Q9ULZ9 (MMP17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-17
Short name=MMP-17
EC=3.4.24.-

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 names

Name:	MMP17
Synonyms:	MT4MMP

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	603 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 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 activity	Cleaves pro-TNF-alpha at the 74-Ala-|-Gln-75 site.
Cofactor	Binds 1 zinc ion per subunit By similarity. Calcium By similarity.
Subcellular location	Isoform Long: Cell membrane; Lipid-anchor › GPI-anchor; Extracellular side. Secreted › extracellular space › extracellular matrix Ref.6.
Tissue specificity	Expressed in brain, leukocytes, colon, ovary testis and breast cancer. Expressed also in many transformed and non-transformed cell types.
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
Cellular component	Cell membrane Extracellular matrix Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond GPI-anchor Glycoprotein Lipoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement Ref.3. 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.3. Source: ProtInc metalloendopeptidase activity Traceable author statement Ref.3. Source: ProtInc zinc ion binding Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: Q9ULZ9-1)

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: Q9ULZ9-2)

Also known as: Puente;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Propeptide	36 – 125	90	By similarity		PRO_0000028818
	Chain	126 – 565	440	Matrix metalloproteinase-17		PRO_0000028819
	Propeptide	566 – 603	38	Removed in mature form Potential		PRO_0000028820
Regions
	Domain	336 – 380	45	Hemopexin-like 1
	Domain	385 – 428	44	Hemopexin-like 2
	Domain	431 – 477	47	Hemopexin-like 3
	Domain	479 – 523	45	Hemopexin-like 4
	Motif	108 – 115	8	Cysteine switch By similarity
	Compositional bias	122 – 125	4	Poly-Arg
Sites
	Active site	249	1	By similarity
	Metal binding	110	1	Zinc; in inhibited form By similarity
	Metal binding	248	1	Zinc; catalytic By similarity
	Metal binding	252	1	Zinc; catalytic By similarity
	Metal binding	258	1	Zinc; catalytic By similarity
Amino acid modifications
	Lipidation	565	1	GPI-anchor amidated serine Potential
	Glycosylation	137	1	N-linked (GlcNAc...) Potential
	Glycosylation	318	1	N-linked (GlcNAc...) Potential
	Disulfide bond	332 ↔ 523		By similarity
Natural variations
	Alternative sequence	1 – 84	84	Missing in isoform Short.		VSP_005456
Experimental info
	Sequence conflict	23	1	L → LLPL in BAA82707. Ref.1
	Sequence conflict	23	1	L → LLPL in CAA61753. Ref.2
	Sequence conflict	182	1	A → T in BAA82707. Ref.1
	Sequence conflict	182	1	A → T in CAA61753. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 18, 2010. Version 4. Checksum: BB297B21973C7A0B	FASTA	603	66,653
	10 20 30 40 50 60 MRRRAARGPG PPPPGPGLSR LPLPLLLLLA LGTRGGCAAP APAPRAEDLS LGVEWLSRFG 70 80 90 100 110 120 YLPPADPTTG QLQTQEELSK AITAMQQFGG LEATGILDEA TLALMKTPRC SLPDLPVLTQ 130 140 150 160 170 180 ARRRRQAPAP TKWNKRNLSW RVRTFPRDSP LGHDTVRALM YYALKVWSDI APLNFHEVAG 190 200 210 220 230 240 SAADIQIDFS KADHNDGYPF DGPGGTVAHA FFPGHHHTAG DTHFDDDEAW TFRSSDAHGM 250 260 270 280 290 300 DLFAVAVHEF GHAIGLSHVA AAHSIMRPYY QGPVGDPLRY GLPYEDKVRV WQLYGVRESV 310 320 330 340 350 360 SPTAQPEEPP LLPEPPDNRS SAPPRKDVPH RCSTHFDAVA QIRGEAFFFK GKYFWRLTRD 370 380 390 400 410 420 RHLVSLQPAQ MHRFWRGLPL HLDSVDAVYE RTSDHKIVFF KGDRYWVFKD NNVEEGYPRP 430 440 450 460 470 480 VSDFSLPPGG IDAAFSWAHN DRTYFFKDQL YWRYDDHTRH MDPGYPAQSP LWRGVPSTLD 490 500 510 520 530 540 DAMRWSDGAS YFFRGQEYWK VLDGELEVAP GYPQSTARDW LVCGDSQADG SVAAGVDAAE 550 560 570 580 590 600 GPRAPPGQHD QSRSEDGYEV CSCTSGASSP PGAPGPLVAA TMLLLLPPLS PGALWTAAQA LTL
	Isoform Short (Puente) [UniParc]. Checksum: EB74B32E8A7619C3	FASTA	519	57,938
	10 20 30 40 50 60 MQQFGGLEAT GILDEATLAL MKTPRCSLPD LPVLTQARRR RQAPAPTKWN KRNLSWRVRT 70 80 90 100 110 120 FPRDSPLGHD TVRALMYYAL KVWSDIAPLN FHEVAGSAAD IQIDFSKADH NDGYPFDGPG 130 140 150 160 170 180 GTVAHAFFPG HHHTAGDTHF DDDEAWTFRS SDAHGMDLFA VAVHEFGHAI GLSHVAAAHS 190 200 210 220 230 240 IMRPYYQGPV GDPLRYGLPY EDKVRVWQLY GVRESVSPTA QPEEPPLLPE PPDNRSSAPP 250 260 270 280 290 300 RKDVPHRCST HFDAVAQIRG EAFFFKGKYF WRLTRDRHLV SLQPAQMHRF WRGLPLHLDS 310 320 330 340 350 360 VDAVYERTSD HKIVFFKGDR YWVFKDNNVE EGYPRPVSDF SLPPGGIDAA FSWAHNDRTY 370 380 390 400 410 420 FFKDQLYWRY DDHTRHMDPG YPAQSPLWRG VPSTLDDAMR WSDGASYFFR GQEYWKVLDG 430 440 450 460 470 480 ELEVAPGYPQ STARDWLVCG DSQADGSVAA GVDAAEGPRA PPGQHDQSRS EDGYEVCSCT 490 500 510 SGASSPPGAP GPLVAATMLL LLPPLSPGAL WTAAQALTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB021225 mRNA. Translation: BAA82707.2. X89576 mRNA. Translation: CAA61753.1. AC131009 Genomic DNA. No translation available.
IPI	IPI00008533. IPI00472696.
RefSeq	NP_057239.4. NM_016155.4.
UniGene	Hs.709245.
3D structure databases
ProteinModelPortal	Q9ULZ9.
SMR	Q9ULZ9. Positions 39-523.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000353767.
Protein family/group databases
MEROPS	M10.017.
PTM databases
PhosphoSite	Q9ULZ9.
Polymorphism databases
DMDM	296439485.
Proteomic databases
PaxDb	Q9ULZ9.
PRIDE	Q9ULZ9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360564; ENSP00000353767; ENSG00000198598. ENST00000535291; ENSP00000441106; ENSG00000198598.
GeneID	4326.
KEGG	hsa:4326.
UCSC	uc001ujc.1. human.
Organism-specific databases
CTD	4326.
GeneCards	GC12P132312.
H-InvDB	HIX0036662.
HGNC	HGNC:7163. MMP17.
MIM	602285. gene.
neXtProt	NX_Q9ULZ9.
PharmGKB	PA30875.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295915.
HOVERGEN	HBG052484.
InParanoid	Q9ULZ9.
KO	K07997.
OMA	WRGLPLH.
OrthoDB	EOG40VVPC.
PhylomeDB	Q9ULZ9.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
ArrayExpress	Q9ULZ9.
Bgee	Q9ULZ9.
CleanEx	HS_MMP17.
Genevestigator	Q9ULZ9.
GermOnline	ENSG00000198598. 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. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR016293. Pept_M10A_Metazoans. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	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. False negative. PS00024. HEMOPEXIN. False negative. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2937.
GenomeRNAi	4326.
NextBio	17023.
SOURCE	Search...

Entry information

Entry name

MMP17_HUMAN

Accession

Primary (citable) accession number: Q9ULZ9
Secondary accession number(s): Q14850

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 128 of the entry and version 4 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.