P35858 (ALS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein complex acid labile subunit
Short name=ALS

Gene names

Name:	IGFALS
Synonyms:	ALS

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	605 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)

Function	Involved in protein-protein interactions that result in protein complexes, receptor-ligand binding or cell adhesion.
Subunit structure	Forms a ternary complex of about 140 to 150 kDa with IGF-I or IGF-II and IGFBP-3.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Plasma.
Sequence similarities	Contains 19 LRR (leucine-rich) repeats. Contains 1 LRRCT domain. Contains 1 LRRNT domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat Signal
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Traceable author statement PubMed 1384485. Source: ProtInc
Cellular_component	extracellular space Traceable author statement PubMed 1384485. Source: ProtInc nucleus Inferred from direct assay. Source: HPA
Molecular_function	insulin-like growth factor binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P35858-1)

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: P35858-2)

The sequence of this isoform differs from the canonical sequence as follows:
     5-5: K → KAGDLEPQFTPERRFRLCWYQAHSGRALLGPPPQASPPA

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Ref.5
	Chain	28 – 605	578	Insulin-like growth factor-binding protein complex acid labile subunit		PRO_0000020695
Regions
	Domain	32 – 74	43	LRRNT
	Repeat	75 – 96	22	LRR 1
	Repeat	99 – 120	22	LRR 2
	Repeat	123 – 144	22	LRR 3
	Repeat	147 – 168	22	LRR 4
	Repeat	171 – 192	22	LRR 5
	Repeat	195 – 216	22	LRR 6
	Repeat	219 – 240	22	LRR 7
	Repeat	243 – 264	22	LRR 8
	Repeat	267 – 288	22	LRR 9
	Repeat	291 – 312	22	LRR 10
	Repeat	315 – 336	22	LRR 11
	Repeat	339 – 360	22	LRR 12
	Repeat	363 – 384	22	LRR 13
	Repeat	387 – 408	22	LRR 14
	Repeat	411 – 432	22	LRR 15
	Repeat	435 – 456	22	LRR 16
	Repeat	459 – 480	22	LRR 17
	Repeat	483 – 504	22	LRR 18
	Repeat	507 – 528	22	LRR 19
	Domain	536 – 605	70	LRRCT
Amino acid modifications
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	85	1	N-linked (GlcNAc...) Potential
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	368	1	N-linked (GlcNAc...) Ref.6 Ref.7
	Glycosylation	515	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	580	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	5	1	K → KAGDLEPQFTPERRFRLCWY QAHSGRALLGPPPQASPPA in isoform 2.		VSP_044605
	Natural variant	97	1	L → F. Corresponds to variant rs35947557 [ dbSNP | Ensembl ].		VAR_050658
	Natural variant	307	1	P → L. Corresponds to variant rs34297640 [ dbSNP | Ensembl ].		VAR_050659
	Natural variant	498	1	P → S. Corresponds to variant rs9282730 [ dbSNP | Ensembl ].		VAR_022034
	Natural variant	548	1	R → W. Corresponds to variant rs9282731 [ dbSNP | Ensembl ].		VAR_022035
Experimental info
	Sequence conflict	10	1	L → P in BAG64250. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: F6562A23CBE918F6	FASTA	605	66,035
	10 20 30 40 50 60 MALRKGGLAL ALLLLSWVAL GPRSLEGADP GTPGEAEGPA CPAACVCSYD DDADELSVFC 70 80 90 100 110 120 SSRNLTRLPD GVPGGTQALW LDGNNLSSVP PAAFQNLSSL GFLNLQGGQL GSLEPQALLG 130 140 150 160 170 180 LENLCHLHLE RNQLRSLALG TFAHTPALAS LGLSNNRLSR LEDGLFEGLG SLWDLNLGWN 190 200 210 220 230 240 SLAVLPDAAF RGLGSLRELV LAGNRLAYLQ PALFSGLAEL RELDLSRNAL RAIKANVFVQ 250 260 270 280 290 300 LPRLQKLYLD RNLIAAVAPG AFLGLKALRW LDLSHNRVAG LLEDTFPGLL GLRVLRLSHN 310 320 330 340 350 360 AIASLRPRTF KDLHFLEELQ LGHNRIRQLA ERSFEGLGQL EVLTLDHNQL QEVKAGAFLG 370 380 390 400 410 420 LTNVAVMNLS GNCLRNLPEQ VFRGLGKLHS LHLEGSCLGR IRPHTFTGLS GLRRLFLKDN 430 440 450 460 470 480 GLVGIEEQSL WGLAELLELD LTSNQLTHLP HRLFQGLGKL EYLLLSRNRL AELPADALGP 490 500 510 520 530 540 LQRAFWLDVS HNRLEALPNS LLAPLGRLRY LSLRNNSLRT FTPQPPGLER LWLEGNPWDC 550 560 570 580 590 600 GCPLKALRDF ALQNPSAVPR FVQAICEGDD CQPPAYTYNN ITCASPPEVV GLDLRDLSEA HFAPC
	Isoform 2 [UniParc]. Checksum: D9DFE527D566B271	FASTA	643	70,236
	10 20 30 40 50 60 MALRKAGDLE PQFTPERRFR LCWYQAHSGR ALLGPPPQAS PPAGGLALAL LLLSWVALGP 70 80 90 100 110 120 RSLEGADPGT PGEAEGPACP AACVCSYDDD ADELSVFCSS RNLTRLPDGV PGGTQALWLD 130 140 150 160 170 180 GNNLSSVPPA AFQNLSSLGF LNLQGGQLGS LEPQALLGLE NLCHLHLERN QLRSLALGTF 190 200 210 220 230 240 AHTPALASLG LSNNRLSRLE DGLFEGLGSL WDLNLGWNSL AVLPDAAFRG LGSLRELVLA 250 260 270 280 290 300 GNRLAYLQPA LFSGLAELRE LDLSRNALRA IKANVFVQLP RLQKLYLDRN LIAAVAPGAF 310 320 330 340 350 360 LGLKALRWLD LSHNRVAGLL EDTFPGLLGL RVLRLSHNAI ASLRPRTFKD LHFLEELQLG 370 380 390 400 410 420 HNRIRQLAER SFEGLGQLEV LTLDHNQLQE VKAGAFLGLT NVAVMNLSGN CLRNLPEQVF 430 440 450 460 470 480 RGLGKLHSLH LEGSCLGRIR PHTFTGLSGL RRLFLKDNGL VGIEEQSLWG LAELLELDLT 490 500 510 520 530 540 SNQLTHLPHR LFQGLGKLEY LLLSRNRLAE LPADALGPLQ RAFWLDVSHN RLEALPNSLL 550 560 570 580 590 600 APLGRLRYLS LRNNSLRTFT PQPPGLERLW LEGNPWDCGC PLKALRDFAL QNPSAVPRFV 610 620 630 640 QAICEGDDCQ PPAYTYNNIT CASPPEVVGL DLRDLSEAHF APC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and functional expression of the acid-labile subunit of the insulin-like growth factor-binding protein complex." Leong S.R., Baxter R.C., Camerato T., Dai J., Wood W.I. Mol. Endocrinol. 6:870-876(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Conservation of a growth hormone-responsive promoter element in the human and mouse acid-labile subunit genes." Suwanichkul A., Boisclair Y.R., Olney R.C., Durham S.K., Powell D.R. Endocrinology 141:833-838(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Thymus.
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum." Baxter R.C., Martin J.L., Beniac V.A. J. Biol. Chem. 264:11843-11848(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-35.
[6]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-368 AND ASN-515, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-368, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M86826 mRNA. Translation: AAA36047.1. AF192554 Genomic DNA. Translation: AAF06774.1. AK303146 mRNA. Translation: BAG64250.1. AC012180 Genomic DNA. No translation available. AL031724 Genomic DNA. Translation: CAC36078.1.
IPI	IPI00020996. IPI00925635.
PIR	A41915.
RefSeq	NP_001139478.1. NM_001146006.1. NP_004961.1. NM_004970.2.
UniGene	Hs.839.
3D structure databases
ProteinModelPortal	P35858.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000215539.
Polymorphism databases
DMDM	543800.
Proteomic databases
PaxDb	P35858.
PeptideAtlas	P35858.
PRIDE	P35858.
Protocols and materials databases
DNASU	3483.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000215539; ENSP00000215539; ENSG00000099769. ENST00000415638; ENSP00000416683; ENSG00000099769.
GeneID	3483.
KEGG	hsa:3483.
UCSC	uc002cmy.3. human.
Organism-specific databases
CTD	3483.
GeneCards	GC16M001840.
HGNC	HGNC:5468. IGFALS.
HPA	HPA040692. HPA040948.
MIM	601489. gene+phenotype.
neXtProt	NX_P35858.
Orphanet	140941. Short stature due to primary acid-labile subunit deficiency.
PharmGKB	PA29702.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOGENOM	HOG000033909.
HOVERGEN	HBG000327.
InParanoid	P35858.
OMA	HLDRGCL.
OrthoDB	EOG4FFD1R.
PhylomeDB	P35858.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Gene expression databases
ArrayExpress	P35858.
Bgee	P35858.
CleanEx	HS_IGFALS.
Genevestigator	P35858.
GermOnline	ENSG00000099769. Homo sapiens.
Family and domain databases
InterPro	IPR000483. Cys-rich_flank_reg_C. IPR001611. Leu-rich_rpt. IPR003591. Leu-rich_rpt_typical-subtyp. IPR000372. LRR-contain_N. [Graphical view]
Pfam	PF00560. LRR_1. 1 hit. PF01462. LRRNT. 1 hit. [Graphical view]
SMART	SM00369. LRR_TYP. 11 hits. SM00082. LRRCT. 1 hit. SM00013. LRRNT. 1 hit. [Graphical view]
PROSITE	PS51450. LRR. 18 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3483.
NextBio	13696.
SOURCE	Search...

Entry information

Entry name

ALS_HUMAN

Accession

Primary (citable) accession number: P35858
Secondary accession number(s): B4DZY8, E9PGU3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 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.