P54257 (HAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Huntingtin-associated protein 1
Short name=HAP-1

Alternative name(s):
Neuroan 1

Gene names

Name:	HAP1
Synonyms:	HAP2, HLP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	671 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Associates specifically with huntingtin. This binding is enhanced by an expanded polyglutamine repeat.
Tissue specificity	Predominantly expressed in brain. Selectively expressed in neurons.
Sequence similarities	Contains 1 HAP1 N-terminal domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	brain development Non-traceable author statement Ref.7. Source: UniProtKB protein localization Inferred from mutant phenotype. Source: UniProtKB synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	actin cytoskeleton Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P54257-1)

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: P54257-2)

The sequence of this isoform differs from the canonical sequence as follows:
     426-477: Missing.

Isoform 3 (identifier: P54257-3)

The sequence of this isoform differs from the canonical sequence as follows:
     401-477: Missing.

Isoform 4 (identifier: P54257-4)

The sequence of this isoform differs from the canonical sequence as follows:
     183-183: E → EVCTAFLIQ
     401-477: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 671	671	Huntingtin-associated protein 1		PRO_0000083894
Regions
	Domain	106 – 461	356	HAP1 N-terminal
	Compositional bias	261 – 601	341	Glu-rich
Natural variations
	Alternative sequence	183	1	E → EVCTAFLIQ in isoform 4.		VSP_038754
	Alternative sequence	401 – 477	77	Missing in isoform 3 and isoform 4.		VSP_004277
	Alternative sequence	426 – 477	52	Missing in isoform 2.		VSP_004278
	Natural variant	4	1	K → R. Ref.1 Ref.2 Ref.5 Corresponds to variant rs4796604 [ dbSNP | Ensembl ].		VAR_046736
	Natural variant	58	1	S → T. Ref.1 Ref.2 Ref.5 Corresponds to variant rs4796603 [ dbSNP | Ensembl ].		VAR_046737
	Natural variant	357	1	S → L. Ref.3 Ref.6 Ref.8 Corresponds to variant rs4796693 [ dbSNP | Ensembl ].		VAR_046738
	Natural variant	408	1	L → F. Corresponds to variant rs35612698 [ dbSNP | Ensembl ].		VAR_056906
	Natural variant	437	1	R → W. Ref.8		VAR_046739
	Natural variant	441	1	M → T May influence the age-at-onset of Huntington disease; decreases binding to mutated HTT; influences HTT degradation. Ref.8		VAR_046740
	Natural variant	483	1	F → L. Corresponds to variant rs8075017 [ dbSNP | Ensembl ].		VAR_046741
	Natural variant	488	1	A → V. Corresponds to variant rs34853043 [ dbSNP | Ensembl ].		VAR_046742
	Natural variant	493	1	T → M. Ref.3 Corresponds to variant rs4523977 [ dbSNP | Ensembl ].		VAR_056907
	Natural variant	557	1	A → V. Corresponds to variant rs34853043 [ dbSNP | Ensembl ].		VAR_056908
	Natural variant	560	1	F → L. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.7 Corresponds to variant rs8075017 [ dbSNP | Ensembl ].		VAR_062817
	Natural variant	656	1	G → R. Corresponds to variant rs34044330 [ dbSNP | Ensembl ].		VAR_056909
Experimental info
	Sequence conflict	184 – 199	16	Missing in CAB82785. Ref.6
	Sequence conflict	573	1	P → L in BAB13952. Ref.3
	Sequence conflict	579	1	M → V in AAC39861. Ref.1
	Sequence conflict	611	1	A → T in AAC50297. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 2, 2010. Version 3. Checksum: 10971B807941B4EE	FASTA	671	75,506
	10 20 30 40 50 60 MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF 70 80 90 100 110 120 LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR 130 140 150 160 170 180 GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL 190 200 210 220 230 240 LEELLPPVWE SVTYGMVLQR ERDLNTAARI GQSLVKQNSV LMEENSKLEA LLGSAKEEIL 250 260 270 280 290 300 YLRHQVNLRD ELLQLYSDSD EEDEDEEEEE EEKEAEEEQE EEEAEEDLQC AHPCDAPKLI 310 320 330 340 350 360 SQEALLHQHH CPQLEALQEK LRLLEEENHQ LREEASQLDT LEDEEQMLIL ECVEQFSEAS 370 380 390 400 410 420 QQMAELSEVL VLRLENYERQ QQEVARLQAQ VLKLQQRCRM YGAETEKLQK QLASEKEIQM 430 440 450 460 470 480 QLQEESVWVG SQLQDLREKY MDCGGMLIEM QEEVKTLRQQ PPVSTGSATH YPYSVPLETL 490 500 510 520 530 540 PGFQETLAEE LRTSLRRMIS DPVYFMERNY EMPRGDTSSL RYDFRYSEDR EQVRGFEAEE 550 560 570 580 590 600 GLMLAADIMR GEDFTPAEEF VPQEELGAAK KVPAEEGVME EAELVSEETE GWEEVELELD 610 620 630 640 650 660 EATRMNVVTS ALEASGLGPS HLDMNYVLQQ LANWQDAHYR RQLRWKMLQK GECPHGALPA 670 ASRTSCRSSC R
	Isoform 2 [UniParc]. Checksum: 6BF49457C5178317	FASTA	619	69,640
	10 20 30 40 50 60 MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF 70 80 90 100 110 120 LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR 130 140 150 160 170 180 GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL 190 200 210 220 230 240 LEELLPPVWE SVTYGMVLQR ERDLNTAARI GQSLVKQNSV LMEENSKLEA LLGSAKEEIL 250 260 270 280 290 300 YLRHQVNLRD ELLQLYSDSD EEDEDEEEEE EEKEAEEEQE EEEAEEDLQC AHPCDAPKLI 310 320 330 340 350 360 SQEALLHQHH CPQLEALQEK LRLLEEENHQ LREEASQLDT LEDEEQMLIL ECVEQFSEAS 370 380 390 400 410 420 QQMAELSEVL VLRLENYERQ QQEVARLQAQ VLKLQQRCRM YGAETEKLQK QLASEKEIQM 430 440 450 460 470 480 QLQEEETLPG FQETLAEELR TSLRRMISDP VYFMERNYEM PRGDTSSLRY DFRYSEDREQ 490 500 510 520 530 540 VRGFEAEEGL MLAADIMRGE DFTPAEEFVP QEELGAAKKV PAEEGVMEEA ELVSEETEGW 550 560 570 580 590 600 EEVELELDEA TRMNVVTSAL EASGLGPSHL DMNYVLQQLA NWQDAHYRRQ LRWKMLQKGE 610 CPHGALPAAS RTSCRSSCR
	Isoform 3 [UniParc]. Checksum: F308765B0A0DCFDA	FASTA	594	66,705
	10 20 30 40 50 60 MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF 70 80 90 100 110 120 LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR 130 140 150 160 170 180 GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL 190 200 210 220 230 240 LEELLPPVWE SVTYGMVLQR ERDLNTAARI GQSLVKQNSV LMEENSKLEA LLGSAKEEIL 250 260 270 280 290 300 YLRHQVNLRD ELLQLYSDSD EEDEDEEEEE EEKEAEEEQE EEEAEEDLQC AHPCDAPKLI 310 320 330 340 350 360 SQEALLHQHH CPQLEALQEK LRLLEEENHQ LREEASQLDT LEDEEQMLIL ECVEQFSEAS 370 380 390 400 410 420 QQMAELSEVL VLRLENYERQ QQEVARLQAQ VLKLQQRCRM ETLPGFQETL AEELRTSLRR 430 440 450 460 470 480 MISDPVYFME RNYEMPRGDT SSLRYDFRYS EDREQVRGFE AEEGLMLAAD IMRGEDFTPA 490 500 510 520 530 540 EEFVPQEELG AAKKVPAEEG VMEEAELVSE ETEGWEEVEL ELDEATRMNV VTSALEASGL 550 560 570 580 590 GPSHLDMNYV LQQLANWQDA HYRRQLRWKM LQKGECPHGA LPAASRTSCR SSCR
	Isoform 4 [UniParc]. Checksum: 3100300659F29F84	FASTA	602	67,582
	10 20 30 40 50 60 MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF 70 80 90 100 110 120 LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR 130 140 150 160 170 180 GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL 190 200 210 220 230 240 LEEVCTAFLI QLLPPVWESV TYGMVLQRER DLNTAARIGQ SLVKQNSVLM EENSKLEALL 250 260 270 280 290 300 GSAKEEILYL RHQVNLRDEL LQLYSDSDEE DEDEEEEEEE KEAEEEQEEE EAEEDLQCAH 310 320 330 340 350 360 PCDAPKLISQ EALLHQHHCP QLEALQEKLR LLEEENHQLR EEASQLDTLE DEEQMLILEC 370 380 390 400 410 420 VEQFSEASQQ MAELSEVLVL RLENYERQQQ EVARLQAQVL KLQQRCRMET LPGFQETLAE 430 440 450 460 470 480 ELRTSLRRMI SDPVYFMERN YEMPRGDTSS LRYDFRYSED REQVRGFEAE EGLMLAADIM 490 500 510 520 530 540 RGEDFTPAEE FVPQEELGAA KKVPAEEGVM EEAELVSEET EGWEEVELEL DEATRMNVVT 550 560 570 580 590 600 SALEASGLGP SHLDMNYVLQ QLANWQDAHY RRQLRWKMLQ KGECPHGALP AASRTSCRSS CR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human HAP1 homologue. Cloning, expression, and interaction with huntingtin." Li S.-H., Hosseini S.H., Gutekunst C.-A., Hersch S.M., Ferrante R.J., Li X.-J. J. Biol. Chem. 273:19220-19227(1998) [PubMed: 9668110] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-4; THR-58 AND LEU-560.
[2]	"Human huntingtin-associated protein (HAP-1) gene: genomic organisation and an intragenic polymorphism." Nasir J., Lafuente M.-J., Duan K., Colomer V., Engelender S., Ingersoll R., Margolis R.L., Ross C.A., Hayden M.R. Gene 254:181-187(2000) [PubMed: 10974549] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS ARG-4; THR-58 AND LEU-560.
[3]	"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] (ISOFORMS 3 AND 4), VARIANTS LEU-357; MET-493 AND LEU-560. Tissue: Embryo.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-671 (ISOFORM 3), VARIANTS ARG-4; THR-58 AND LEU-560. Tissue: Brain.
[6]	Nasir J., Duan K., Nichol K., Engelender S., Ashworth R., Colomer V., Thomas S., Disteche C., Hayden M.R., Ross C.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 96-671 (ISOFORM 1), VARIANTS LEU-357 AND LEU-560.
[7]	"A huntingtin-associated protein enriched in brain with implications for pathology." Li X.-J., Li S.-H., Sharp A.H., Nucifora F.C. Jr., Schilling G., Lanahan A., Worley P., Snyder S.H., Ross C.A. Nature 378:398-402(1995) [PubMed: 7477378] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 255-626 (ISOFORM 2), VARIANT LEU-560. Tissue: Caudate nucleus.
[8]	"Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease." Metzger S., Rong J., Nguyen H.-P., Cape A., Tomiuk J., Soehn A.S., Propping P., Freudenberg-Hua Y., Freudenberg J., Tong L., Li S.-H., Li X.-J., Riess O. Hum. Mol. Genet. 17:1137-1146(2008) [PubMed: 18192679] [Abstract] Cited for: VARIANTS LEU-357; TRP-437 AND THR-441, CHARACTERIZATION OF VARIANT THR-441.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF040723 mRNA. Translation: AAC39861.1. AJ012824 Genomic DNA. Translation: CAC09418.1. AK022007 mRNA. Translation: BAB13952.1. AC109319 Genomic DNA. No translation available. AB209105 mRNA. Translation: BAD92342.1. AJ224877 Genomic DNA. Translation: CAB82785.1. U38371 mRNA. Translation: AAC50297.1.
IPI	IPI00302434. IPI00302435. IPI00793761. IPI00955471.
PIR	S72555.
RefSeq	NP_001073339.1. NM_001079870.1. NP_001073340.1. NM_001079871.1. NP_817084.2. NM_177977.2.
UniGene	Hs.158300.
3D structure databases
ProteinModelPortal	P54257.
ModBase	Search...
Protein-protein interaction databases
IntAct	P54257. 41 interactions.
MINT	MINT-1410317.
STRING	P54257.
PTM databases
PhosphoSite	P54257.
Polymorphism databases
DMDM	290457683.
Proteomic databases
PRIDE	P54257.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310778; ENSP00000309392; ENSG00000173805.
GeneID	9001.
KEGG	hsa:9001.
UCSC	uc002hxm.1. human. uc002hxn.1. human. uc002hxp.1. human.
Organism-specific databases
CTD	9001.
GeneCards	GC17M039873.
HGNC	HGNC:4812. HAP1.
HPA	HPA023394.
MIM	600947. gene.
neXtProt	NX_P54257.
PharmGKB	PA29188.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19312.
GeneTree	ENSGT00390000003132.
HOGENOM	HBG127291.
HOVERGEN	HBG031599.
InParanoid	P54257.
OMA	EKEIQMQ.
Gene expression databases
ArrayExpress	P54257.
Bgee	P54257.
CleanEx	HS_HAP1.
Genevestigator	P54257.
GermOnline	ENSG00000173805. Homo sapiens.
Family and domain databases
InterPro	IPR006933. HAP1_N. [Graphical view]
KO	K04647.
Pfam	PF04849. HAP1_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33751.
SOURCE	Search...

Entry information

Entry name

HAP1_HUMAN

Accession

Primary (citable) accession number: P54257
Secondary accession number(s): A8MQB5 , O75358, Q59GK4, Q9H4G3, Q9HA98, Q9NY90

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	March 2, 2010
Last modified:	January 25, 2012
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.