Reviewed, UniProtKB/Swiss-Prot Q99758 (ABCA3_HUMAN)

Names and origin

Protein names

Recommended name:
    ATP-binding cassette sub-family A member 3
Alternative name(s):
    ATP-binding cassette transporter 3
      Short name=ATP-binding cassette 3
    ABC-C transporter

Gene names

Name:	ABCA3
Synonyms:	ABC3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1704 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays an important role in the formation of pulmonary surfactant, probably by transporting lipids such as cholesterol.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Highly expressed in lung, followed by brain, pancreas, skeletal muscle and heart. Weakly expressed in placenta, kidney and liver. Also expressed in medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma.
Domain	Multifunctional polypeptide with two homologous halves, each containing an hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain By similarity.
Involvement in disease	Defects in ABCA3 are the cause of pulmonary surfactant metabolism dysfunction type 3 (SMDP3) [MIM:610921]; also called pulmonary alveolar proteinosis due to ABCA3 deficiency. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. Ref.6
Sequence similarities	Belongs to the ABC transporter superfamily. ABCA family. Contains 2 ABC transporter domains.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	response to drug Ref.1 Traceable author statement. Source: ProtInc transport Ref.2 Inferred from direct assay. Source: MGI
Cellular component	integral to membrane Ref.2 Traceable author statement. Source: ProtInc lamellar body Ref.3 Inferred from direct assay. Source: MGI membrane fraction Ref.2 Traceable author statement. Source: ProtInc plasma membrane Ref.3 Inferred from direct assay. Source: MGI
Molecular function	ATP binding Ref.2 Traceable author statement. Source: ProtInc ATPase activity, coupled to transmembrane movement of substances Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1704	1704	ATP-binding cassette sub-family A member 3		PRO_0000093293
Regions
	Transmembrane	22 – 42	21	Potential
	Transmembrane	261 – 283	23	Potential
	Transmembrane	307 – 327	21	Potential
	Transmembrane	344 – 364	21	Potential
	Transmembrane	373 – 393	21	Potential
	Transmembrane	405 – 425	21	Potential
	Transmembrane	447 – 467	21	Potential
	Transmembrane	925 – 945	21	Potential
	Transmembrane	1100 – 1120	21	Potential
	Transmembrane	1144 – 1164	21	Potential
	Transmembrane	1183 – 1203	21	Potential
	Transmembrane	1213 – 1233	21	Potential
	Transmembrane	1245 – 1265	21	Potential
	Transmembrane	1306 – 1326	21	Potential
	Domain	530 – 763	234	ABC transporter 1
	Domain	1381 – 1614	234	ABC transporter 2
	Nucleotide binding	566 – 573	8	ATP 1 Potential
	Nucleotide binding	1416 – 1423	8	ATP 2 Potential
Amino acid modifications
	Modified residue	1265	1	Phosphotyrosine Ref.5
	Modified residue	1268	1	Phosphotyrosine Ref.5
Natural variations
	Natural variant	101	1	L → P in SMDP3. dbSNP rs28936412.		VAR_023497
	Natural variant	140	1	N → H: dbSNP rs45447801. Ref.4		VAR_025061
	Natural variant	290	1	L → M in a breast cancer sample; somatic mutation. Ref.7		VAR_035728
	Natural variant	568	1	N → D in SMDP3. Ref.6		VAR_023498
	Natural variant	766	1	P → S: dbSNP rs45592239. Ref.4		VAR_025062
	Natural variant	801	1	E → D in a breast cancer sample; somatic mutation. Ref.7		VAR_035729
	Natural variant	1069	1	H → Q in a breast cancer sample; somatic mutation. Ref.7		VAR_035730
	Natural variant	1553	1	L → P in SMDP3. Ref.6		VAR_023499
	Natural variant	1591	1	Q → P in SMDP3. dbSNP rs28936691. Ref.6		VAR_023500
Experimental info
	Sequence conflict	36	1	S → P in AAC50967. Ref.1
	Sequence conflict	196	1	P → L in AAC50967. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99758-1 [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 606735C504839D0D	FASTA	1,704	191,362
	10 20 30 40 50 60 MAVLRQLALL LWKNYTLQKR KVLVTVLELF LPLLFSGILI WLRLKIQSEN VPNATIYPGQ 70 80 90 100 110 120 SIQELPLFFT FPPPGDTWEL AYIPSHSDAA KTVTETVRRA LVINMRVRGF PSEKDFEDYI 130 140 150 160 170 180 RYDNCSSSVL AAVVFEHPFN HSKEPLPLAV KYHLRFSYTR RNYMWTQTGS FFLKETEGWH 190 200 210 220 230 240 TTSLFPLFPN PGPREPTSPD GGEPGYIREG FLAVQHAVDR AIMEYHADAA TRQLFQRLTV 250 260 270 280 290 300 TIKRFPYPPF IADPFLVAIQ YQLPLLLLLS FTYTALTIAR AVVQEKERRL KEYMRMMGLS 310 320 330 340 350 360 SWLHWSAWFL LFFLFLLIAA SFMTLLFCVK VKPNVAVLSR SDPSLVLAFL LCFAISTISF 370 380 390 400 410 420 SFMVSTFFSK ANMAAAFGGF LYFFTYIPYF FVAPRYNWMT LSQKLCSCLL SNVAMAMGAQ 430 440 450 460 470 480 LIGKFEAKGM GIQWRDLLSP VNVDDDFCFG QVLGMLLLDS VLYGLVTWYM EAVFPGQFGV 490 500 510 520 530 540 PQPWYFFIMP SYWCGKPRAV AGKEEEDSDP EKALRNEYFE AEPEDLVAGI KIKHLSKVFR 550 560 570 580 590 600 VGNKDRAAVR DLNLNLYEGQ ITVLLGHNGA GKTTTLSMLT GLFPPTSGRA YISGYEISQD 610 620 630 640 650 660 MVQIRKSLGL CPQHDILFDN LTVAEHLYFY AQLKGLSRQK CPEEVKQMLH IIGLEDKWNS 670 680 690 700 710 720 RSRFLSGGMR RKLSIGIALI AGSKVLILDE PTSGMDAISR RAIWDLLQRQ KSDRTIVLTT 730 740 750 760 770 780 HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHHH 790 800 810 820 830 840 VPNATLESSA GAELSFILPR ESTHRFEGLF AKLEKKQKEL GIASFGASIT TMEEVFLRVG 850 860 870 880 890 900 KLVDSSMDIQ AIQLPALQYQ HERRASDWAV DSNLCGAMDP SDGIGALIEE ERTAVKLNTG 910 920 930 940 950 960 LALHCQQFWA MFLKKAAYSW REWKMVAAQV LVPLTCVTLA LLAINYSSEL FDDPMLRLTL 970 980 990 1000 1010 1020 GEYGRTVVPF SVPGTSQLGQ QLSEHLKDAL QAEGQEPREV LGDLEEFLIF RASVEGGGFN 1030 1040 1050 1060 1070 1080 ERCLVAASFR DVGERTVVNA LFNNQAYHSP ATALAVVDNL LFKLLCGPHA SIVVSNFPQP 1090 1100 1110 1120 1130 1140 RSALQAAKDQ FNEGRKGFDI ALNLLFAMAF LASTFSILAV SERAVQAKHV QFVSGVHVAS 1150 1160 1170 1180 1190 1200 FWLSALLWDL ISFLIPSLLL LVVFKAFDVR AFTRDGHMAD TLLLLLLYGW AIIPLMYLMN 1210 1220 1230 1240 1250 1260 FFFLGAATAY TRLTIFNILS GIATFLMVTI MRIPAVKLEE LSKTLDHVFL VLPNHCLGMA 1270 1280 1290 1300 1310 1320 VSSFYENYET RRYCTSSEVA AHYCKKYNIQ YQENFYAWSA PGVGRFVASM AASGCAYLIL 1330 1340 1350 1360 1370 1380 LFLIETNLLQ RLRGILCALR RRRTLTELYT RMPVLPEDQD VADERTRILA PSPDSLLHTP 1390 1400 1410 1420 1430 1440 LIIKELSKVY EQRVPLLAVD RLSLAVQKGE CFGLLGFNGA GKTTTFKMLT GEESLTSGDA 1450 1460 1470 1480 1490 1500 FVGGHRISSD VGKVRQRIGY CPQFDALLDH MTGREMLVMY ARLRGIPERH IGACVENTLR 1510 1520 1530 1540 1550 1560 GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDE PSTGMDPVAR RLLWDTVARA 1570 1580 1590 1600 1610 1620 RESGKAIIIT SHSMEECEAL CTRLAIMVQG QFKCLGSPQH LKSKFGSGYS LRAKVQSEGQ 1630 1640 1650 1660 1670 1680 QEALEEFKAF VDLTFPGSVL EDEHQGMVHY HLPGRDLSWA KVFGILEKAK EKYGVDDYSV 1690 1700 SQISLEQVFL SFAHLQPPTA EEGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance-associated protein." Klugbauer N., Hofmann F. FEBS Lett. 391:61-65(1996) [PubMed: 8706931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Thyroid carcinoma.
[2]	"The cloning of a human ABC gene (ABC3) mapping to chromosome 16p13.3." Connors T.D., van Raay T.J., Petry L.R., Klinger K.W., Landes G.M., Burn T.C. Genomics 39:231-234(1997) [PubMed: 9027511] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"ABCA3 is a lamellar body membrane protein in human lung alveolar type II cells." Yamano G., Funahashi H., Kawanami O., Zhao L., Ban N., Uchida Y., Morohoshi T., Ogawa J., Shioda S., Inagaki N. FEBS Lett. 508:221-225(2001) [PubMed: 11718719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[4]	SeattleSNPs variation discovery resource Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-140 AND SER-766.
[5]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1265 AND TYR-1268, MASS SPECTROMETRY.
[6]	"ABCA3 gene mutations in newborns with fatal surfactant deficiency." Shulenin S., Nogee L.M., Annilo T., Wert S.E., Whitsett J.A., Dean M. N. Engl. J. Med. 350:1296-1303(2004) [PubMed: 15044640] [Abstract] Cited for: VARIANTS SMDP3 PRO-101; ASP-568; PRO-1553 AND PRO-1591.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-290; ASP-801 AND GLN-1069.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U78735 mRNA. Translation: AAC50967.1. X97187 mRNA. Translation: CAA65825.1. AB070929 mRNA. Translation: BAB86781.1. DQ073080 Genomic DNA. Translation: AAY57325.1.
IPI	IPI00017800.
PIR	A59188. S71363.
RefSeq	NP_001080.2.
UniGene	Hs.26630
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q99758.
Protein family/group databases
TCDB	3.A.1.211.5. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	Q99758.
Proteomic databases
PRIDE	Q99758.
Genome annotation databases
Ensembl	ENST00000301732; ENSP00000301732; ENSG00000167972; Homo sapiens. [Genome view]
GeneID	21.
KEGG	hsa:21.
UCSC	uc002cpy.1. human.
Organism-specific databases
CTD	21.
GeneCards	GC16M002265.
HGNC	HGNC:33. ABCA3.
HPA	HPA007884.
MIM	601615. gene. 610921. phenotype.
Orphanet	100049. Pulmonary surfactant protein anomalies.
PharmGKB	PA24378.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q99758.
Gene expression databases
ArrayExpress	Q99758.
Bgee	Q99758.
CleanEx	HS_ABCA3.
Genevestigator	Q99758.
GermOnline	ENSG00000167972. Homo sapiens.
Family and domain databases
InterPro	IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. IPR003593. ATPase_AAA+_core. [Graphical view]
Pfam	PF00005. ABC_tran. 2 hits. [Graphical view]
SMART	SM00382. AAA. 2 hits. [Graphical view]
PROSITE	PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	61.
SOURCE	Search...

Entry information

Entry name

ABCA3_HUMAN

Accession

Primary (citable) accession number: Q99758
Secondary accession number(s): Q54A95, Q92473

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 24, 2006
Last modified:	November 24, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.