Protein: Cell migration-inducing and hyaluronan-binding protein (EC 3.2.1.35) (Hyaluronan binding protein involved in hyaluronan depolymerization) (Protein 12H19.01.T7) (Q8BI06)
Organism: Mus musculus (Mouse)
Function: Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.
Subcellular location: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Cell membrane {ECO:0000250}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:18448257, ECO:0000269|PubMed:24251095}. Secreted {ECO:0000250}. Note=Retained in the endoplasmic reticulum (ER) in a HSPA5/BIP-dependent manner. Strongly detected in the cytoplasm of breast carcinoma cells, whereas poorly detected in adjacent normal epithelial cells, stromal cells, or benign breast tissues. Localized in the nucleus and cytoplasm of colon adenocarcinomas (By similarity). Colocalized with clathrin heavy chain/CLTC in clathrin-coated vesicles. {ECO:0000250}.
Sequence: MRASGRHDVSLKIVLATGCLLLANFSGASSAVATECPDQSPELQPWSPGHNRDYQVHIGHGRKLLLTSSATVHSITISGGGKLVIKDHHEHIVLRTRYILIDDGGELHAGSALCPFEGNFSIVLYGRADENILPDPYYGLKYIGVDKGGTLELHGQKKLSWTFLNKTLHPGGMQEGGYFFERSWGHRGVIVHVIDAKLGTVVHSDRFDTYRSKKESERLVQYLNAVPDGRILSVAVNDEGSRNLDDTARKAMTKLGSKHFLHLGFRHPWSFITVKGNPSSSVEDHIEYHGHKGSAAARVFKLFQTEHGEHFNVSSSSEWVQDVEWTEWFDHDKVPQSKGGEKISDLRAAYPGKICNRPIDIQATTMDGVALSTEVVYKNGQDYRFACYTRGRACRSYRVRFLCGKPVRPKLTVSIDTNVNSTILSLVDNVRSWRPGDTLVVASTDYSMYQAEEFRVLPCKACTSTQVKVAGKPQYLHIGEEIDGVDMRAEVGLLTRNIVVMGEMEDRCYPYTNHICDFFDFDTFGGHIKFALGFKAAHLEGVELKYMGQQLVGQYPIHFHLAGDLDEQGGYDPPTYIRDLSIHHTFSRCITVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSRMCKVITEDSYPGYIPKPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSIISARYSPHQDADPLKPREPAIIRHFTAYKNQDHGAWLRGGDVWLDSCRFADNGIGLTLASGGTFPYDDGSKQEIKNSLFVGESGNVGTEMMDNRIWGPGGLDHSGRTLPIGQNFPIRGIQFYDGPINIQNCTFRKFAALEGRHTSALAFRLNNAWQSCPHNNVTNIAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDLDGSVSEYPGSYLTKDDNWLVRHPDCINVPDWRGAICSGRYAQMYIQAYKSSNLRMKIIKNDFPSHPLYLEGALTRSTHYQQYQPVITLQKGYTIHWDQTAPAELAIWLINFNKGDWIRVGLCYPRGTTFSILSDVHNRLLKQTSKTGTFVRTLQMDKVEQSYPGRSHYYWDEDSGLLFLKLKAQNEREKFAFCSMKGCERIKIKALLPRNAGISDCTATAYPRFTERAIVDVPMPRKLFGAQLKTKDHFLEVKMESSRQHFFHLRNDFAYIEVDGRRYPCSEDGIQIVVIDGSRGHVVSHGSFRNAILQGIPWQLFNYVAAIPDNSIVLMASKGRYITRGPWTRVLEKLGADKGLKLKEKMAFVGFKGSFRPIWVTLETEDHKAKIFQVVPIPVVRKKKL
InterPro domains: - IPR039477: ILEI/PANDER domain (domain) [187-1330]
- IPR055400: CEMIP, domain X (domain) [1001-1185]
- IPR039473: Cell surface hyaluronidase, PANDER-like domain (domain) [141-303]
- IPR011050: Pectin lyase fold/virulence factor (homologous_superfamily) [409-995]
- IPR052252: Cell surface hyaluronidase CEMIP/CEMIP2 (family) [20-1354]
- IPR055401: CEMIP, beta-helix domain (domain) [523-737]
- IPR025155: WxxW domain (domain) [325-514]
- IPR019316: G8 domain (domain) [44-166]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0016798 (hydrolase activity, acting on glycosyl bonds), GO:0004553 (hydrolase activity, hydrolyzing O-glycosyl compounds), GO:0015929 (hexosaminidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0009058 (biosynthetic process), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0051050 (positive regulation of transport), GO:0009056 (catabolic process), GO:0003008 (system process), GO:0048522 (positive regulation of cellular process), GO:0040017 (positive regulation of locomotion), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0065009 (regulation of molecular function), GO:0040012 (regulation of locomotion), GO:0050790 (regulation of catalytic activity), GO:1903829 (positive regulation of protein localization), GO:0051049 (regulation of transport), GO:0044093 (positive regulation of molecular function), GO:1901564 (organonitrogen compound metabolic process), GO:0032388 (positive regulation of intracellular transport), GO:2000145 (regulation of cell motility), GO:1901576 (organic substance biosynthetic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0051282 (regulation of sequestering of calcium ion), GO:0060341 (regulation of cellular localization), GO:0034762 (regulation of transmembrane transport), GO:0060255 (regulation of macromolecule metabolic process), GO:0034764 (positive regulation of transmembrane transport), GO:0043170 (macromolecule metabolic process), GO:2000147 (positive regulation of cell motility), GO:1901135 (carbohydrate derivative metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0043270 (positive regulation of monoatomic ion transport), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0050877 (nervous system process), GO:0080090 (regulation of primary metabolic process), GO:0051222 (positive regulation of protein transport), GO:1901575 (organic substance catabolic process), GO:0009059 (macromolecule biosynthetic process), GO:0090316 (positive regulation of intracellular protein transport), GO:0010562 (positive regulation of phosphorus metabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0051246 (regulation of protein metabolic process), GO:1904951 (positive regulation of establishment of protein localization), GO:0070201 (regulation of establishment of protein localization), GO:0034765 (regulation of monoatomic ion transmembrane transport), GO:0032880 (regulation of protein localization), GO:0030334 (regulation of cell migration), GO:1905477 (positive regulation of protein localization to membrane), GO:0007600 (sensory perception), GO:0006022 (aminoglycan metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:0009057 (macromolecule catabolic process), GO:0034767 (positive regulation of monoatomic ion transmembrane transport), GO:0051223 (regulation of protein transport), GO:1901136 (carbohydrate derivative catabolic process), GO:0051928 (positive regulation of calcium ion transport), GO:0051247 (positive regulation of protein metabolic process), GO:0030335 (positive regulation of cell migration), GO:0051338 (regulation of transferase activity), GO:0043269 (regulation of monoatomic ion transport), GO:1901137 (carbohydrate derivative biosynthetic process), GO:0043085 (positive regulation of catalytic activity), GO:0051174 (regulation of phosphorus metabolic process), GO:0051279 (regulation of release of sequestered calcium ion into cytosol), GO:0032386 (regulation of intracellular transport), GO:0006026 (aminoglycan catabolic process), GO:1905475 (regulation of protein localization to membrane), GO:0051347 (positive regulation of transferase activity), GO:0031399 (regulation of protein modification process), GO:1904064 (positive regulation of cation transmembrane transport), GO:0045937 (positive regulation of phosphate metabolic process), GO:0033157 (regulation of intracellular protein transport), GO:0010959 (regulation of metal ion transport), GO:0019220 (regulation of phosphate metabolic process), GO:1904427 (positive regulation of calcium ion transmembrane transport), GO:0043549 (regulation of kinase activity), GO:0090314 (positive regulation of protein targeting to membrane), GO:0051281 (positive regulation of release of sequestered calcium ion into cytosol), GO:1904062 (regulation of monoatomic cation transmembrane transport), GO:0030203 (glycosaminoglycan metabolic process), GO:0050954 (sensory perception of mechanical stimulus), GO:0031401 (positive regulation of protein modification process), GO:0006023 (aminoglycan biosynthetic process), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0033674 (positive regulation of kinase activity), GO:0045859 (regulation of protein kinase activity), GO:0007605 (sensory perception of sound), GO:0006027 (glycosaminoglycan catabolic process), GO:0006024 (glycosaminoglycan biosynthetic process), GO:0051924 (regulation of calcium ion transport), GO:0042327 (positive regulation of phosphorylation), GO:1903510 (mucopolysaccharide metabolic process), GO:0090313 (regulation of protein targeting to membrane), GO:1903169 (regulation of calcium ion transmembrane transport), GO:0001934 (positive regulation of protein phosphorylation), GO:1903533 (regulation of protein targeting), GO:0030214 (hyaluronan catabolic process), GO:0071900 (regulation of protein serine/threonine kinase activity), GO:0030212 (hyaluronan metabolic process), GO:0010799 (regulation of peptidyl-threonine phosphorylation), GO:0045860 (positive regulation of protein kinase activity), GO:0010800 (positive regulation of peptidyl-threonine phosphorylation), GO:0071902 (positive regulation of protein serine/threonine kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0005783 (endoplasmic reticulum), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0030139 (endocytic vesicle), GO:0030135 (coated vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0030136 (clathrin-coated vesicle), GO:0045334 (clathrin-coated endocytic vesicle), GO:0097708 (intracellular vesicle)