Q16586 (SGCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-sarcoglycan
Short name=Alpha-SG

Alternative name(s):
50 kDa dystrophin-associated glycoprotein
Short name=50DAG
Adhalin
Dystroglycan-2

Gene names

Name:	SGCA
Synonyms:	ADL, DAG2

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	387 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	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
Subunit structure	Interacts with the syntrophin SNTA1. Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans By similarity.
Subcellular location	Cell membrane › sarcolemma; Single-pass type I membrane protein By similarity. Cytoplasm › cytoskeleton By similarity.
Tissue specificity	Most strongly expressed in skeletal muscle. Also expressed in cardiac muscle and, at much lower levels, in lung. In the fetus, most abundant in cardiac muscle and, at lower levels, in lung. Also detected in liver and kidney. Not expressed in brain.
Involvement in disease	Limb-girdle muscular dystrophy 2D (LGMD2D) [MIM:608099]: An autosomal recessive degenerative myopathy characterized by progressive muscle wasting from early childhood with loss of independent ambulation by teenage years. Muscle biopsy shows necrosis, decreased immunostaining for alpha sarcoglycan, and adhalin deficiency. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the sarcoglycan alpha/epsilon family.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Limb-girdle muscular dystrophy
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	muscle contraction Traceable author statement Ref.1. Source: ProtInc muscle organ development Traceable author statement Ref.9. Source: ProtInc
Cellular_component	cell-cell junction Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell dystrophin-associated glycoprotein complex Traceable author statement Ref.2. Source: ProtInc integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane raft Inferred from electronic annotation. Source: Compara sarcoglycan complex Inferred from electronic annotation. Source: InterPro sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform SGCA-1 (identifier: Q16586-1)

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 SGCA-2 (identifier: Q16586-2)

The sequence of this isoform differs from the canonical sequence as follows:
     196-319: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 387	364	Alpha-sarcoglycan		PRO_0000031673
Regions
	Topological domain	24 – 290	267	Extracellular Potential
	Transmembrane	291 – 311	21	Helical; Potential
	Topological domain	312 – 387	76	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	174	1	N-linked (GlcNAc...) Potential
	Glycosylation	246	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	196 – 319	124	Missing in isoform SGCA-2.		VSP_006017
	Natural variant	30	1	P → L in LGMD2D. Ref.11		VAR_010402
	Natural variant	31	1	L → P in LGMD2D.		VAR_010403
	Natural variant	34	1	R → C in LGMD2D. Ref.11		VAR_010404
	Natural variant	34	1	R → H in LGMD2D. Ref.9		VAR_010405
	Natural variant	62	1	Y → H in LGMD2D. Ref.9		VAR_010406
	Natural variant	68	1	G → E in LGMD2D. Ref.9		VAR_010407
	Natural variant	74	1	R → W in LGMD2D.		VAR_010408
	Natural variant	77	1	R → C in LGMD2D. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Corresponds to variant rs28933693 [ dbSNP | Ensembl ].		VAR_010387
	Natural variant	89	1	L → P in LGMD2D.		VAR_010409
	Natural variant	91	1	G → R in LGMD2D. Ref.11		VAR_010410
	Natural variant	93	1	A → V in LGMD2D. Ref.12		VAR_010411
	Natural variant	97	1	D → G in LGMD2D. Ref.12		VAR_010412
	Natural variant	98	1	R → C in LGMD2D.		VAR_010413
	Natural variant	98	1	R → H in LGMD2D. Ref.1 Ref.9		VAR_010388
	Natural variant	103	1	I → T in LGMD2D.		VAR_010414
	Natural variant	124	1	I → T in LGMD2D. Ref.11 Ref.12		VAR_010415
	Natural variant	136	1	A → APGAQP in LGMD2D; associated with G-137.		VAR_037965
	Natural variant	137	1	E → G in LGMD2D; associated with P-G-A-Q-P-136 ins. Ref.8 Corresponds to variant rs28933694 [ dbSNP | Ensembl ].		VAR_037966
	Natural variant	137	1	E → K in LGMD2D. Ref.11		VAR_010416
	Natural variant	158	1	L → F in LGMD2D. Ref.12		VAR_010417
	Natural variant	173	1	L → P in LGMD2D. Ref.11 Ref.12		VAR_010431
	Natural variant	175	1	V → A in LGMD2D. Ref.1		VAR_010389
	Natural variant	196	1	V → I in LGMD2D. Ref.12		VAR_010418
	Natural variant	205	1	P → H in LGMD2D. Ref.12		VAR_010419
	Natural variant	228	1	P → Q in LGMD2D.		VAR_010432
	Natural variant	242	1	V → A in LGMD2D.		VAR_010420
	Natural variant	247	1	V → M in LGMD2D.		VAR_010433
	Natural variant	284	1	R → C in LGMD2D. Ref.11 Ref.13		VAR_010390

Sequences

	Sequence		Length	Mass (Da)
	Isoform SGCA-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 9CD0270A00BE03E6	FASTA	387	42,875
	10 20 30 40 50 60 MAETLFWTPL LVVLLAGLGD TEAQQTTLHP LVGRVFVHTL DHETFLSLPE HVAVPPAVHI 70 80 90 100 110 120 TYHAHLQGHP DLPRWLRYTQ RSPHHPGFLY GSATPEDRGL QVIEVTAYNR DSFDTTRQRL 130 140 150 160 170 180 VLEIGDPEGP LLPYQAEFLV RSHDAEEVLP STPASRFLSA LGGLWEPGEL QLLNVTSALD 190 200 210 220 230 240 RGGRVPLPIE GRKEGVYIKV GSASPFSTCL KMVASPDSHA RCAQGQPPLL SCYDTLAPHF 250 260 270 280 290 300 RVDWCNVTLV DKSVPEPADE VPTPGDGILE HDPFFCPPTE APDRDFLVDA LVTLLVPLLV 310 320 330 340 350 360 ALLLTLLLAY VMCCRREGRL KRDLATSDIQ MVHHCTIHGN TEELRQMAAS REVPRPLSTL 370 380 PMFNVHTGER LPPRVDSAQV PLILDQH
	Isoform SGCA-2 [UniParc]. Checksum: A5437E496658776B	FASTA	263	29,354
	10 20 30 40 50 60 MAETLFWTPL LVVLLAGLGD TEAQQTTLHP LVGRVFVHTL DHETFLSLPE HVAVPPAVHI 70 80 90 100 110 120 TYHAHLQGHP DLPRWLRYTQ RSPHHPGFLY GSATPEDRGL QVIEVTAYNR DSFDTTRQRL 130 140 150 160 170 180 VLEIGDPEGP LLPYQAEFLV RSHDAEEVLP STPASRFLSA LGGLWEPGEL QLLNVTSALD 190 200 210 220 230 240 RGGRVPLPIE GRKEGLKRDL ATSDIQMVHH CTIHGNTEEL RQMAASREVP RPLSTLPMFN 250 260 VHTGERLPPR VDSAQVPLIL DQH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy." Roberds S.L., Leturcq F., Allamand V., Piccolo F., Jeanpierre M., Anderson R.D., Lim L.E., Lee J.C., Tome F.M.S., Romero N.B., Fardeau M., Beckmann J.S., Kaplan J.-C., Campbell K.P. Cell 78:625-633(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LGMD2D HIS-98 AND ALA-175. Tissue: Skeletal muscle.
[2]	"Human adhalin is alternatively spliced and the gene is on chromosome 17q21." McNally E., Yoshida M., Mizuno Y., Ozawa E., Kunkel L.M. Proc. Natl. Acad. Sci. U.S.A. 91:9690-9694(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Heart ventricle.
[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]. Tissue: Heart.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases 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]. Tissue: Pancreas and Spleen.
[7]	"A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy." Bueno M.R.P., Moreira E.S., Vainzof M., Chamberlain J., Marie S.K., Pereira L., Akiyama J., Roberds S.L., Campbell K.P., Zatz M. Hum. Mol. Genet. 4:1163-1167(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-214, VARIANT LGMD2D CYS-77.
[8]	"Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency." Kawai H., Akaike M., Endo T., Adachi K., Inui T., Mitsui T., Kashiwagi S., Fujiwara T., Okuno S., Shin S., Miyoshi K., Campbell K.P., Yamada H., Shimizu T., Matsumura K., Saito S. J. Clin. Invest. 96:1202-1207(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LGMD2D CYS-77; PRO-GLY-ALA-GLN-PRO-136 INS AND GLY-137.
[9]	"Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity." Piccolo F., Roberds S.L., Jeanpierre M., Leturcq F., Azibi K., Beldjord C., Carrie A., Recan D., Chaouch M., Reghis A., El Kerch F., Sefiani A., Voit T., Merlini L., Collin H., Eymard B., Beckmann J.S., Romero N.B. , Tome F.M.S., Fardeau M., Campbell K.P., Kaplan J.-C. Nat. Genet. 10:243-245(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LGMD2D HIS-34; HIS-62; GLU-68; CYS-77 AND HIS-98.
[10]	Erratum Piccolo F., Roberds S.L., Jeanpierre M., Leturcq F., Azibi K., Beldjord C., Carrie A., Recan D., Chaouch M., Reghis A., El Kerch F., Sefiani A., Voit T., Merlini L., Collin H., Eymard B., Beckmann J.S., Romero N.B. , Tome F.M.S., Fardeau M., Campbell K.P., Kaplan J.-C. Nat. Genet. 11:104-104(1995)
[11]	"Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D)." Carrie A., Piccolo F., Leturcq F., de Toma C., Azibi K., Beldjord C., Vallat J.-M., Merlini L., Voit T., Sewry C., Urtizberea J.A., Romero N.B., Tome F.M.S., Fardeau M., Sunada Y., Campbell K.P., Kaplan J.-C., Jeanpierre M. J. Med. Genet. 34:470-475(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LGMD2D LEU-30; CYS-34; CYS-77; ARG-91; THR-124; LYS-137; PRO-173 AND CYS-284.
[12]	"Mutations in the sarcoglycan genes in patients with myopathy." Duggan D.J., Gorospe J.R., Fanin M., Hoffman E.P., Angelini C. N. Engl. J. Med. 336:618-624(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LGMD2D CYS-77; VAL-93; GLY-97; THR-124; PHE-158; PRO-173; ILE-196 AND HIS-205.
[13]	"Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient." Angelini C., Fanin M., Menegazzo E., Freda M.P., Duggan D.J., Hoffman E.P. Muscle Nerve 21:769-775(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LGMD2D CYS-284.
+	Additional computationally mapped references.

Web resources

Leiden Muscular Dystrophy pages

SGCA mutations in LGMD2D

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U08895 mRNA. Translation: AAA81637.1. L34355 mRNA. Translation: AAA35510.1. L35853 mRNA. Translation: AAA50461.1. AK290622 mRNA. Translation: BAF83311.1. AC015909 Genomic DNA. No translation available. CH471109 Genomic DNA. Translation: EAW94635.1. BC025702 mRNA. Translation: AAH25702.1. L46810 mRNA. Translation: AAC37583.1.
IPI	IPI00301464. IPI00412663.
PIR	A54746.
RefSeq	NP_000014.1. NM_000023.2. NP_001129169.1. NM_001135697.1.
UniGene	Hs.463412.
3D structure databases
ProteinModelPortal	Q16586.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16586. 4 interactions.
STRING	9606.ENSP00000262018.
PTM databases
PhosphoSite	Q16586.
Polymorphism databases
DMDM	13431858.
Proteomic databases
PaxDb	Q16586.
PRIDE	Q16586.
Protocols and materials databases
DNASU	6442.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262018; ENSP00000262018; ENSG00000108823. ENST00000344627; ENSP00000345522; ENSG00000108823.
GeneID	6442.
KEGG	hsa:6442.
UCSC	uc002iqi.3. human. uc002iqj.3. human.
Organism-specific databases
CTD	6442.
GeneCards	GC17P048243.
HGNC	HGNC:10805. SGCA.
HPA	HPA007537.
MIM	600119. gene. 608099. phenotype.
neXtProt	NX_Q16586.
Orphanet	62. Autosomal recessive limb-girdle muscular dystrophy type 2D.
PharmGKB	PA35716.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG323743.
HOGENOM	HOG000074154.
HOVERGEN	HBG006891.
InParanoid	Q16586.
KO	K12565.
OMA	HTLDHET.
Gene expression databases
ArrayExpress	Q16586.
Bgee	Q16586.
CleanEx	HS_SGCA.
Genevestigator	Q16586.
GermOnline	ENSG00000108823. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR006644. Cadg. IPR015919. Cadherin-like. IPR013783. Ig-like_fold. IPR008908. Sarcoglycan_2. [Graphical view]
PANTHER	PTHR10132. PTHR10132. 1 hit.
Pfam	PF05510. Sarcoglycan_2. 1 hit. [Graphical view]
SMART	SM00736. CADG. 1 hit. [Graphical view]
SUPFAM	SSF49313. Cadherin. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	6442.
NextBio	25035.
SOURCE	Search...

Entry information

Entry name

SGCA_HUMAN

Accession

Primary (citable) accession number: Q16586
Secondary accession number(s): A6NEB8 , A8K3K7, Q13710, Q13712

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 128 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.