P49639 (HXA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein Hox-A1

Alternative name(s):
Homeobox protein Hox-1F

Gene names

Name:	HOXA1
Synonyms:	HOX1F

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	335 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. Seems to act in the maintenance and/or generation of hindbrain segments.
Subcellular location	Nucleus.
Involvement in disease	Athabaskan brainstem dysgenesis syndrome (ABDS) [MIM:601536]: Characterized by horizontal gaze palsy, sensorineural deafness, central hypoventilation, and developmental delay. Some patients had swallowing dysfunction, vocal cord paralysis, facial paresis, seizures, and cardiac outflow tract anomalies. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Bosley-Salih-Alorainy syndrome (BSAS) [MIM:601536]: Affected individuals show horizontal gaze abnormalities, deafness, facial weakness, vascular malformations of the internal carotid arteries and cardiac outflow trac. Some patients manifest mental retardation and autism spectrum disorder. In contrast to individuals with ABSD, central hypoventilation is not observed in individuals with BSAS. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the Antp homeobox family. Labial subfamily. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	abducens nerve formation Inferred from mutant phenotype Ref.9. Source: DFLAT anterior/posterior pattern specification Inferred from electronic annotation. Source: Compara artery morphogenesis Inferred from mutant phenotype Ref.9. Source: DFLAT central nervous system neuron differentiation Inferred from electronic annotation. Source: Compara cochlea morphogenesis Inferred from mutant phenotype Ref.9. Source: DFLAT cognition Inferred from direct assay Ref.9. Source: DFLAT embryonic neurocranium morphogenesis Inferred from mutant phenotype Ref.9. Source: DFLAT facial nerve structural organization Inferred from electronic annotation. Source: Compara facial nucleus development Inferred from electronic annotation. Source: Compara motor neuron axon guidance Inferred from electronic annotation. Source: Compara neuromuscular process Inferred from direct assay Ref.9. Source: DFLAT optokinetic behavior Inferred from direct assay Ref.9. Source: DFLAT outer ear morphogenesis Inferred from direct assay Ref.9. Source: DFLAT positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of behavior Inferred from direct assay Ref.9. Source: DFLAT rhombomere 3 development Inferred from electronic annotation. Source: Compara rhombomere 4 development Inferred from electronic annotation. Source: Compara rhombomere 5 development Inferred from electronic annotation. Source: Compara semicircular canal formation Inferred from mutant phenotype Ref.9. Source: DFLAT sensory perception of sound Inferred from direct assay Ref.9. Source: DFLAT transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hoxa1	P09022	4	EBI-740785,EBI-3957603	From a different organism.
PRNP	P04156	4	EBI-740785,EBI-977302

Alternative products

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

Isoform 3 (identifier: P49639-1)

Also known as: 36 kDa;

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 1 (identifier: P49639-2)

Also known as: 14 kDa;

The sequence of this isoform differs from the canonical sequence as follows:
     119-137: VSGGYPQCAPAVYSGNLSS → PPRSLSLPRIGDIFSSADF
     138-335: Missing.

Note: Lacks the homeobox domain.

Isoform 2 (identifier: P49639-3)

Also known as: 24 kDa;

The sequence of this isoform differs from the canonical sequence as follows:
     219-227: KVGEYGYLG → QSCWLVDAP
     228-335: Missing.

Note: Lacks the homeobox domain.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 335	335	Homeobox protein Hox-A1		PRO_0000200030
Regions
	DNA binding	229 – 288	60	Homeobox
	Motif	204 – 209	6	Antp-type hexapeptide
	Compositional bias	65 – 74	10	Poly-His
	Compositional bias	142 – 146	5	Poly-His
	Compositional bias	314 – 317	4	Poly-Ser
Natural variations
	Alternative sequence	119 – 137	19	VSGGY…GNLSS → PPRSLSLPRIGDIFSSADF in isoform 1.		VSP_002376
	Alternative sequence	138 – 335	198	Missing in isoform 1.		VSP_002377
	Alternative sequence	219 – 227	9	KVGEYGYLG → QSCWLVDAP in isoform 2.		VSP_002378
	Alternative sequence	228 – 335	108	Missing in isoform 2.		VSP_002379
	Natural variant	73	1	H → R Frequent polymorphism in individuals of European or African origin. Ref.2 Ref.8 Corresponds to variant rs10951154 [ dbSNP | Ensembl ].		VAR_010305
	Natural variant	189	1	E → A. Corresponds to variant rs17500494 [ dbSNP | Ensembl ].		VAR_030576

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 (36 kDa) [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 3C3A2D0A59A4181C	FASTA	335	36,641
	10 20 30 40 50 60 MDNARMNSFL EYPILSSGDS GTCSARAYPS DHRITTFQSC AVSANSCGGD DRFLVGRGVQ 70 80 90 100 110 120 IGSPHHHHHH HHHHPQPATY QTSGNLGVSY SHSSCGPSYG SQNFSAPYSP YALNQEADVS 130 140 150 160 170 180 GGYPQCAPAV YSGNLSSPMV QHHHHHQGYA GGAVGSPQYI HHSYGQEHQS LALATYNNSL 190 200 210 220 230 240 SPLHASHQEA CRSPASETSS PAQTFDWMKV KRNPPKTGKV GEYGYLGQPN AVRTNFTTKQ 250 260 270 280 290 300 LTELEKEFHF NKYLTRARRV EIAASLQLNE TQVKIWFQNR RMKQKKREKE GLLPISPATP 310 320 330 PGNDEKAEES SEKSSSSPCV PSPGSSTSDT LTTSH
	Isoform 1 (14 kDa) [UniParc]. Checksum: 9F0067A9E6AD51DE	FASTA	137	14,816
	10 20 30 40 50 60 MDNARMNSFL EYPILSSGDS GTCSARAYPS DHRITTFQSC AVSANSCGGD DRFLVGRGVQ 70 80 90 100 110 120 IGSPHHHHHH HHHHPQPATY QTSGNLGVSY SHSSCGPSYG SQNFSAPYSP YALNQEADPP 130 RSLSLPRIGD IFSSADF
	Isoform 2 (24 kDa) [UniParc]. Checksum: 81A54EF51FB0F033	FASTA	227	24,489
	10 20 30 40 50 60 MDNARMNSFL EYPILSSGDS GTCSARAYPS DHRITTFQSC AVSANSCGGD DRFLVGRGVQ 70 80 90 100 110 120 IGSPHHHHHH HHHHPQPATY QTSGNLGVSY SHSSCGPSYG SQNFSAPYSP YALNQEADVS 130 140 150 160 170 180 GGYPQCAPAV YSGNLSSPMV QHHHHHQGYA GGAVGSPQYI HHSYGQEHQS LALATYNNSL 190 200 210 220 SPLHASHQEA CRSPASETSS PAQTFDWMKV KRNPPKTGQS CWLVDAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and function of the HOX A1 human homeobox gene cDNA." Hong Y.S., Kim S.Y., Bhattacharya A., Pratt D.R., Hong W.K., Tainsky M.A. Gene 159:209-214(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Ovary.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ARG-73.
[3]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Skin.
[7]	"Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells." Chariot A., Moreau L., Senterre G., Sobel M., Castronovo V. Biochem. Biophys. Res. Commun. 215:713-720(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-335 (ISOFORMS 1; 2 AND 3).
[8]	"Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders." Ingram J.L., Stodgell C.J., Hyman S.L., Figlewicz D.A., Weitkamp L.R., Rodier P.M. Teratology 62:393-405(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-73.
[9]	"Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development." Tischfield M.A., Bosley T.M., Salih M.A.M., Alorainy I.A., Sener E.C., Nester M.J., Oystreck D.T., Chan W.-M., Andrews C., Erickson R.P., Engle E.C. Nat. Genet. 37:1035-1037(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ABDS AND BSAS.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U10421 mRNA. Translation: AAA86954.1. AK313514 mRNA. Translation: BAG36294.1. AC004079 Genomic DNA. Translation: AAS00374.1. CH236948 Genomic DNA. Translation: EAL24228.1. CH471073 Genomic DNA. Translation: EAW93861.1. BC032547 mRNA. Translation: AAH32547.1. U37431 mRNA. Translation: AAC50248.1. U37431 mRNA. Translation: AAC50249.1. U37431 mRNA. Translation: AAC50250.1. S79869 mRNA. Translation: AAB35424.2. S79871 mRNA. Translation: AAB35425.1. S79910 mRNA. Translation: AAB35423.2.
IPI	IPI00027694. IPI00218317. IPI00218318.
PIR	G01448.
RefSeq	NP_005513.1. NM_005522.4. NP_705873.2. NM_153620.2.
UniGene	Hs.67397.
3D structure databases
ProteinModelPortal	P49639.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49639. 13 interactions.
MINT	MINT-1437157.
STRING	9606.ENSP00000343246.
PTM databases
PhosphoSite	P49639.
Polymorphism databases
DMDM	6166216.
Proteomic databases
PaxDb	P49639.
PRIDE	P49639.
Protocols and materials databases
DNASU	3198.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000343060; ENSP00000343246; ENSG00000105991.
GeneID	3198.
KEGG	hsa:3198.
UCSC	uc003syd.3. human. uc003sye.3. human. uc022aao.1. human.
Organism-specific databases
CTD	3198.
GeneCards	GC07M027099.
HGNC	HGNC:5099. HOXA1.
HPA	HPA004933.
MIM	142955. gene. 601536. phenotype.
neXtProt	NX_P49639.
Orphanet	69739. Athabaskan brainstem dysgenesis syndrome. 69737. Bosley-Salih-Alorainy syndrome.
PharmGKB	PA29376.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG236971.
HOGENOM	HOG000247020.
HOVERGEN	HBG006089.
InParanoid	P49639.
KO	K09301.
OrthoDB	EOG47H5QN.
Gene expression databases
ArrayExpress	P49639.
Bgee	P49639.
CleanEx	HS_HOXA1.
Genevestigator	P49639.
GermOnline	ENSG00000105991. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR020479. Homeobox_metazoa. IPR001356. Homeodomain. IPR009057. Homeodomain-like. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00024. HOMEOBOX.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00032. ANTENNAPEDIA. False negative. PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P49639.
ChEMBL	CHEMBL4950.
GenomeRNAi	3198.
NextBio	12718.
SOURCE	Search...

Entry information

Entry name

HXA1_HUMAN

Accession

Primary (citable) accession number: P49639
Secondary accession number(s): A4D184, B2R8U7, O43363

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 139 of the entry and version 2 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.