MELPH_MOUSE
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 25-MAY-2022, entry version 141.
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}.
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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 PRIDE; Q91V27; -.
DR ProteomicsDB; 295854; -.
DR GeneID; 171531; -.
DR KEGG; mmu:171531; -.
DR UCSC; uc007bzm.2; mouse.
DR CTD; 79083; -.
DR MGI; MGI:2176380; Mlph.
DR eggNOG; ENOG502RJPZ; Eukaryota.
DR InParanoid; Q91V27; -.
DR OrthoDB; 492485at2759; -.
DR PhylomeDB; Q91V27; -.
DR TreeFam; TF331599; -.
DR BioGRID-ORCS; 171531; 2 hits in 70 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: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; -; 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; 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
