Reviewed, UniProtKB/Swiss-Prot Q6UW56 (APR3_HUMAN)

Names and origin

Protein names

Recommended name:
    Apoptosis-related protein 3
      Short name=APR-3
Alternative name(s):
    p18

Gene names

Name:	APR3
Synonyms:	C2orf28
ORF Names:	HSPC013, UNQ214/PRO240

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	229 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May play a critical role in inducing the cell cycle arrest via inhibiting CCND1 expression in all-trans-retinoic acid (ATRA) signal pathway. Ref.12
Subcellular location	Cell membrane; Single-pass membrane protein Ref.12.
Tissue specificity	Weakly expressed in hematopoietic cell lines. Ref.4
Induction	Up-regulated by ATRA in several tumor cell lines. Ref.12
Sequence similarities	Contains 1 EGF-like domain.
Sequence caution	The sequence AAD27770.1 differs from that shown. Reason: Frameshift at position 19. The sequence AAD31317.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAD31317.2 differs from that shown. Reason: Frameshift at position 189. The sequence AAX93173.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Domain	EGF-like domain Signal Transmembrane
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6UW56-1)

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: Q6UW56-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.

Isoform 3 (identifier: Q6UW56-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKTSAELHEQEKPPSSPRATGPGRLGHARGRGPDALRGGAAGPGRASSGAPRERKM

Note: Produced by alternative promoter usage.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Ref.11
	Chain	31 – 229	199	Apoptosis-related protein 3		PRO_0000020752
Regions
	Topological domain	31 – 199	169	Extracellular Potential
	Transmembrane	200 – 220	21	Potential
	Topological domain	221 – 229	9	Cytoplasmic Potential
	Domain	152 – 193	42	EGF-like
Amino acid modifications
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	157	1	N-linked (GlcNAc...) Potential
	Glycosylation	168	1	N-linked (GlcNAc...) Potential
	Disulfide bond	156 ↔ 171		By similarity
	Disulfide bond	165 ↔ 181		By similarity
	Disulfide bond	183 ↔ 192		By similarity
Natural variations
	Alternative sequence	1 – 58	58	Missing in isoform 2.		VSP_014108
	Alternative sequence	1	1	M → MKTSAELHEQEKPPSSPRAT GPGRLGHARGRGPDALRGGA AGPGRASSGAPRERKM in isoform 3.		VSP_037521
	Natural variant	209	1	A → S: dbSNP rs7437. Ref.1		VAR_057991
Experimental info
	Sequence conflict	5	1	D → G in BAF80618. Ref.1
	Sequence conflict	5	1	D → G in AAD27770. Ref.4
	Sequence conflict	5	1	D → G in AAQ89327. Ref.5
	Sequence conflict	5	1	D → G in AAH02846. Ref.10
	Sequence conflict	5	1	D → G in AAH11006. Ref.10
	Sequence conflict	5	1	D → G in AAH35850. Ref.10
	Sequence conflict	33	1	E → EP in AAK69412. Ref.3
	Sequence conflict	219	1	W → S in BAF80618. Ref.1
	Sequence conflict	221	1	T → A in AAK69412. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: CF051C5E886BCFF1	FASTA	229	24,747
	10 20 30 40 50 60 MAPHDPGSLT TLVPWAAALL LALGVERALA LPEICTQCPG SVQNLSKVAF YCKTTRELML 70 80 90 100 110 120 HARCCLNQKG TILGLDLQNC SLEDPGPNFH QAHTTVIIDL QANPLKGDLA NTFRGFTQLQ 130 140 150 160 170 180 TLILPQHVNC PGGINAWNTI TSYIDNQICQ GQKNLCNNTG DPEMCPENGS CVPDGPGLLQ 190 200 210 220 CVCADGFHGY KCMRQGSFSL LMFFGILGAT TLSVSILLWA TQRRKAKTS
	Isoform 2. Checksum: 91A42CD2B2CB0883	FASTA	171	18,597
	10 20 30 40 50 60 MLHARCCLNQ KGTILGLDLQ NCSLEDPGPN FHQAHTTVII DLQANPLKGD LANTFRGFTQ 70 80 90 100 110 120 LQTLILPQHV NCPGGINAWN TITSYIDNQI CQGQKNLCNN TGDPEMCPEN GSCVPDGPGL 130 140 150 160 170 LQCVCADGFH GYKCMRQGSF SLLMFFGILG ATTLSVSILL WATQRRKAKT S
	Isoform 3. Checksum: F7F1A5CEC82ABB39	FASTA	284	30,342
	10 20 30 40 50 60 MKTSAELHEQ EKPPSSPRAT GPGRLGHARG RGPDALRGGA AGPGRASSGA PRERKMAPHD 70 80 90 100 110 120 PGSLTTLVPW AAALLLALGV ERALALPEIC TQCPGSVQNL SKVAFYCKTT RELMLHARCC 130 140 150 160 170 180 LNQKGTILGL DLQNCSLEDP GPNFHQAHTT VIIDLQANPL KGDLANTFRG FTQLQTLILP 190 200 210 220 230 240 QHVNCPGGIN AWNTITSYID NQICQGQKNL CNNTGDPEMC PENGSCVPDG PGLLQCVCAD 250 260 270 280 GFHGYKCMRQ GSFSLLMFFG ILGATTLSVS ILLWATQRRK AKTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel protein with four putative transmembrane domains." Mori K., Ogawa Y., Tashiro K., Ozaki S., Mukoyama M., Tanaka I., Nakao K. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-209. Tissue: Kidney.
[2]	"Improved PCR-based subtractive hybridization strategy for cloning differentially expressed genes." Zhu F., Yan W., Zhao Z.L., Chai Y.B., Lu F., Wang Q., Peng W.D., Yang A.G., Wang C.J. BioTechniques 29:310-313(2000) [PubMed: 10948432] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Cloning and characterization of p18." Yang Y.C., Chen S.Y., Chang M.S. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Umbilical cord blood.
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skeletal muscle.
[7]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Neuroblastoma.
[8]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain, Placenta and Uterus.
[11]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-45.
[12]	"Apoptosis related protein 3, an ATRA-upregulated membrane protein arrests the cell cycle at G1/S phase by decreasing the expression of cyclin D1." Yu F., Yang G., Zhao Z., Ji L., Cao Y., Bai L., Lu F., Fu H., Huang B., Li H., Zhang J., Yao L., Lu Z. Biochem. Biophys. Res. Commun. 358:1041-1046(2007) [PubMed: 17524364] [Abstract] Cited for: INDUCTION, SUBCELLULAR LOCATION, POSSIBLE FUNCTION.
[13]	"Identification of the distinct promoters for the two transcripts of apoptosis related protein 3 and their transcriptional regulation by NFAT and NFkappaB." Yang G., Yu F., Fu H., Lu F., Huang B., Bai L., Zhao Z., Yao L., Lu Z. Mol. Cell. Biochem. 302:187-194(2007) [PubMed: 17387583] [Abstract] Cited for: ALTERNATIVE PROMOTER USAGE.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB009017 mRNA. Translation: BAF80618.1. AF144055 mRNA. Translation: AAD31317.2. Sequence problems. AF275744 mRNA. Translation: AAK69412.1. AF077037 mRNA. Translation: AAD27770.1. Frameshift. AY358968 mRNA. Translation: AAQ89327.1. AK291894 mRNA. Translation: BAF84583.1. CR600041 mRNA. No translation available. AC013403 Genomic DNA. Translation: AAX93173.1. Sequence problems. CH471053 Genomic DNA. Translation: EAX00617.1. BC002846 mRNA. Translation: AAH02846.2. Different initiation. BC011006 mRNA. Translation: AAH11006.3. Different initiation. BC021237 mRNA. Translation: AAH21237.1. BC035850 mRNA. Translation: AAH35850.1. Different initiation.
IPI	IPI00335629. IPI00412376. IPI00930484.
RefSeq	NP_057169.2. NP_542159.2.
UniGene	Hs.9527
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6UW56. 1 interaction.
STRING	Q6UW56.
Proteomic databases
PRIDE	Q6UW56.
Genome annotation databases
Ensembl	ENST00000380171; ENSP00000369518; ENSG00000138085; Homo sapiens. [Genome view]
GeneID	51374.
KEGG	hsa:51374.
UCSC	uc002rjf.1. human.
Organism-specific databases
CTD	51374.
GeneCards	GC02P027347.
H-InvDB	HIX0001912.
HGNC	HGNC:24090. C2orf28.
PharmGKB	PA134964154.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14897.
HOVERGEN	Q6UW56.
InParanoid	Q6UW56.
OMA	FRGFTQL.
OrthoDB	EOG9F4VXM.
Gene expression databases
ArrayExpress	Q6UW56.
Bgee	Q6UW56.
CleanEx	HS_C2orf28.
Genevestigator	Q6UW56.
GermOnline	ENSG00000138085. Homo sapiens.
Family and domain databases
InterPro	IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. [Graphical view]
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	54863.

Entry information

Entry name

APR3_HUMAN

Accession

Primary (citable) accession number: Q6UW56
Secondary accession number(s): A8C1S2 , A8K779, Q96FF6, Q96RT2, Q9Y2R7, Q9Y5L7

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2005
Last sequence update:	June 16, 2009
Last modified:	January 19, 2010
This is version 55 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.