Reviewed, UniProtKB/Swiss-Prot P49639 (HXA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Homeobox protein Hox-A1
Alternative name(s):
    Hox-1F

Gene names

Name:	HOXA1
Synonyms:	HOX1F

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	335 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript 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	Defects in HOXA1 are the cause of Athabaskan brainstem dysgenesis syndrome (ABSD) [MIM:601536]; also known as Narvajo brainstem syndrome. This syndrome is 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. Defects in HOXA1 are the cause of 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.
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
Gene Ontology (GO)
Biological process	multicellular organismal development Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	RNA polymerase II transcription factor activity Ref.1 Traceable author statement. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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.

Notes: 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.

Notes: 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. dbSNP rs10951154.		VAR_010305
	Natural variant	189	1	E → A: dbSNP rs17500494.		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		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		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: 7622051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Ovary.
[2]	"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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 3). Tissue: Skin.
[4]	"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: 7488013] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-335 (ISOFORMS 1; 2 AND 3).
[5]	"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: 11091361] [Abstract] Cited for: VARIANT ARG-73.
[6]	"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: 16155570] [Abstract] Cited for: INVOLVEMENT IN ABSD AND BSAS.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U10421 mRNA. Translation: AAA86954.1. AC004079 Genomic DNA. Translation: AAS00374.1. 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.
PIR	G01448.
RefSeq	NP_005513.1. NP_705873.2.
UniGene	Hs.67397
3D structure databases
HSSP	HSSP built from PDB template 1B72 based on UniProtKB P14653.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49639.
Genome annotation databases
Ensembl	ENSG00000105991. Homo sapiens. [Contig view]
GeneID	3198.
KEGG	hsa:3198.
Organism-specific databases
HGNC	HGNC:5099. HOXA1.
HPA	HPA004933.
MIM	142955. gene. 601536. phenotype.
Orphanet	69739. Athabaskan brainstem dysgenesis syndrome. 69737. Bosley-Salih-Alorainy syndrome.
PharmGKB	PA29376.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P49639.
HOVERGEN	P49639.
Gene expression databases
ArrayExpress	P49639.
CleanEx	HS_HOXA1.
GermOnline	ENSG00000105991. Homo sapiens.
Family and domain databases
InterPro	IPR001827. Antennapedia. IPR001356. Homeobox. IPR012287. Homeodomain-rel. IPR000047. HTH_lambrepressr. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00024. HOMEOBOX. PR00031. HTHREPRESSR.
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00032. ANTENNAPEDIA. False negative. PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	12718.
SOURCE	Search...

Entry information

Entry name

HXA1_HUMAN

Accession

Primary (citable) accession number: P49639
Secondary accession number(s): O43363

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	July 15, 1999
Last modified:	November 25, 2008
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)