Reviewed, UniProtKB/Swiss-Prot Q96AP0 (ACD_HUMAN)

Names and origin

Protein names

Recommended name:
    Adrenocortical dysplasia protein homolog
Alternative name(s):
    POT1 and TIN2-interacting protein

Gene names

Name:	ACD
Synonyms:	PIP1, PTOP, TINT1, TPP1

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

General annotation (Comments)

Function	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Controls POT1 telomeric recruitement and telomere elongation by inhibition of telomerase activity. Plays a role in shelterin complex assembly. May play a role in organogenesis. Ref.1 Ref.8 Ref.9
Subunit structure	Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Forms heterodimers with POT1. Interacts with TINF2. Ref.1 Ref.5
Subcellular location	Nucleus Potential. Telomere Probable.

Ontologies

Keywords
Cellular component	Chromosomal protein Nucleus Telomere
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	intracellular protein transport Ref.1 Inferred from mutant phenotype. Source: UniProtKB negative regulation of telomere maintenance via telomerase Ref.1 Inferred from mutant phenotype. Source: UniProtKB positive regulation of single-stranded telomeric DNA binding Inferred from direct assay. Source: UniProtKB positive regulation of telomerase activity Inferred from direct assay. Source: UniProtKB protection from non-homologous end joining at telomere Inferred from sequence or structural similarity. Source: UniProtKB protein localization to telomere Ref.1 Inferred from mutant phenotype. Source: UniProtKB telomere assembly Ref.9 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	nuclear telomere cap complex Ref.1 Ref.9 Inferred from direct assay. Source: UniProtKB nucleoplasm Ref.8 Inferred from Experiment. Source: Reactome
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA polymerase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96AP0-1)

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: Q96AP0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     120-122: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 544

544

Adrenocortical dysplasia protein homolog

PRO_0000239019

Regions

Region

244 – 337

94

Interaction with POT1

Motif

97 – 99

3

PWI

Compositional bias

354 – 442

89

Ser-rich

Amino acid modifications

Modified residue

111

1

Phosphoserine

Modified residue

422

1

Phosphothreonine Ref.10

Modified residue

424

1

Phosphoserine

Modified residue

425

1

Phosphoserine Ref.10

Modified residue

435

1

Phosphoserine

Natural variations

Alternative sequence

120 – 122

3

Missing in isoform 2.

VSP_019066

Natural variant

301

1

T → M: dbSNP rs72547495.

VAR_060224

Natural variant

518

1

A → V: dbSNP rs6979. Ref.2 Ref.4

VAR_060225

Experimental info

Sequence conflict

224

1

R → C in AAS80318. Ref.1

Sequence conflict

224

1

R → C in AAH16904. Ref.3

Sequence conflict

224

1

R → C in AAX82621. Ref.4

Secondary structure

1

.

.

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.

.

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.

.

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.

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544

Helix Strand Turn

Details...

Helix

99 – 104

6

Beta strand

105 – 107

3

Beta strand

113 – 122

10

Beta strand

142 – 147

6

Beta strand

152 – 157

6

Helix

159 – 163

5

Beta strand

180 – 192

13

Beta strand

201 – 215

15

Helix

224 – 226

3

Helix

228 – 238

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 342E3845689E118C	FASTA	544	57,758
	10 20 30 40 50 60 MPGRCQSDAA MRVNGPASRA PAGWTSGSLH TGPRAGRPRA QARGVRGRGL LLRPRPAKEL 70 80 90 100 110 120 PLPRKGGAWA PAGNPGPLHP LGVAVGMAGS GRLVLRPWIR ELILGSETPS SPRAGQLLEV 130 140 150 160 170 180 LQDAEAAVAG PSHAPDTSDV GATLLVSDGT HSVRCLVTRE ALDTSDWEEK EFGFRGTEGR 190 200 210 220 230 240 LLLLQDCGVH VQVAEGGAPA EFYLQVDRFS LLPTEQPRLR VPGRNQDLDV QKKLYDCLEE 250 260 270 280 290 300 HLSESTSSNA GLSLSQLLDE MREDQEHQGA LVCLAESCLT LEGPCTAPPV THWAASRCKA 310 320 330 340 350 360 TGEAVYTVPS SMLCISENDQ LILSSLGPCQ RTQGPELPPP DPALQDLSLT LIASPPSSPS 370 380 390 400 410 420 SSGTPALPGH MSSEESGTSI SLLPALSLAA PDPGQRSSSQ PSPAICSAPA TLTPRSPHAS 430 440 450 460 470 480 RTPSSPLQSC TPSLSPRSHV PSPHQALVTR PQKPSLEFKE FVGLPCKNRP PFPRTGATRG 490 500 510 520 530 540 AQEPCSVWEP PKRHRDGSAF QYEYEPPCTS LCARVQAARL PPQLMAWALH FLMDAQPGSE PTPM
	Isoform 2. Checksum: 19701FACD6288490	FASTA	541	57,418
	10 20 30 40 50 60 MPGRCQSDAA MRVNGPASRA PAGWTSGSLH TGPRAGRPRA QARGVRGRGL LLRPRPAKEL 70 80 90 100 110 120 PLPRKGGAWA PAGNPGPLHP LGVAVGMAGS GRLVLRPWIR ELILGSETPS SPRAGQLLED 130 140 150 160 170 180 AEAAVAGPSH APDTSDVGAT LLVSDGTHSV RCLVTREALD TSDWEEKEFG FRGTEGRLLL 190 200 210 220 230 240 LQDCGVHVQV AEGGAPAEFY LQVDRFSLLP TEQPRLRVPG RNQDLDVQKK LYDCLEEHLS 250 260 270 280 290 300 ESTSSNAGLS LSQLLDEMRE DQEHQGALVC LAESCLTLEG PCTAPPVTHW AASRCKATGE 310 320 330 340 350 360 AVYTVPSSML CISENDQLIL SSLGPCQRTQ GPELPPPDPA LQDLSLTLIA SPPSSPSSSG 370 380 390 400 410 420 TPALPGHMSS EESGTSISLL PALSLAAPDP GQRSSSQPSP AICSAPATLT PRSPHASRTP 430 440 450 460 470 480 SSPLQSCTPS LSPRSHVPSP HQALVTRPQK PSLEFKEFVG LPCKNRPPFP RTGATRGAQE 490 500 510 520 530 540 PCSVWEPPKR HRDGSAFQYE YEPPCTSLCA RVQAARLPPQ LMAWALHFLM DAQPGSEPTP M

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PTOP interacts with POT1 and regulates its localization to telomeres." Liu D., Safari A., O'Connor M.S., Chan D.W., Laegeler A., Qin J., Songyang Z. Nat. Cell Biol. 6:673-680(2004) [PubMed: 15181449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MOTIF, INTERACTION WITH POT1 AND TINF2, FUNCTION.
[2]	"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), VARIANT VAL-518. Tissue: Placenta.
[3]	"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] (ISOFORM 1). Tissue: Duodenum.
[4]	"Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator." Keegan C.E., Hutz J.E., Else T., Adamska M., Shah S.P., Kent A.E., Howes J.M., Beamer W.G., Hammer G.D. Hum. Mol. Genet. 14:113-123(2005) [PubMed: 15537664] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 65-544, ALTERNATIVE SPLICING (ISOFORM 1), VARIANT VAL-518.
[5]	"POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex." Ye J.Z.-S., Hockemeyer D., Krutchinsky A.N., Loayza D., Hooper S.M., Chait B.T., de Lange T. Genes Dev. 18:1649-1654(2004) [PubMed: 15231715] [Abstract] Cited for: MASS SPECTROMETRY, INTERACTION WITH POT1 AND TINF2.
[6]	"TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres." Ye J.Z.-S., Donigian J.R., van Overbeek M., Loayza D., Luo Y., Krutchinsky A.N., Chait B.T., de Lange T. J. Biol. Chem. 279:47264-47271(2004) [PubMed: 15316005] [Abstract] Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[7]	"Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins." Liu D., O'Connor M.S., Qin J., Songyang Z. J. Biol. Chem. 279:51338-51342(2004) [PubMed: 15383534] [Abstract] Cited for: IDENTIFICATION IN THE SHELTERIN COMPLEX.
[8]	"Shelterin: the protein complex that shapes and safeguards human telomeres." de Lange T. Genes Dev. 19:2100-2110(2005) [PubMed: 16166375] [Abstract] Cited for: FUNCTION OF THE SHELTERIN COMPLEX.
[9]	"A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly." O'Connor M.S., Safari A., Xin H., Liu D., Songyang Z. Proc. Natl. Acad. Sci. U.S.A. 103:11874-11879(2006) [PubMed: 16880378] [Abstract] Cited for: FUNCTION IN SHELTERIN COMPLEX ASSEMBLY.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-422 AND SER-425, MASS SPECTROMETRY.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-422; SER-424; SER-425 AND SER-435, MASS SPECTROMETRY.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, MASS SPECTROMETRY. Tissue: T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AY502940 mRNA. Translation: AAS80318.1.
AK023726 mRNA. Translation: BAB14658.1.
BC016904 mRNA. Translation: AAH16904.1.
AY971883 Genomic DNA. Translation: AAX82621.1. Different initiation.

IPI

IPI00254484.
IPI00639852.

RefSeq

NP_001075955.1.
NP_001075956.1.
NP_075065.2.

UniGene

Hs.78019

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I46	X-ray	2.70	A/B	90-250	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96AP0. 8 interactions.

STRING

Q96AP0.

PTM databases

PhosphoSite

Q96AP0.

Proteomic databases

PRIDE

Q96AP0.

Genome annotation databases

Ensembl

ENST00000393919; ENSP00000377496; ENSG00000102977; Homo sapiens. [Genome view]

GeneID

65057.

KEGG

hsa:65057.

UCSC

uc002etp.2. human.
uc002etq.2. human.

Organism-specific databases

CTD

65057.

GeneCards

GC16M066249.

HGNC

HGNC:25070. ACD.

MIM

609377. gene.

PharmGKB

PA134882431.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96AP0.

HOVERGEN

Q96AP0.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Reactome

REACT_7970. Telomere Maintenance.

Gene expression databases

ArrayExpress

Q96AP0.

Bgee

Q96AP0.

CleanEx

HS_ACD.
HS_TPP1.

Genevestigator

Q96AP0.

GermOnline

ENSG00000102977. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other Resources

NextBio

67230.

SOURCE

Search...

Entry information

Entry name

ACD_HUMAN

Accession

Primary (citable) accession number: Q96AP0
Secondary accession number(s): Q562H5, Q9H8F9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	May 30, 2006
Last modified:	November 24, 2009
This is version 56 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.