Q9BV36 (MELPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Melanophilin

Alternative name(s):
Exophilin-3
Slp homolog lacking C2 domains a
Short name=SlaC2-a
Synaptotagmin-like protein 2a

Gene names

Name:	MLPH
Synonyms:	SLAC2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	600 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. Ref.3
Subunit structure	Binds RAB27A that has been activated by GTP-binding via its N-terminus. Binds MYO5A via its C-terminal coiled coil domain.
Subcellular location	Cytoplasm.
Involvement in disease	Griscelli syndrome 3 (GS3) [MIM:609227]: Rare autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes, without other clinical manifestations. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4
Sequence similarities	Contains 1 FYVE-type zinc finger. Contains 1 RabBD (Rab-binding) domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	melanocyte differentiation Inferred from electronic annotation. Source: Compara melanosome localization Inferred from electronic annotation. Source: Compara protein targeting Inferred from electronic annotation. Source: Compara
Cellular_component	cortical actin cytoskeleton Inferred from electronic annotation. Source: Compara microtubule organizing center Inferred from electronic annotation. Source: Compara microtubule plus end Inferred from electronic annotation. Source: Compara stress fiber Inferred from electronic annotation. Source: Compara
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BV36-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BV36-2)

The sequence of this isoform differs from the canonical sequence as follows:
     341-368: Missing.

Isoform 3 (identifier: Q9BV36-3)

The sequence of this isoform differs from the canonical sequence as follows:
     186-225: Missing.
     341-368: Missing.
     430-481: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 600	600	Melanophilin		PRO_0000190222
Regions
	Domain	4 – 124	121	RabBD
	Zinc finger	64 – 107	44	FYVE-type
	Coiled coil	373 – 496	124	Potential
Amino acid modifications
	Modified residue	162	1	Phosphoserine By similarity
	Modified residue	165	1	Phosphothreonine By similarity
	Modified residue	314	1	Phosphoserine By similarity
	Modified residue	458	1	Phosphothreonine By similarity
	Modified residue	552	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	186 – 225	40	Missing in isoform 3.		VSP_042158
	Alternative sequence	341 – 368	28	Missing in isoform 2 and isoform 3.		VSP_007554
	Alternative sequence	430 – 481	52	Missing in isoform 3.		VSP_042159
	Natural variant	35	1	R → W in GS3; abolishes RAB27A binding. Ref.4		VAR_018724
	Natural variant	139	1	R → W. Corresponds to variant rs2292880 [ dbSNP | Ensembl ].		VAR_015690
	Natural variant	153	1	L → P. Corresponds to variant rs3751109 [ dbSNP | Ensembl ].		VAR_015691
	Natural variant	163	1	D → N. Corresponds to variant rs3751108 [ dbSNP | Ensembl ].		VAR_015692
	Natural variant	172	1	G → D. Corresponds to variant rs3751107 [ dbSNP | Ensembl ].		VAR_015693
	Natural variant	289	1	T → I. Corresponds to variant rs11883500 [ dbSNP | Ensembl ].		VAR_038410
	Natural variant	347	1	H → R. Corresponds to variant rs2292884 [ dbSNP | Ensembl ].		VAR_015694
	Natural variant	374	1	V → A. Ref.1 Corresponds to variant rs3817362 [ dbSNP | Ensembl ].		VAR_015695
	Natural variant	451	1	P → S. Corresponds to variant rs58256353 [ dbSNP | Ensembl ].		VAR_061754
Experimental info
	Mutagenesis	14	1	E → A: Abolishes RAB27A binding. Ref.3
	Mutagenesis	24	1	R → A: Decreases RAB27A binding. Ref.3
	Mutagenesis	32	1	E → A: Abolishes RAB27A binding. Ref.3
	Sequence conflict	109	1	L → P in BAB13984. Ref.1
	Sequence conflict	253	1	G → R in AK225381. Ref.1
	Sequence conflict	577	1	Q → R in BAB13984. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 90F48D0B3250AD98	FASTA	600	65,949
	10 20 30 40 50 60 MGKKLDLSKL TDEEAQHVLE VVQRDFDLRR KEEERLEALK GKIKKESSKR ELLSDTAHLN 70 80 90 100 110 120 ETHCARCLQP YQLLVNSKRQ CLECGLFTCK SCGRVHPEEQ GWICDPCHLA RVVKIGSLEW 130 140 150 160 170 180 YYEHVKARFK RFGSAKVIRS LHGRLQGGAG PELISEERSG DSDQTDEDGE PGSEAQAQAQ 190 200 210 220 230 240 PFGSKKKRLL SVHDFDFEGD SDDSTQPQGH SLHLSSVPEA RDSPQSLTDE SCSEKAAPHK 250 260 270 280 290 300 AEGLEEADTG ASGCHSHPEE QPTSISPSRH GALAELCPPG GSHRMALGTA AALGSNVIRN 310 320 330 340 350 360 EQLPLQYLAD VDTSDEESIR AHVMASHHSK RRGRASSESQ IFELNKHISA VECLLTYLEN 370 380 390 400 410 420 TVVPPLAKGL GAGVRTEADV EEEALRRKLE ELTSNVSDQE TSSEEEEAKD EKAEPNRDKS 430 440 450 460 470 480 VGPLPQADPE VGTAAHQTNR QEKSPQDPGD PVQYNRTTDE ELSELEDRVA VTASEVQQAE 490 500 510 520 530 540 SEVSDIESRI AALRAAGLTV KPSGKPRRKS NLPIFLPRVA GKLGKRPEDP NADPSSEAKA 550 560 570 580 590 600 MAVPYLLRRK FSNSLKSQGK DDDSFDRKSV YRGSLTQRNP NARKGMASHT FAKPVVAHQS
	Isoform 2 [UniParc]. Checksum: C11EDAE008804679	FASTA	572	62,811
	10 20 30 40 50 60 MGKKLDLSKL TDEEAQHVLE VVQRDFDLRR KEEERLEALK GKIKKESSKR ELLSDTAHLN 70 80 90 100 110 120 ETHCARCLQP YQLLVNSKRQ CLECGLFTCK SCGRVHPEEQ GWICDPCHLA RVVKIGSLEW 130 140 150 160 170 180 YYEHVKARFK RFGSAKVIRS LHGRLQGGAG PELISEERSG DSDQTDEDGE PGSEAQAQAQ 190 200 210 220 230 240 PFGSKKKRLL SVHDFDFEGD SDDSTQPQGH SLHLSSVPEA RDSPQSLTDE SCSEKAAPHK 250 260 270 280 290 300 AEGLEEADTG ASGCHSHPEE QPTSISPSRH GALAELCPPG GSHRMALGTA AALGSNVIRN 310 320 330 340 350 360 EQLPLQYLAD VDTSDEESIR AHVMASHHSK RRGRASSESQ GLGAGVRTEA DVEEEALRRK 370 380 390 400 410 420 LEELTSNVSD QETSSEEEEA KDEKAEPNRD KSVGPLPQAD PEVGTAAHQT NRQEKSPQDP 430 440 450 460 470 480 GDPVQYNRTT DEELSELEDR VAVTASEVQQ AESEVSDIES RIAALRAAGL TVKPSGKPRR 490 500 510 520 530 540 KSNLPIFLPR VAGKLGKRPE DPNADPSSEA KAMAVPYLLR RKFSNSLKSQ GKDDDSFDRK 550 560 570 SVYRGSLTQR NPNARKGMAS HTFAKPVVAH QS
	Isoform 3 [UniParc]. Checksum: 2F014885D1BF691F	FASTA	480	52,642
	10 20 30 40 50 60 MGKKLDLSKL TDEEAQHVLE VVQRDFDLRR KEEERLEALK GKIKKESSKR ELLSDTAHLN 70 80 90 100 110 120 ETHCARCLQP YQLLVNSKRQ CLECGLFTCK SCGRVHPEEQ GWICDPCHLA RVVKIGSLEW 130 140 150 160 170 180 YYEHVKARFK RFGSAKVIRS LHGRLQGGAG PELISEERSG DSDQTDEDGE PGSEAQAQAQ 190 200 210 220 230 240 PFGSKSLTDE SCSEKAAPHK AEGLEEADTG ASGCHSHPEE QPTSISPSRH GALAELCPPG 250 260 270 280 290 300 GSHRMALGTA AALGSNVIRN EQLPLQYLAD VDTSDEESIR AHVMASHHSK RRGRASSESQ 310 320 330 340 350 360 GLGAGVRTEA DVEEEALRRK LEELTSNVSD QETSSEEEEA KDEKAEPNRD KSVGPLPQAD 370 380 390 400 410 420 PEVSDIESRI AALRAAGLTV KPSGKPRRKS NLPIFLPRVA GKLGKRPEDP NADPSSEAKA 430 440 450 460 470 480 MAVPYLLRRK FSNSLKSQGK DDDSFDRKSV YRGSLTQRNP NARKGMASHT FAKPVVAHQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT ALA-374. Tissue: Kidney and Mammary gland.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney and Skin.
[3]	"Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil regions." Nagashima K., Torii S., Yi Z., Igarashi M., Okamoto K., Takeuchi T., Izumi T. FEBS Lett. 517:233-238(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-14; ARG-24 AND GLU-32, INTERACTION WITH MYO5A AND RAB27A, FUNCTION.
[4]	"Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1)." Menasche G., Ho C.H., Sanal O., Feldmann J., Tezcan I., Ersoy F., Houdusse A., Fischer A., de Saint Basile G. J. Clin. Invest. 112:450-456(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GS3 TRP-35.
+	Additional computationally mapped references.

Web resources

MLPHbase

MLPH mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK022207 mRNA. Translation: BAB13984.1. AK225381 mRNA. No translation available. BC001653 mRNA. Translation: AAH01653.1. BC051269 mRNA. Translation: AAH51269.1.
IPI	IPI00012201. IPI00328101.
RefSeq	NP_001035932.1. NM_001042467.1. NP_077006.1. NM_024101.5.
UniGene	Hs.102406.
3D structure databases
ProteinModelPortal	Q9BV36.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44046N.
MINT	MINT-3388002.
STRING	9606.ENSP00000264605.
PTM databases
PhosphoSite	Q9BV36.
Polymorphism databases
DMDM	32129730.
Proteomic databases
PaxDb	Q9BV36.
PRIDE	Q9BV36.
Protocols and materials databases
DNASU	79083.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264605; ENSP00000264605; ENSG00000115648. ENST00000338530; ENSP00000341845; ENSG00000115648. ENST00000409373; ENSP00000386780; ENSG00000115648.
GeneID	79083.
KEGG	hsa:79083.
UCSC	uc002vws.3. human. uc002vwu.3. human.
Organism-specific databases
CTD	79083.
GeneCards	GC02P238411.
HGNC	HGNC:29643. MLPH.
HPA	HPA014685.
MIM	606526. gene. 609227. phenotype.
neXtProt	NX_Q9BV36.
Orphanet	79478. Griscelli disease type 3.
PharmGKB	PA134899891.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG135976.
HOGENOM	HOG000089970.
HOVERGEN	HBG052454.
InParanoid	Q9BV36.
OMA	CLECGLF.
OrthoDB	EOG4MGS78.
PhylomeDB	Q9BV36.
Gene expression databases
ArrayExpress	Q9BV36.
Bgee	Q9BV36.
CleanEx	HS_MLPH.
Genevestigator	Q9BV36.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR006788. Myrip/Melanophilin. IPR010911. Rab-bd_domain. IPR011011. Znf_FYVE_PHD. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF04698. MOBP_C-Myrip. 1 hit. [Graphical view]
SUPFAM	SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS50916. RABBD. 1 hit. PS50178. ZF_FYVE. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MLPH. human.
GenomeRNAi	79083.
NextBio	67891.
SOURCE	Search...

Entry information

Entry name

MELPH_HUMAN

Accession

Primary (citable) accession number: Q9BV36
Secondary accession number(s): Q9HA71

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 16, 2003
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.