MMP10_HUMAN
ID MMP10_HUMAN Reviewed; 476 AA.
AC P09238; B2R9X9; Q53HH9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Stromelysin-2;
DE Short=SL-2;
DE EC=3.4.24.22;
DE AltName: Full=Matrix metalloproteinase-10;
DE Short=MMP-10;
DE AltName: Full=Transin-2;
DE Flags: Precursor;
GN Name=MMP10; Synonyms=STMY2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2844164; DOI=10.1042/bj2530187;
RA Muller D., Quantin B., Gesnel M.-C., Millon-Collard R., Abecassis J.,
RA Breathnach R.;
RT "The collagenase gene family in humans consists of at least four members.";
RL Biochem. J. 253:187-192(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Esophagus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-53.
RC TISSUE=Coronary artery;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-4; LYS-53; ARG-65;
RP LEU-226; GLU-282; PHE-440 AND LEU-475.
RG NIEHS SNPs program;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 99-263, CATALYTIC ACTIVITY, ACTIVE
RP SITE, COFACTOR, CALCIUM-BINDING, AND ZINC-BINDING SITES.
RX PubMed=15095982; DOI=10.1016/j.jmb.2003.12.033;
RA Bertini I., Calderone V., Fragai M., Luchinat C., Mangani S., Terni B.;
RT "Crystal structure of the catalytic domain of human matrix
RT metalloproteinase 10.";
RL J. Mol. Biol. 336:707-716(2004).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-142.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Can degrade fibronectin, gelatins of type I, III, IV, and V;
CC weakly collagens III, IV, and V. Activates procollagenase.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Similar to stromelysin 1, but action on collagen types III, IV
CC and V is weak.; EC=3.4.24.22; Evidence={ECO:0000269|PubMed:15095982};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15095982};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:15095982};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:15095982};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305}.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp10/";
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DR EMBL; X07820; CAA30679.1; -; mRNA.
DR EMBL; BT007442; AAP36110.1; -; mRNA.
DR EMBL; AK222601; BAD96321.1; -; mRNA.
DR EMBL; AK313960; BAG36676.1; -; mRNA.
DR EMBL; AY744675; AAU21039.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67029.1; -; Genomic_DNA.
DR EMBL; BC002591; AAH02591.1; -; mRNA.
DR CCDS; CCDS8321.1; -.
DR PIR; A28816; KCHUS2.
DR RefSeq; NP_002416.1; NM_002425.2.
DR PDB; 1Q3A; X-ray; 2.10 A; A/B/C=99-263.
DR PDB; 3V96; X-ray; 1.90 A; B=99-263.
DR PDB; 4ILW; X-ray; 2.10 A; D/F=99-263.
DR PDBsum; 1Q3A; -.
DR PDBsum; 3V96; -.
DR PDBsum; 4ILW; -.
DR AlphaFoldDB; P09238; -.
DR SMR; P09238; -.
DR BioGRID; 110462; 21.
DR IntAct; P09238; 14.
DR STRING; 9606.ENSP00000279441; -.
DR BindingDB; P09238; -.
DR ChEMBL; CHEMBL4270; -.
DR DrugBank; DB00786; Marimastat.
DR DrugBank; DB08271; N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID.
DR GuidetoPHARMACOLOGY; 1634; -.
DR MEROPS; M10.006; -.
DR iPTMnet; P09238; -.
DR PhosphoSitePlus; P09238; -.
DR BioMuta; MMP10; -.
DR DMDM; 116869; -.
DR jPOST; P09238; -.
DR MassIVE; P09238; -.
DR PaxDb; P09238; -.
DR PeptideAtlas; P09238; -.
DR PRIDE; P09238; -.
DR ProteomicsDB; 52211; -.
DR TopDownProteomics; P09238; -.
DR Antibodypedia; 3688; 624 antibodies from 36 providers.
DR DNASU; 4319; -.
DR Ensembl; ENST00000279441.9; ENSP00000279441.4; ENSG00000166670.10.
DR GeneID; 4319; -.
DR KEGG; hsa:4319; -.
DR MANE-Select; ENST00000279441.9; ENSP00000279441.4; NM_002425.3; NP_002416.1.
DR UCSC; uc001phg.3; human.
DR CTD; 4319; -.
DR DisGeNET; 4319; -.
DR GeneCards; MMP10; -.
DR HGNC; HGNC:7156; MMP10.
DR HPA; ENSG00000166670; Tissue enriched (endometrium).
DR MIM; 185260; gene.
DR neXtProt; NX_P09238; -.
DR OpenTargets; ENSG00000166670; -.
DR PharmGKB; PA30868; -.
DR VEuPathDB; HostDB:ENSG00000166670; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000163375; -.
DR HOGENOM; CLU_015489_6_0_1; -.
DR InParanoid; P09238; -.
DR OMA; YVWRKSP; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; P09238; -.
DR TreeFam; TF315428; -.
DR BRENDA; 3.4.24.22; 2681.
DR PathwayCommons; P09238; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR SignaLink; P09238; -.
DR SIGNOR; P09238; -.
DR BioGRID-ORCS; 4319; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; MMP10; human.
DR EvolutionaryTrace; P09238; -.
DR GeneWiki; MMP10; -.
DR GenomeRNAi; 4319; -.
DR Pharos; P09238; Tchem.
DR PRO; PR:P09238; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P09238; protein.
DR Bgee; ENSG00000166670; Expressed in mucosa of paranasal sinus and 86 other tissues.
DR ExpressionAtlas; P09238; baseline and differential.
DR Genevisible; P09238; HS.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR000585; Hemopexin-like_dom.
DR InterPro; IPR036375; Hemopexin-like_dom_sf.
DR InterPro; IPR018487; Hemopexin-like_repeat.
DR InterPro; IPR018486; Hemopexin_CS.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR021158; Pept_M10A_Zn_BS.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR Pfam; PF00045; Hemopexin; 4.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Collagen degradation; Disulfide bond;
KW Extracellular matrix; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000305"
FT PROPEP 18..98
FT /note="Activation peptide"
FT /id="PRO_0000028764"
FT CHAIN 99..476
FT /note="Stromelysin-2"
FT /id="PRO_0000028765"
FT REPEAT 286..335
FT /note="Hemopexin 1"
FT REPEAT 336..382
FT /note="Hemopexin 2"
FT REPEAT 384..432
FT /note="Hemopexin 3"
FT REPEAT 433..476
FT /note="Hemopexin 4"
FT MOTIF 89..96
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:15095982"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT BINDING 221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT DISULFID 289..476
FT /evidence="ECO:0000250"
FT VARIANT 4
FT /note="L -> V (in dbSNP:rs17435959)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020949"
FT VARIANT 53
FT /note="R -> K (in dbSNP:rs486055)"
FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.5"
FT /id="VAR_020950"
FT VARIANT 65
FT /note="G -> R (in dbSNP:rs17293607)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020951"
FT VARIANT 142
FT /note="E -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036139"
FT VARIANT 226
FT /note="F -> L (in dbSNP:rs17860971)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020952"
FT VARIANT 282
FT /note="G -> E (in dbSNP:rs17860973)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020953"
FT VARIANT 440
FT /note="L -> F (in dbSNP:rs17860996)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020954"
FT VARIANT 475
FT /note="H -> L (in dbSNP:rs17861009)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_020955"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 126..141
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 175..183
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3V96"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 202..210
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 211..223
FT /evidence="ECO:0007829|PDB:3V96"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:1Q3A"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 242..247
FT /evidence="ECO:0007829|PDB:3V96"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:3V96"
SQ SEQUENCE 476 AA; 54151 MW; 516DCDDFEF92A0D6 CRC64;
MMHLAFLVLL CLPVCSAYPL SGAAKEEDSN KDLAQQYLEK YYNLEKDVKQ FRRKDSNLIV
KKIQGMQKFL GLEVTGKLDT DTLEVMRKPR CGVPDVGHFS SFPGMPKWRK THLTYRIVNY
TPDLPRDAVD SAIEKALKVW EEVTPLTFSR LYEGEADIMI SFAVKEHGDF YSFDGPGHSL
AHAYPPGPGL YGDIHFDDDE KWTEDASGTN LFLVAAHELG HSLGLFHSAN TEALMYPLYN
SFTELAQFRL SQDDVNGIQS LYGPPPASTE EPLVPTKSVP SGSEMPAKCD PALSFDAIST
LRGEYLFFKD RYFWRRSHWN PEPEFHLISA FWPSLPSYLD AAYEVNSRDT VFIFKGNEFW
AIRGNEVQAG YPRGIHTLGF PPTIRKIDAA VSDKEKKKTY FFAADKYWRF DENSQSMEQG
FPRLIADDFP GVEPKVDAVL QAFGFFYFFS GSSQFEFDPN ARMVTHILKS NSWLHC
