LOCUS       NP_000341               2273 aa            linear   PRI 09-FEB-2025
DEFINITION  retinal-specific phospholipid-transporting ATPase ABCA4 isoform 1
            [Homo sapiens].
ACCESSION   NP_000341
VERSION     NP_000341.2
DBSOURCE    REFSEQ: accession NM_000350.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 2273)
  AUTHORS   Cevik,S., Biswas,S.B., Ghosh,A. and Biswas-Fiss,E.E.
  TITLE     Virus-like particles as robust tools for functional assessment:
            Deciphering the pathogenicity of ABCA4 genetic variants of
            uncertain significance
  JOURNAL   J Biol Chem 300 (10), 107739 (2024)
   PUBMED   39222682
  REMARK    GeneRIF: Virus-like particles as robust tools for functional
            assessment: Deciphering the pathogenicity of ABCA4 genetic variants
            of uncertain significance.
REFERENCE   2  (residues 1 to 2273)
  AUTHORS   Scortecci,J.F., Garces,F.A., Mahto,J.K., Molday,L.L., Van
            Petegem,F. and Molday,R.S.
  TITLE     Structural and functional characterization of the
            nucleotide-binding domains of ABCA4 and their role in Stargardt
            disease
  JOURNAL   J Biol Chem 300 (9), 107666 (2024)
   PUBMED   39128720
  REMARK    GeneRIF: Structural and functional characterization of the
            nucleotide-binding domains of ABCA4 and their role in Stargardt
            disease.
REFERENCE   3  (residues 1 to 2273)
  AUTHORS   Chacon-Camacho,O.F., Xilotl-de Jesus,N., Calderon-Martinez,E.,
            Ordonez-Labastida,V., Neria-Gonzalez,M.I., Villafuerte-de la
            Cruz,R., Martinez-Rojas,A. and Zenteno,J.C.
  TITLE     Genotypic spectrum of ABCA4-associated retinal degenerations in 211
            unrelated Mexican patients: identification of 22 novel
            disease-causing variants
  JOURNAL   Mol Genet Genomics 299 (1), 79 (2024)
   PUBMED   39162841
  REMARK    GeneRIF: Genotypic spectrum of ABCA4-associated retinal
            degenerations in 211 unrelated Mexican patients: identification of
            22 novel disease-causing variants.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 2273)
  AUTHORS   Corradi,Z., Dhaenens,C.M., Grunewald,O., Kocabas,I.S., Meunier,I.,
            Banfi,S., Karali,M., Cremers,F.P.M. and Hitti-Malin,R.J.
  TITLE     Novel and Recurrent Copy Number Variants in ABCA4-Associated
            Retinopathy
  JOURNAL   Int J Mol Sci 25 (11), 5940 (2024)
   PUBMED   38892127
  REMARK    GeneRIF: Novel and Recurrent Copy Number Variants in
            ABCA4-Associated Retinopathy.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 2273)
  AUTHORS   Allikmets,R., Wasserman,W.W., Hutchinson,A., Smallwood,P.,
            Nathans,J., Rogan,P.K., Schneider,T.D. and Dean,M.
  TITLE     Organization of the ABCR gene: analysis of promoter and splice
            junction sequences
  JOURNAL   Gene 215 (1), 111-122 (1998)
   PUBMED   9666097
REFERENCE   6  (residues 1 to 2273)
  AUTHORS   Azarian,S.M., Megarity,C.F., Weng,J., Horvath,D.H. and Travis,G.H.
  TITLE     The human photoreceptor rim protein gene (ABCR): genomic structure
            and primer set information for mutation analysis
  JOURNAL   Hum Genet 102 (6), 699-705 (1998)
   PUBMED   9703434
REFERENCE   7  (residues 1 to 2273)
  AUTHORS   Allikmets,R., Singh,N., Sun,H., Shroyer,N.F., Hutchinson,A.,
            Chidambaram,A., Gerrard,B., Baird,L., Stauffer,D., Peiffer,A.,
            Rattner,A., Smallwood,P., Li,Y., Anderson,K.L., Lewis,R.A.,
            Nathans,J., Leppert,M., Dean,M. and Lupski,J.R.
  TITLE     A photoreceptor cell-specific ATP-binding transporter gene (ABCR)
            is mutated in recessive Stargardt macular dystrophy
  JOURNAL   Nat Genet 15 (3), 236-246 (1997)
   PUBMED   9054934
  REMARK    Erratum:[Nat Genet. 1997 Sep;17(1):122. doi: 10.1038/ng0997-122a..
            PMID: 9288113]
REFERENCE   8  (residues 1 to 2273)
  AUTHORS   Martinez-Mir,A., Bayes,M., Vilageliu,L., Grinberg,D., Ayuso,C., del
            Rio,T., Garcia-Sandoval,B., Bussaglia,E., Baiget,M.,
            Gonzalez-Duarte,R. and Balcells,S.
  TITLE     A new locus for autosomal recessive retinitis pigmentosa (RP19)
            maps to 1p13-1p21
  JOURNAL   Genomics 40 (1), 142-146 (1997)
   PUBMED   9070931
REFERENCE   9  (residues 1 to 2273)
  AUTHORS   Allikmets,R., Gerrard,B., Hutchinson,A. and Dean,M.
  TITLE     Characterization of the human ABC superfamily: isolation and
            mapping of 21 new genes using the expressed sequence tags database
  JOURNAL   Hum Mol Genet 5 (10), 1649-1655 (1996)
   PUBMED   8894702
REFERENCE   10 (residues 1 to 2273)
  AUTHORS   Fahim,A.T., Daiger,S.P. and Weleber,R.G.
  TITLE     Nonsyndromic Retinitis Pigmentosa Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301590
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC093579.2 and AC105278.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 1, 2006 this sequence version replaced NP_000341.1.
            
            Summary: The membrane-associated protein encoded by this gene is a
            member of the superfamily of ATP-binding cassette (ABC)
            transporters. ABC proteins transport various molecules across
            extra- and intracellular membranes. ABC genes are divided into
            seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20,
            White). This protein is a member of the ABC1 subfamily. Members of
            the ABC1 subfamily comprise the only major ABC subfamily found
            exclusively in multicellular eukaryotes. This protein is a
            retina-specific ABC transporter with N-retinylidene-PE as a
            substrate. It is expressed exclusively in retina photoreceptor
            cells, and the gene product mediates transport of an essental
            molecule, all-trans-retinal aldehyde (atRAL), across the
            photoreceptor cell membrane. Mutations in this gene are found in
            patients diagnosed with Stargardt disease, a form of juvenile-onset
            macular degeneration. Mutations in this gene are also associated
            with retinitis pigmentosa-19, cone-rod dystrophy type 3,
            early-onset severe retinal dystrophy, fundus flavimaculatus, and
            macular degeneration age-related 2. [provided by RefSeq, Sep 2019].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AB210040.1, AF000148.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000370225.4/ ENSP00000359245.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..2273
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p22.1"
     Protein         1..2273
                     /product="retinal-specific phospholipid-transporting
                     ATPase ABCA4 isoform 1"
                     /EC_number="7.6.2.1"
                     /note="ATP binding cassette transporter; ATP-binding
                     transporter, retina-specific; ATP-binding cassette
                     transporter, retinal-specific; retinal-specific
                     ATP-binding cassette transporter; photoreceptor rim
                     protein; retinal-specific phospholipid-transporting ATPase
                     ABCA4; retina-specific ABC transporter; RIM protein; RIM
                     ABC transporter; stargardt disease protein; ATP-binding
                     cassette sub-family A member 4; ATP-binding cassette,
                     sub-family A (ABC1), member 4; RIM proteinv"
                     /calculated_mol_wt=255814
     Region          1..2272
                     /region_name="rim_protein"
                     /note="retinal-specific rim ABC transporter; TIGR01257"
                     /db_xref="CDD:130324"
     Site            22..42
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            98
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            415
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            444
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            504
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP;
                     propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            647..667
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            700..720
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            731..751
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            760..780
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            836..856
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Region          891..911
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            901
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000250|UniProtKB:F1MWM0; propagated from
                     UniProtKB/Swiss-Prot (P78363.3)"
     Site            1185
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:F1MWM0; propagated from
                     UniProtKB/Swiss-Prot (P78363.3)"
     Region          1284..1345
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1309
                     /site_type="cleavage"
                     /note="Cleavage, by trypsin.
                     /evidence=ECO:0000250|UniProtKB:F1MWM0; propagated from
                     UniProtKB/Swiss-Prot (P78363.3)"
     Site            1313
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000250|UniProtKB:F1MWM0; propagated from
                     UniProtKB/Swiss-Prot (P78363.3)"
     Site            1317
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:F1MWM0; propagated from
                     UniProtKB/Swiss-Prot (P78363.3)"
     Site            1377..1397
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1469
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            1529
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            1588
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            1662
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:11320094,
                     ECO:0000269|PubMed:33605212, ECO:0007744|PDB:7LKP,
                     ECO:0007744|PDB:7LKZ; propagated from UniProtKB/Swiss-Prot
                     (P78363.3)"
     Site            1728..1748
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1760..1780
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1793..1813
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1832..1852
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Site            1874..1894
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     Region          2244..2249
                     /region_name="Essential for ATP binding and ATPase
                     activity. /evidence=ECO:0000269|PubMed:31481235"
                     /note="propagated from UniProtKB/Swiss-Prot (P78363.3)"
     CDS             1..2273
                     /gene="ABCA4"
                     /gene_synonym="ABC10; ABCR; ARMD2; CORD3; FFM; RMP; RP19;
                     STGD; STGD1"
                     /coded_by="NM_000350.3:104..6925"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS747.1"
                     /db_xref="GeneID:24"
                     /db_xref="HGNC:HGNC:34"
                     /db_xref="MIM:601691"
ORIGIN      
        1 mgfvrqiqll lwknwtlrkr qkirfvvelv wplslflvli wlrnanplys hhechfpnka
       61 mpsagmlpwl qgifcnvnnp cfqsptpges pgivsnynns ilarvyrdfq ellmnapesq
      121 hlgriwtelh ilsqfmdtlr thperiagrg irirdilkde etltlflikn iglsdsvvyl
      181 linsqvrpeq fahgvpdlal kdiacseall erfiifsqrr gaktvryalc slsqgtlqwi
      241 edtlyanvdf fklfrvlptl ldsrsqginl rswggilsdm spriqefihr psmqdllwvt
      301 rplmqnggpe tftklmgils dllcgypegg gsrvlsfnwy ednnykaflg idstrkdpiy
      361 sydrrttsfc naliqslesn pltkiawraa kpllmgkily tpdspaarri lknanstfee
      421 lehvrklvka weevgpqiwy ffdnstqmnm irdtlgnptv kdflnrqlge egitaeailn
      481 flykgpresq addmanfdwr difnitdrtl rlvnqylecl vldkfesynd etqltqrals
      541 lleenmfwag vvfpdmypwt sslpphvkyk irmdidvvek tnkikdrywd sgpradpved
      601 fryiwggfay lqdmveqgit rsqvqaeapv giylqqmpyp cfvddsfmii lnrcfpifmv
      661 lawiysvsmt vksivlekel rlketlknqg vsnaviwctw fldsfsimsm siflltifim
      721 hgrilhysdp filflfllaf statimlcfl lstffskasl aaacsgviyf tlylphilcf
      781 awqdrmtael kkavsllspv afgfgteylv rfeeqglglq wsnignspte gdefsfllsm
      841 qmmlldaavy gllawyldqv fpgdygtplp wyfllqesyw lggegcstre eralektepl
      901 teetedpehp egihdsffer ehpgwvpgvc vknlvkifep cgrpavdrln itfyenqita
      961 flghngagkt ttlsiltgll pptsgtvlvg grdietslda vrqslgmcpq hnilfhhltv
     1021 aehmlfyaql kgksqeeaql emeamledtg lhhkrneeaq dlsggmqrkl svaiafvgda
     1081 kvvildepts gvdpysrrsi wdlllkyrsg rtiimsthhm deadllgdri aiiaqgrlyc
     1141 sgtplflknc fgtglyltlv rkmkniqsqr kgsegtcscs skgfsttcpa hvddltpeqv
     1201 ldgdvnelmd vvlhhvpeak lvecigqeli fllpnknfkh rayaslfrel eetladlgls
     1261 sfgisdtple eiflkvteds dsgplfagga qqkrenvnpr hpclgpreka gqtpqdsnvc
     1321 spgapaahpe gqpppepecp gpqlntgtql vlqhvqallv krfqhtirsh kdflaqivlp
     1381 atfvflalml sivippfgey paltlhpwiy gqqytffsmd epgseqftvl advllnkpgf
     1441 gnrclkegwl peypcgnstp wktpsvspni tqlfqkqkwt qvnpspscrc strekltmlp
     1501 ecpegagglp ppqrtqrste ilqdltdrni sdflvktypa lirsslkskf wvneqryggi
     1561 siggklpvvp itgealvgfl sdlgrimnvs ggpitreask eipdflkhle tednikvwfn
     1621 nkgwhalvsf lnvahnailr aslpkdrspe eygitvisqp lnltkeqlse itvlttsvda
     1681 vvaicvifsm sfvpasfvly liqervnksk hlqfisgvsp ttywvtnflw dimnysvsag
     1741 lvvgifigfq kkaytspenl palvalllly gwavipmmyp asflfdvpst ayvalscanl
     1801 figinssait filelfennr tllrfnavlr kllivfphfc lgrglidlal sqavtdvyar
     1861 fgeehsanpf hwdligknlf amvvegvvyf lltllvqrhf flsqwiaept kepivdeddd
     1921 vaeerqriit ggnktdilrl heltkiypgt sspavdrlcv gvrpgecfgl lgvngagktt
     1981 tfkmltgdtt vtsgdatvag ksiltnisev hqnmgycpqf daidelltgr ehlylyarlr
     2041 gvpaeeiekv anwsikslgl tvyadclagt ysggnkrkls taialigcpp lvlldepttg
     2101 mdpqarrmlw nvivsiireg ravvltshsm eecealctrl aimvkgafrc mgtiqhlksk
     2161 fgdgyivtmk ikspkddllp dlnpveqffq gnfpgsvqre rhynmlqfqv sssslarifq
     2221 lllshkdsll ieeysvtqtt ldqvfvnfak qqteshdlpl hpraagasrq aqd
//
