHs.709245.

3D structure databases

ProteinModelPortaliQ9ULZ9.
SMRiQ9ULZ9. Positions 39-523.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110469. 1 interaction.
STRINGi9606.ENSP00000353767.

Chemistry

BindingDBiQ9ULZ9.
ChEMBLiCHEMBL2937.
DrugBankiDB00786. Marimastat.

Protein family/group databases

MEROPSiM10.017.

PTM databases

PhosphoSiteiQ9ULZ9.

Polymorphism databases

DMDMi296439485.

Proteomic databases

PaxDbiQ9ULZ9.
PRIDEiQ9ULZ9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360564; ENSP00000353767; ENSG00000198598. [Q9ULZ9-1]
ENST00000535291; ENSP00000441106; ENSG00000198598. [Q9ULZ9-2]
GeneIDi4326.
KEGGihsa:4326.
UCSCiuc001ujc.1. human. [Q9ULZ9-1]

Organism-specific databases

CTDi4326.
GeneCardsiGC12P132312.
H-InvDBHIX0036662.
HGNCiHGNC:7163. MMP17.
MIMi602285. gene.
neXtProtiNX_Q9ULZ9.
PharmGKBiPA30875.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG295915.
GeneTreeiENSGT00760000118870.
HOVERGENiHBG052484.
InParanoidiQ9ULZ9.
KOiK07997.
OMAiAHNDRTY.
OrthoDBiEOG7XPZ57.
PhylomeDBiQ9ULZ9.
TreeFamiTF315428.

Enzyme and pathway databases

ReactomeiREACT_118682. Activation of Matrix Metalloproteinases.

Miscellaneous databases

GeneWikiiMMP17.
GenomeRNAii4326.
NextBioi17023.
PROiQ9ULZ9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9ULZ9.
CleanExiHS_MMP17.
ExpressionAtlasiQ9ULZ9. baseline and differential.
GenevestigatoriQ9ULZ9.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR028726. MMP17.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF118. PTHR10201:SF118. 1 hit.
PfamiPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human membrane type-4 matrix metalloproteinase (MT4-MMP) is encoded by a novel major transcript: isolation of complementary DNA clones for human and mouse mt4-mmp transcripts."
    Kajita M., Kinoh H., Ito N., Takamura A., Itoh Y., Okada A., Sato H., Seiki M.
    FEBS Lett. 457:353-356(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    Tissue: Monocytic leukemia.
  2. Seiki M.
    Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO 41; 44; 202-207; 221 AND 225.
  3. "Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma."
    Puente X.S., Pendas A.M., Llano E., Velasco G., Lopez-Otin C.
    Cancer Res. 56:944-949(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
    Tissue: Mammary carcinoma.
  4. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Catalytic activities and substrate specificity of the human membrane type 4 matrix metalloproteinase catalytic domain."
    Wang Y., Johnson A.R., Ye Q.-Z., Dyer R.D.
    J. Biol. Chem. 274:33043-33049(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 126-299, CHARACTERIZATION.
  6. "Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase."
    Itoh Y., Kajita M., Kinoh H., Mori H., Okada A., Seiki M.
    J. Biol. Chem. 274:34260-34266(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: GPI-ANCHOR.
  7. "Biochemical characterization of the catalytic domain of membrane-type 4 matrix metalloproteinase."
    Kolkenbrock H., Essers L., Ulbrich N., Will H.
    Biol. Chem. 380:1103-1108(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.

Entry informationi

Entry nameiMMP17_HUMAN
AccessioniPrimary (citable) accession number: Q9ULZ9
Secondary accession number(s): Q14850
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: May 18, 2010
Last modified: March 4, 2015
This is version 147 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.