ID   P_MOUSE                 Reviewed;         833 AA.
AC   Q62052; Q0VBP9;
DT   21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 158.
DE   RecName: Full=P protein;
DE   AltName: Full=Melanocyte-specific transporter protein;
DE   AltName: Full=Pink-eyed dilution protein;
GN   Name=Oca2; Synonyms=P;
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], TISSUE SPECIFICITY, AND DISEASE.
RC   STRAIN=C57BL/6J; TISSUE=Skin;
RX   PubMed=1509264; DOI=10.1126/science.257.5073.1121;
RA   Gardner J.M., Nakatsu Y., Gondo Y., Lee S., Lyon M.F., King R.A.,
RA   Brilliant M.H.;
RT   "The mouse pink-eyed dilution gene: association with human Prader-Willi and
RT   Angelman syndromes.";
RL   Science 257:1121-1124(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   CHARACTERIZATION OF PROTEIN PRODUCT, AND SUBCELLULAR LOCATION.
RX   PubMed=7991586; DOI=10.1073/pnas.91.25.12071;
RA   Rosemblat S., Durham-Pierre D., Gardner J.M., Nakatsu Y., Brilliant M.H.,
RA   Orlow S.J.;
RT   "Identification of a melanosomal membrane protein encoded by the pink-eyed
RT   dilution (type II oculocutaneous albinism) gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:12071-12075(1994).
RN   [4]
RP   REVIEW OF FUNCTION.
RX   PubMed=11310796; DOI=10.1034/j.1600-0749.2001.140203.x;
RA   Brilliant M.H.;
RT   "The mouse p (pink-eyed dilution) and human P genes, oculocutaneous
RT   albinism type 2 (OCA2), and melanosomal pH.";
RL   Pigment Cell Res. 14:86-93(2001).
RN   [5]
RP   INDUCTION OF MELANINE SYNTHESIS BY BAFILOMYCIN A1 ON P-NULL MELANOCYTES.
RX   PubMed=11601658; DOI=10.1034/j.1600-0749.2001.140508.x;
RA   Manga P., Orlow S.J.;
RT   "Inverse correlation between pink-eyed dilution protein expression and
RT   induction of melanogenesis by bafilomycin A1.";
RL   Pigment Cell Res. 14:362-367(2001).
RN   [6]
RP   INVOLVEMENT IN POST-TRANSLATIONAL PROCESSING OF TYROSINASE.
RX   PubMed=12058062; DOI=10.1091/mbc.02-02-0022;
RA   Chen K., Manga P., Orlow S.J.;
RT   "Pink-eyed dilution protein controls the processing of tyrosinase.";
RL   Mol. Biol. Cell 13:1953-1964(2002).
RN   [7]
RP   INVOLVEMENT IN INTRACELLULAR GLUTATHIONE METABOLISM.
RX   PubMed=12475946; DOI=10.1091/mbc.e02-05-0282;
RA   Staleva L., Manga P., Orlow S.J.;
RT   "Pink-eyed dilution protein modulates arsenic sensitivity and intracellular
RT   glutathione metabolism.";
RL   Mol. Biol. Cell 13:4206-4220(2002).
CC   -!- FUNCTION: Contributes to a melanosome-specific anion (chloride) current
CC       that modulates melanosomal pH for optimal tyrosinase activity required
CC       for melanogenesis and the melanosome maturation. One of the components
CC       of the mammalian pigmentary system (By similarity). May serve as a key
CC       control point at which color variation is determined. Major determinant
CC       of eye color (Probable). Seems to regulate the post-translational
CC       processing of tyrosinase, which catalyzes the limiting reaction in
CC       melanin synthesis (PubMed:12058062). {ECO:0000250|UniProtKB:Q04671,
CC       ECO:0000269|PubMed:12058062, ECO:0000305|PubMed:11310796}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q04671};
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:7991586};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:7991586}.
CC   -!- TISSUE SPECIFICITY: Most abundant in melanocytes. Also present in
CC       neonatal and adult eye tissue presumably as a result of expression in
CC       the retinal pigmented epithelium and choroid body, known sites of
CC       melanogenesis in the eye. Small but detectable amounts also observed in
CC       fetal, neonatal and adult brain. Moderate amounts detected in adult
CC       testis and ovary. Not detected in heart, kidney, spleen, liver or
CC       thymus. {ECO:0000269|PubMed:1509264}.
CC   -!- DISEASE: Note=Defects in Oca2 are a cause of hypopigmentation of the
CC       eyes, skin, and fur. The protein is missing or altered in six
CC       independent mutant alleles of the OCA2 locus, suggesting that
CC       disruption of this gene results in hypopigmentation phenotype that
CC       defines mutant OCA2 alleles. {ECO:0000269|PubMed:1509264}.
CC   -!- SIMILARITY: Belongs to the CitM (TC 2.A.11) transporter family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Questioning colour - Issue
CC       54 of January 2005;
CC       URL="https://web.expasy.org/spotlight/back_issues/054";
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DR   EMBL; M97900; AAA39908.1; -; mRNA.
DR   EMBL; BC119220; AAI19221.1; -; mRNA.
DR   EMBL; BC120549; AAI20550.1; -; mRNA.
DR   CCDS; CCDS21319.1; -.
DR   RefSeq; NP_068679.1; NM_021879.2.
DR   RefSeq; XP_006540762.1; XM_006540699.1.
DR   AlphaFoldDB; Q62052; -.
DR   STRING; 10090.ENSMUSP00000032633; -.
DR   GlyCosmos; Q62052; 3 sites, No reported glycans.
DR   GlyGen; Q62052; 3 sites.
DR   iPTMnet; Q62052; -.
DR   PhosphoSitePlus; Q62052; -.
DR   PaxDb; 10090-ENSMUSP00000032633; -.
DR   ProteomicsDB; 300366; -.
DR   Antibodypedia; 22329; 206 antibodies from 25 providers.
DR   DNASU; 18431; -.
DR   Ensembl; ENSMUST00000032633.12; ENSMUSP00000032633.6; ENSMUSG00000030450.12.
DR   GeneID; 18431; -.
DR   KEGG; mmu:18431; -.
DR   UCSC; uc009hdy.1; mouse.
DR   AGR; MGI:97454; -.
DR   CTD; 4948; -.
DR   MGI; MGI:97454; Oca2.
DR   VEuPathDB; HostDB:ENSMUSG00000030450; -.
DR   eggNOG; KOG2639; Eukaryota.
DR   GeneTree; ENSGT01030000234550; -.
DR   HOGENOM; CLU_011920_2_1_1; -.
DR   InParanoid; Q62052; -.
DR   OMA; HHRIRDK; -.
DR   OrthoDB; 5481761at2759; -.
DR   PhylomeDB; Q62052; -.
DR   TreeFam; TF323556; -.
DR   Reactome; R-MMU-5662702; Melanin biosynthesis.
DR   BioGRID-ORCS; 18431; 3 hits in 76 CRISPR screens.
DR   ChiTaRS; Oca2; mouse.
DR   PRO; PR:Q62052; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q62052; Protein.
DR   Bgee; ENSMUSG00000030450; Expressed in iris and 54 other cell types or tissues.
DR   ExpressionAtlas; Q62052; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR   GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR   GO; GO:0033162; C:melanosome membrane; ISO:MGI.
DR   GO; GO:0061778; F:intracellular chloride channel activity; ISS:UniProtKB.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0048066; P:developmental pigmentation; IMP:MGI.
DR   GO; GO:0035752; P:lysosomal lumen pH elevation; ISS:UniProtKB.
DR   GO; GO:0042438; P:melanin biosynthetic process; IMP:MGI.
DR   GO; GO:0006583; P:melanin biosynthetic process from tyrosine; ISS:UniProtKB.
DR   GO; GO:0030318; P:melanocyte differentiation; IMP:MGI.
DR   GO; GO:0043473; P:pigmentation; IMP:MGI.
DR   GO; GO:0007286; P:spermatid development; IMP:MGI.
DR   CDD; cd01116; P_permease; 1.
DR   InterPro; IPR004680; Cit_transptr-like_dom.
DR   PANTHER; PTHR43568; P PROTEIN; 1.
DR   PANTHER; PTHR43568:SF1; P PROTEIN; 1.
DR   Pfam; PF03600; CitMHS; 1.
DR   Genevisible; Q62052; MM.
PE   1: Evidence at protein level;
KW   Albinism; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..833
FT                   /note="P protein"
FT                   /id="PRO_0000172510"
FT   TOPO_DOM        1..172
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        173..193
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        194..325
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        326..346
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        347..348
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        349..369
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        370..381
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        382..402
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        403..417
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        418..438
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        439..501
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        502..522
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        523..617
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        618..638
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        639
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        640..660
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        661..675
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        676..696
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        697..718
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        719..739
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        740..759
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        760..780
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        781..810
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        811..831
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        832..833
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        210
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        214
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        269
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   833 AA;  91869 MW;  41B9F6491EFAFEE3 CRC64;
     MRLENKDIRL ASAVLEVELH QTSALSVPTC PDPGRLLTVK PATSNYKLGQ ADPCIPYAGE
     AAGKSVCVPE HTEFGSFLVK GSSSLKDLSF KEDTPLLWNS SQKKRSQLMP VHHPEFIATE
     GSWENGLTAW EQKCMLGKEV ADLSALASSE KRDLAGSVHL RAQVSKLGCC VRWIKITGLF
     VFVVLCSILF SLYPDQGKFW QLLAVSPLEN YSVNLSGHAD SMILQLDLAG ALMAGGPSGS
     GKEEHVVVVV TQTDAAGNRR RRPQQLTYNW TVLLNPRSEH VVVSRTFEIV SREAVSISIQ
     ASLQQTRLVP LLLAHQFLGA SVEAQVASAV AILAGVYTLI IFEIVHRTLA AMLGALAALA
     ALAVVGDRPS LTHVVEWIDF ETLALLFGMM ILVAVFSETG FFDYCAVKAY QLSRGRVWAM
     IFMLCLMAAI LSAFLDNVTT MLLFTPVTIR LCEVLNLDPR QVLIAEVIFT NIGGAATAIG
     DPPNVIIVSN QELRKMGLDF AGFTAHMFLG ICLVLLVSFP LLRLLYWNKK LYNKEPSEIV
     ELKHEIHVWR LTAQRISPAS REETAVRGLL LEKVLALEHL LAQRLHTFHR QISQEDKNWE
     TNIQELQRKH RISDRSLLVK CLTVLGFVIS MFFLNSFVPG IHLDLGWIAI LGAIWLLILA
     DIHDFEIILH RVEWATLLFF AALFVLMEAL THLHLVEYVG EQTALLIKMV PEDQRFAAAI
     VLIVWVSALA SSLIDNIPFT ATMIPVLLNL SQDPEISLPA LPLMYALALG ACLGGNGTLI
     GASTNVVCAG IAEKHGYGFS FMEFFRLGFP VMLMSCTIGM CYLLIAHIVV GWN
//