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   27-MAR-2024, entry version 147.
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; 10090-ENSMUSP00000027528; -.
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:0006886; P:intracellular protein transport; IEA:InterPro.
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
//