ID MELPH_MOUSE Reviewed; 590 AA. AC Q91V27; Q3UFV7; Q99N53; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 22-FEB-2023, entry version 144. DE RecName: Full=Melanophilin; DE AltName: Full=Exophilin-3; DE AltName: Full=Leaden protein; DE AltName: Full=Slp homolog lacking C2 domains a; DE Short=SlaC2-a; DE AltName: Full=Synaptotagmin-like protein 2a; GN Name=Mlph; Synonyms=Ln, Slac2a; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; TISSUE=Brain; RX PubMed=11327731; DOI=10.1006/bbrc.2001.4803; RA Fukuda M., Saegusa C., Mikoshiba K.; RT "Novel splicing isoforms of synaptotagmin-like proteins 2 and 3: RT identification of the Slp homology domain."; RL Biochem. Biophys. Res. Commun. 283:513-519(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=11504925; DOI=10.1073/pnas.181336698; RA Matesic L.E., Yip R., Reuss A.E., Swing D.A., O'Sullivan T.N., RA Fletcher C.F., Copeland N.G., Jenkins N.A.; RT "Mutations in Mlph, encoding a member of the Rab effector family, cause the RT melanosome transport defects observed in leaden mice."; RL Proc. Natl. Acad. Sci. U.S.A. 98:10238-10243(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Melanoma; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP INTERACTION WITH RAB27A AND MYO5A, AND FUNCTION. RX PubMed=11887186; DOI=10.1038/ncb760; RA Wu X.S., Rao K., Zhang H., Wang F., Sellers J.R., Matesic L.E., RA Copeland N.G., Jenkins N.A., Hammer J.A. III; RT "Identification of an organelle receptor for myosin-Va."; RL Nat. Cell Biol. 4:271-278(2002). RN [5] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-146 IN COMPLEX WITH RAB27B, AND RP SUBUNIT. RX PubMed=18940604; DOI=10.1016/j.str.2008.07.014; RA Kukimoto-Niino M., Sakamoto A., Kanno E., Hanawa-Suetsugu K., Terada T., RA Shirouzu M., Fukuda M., Yokoyama S.; RT "Structural basis for the exclusive specificity of Slac2-a/melanophilin for RT the Rab27 GTPases."; RL Structure 16:1478-1490(2008). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 170-208 IN COMPLEX WITH MYO5A, AND RP SUBUNIT. RX PubMed=23798443; DOI=10.1073/pnas.1306768110; RA Wei Z., Liu X., Yu C., Zhang M.; RT "Structural basis of cargo recognitions for class V myosins."; RL Proc. Natl. Acad. Sci. U.S.A. 110:11314-11319(2013). CC -!- FUNCTION: Rab effector protein involved in melanosome transport. Serves CC as link between melanosome-bound RAB27A and the motor protein MYO5A. CC {ECO:0000269|PubMed:11504925, ECO:0000269|PubMed:11887186}. CC -!- SUBUNIT: Binds RAB27A that has been activated by GTP-binding via its N- CC terminus. Binds MYO5A via its C-terminal coiled coil domain. CC {ECO:0000269|PubMed:18940604, ECO:0000269|PubMed:23798443}. CC -!- INTERACTION: CC Q91V27; Q9ERI2: Rab27a; NbExp=2; IntAct=EBI-398308, EBI-398172; CC Q91V27; Q99P58: Rab27b; NbExp=2; IntAct=EBI-398308, EBI-11565917; CC -!- SUBCELLULAR LOCATION: Melanosome. CC -!- TISSUE SPECIFICITY: Highly expressed in embryos at day 7; not CC detectable at day 11. Highly expressed in adult stomach; detected at CC lower levels in kidney, lung, skin and small intestine. Detected in CC melanocytes. {ECO:0000269|PubMed:11504925}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB057759; BAB41087.1; -; mRNA. DR EMBL; AF384098; AAK97435.1; -; mRNA. DR EMBL; AK148274; BAE28452.1; -; mRNA. DR CCDS; CCDS15155.1; -. DR RefSeq; NP_443748.2; NM_053015.3. DR PDB; 2ZET; X-ray; 3.00 A; C/D=1-146. DR PDB; 4KP3; X-ray; 2.40 A; E/F=170-208. DR PDB; 4LX2; X-ray; 1.50 A; B=176-201. DR PDBsum; 2ZET; -. DR PDBsum; 4KP3; -. DR PDBsum; 4LX2; -. DR AlphaFoldDB; Q91V27; -. DR SMR; Q91V27; -. DR BioGRID; 228608; 2. DR CORUM; Q91V27; -. DR DIP; DIP-31495N; -. DR ELM; Q91V27; -. DR IntAct; Q91V27; 3. DR STRING; 10090.ENSMUSP00000027528; -. DR iPTMnet; Q91V27; -. DR PhosphoSitePlus; Q91V27; -. DR MaxQB; Q91V27; -. DR PaxDb; Q91V27; -. DR ProteomicsDB; 295854; -. DR GeneID; 171531; -. DR KEGG; mmu:171531; -. DR UCSC; uc007bzm.2; mouse. DR AGR; MGI:2176380; -. DR CTD; 79083; -. DR MGI; MGI:2176380; Mlph. DR eggNOG; ENOG502RJPZ; Eukaryota. DR InParanoid; Q91V27; -. DR OrthoDB; 2967336at2759; -. DR PhylomeDB; Q91V27; -. DR TreeFam; TF331599; -. DR BioGRID-ORCS; 171531; 2 hits in 75 CRISPR screens. DR ChiTaRS; Mlph; mouse. DR EvolutionaryTrace; Q91V27; -. DR PRO; PR:Q91V27; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; Q91V27; protein. DR GO; GO:0015629; C:actin cytoskeleton; IDA:MGI. DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0042470; C:melanosome; IDA:MGI. DR GO; GO:0005815; C:microtubule organizing center; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0001725; C:stress fiber; IDA:MGI. DR GO; GO:0016461; C:unconventional myosin complex; IMP:CAFA. DR GO; GO:0003779; F:actin binding; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051010; F:microtubule plus-end binding; IDA:MGI. DR GO; GO:0060090; F:molecular adaptor activity; IDA:DisProt. DR GO; GO:0017022; F:myosin binding; IDA:MGI. DR GO; GO:0031489; F:myosin V binding; IPI:CAFA. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI. DR GO; GO:0031267; F:small GTPase binding; IDA:MGI. DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI. DR GO; GO:0032400; P:melanosome localization; IMP:MGI. DR GO; GO:0043473; P:pigmentation; IMP:MGI. DR GO; GO:0006605; P:protein targeting; IMP:MGI. DR CDD; cd15752; FYVE_SlaC2-a; 1. DR DisProt; DP00541; -. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR041282; FYVE_2. DR InterPro; IPR037442; Melanophilin_FYVE-rel_dom. DR InterPro; IPR006788; Myrip/Melanophilin. DR InterPro; IPR010911; Rab_BD. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR14555:SF1; MELANOPHILIN; 1. DR PANTHER; PTHR14555; MYELIN-ASSOCIATED OLIGODENDROCYTIC BASIC PROTEIN MOBP -RELATED; 1. DR Pfam; PF02318; FYVE_2; 1. DR Pfam; PF04698; Rab_eff_C; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR PROSITE; PS50916; RABBD; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Metal-binding; Reference proteome; Repeat; Zinc; KW Zinc-finger. FT CHAIN 1..590 FT /note="Melanophilin" FT /id="PRO_0000190223" FT DOMAIN 4..124 FT /note="RabBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00234" FT ZN_FING 64..107 FT /note="FYVE-type" FT REGION 147..182 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 213..276 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 311..335 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 361..472 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 485..590 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 339..485 FT /evidence="ECO:0000255" FT COMPBIAS 159..173 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 213..234 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 374..389 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 390..407 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 430..444 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 539..573 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CONFLICT 192 FT /note="R -> Q (in Ref. 3; BAE28452)" FT /evidence="ECO:0000305" FT CONFLICT 254 FT /note="R -> H (in Ref. 1; BAB41087)" FT /evidence="ECO:0000305" FT CONFLICT 333 FT /note="R -> W (in Ref. 3; BAE28452)" FT /evidence="ECO:0000305" FT CONFLICT 360 FT /note="T -> R (in Ref. 3; BAE28452)" FT /evidence="ECO:0000305" FT CONFLICT 475 FT /note="E -> Q (in Ref. 1; BAB41087)" FT /evidence="ECO:0000305" FT CONFLICT 499 FT /note="G -> S (in Ref. 3; BAE28452)" FT /evidence="ECO:0000305" FT HELIX 12..53 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:2ZET" FT TURN 65..67 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 71..73 FT /evidence="ECO:0007829|PDB:2ZET" FT TURN 82..84 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:2ZET" FT STRAND 97..101 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 105..117 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 119..126 FT /evidence="ECO:0007829|PDB:2ZET" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 133..140 FT /evidence="ECO:0007829|PDB:2ZET" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:4LX2" SQ SEQUENCE 590 AA; 65052 MW; C91444B16B8EFA1D CRC64; MGKRLDLSTL TDEEAEHVWA VVQRDFDLRR REEERLQGLK GKIQKESSKR ELLSDTAHLN ETHCARCLQP YRLLLNSRRQ CLECSLFVCK SCSHAHPEEQ GWLCDPCHLA RVVKIGSLEW YYQHVRARFK RFGSAKVIRS LCGRLQGGGG SEPSLEEGNG DSEQTDEDGD LDTEARDQPL NSKKKKRLLS FRDVDFEEDS DHLVQPCSQT LGLSSVPESA HSLQSLSGEP YSEDTTSLEP EGLEETGARA LGCRPSPEVQ PCSPLPSGED AHAELDSPAA SCKSAFGTTA MPGTDDVRGK HLPSQYLADV DTSDEDSIQG PRAASQHSKR RARTVPETQI LELNKRMSAV EHLLVHLENT VLPPSAQEPT VETHPSADTE EETLRRRLEE LTSNISGSST SSEDETKPDG TFLGGSPKVC TDTGHMETQE RNPRSPGNPA RPTKSTDEEL SEMEDRVAMT ASEVQQAESE ISDIESRIAA LRAAGLTVKP SGKPRRKSGI PIFLPRVTEK LDRIPKTPPA DPDDQAKMPK ATTAVPSLLR RKYSPSSQGV DSGSFDRKSV YRGSLTQRNP NGRRGTARHI FAKPVMAQQP //