GENOMIC
Mapping
15qA1. View the map and BAC clones (data from UCSC genome browser).
Structure
(assembly 10/03)
Matp/NM_053077: 7 exons, 28,513bp, Chr15: 11,006,252 - 11,034,764.
The figure below shows the structure of the Matp gene (data from UCSC genome browser).
Regulatory Element
Search the 5'UTR and 1kb upstream regions (human and mouse) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
TRANSCRIPT
RefSeq/ORF
Matp (NM_053077), 2,984bp, view ORF and the alignment to genomic.
Expression Pattern
Tissue specificity: Melanocytes, eyes, kidney and uterus.
Affymetrix microarray expression pattern in SymAtlas from GNF is shown below.
PROTEIN
Sequence
Membrane-associated transporter protein (NP_444307): 530aa,
ExPaSy NiceProt view of Swiss-Prot:P58355.
Synonyms: AIM-1 protein (abscent in melanoma-1); Melanoma antigen AIM1; Underwhite protein.
Ortholog
| Species | Human | Rat | Zebrafish | Mosquito | Fruitfly |
| GeneView | OCA4 | LOC310152 | 04302 | 1271101 | CG4484 |
| Protein | NP_057264 (530aa) | XP_226834 (606aa) | 014075 (554aa) | XP_309847 (521aa) | Q9VSV1 (599aa) |
| Identities | 82% /436aa | 82% /499aa | 34% /84aa | 32% /159aa | 30% /167aa |
View multiple sequence alignment (PDF files) by ClustalW and GeneDoc.
Domain
(1) Domains predicted by SMART:
a) Pfam: MFS1 37 - 499
b) transmembrane 504 - 526
Note: multiple transmembrane regions detected within Pfam:MFS1 but were omitted due to overlap.
(2) Transmembrane domains predicted by SOSUI: 11 transmembrane helices detected.
| No. | N terminal | transmembrane region | C terminal | type | length |
| 1 | 46 | EFCYAVEAAYVTPVLLSVGLPKS | 68 | PRIMARY | 23 |
| 2 | 71 | SMVWLLSPILGFLLQPVVGSASD | 93 | SECONDARY | 23 |
| 3 | 108 | TLAIMMLLGMALYLNGDAVVSAL | 130 | PRIMARY | 23 |
| 4 | 137 | KLIWAISITMVGVVLFDFSADFI | 159 | PRIMARY | 23 |
| 5 | 216 | QVMFFFSALVLILCFITHLCSIP | 238 | PRIMARY | 23 |
| 6 | 321 | CVSHLIGWTAFLSNMLFFTDFMG | 343 | SECONDARY | 23 |
| 7 | 366 | GVEVGCWGLCINSVFSSVYSYFQ | 388 | SECONDARY | 23 |
| 8 | 396 | GLKGLYFMGYLLFGLGTGFIGLF | 418 | PRIMARY | 23 |
| 9 | 425 | LVLCSMFGVMSSTLYTVPFNLIA | 447 | PRIMARY | 23 |
| 10 | 475 | DCAALTCMVQLAQILVGGGLGFL | 497 | SECONDARY | 23 |
| 11 | 505 | VVVVITASAVSLIGCCFVALFVR | 527 | PRIMARY | 23 |
Motif/Site
(1) Predicted results by ScanProsite:
a) Casein kinase II phosphorylation site : [occurs frequently]
15 - 18: SlaE,
90 - 93: SasD,
172 - 175: ShqD,
236 - 239: SipE,
251 - 254: SqqD.
b) cAMP- and cGMP-dependent protein kinase phosphorylation site : [occurs frequently]
29 - 32: KRsT,
291 - 294: KKpS.
c) Protein kinase C phosphorylation site : [occurs frequently]
32 - 34: TgR,
297 - 299: SqR,
302 - 304: SmK.
d) Amidation site : [occurs frequently]
99 - 102: wGRR.
e) N-glycosylation site : [occurs frequently]
356 - 359: NSTE.
(2) Predicted results of subprograms by PSORT II:
a) Seems to have no N-terminal signal peptide.
b) KDEL ER retention motif in the C-terminus: none
c) ER Membrane Retention Signals: none
d) VAC possible vacuolar targeting motif: none
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: none
g) memYQRL transport motif from cell surface to Golgi: none
h) Tyrosines in the tail: none
i) Dileucine motif in the tail: none
3D Model
(1)No ModBase entry found.
(2) 3D models predicted by SPARKS (fold recognition) below.View the models by PDB2MGIF.
2D-PAGE
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=57,961Da, pI=6.27 (NP_444307).
FUNCTION
Ontology
a) Biological process: melanin biosynthesis from tyrosine
b) Biological process: visual perception
c) Integral to membrane
d) Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter family (TC 2.A.2).
e) Melanocyte differentiation antigen
Location
Integral membrane protein; melanosome.
Interaction
Similar to the P protein, MATP have 12 transmembrane regions and are predicted to function as transporters (Costin, et al). AIM1 (absent in melanoma), a candidate suppressor of malignancy in melanoma, is a nonlens member of the betagamma-crystallin superfamily, which contains six predicted betagamma domains. The first betagamma-crystallin domain of AIM1 (AIM1-g1) diverges most in sequence from the superfamily consensus. Despite the sequence variation, AIM1-g1 folds as a betagamma domain, binds calcium and undergoes dimerization (Rajini, et al).
The Drosophila homolog, CG4484, is showing interactions in the CuraGen Drosophila interaction database.
Pathway
The MATP gene encodes a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines (Ray, et al). Its homolog in medaka, 'B,' encodes a transporter that mediates melanin synthesis (Fukamachi, et al). Ultrastructural analysis shows that the vesicles secreted from OCA4 melanocytes are mostly early stage melanosomes. Costin, et al concluded that in OCA4 melanocytes, tyrosinase processing and intracellular trafficking to the melanosome is disrupted and the enzyme is abnormally secreted from the cells in immature melanosomes, which disrupts the normal maturation process of those organelles.
MUTATION
Allele or SNP
4 phenotypic alleles described in MGI:2153040.
Distribution
The alleles of uw, uw-dbr, and uw-d have been characterized molecularly (see details in MGI:2153040).
Effect
The identified 3 spontaneous mutations are missense or framshif mutations which may disrupt the function of protein.
PHENOTYPE
Defects in Matp are the cause of the underwhite (uw) phenotype (Newton, et al), an autosomal recessive disorder similar to OCA4 (OMIM 606574). Homozygotes for spontaneous mutations exhibit varied degrees of hypopigmentation of the eyes, skin, and hair, especially the underfur. Eyes are very light at birth but darken with age. For more details of the uw phenotype, view the Mouse Locus Catalog #Matp. The uw mutation arose spontaneously from C57BL/6J. The strain is described in more detail in JAX Mice database (C57BL/6J-Matpuw/J).
Fukamachi, et al reported that mutations in the fish AIM1 orthologous gene, the 'B' gene, reduce melanin content in the medaka (a small, freshwater teleost), a suitable model of OCA in lower vertebrates.
REFERENCE
- Costin GE, Valencia JC, Vieira WD, Lamoreux ML, Hearing VJ. Tyrosinase processing and intracellular trafficking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4. J Cell Sci 2003; 116: 3203-12. PMID: 12829739
- Fukamachi S, Shimada A, Shima A. Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka. Nat Genet 2001; 28: 381-5. PMID: 11479596
- Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant MH. Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4. Am J Hum Genet 2001; 69: 981-8. PMID: 11574907
- Rajini B, Graham C, Wistow G, Sharma Y. Stability, homodimerization, and calcium-binding properties of a single, variant betagamma-crystallin domain of the protein absent in melanoma 1 (AIM1). Biochemistry 2003; 42: 4552-9. PMID: 12693952
- Ray ME, Wistow G, Su YA, Meltzer PS, Trent JM. AIM1, a novel non-lens member of the betagamma-crystallin superfamily, is associated with the control of tumorigenicity in human malignant melanoma. Proc Natl Acad Sci U S A 1997; 94: 3229-34. PMID: 9096375