Reviewed, UniProtKB/Swiss-Prot P13196 (HEM1_HUMAN)

Names and origin

Protein names

Recommended name:
    5-aminolevulinate synthase, nonspecific, mitochondrial
    EC=2.3.1.37
Alternative name(s):
    5-aminolevulinic acid synthase
    Delta-aminolevulinate synthase
    Delta-ALA synthetase
      Short name=ALAS-H

Gene names

Name:	ALAS1
Synonyms:	ALAS3, ALASH
ORF Names:	OK/SW-cl.121

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	640 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)

Catalytic activity	Succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2.
Cofactor	Pyridoxal phosphate.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; 5-aminolevulinate from glycine: step 1/1.
Subunit structure	Homodimer.
Subcellular location	Mitochondrion matrix.
Miscellaneous	There are two delta-ALA synthetase in vertebrates: an erythroid- specific form and one (housekeeping) which is expressed in all tissues.
Sequence similarities	Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Sequence caution	The sequence CAA68506.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Heme biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Acyltransferase Transferase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	heme biosynthetic process Traceable author statement. Source: ProtInc
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	5-aminolevulinate synthase activity Inferred from electronic annotation. Source: EC pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro transferase activity, transferring nitrogenous groups Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P13196-1)

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: P13196-2)

The sequence of this isoform differs from the canonical sequence as follows:
     95-118: HPLPATSQGTASKCPFLAAQMNQR → FRLDTPCLPQARALQANALSWQHR
     119-640: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 56	56	Mitochondrion
	Chain	57 – 640	584	5-aminolevulinate synthase, nonspecific, mitochondrial		PRO_0000001230
Amino acid modifications
	Modified residue	445	1	N6-(pyridoxal phosphate)lysine Probable
Natural variations
	Alternative sequence	95 – 118	24	HPLPA…QMNQR → FRLDTPCLPQARALQANALS WQHR in isoform 2.		VSP_025925
	Alternative sequence	119 – 640	522	Missing in isoform 2.		VSP_025924
Experimental info
	Sequence conflict	2	1	E → D in CAA68506. Ref.2
	Sequence conflict	6	1	R → G in CAA68506. Ref.2
	Sequence conflict	43	1	P → Q in CAA68506. Ref.2
	Sequence conflict	47	1	A → G in CAA68506. Ref.2
	Sequence conflict	56 – 57	2	QQ → HK in CAA68506. Ref.2
	Sequence conflict	69	1	K → Q in CAA68506. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 2. Checksum: 5E952DCCFFD6873F	FASTA	640	70,581
	10 20 30 40 50 60 MESVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRALST AAVHYQQIKE 70 80 90 100 110 120 TPPASEKDKT AKAKVQQTPD GSQQSPDGTQ LPSGHPLPAT SQGTASKCPF LAAQMNQRGS 130 140 150 160 170 180 SVFCKASLEL QEDVQEMNAV RKEVAETSAG PSVVSVKTDG GDPSGLLKNF QDIMQKQRPE 190 200 210 220 230 240 RVSHLLQDNL PKSVSTFQYD RFFEKKIDEK KNDHTYRVFK TVNRRAHIFP MADDYSDSLI 250 260 270 280 290 300 TKKQVSVWCS NDYLGMSRHP RVCGAVMDTL KQHGAGAGGT RNISGTSKFH VDLERELADL 310 320 330 340 350 360 HGKDAALLFS SCFVANDSTL FTLAKMMPGC EIYSDSGNHA SMIQGIRNSR VPKYIFRHND 370 380 390 400 410 420 VSHLRELLQR SDPSVPKIVA FETVHSMDGA VCPLEELCDV AHEFGAITFV DEVHAVGLYG 430 440 450 460 470 480 ARGGGIGDRD GVMPKMDIIS GTLGKAFGCV GGYIASTSSL IDTVRSYAAG FIFTTSLPPM 490 500 510 520 530 540 LLAGALESVR ILKSAEGRVL RRQHQRNVKL MRQMLMDAGL PVVHCPSHII PVRVADAAKN 550 560 570 580 590 600 TEVCDELMSR HNIYVQAINY PTVPRGEELL RIAPTPHHTP QMMNYFLENL LVTWKQVGLE 610 620 630 640 LKPHSSAECN FCRRPLHFEV MSEREKSYFS GLSKLVSAQA
	Isoform 2. Checksum: E4B74A55EDB54F70	FASTA	118	12,961
	10 20 30 40 50 60 MESVVRRCPF LSRVPQAFLQ KAGKSLLFYA QNCPKMMEVG AKPAPRALST AAVHYQQIKE 70 80 90 100 110 TPPASEKDKT AKAKVQQTPD GSQQSPDGTQ LPSGFRLDTP CLPQARALQA NALSWQHR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two different genes encode delta-aminolevulinate synthase in humans: nucleotide sequences of cDNAs for the housekeeping and erythroid genes." Bishop D.F. Nucleic Acids Res. 18:7187-7188(1990) [PubMed: 2263504] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Sequence of human 5-aminolevulinate synthase cDNA." Bawden M.J., Borthwick I.A., Healy H.M., Morris C.P., May B.K., Elliott W.H. Nucleic Acids Res. 15:8563-8563(1987) [PubMed: 3671094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[3]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon adenocarcinoma.
[4]	"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: Muscle.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X56351 mRNA. Translation: CAA39794.1. Y00451 mRNA. Translation: CAA68506.1. Frameshift. AB063322 mRNA. Translation: BAB93514.1. BC011798 mRNA. Translation: AAH11798.1.
IPI	IPI00847214. IPI00941830.
PIR	SYHUAL. S13682.
RefSeq	NP_000679.1. NP_954635.1.
UniGene	Hs.476308
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P13196.
PTM databases
PhosphoSite	P13196.
Proteomic databases
PRIDE	P13196.
Genome annotation databases
Ensembl	ENST00000310271; ENSP00000309259; ENSG00000023330; Homo sapiens. [Genome view] ENST00000394965; ENSP00000378416; ENSG00000023330; Homo sapiens. [Genome view] ENST00000441729; ENSP00000392725; ENSG00000023330; Homo sapiens. [Genome view] ENST00000469224; ENSP00000417719; ENSG00000023330; Homo sapiens. [Genome view] ENST00000484952; ENSP00000418779; ENSG00000023330; Homo sapiens. [Genome view]
GeneID	211.
KEGG	hsa:211.
UCSC	uc003dcy.1. human.
Organism-specific databases
CTD	211.
GeneCards	GC03P052207.
H-InvDB	HIX0003345.
HGNC	HGNC:396. ALAS1.
HPA	CAB017498.
MIM	125290. gene.
PharmGKB	PA24688.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P13196.
HOVERGEN	P13196.
OrthoDB	EOG9K6JPV
Enzyme and pathway databases
BRENDA	2.3.1.37. 247.
Pathway_Interaction_DB	hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
Reactome	REACT_9431. Metabolism of porphyrins.
Gene expression databases
ArrayExpress	P13196.
Bgee	P13196.
CleanEx	HS_ALAS1.
Genevestigator	P13196.
GermOnline	ENSG00000023330. Homo sapiens.
Family and domain databases
InterPro	IPR010961. 4pyrrol_synth_NH2levulA_synth. IPR001917. Aminotrans_II_pyridoxalP_BS. IPR004839. Aminotransferase_I/II. IPR015424. PyrdxlP-dep_Trfase_major. IPR015421. PyrdxlP-dep_Trfase_major_sub1. [Graphical view]
Gene3D	G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.
Pfam	PF00155. Aminotran_1_2. 1 hit. [Graphical view]
TIGRFAMs	TIGR01821. 5aminolev_synth. 1 hit.
PROSITE	PS00599. AA_TRANSFER_CLASS_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00145. Glycine. DB00114. Pyridoxal Phosphate.
NextBio	846.
SOURCE	Search...

Entry information

Entry name

HEM1_HUMAN

Accession

Primary (citable) accession number: P13196

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	August 1, 1991
Last modified:	November 24, 2009
This is version 108 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.