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 03-JUL-2019, entry version 129. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; 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, RT cause the 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA 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, RP AND SUBUNIT. RX PubMed=18940604; DOI=10.1016/j.str.2008.07.014; RA Kukimoto-Niino M., Sakamoto A., Kanno E., Hanawa-Suetsugu K., RA Terada T., Shirouzu M., Fukuda M., Yokoyama S.; RT "Structural basis for the exclusive specificity of Slac2- RT a/melanophilin for the Rab27 GTPases."; RL Structure 16:1478-1490(2008). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 170-208 IN COMPLEX WITH RP MYO5A, AND 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. CC Serves as link between melanosome-bound RAB27A and the motor CC protein MYO5A. {ECO:0000269|PubMed:11504925, CC ECO:0000269|PubMed:11887186}. CC -!- SUBUNIT: Binds RAB27A that has been activated by GTP-binding via CC its N-terminus. Binds MYO5A via its C-terminal coiled coil domain. CC {ECO:0000269|PubMed:18940604, ECO:0000269|PubMed:23798443}. CC -!- INTERACTION: CC Q9ERI2:Rab27a; NbExp=2; IntAct=EBI-398308, EBI-398172; CC 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 CC at lower levels in kidney, lung, skin and small intestine. CC Detected in 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 SMR; Q91V27; -. DR BioGrid; 228608; 1. 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 PRIDE; Q91V27; -. DR GeneID; 171531; -. DR KEGG; mmu:171531; -. DR UCSC; uc007bzm.2; mouse. DR CTD; 79083; -. DR MGI; MGI:2176380; Mlph. DR eggNOG; ENOG410IEPI; Eukaryota. DR eggNOG; ENOG41102EA; LUCA. DR HOGENOM; HOG000089970; -. DR InParanoid; Q91V27; -. DR KO; K22235; -. DR OrthoDB; 492485at2759; -. DR PhylomeDB; Q91V27; -. DR TreeFam; TF331599; -. DR ChiTaRS; Mlph; mouse. DR EvolutionaryTrace; Q91V27; -. DR PRO; PR:Q91V27; -. DR Proteomes; UP000000589; Unplaced. 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; IPI:MGI. 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 binding, bridging; ISO:MGI. DR GO; GO:0017137; F:Rab 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; -; 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 Pfam; PF02318; FYVE_2; 1. DR Pfam; PF04698; Rab_eff_C; 1. DR SUPFAM; SSF57903; SSF57903; 1. DR PROSITE; PS50916; RABBD; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Complete proteome; Metal-binding; KW Reference proteome; Repeat; Zinc; Zinc-finger. FT CHAIN 1 590 Melanophilin. FT /FTId=PRO_0000190223. FT DOMAIN 4 124 RabBD. {ECO:0000255|PROSITE- FT ProRule:PRU00234}. FT ZN_FING 64 107 FYVE-type. FT COILED 339 485 {ECO:0000255}. FT CONFLICT 192 192 R -> Q (in Ref. 3; BAE28452). FT {ECO:0000305}. FT CONFLICT 254 254 R -> H (in Ref. 1; BAB41087). FT {ECO:0000305}. FT CONFLICT 333 333 R -> W (in Ref. 3; BAE28452). FT {ECO:0000305}. FT CONFLICT 360 360 T -> R (in Ref. 3; BAE28452). FT {ECO:0000305}. FT CONFLICT 475 475 E -> Q (in Ref. 1; BAB41087). FT {ECO:0000305}. FT CONFLICT 499 499 G -> S (in Ref. 3; BAE28452). FT {ECO:0000305}. FT HELIX 12 53 {ECO:0000244|PDB:2ZET}. FT HELIX 59 61 {ECO:0000244|PDB:2ZET}. FT TURN 65 67 {ECO:0000244|PDB:2ZET}. FT HELIX 71 73 {ECO:0000244|PDB:2ZET}. FT TURN 82 84 {ECO:0000244|PDB:2ZET}. FT HELIX 90 92 {ECO:0000244|PDB:2ZET}. FT STRAND 97 101 {ECO:0000244|PDB:2ZET}. FT HELIX 105 117 {ECO:0000244|PDB:2ZET}. FT HELIX 119 126 {ECO:0000244|PDB:2ZET}. FT STRAND 129 131 {ECO:0000244|PDB:2ZET}. FT HELIX 133 140 {ECO:0000244|PDB:2ZET}. FT HELIX 193 195 {ECO:0000244|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 //