O60880 (SH21A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SH2 domain-containing protein 1A

Alternative name(s):
Duncan disease SH2-protein
Signaling lymphocytic activation molecule-associated protein
Short name=SLAM-associated protein
T-cell signal transduction molecule SAP

Gene names

Name:	SH2D1A
Synonyms:	DSHP, SAP

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	128 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.
Subunit structure	Interacts with NTRK1, NTRK2 and NTRK3 By similarity. Interacts with CD84, CD244, LY9, SLAMF1 and FYN. Ref.10 Ref.11 Ref.20
Subcellular location	Cytoplasm Probable.
Tissue specificity	Expressed at a high level in thymus and lung, with a lower level of expression in spleen and liver. Expressed in peripheral blood leukocytes, including T lymphocytes. Tends to be expressed at lower levels in peripheral blood leukocytes in patients with rheumatoid arthritis. Ref.3
Involvement in disease	Lymphoproliferative syndrome, X-linked, 1 (XLP1) [MIM:308240]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24
Sequence similarities	Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	SH2 domain
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Inferred from direct assay Ref.2. Source: UniProtKB cellular defense response Non-traceable author statement Ref.2. Source: UniProtKB humoral immune response Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell mediated cytotoxicity Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	SH3/SH2 adaptor activity Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: O60880-1)

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 B (identifier: O60880-2)

The sequence of this isoform differs from the canonical sequence as follows:
     68-128: TAPGVHKRYFRKIKNLISAFQKPDQGIVIPLQYPVEKKSSARSTQGTTGIREDPDVCLKAP → HFRSQIKA

Isoform C (identifier: O60880-3)

The sequence of this isoform differs from the canonical sequence as follows:
     47-128: YHGYIYTYRV...EDPDVCLKAP → QHLGYIKDISGK

Isoform D (identifier: O60880-4)

The sequence of this isoform differs from the canonical sequence as follows:
     114-116: Missing.

Isoform E (identifier: O60880-5)

The sequence of this isoform differs from the canonical sequence as follows:
     40-128: VYCLCVLYHG...EDPDVCLKAP → ITVTFIHTEC...RHCNTSAVSS

Isoform F (identifier: O60880-6)

The sequence of this isoform differs from the canonical sequence as follows:
     47-128: YHGYIYTYRV...EDPDVCLKAP → ISEARSRHCNTSAVSS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 128

128

SH2 domain-containing protein 1A

PRO_0000097722

Regions

Domain

6 – 104

99

SH2

Amino acid modifications

Modified residue

89

1

N6-acetyllysine Ref.12

Natural variations

Alternative sequence

40 – 128

89

VYCLC…CLKAP → ITVTFIHTECPRQKQVLGVL SISEARSRHCNTSAVSS in isoform E.

VSP_004388

Alternative sequence

47 – 128

82

YHGYI…CLKAP → QHLGYIKDISGK in isoform C.

VSP_004387

Alternative sequence

47 – 128

82

YHGYI…CLKAP → ISEARSRHCNTSAVSS in isoform F.

VSP_004389

Alternative sequence

68 – 128

61

TAPGV…CLKAP → HFRSQIKA in isoform B.

VSP_004386

Alternative sequence

114 – 116

3

Missing in isoform D.

VSP_004390

Natural variant

7

1

Y → C in XLP1; reduced protein stability and reduced affinity for SLAMF1. Ref.14 Ref.17 Ref.20

VAR_048005

Natural variant

8

1

H → D in XLP1. Ref.19

VAR_048006

Natural variant

16

1

G → D in XLP1; abolishes interaction with SLAMF1. Ref.23

VAR_048007

Natural variant

27

1

G → S in XLP1. Ref.19

VAR_048008

Natural variant

28

1

S → R in XLP1; reduced protein stability. Ref.14 Ref.17 Ref.20

VAR_048009

Natural variant

31

1

L → P in XLP1; reduced protein stability and reduced affinity for SLAMF1 and FYN. Ref.17 Ref.21

VAR_048010

Natural variant

32

1

R → T in XLP1. Ref.1 Ref.16

VAR_005612

Natural variant

33

1

D → Y in XLP1. Ref.19

VAR_048011

Natural variant

42

1

C → W in XLP1; loss of interaction with CD84 and reduced affinity for SLAMF1. Ref.17 Ref.20

VAR_048012

Natural variant

49

1

G → V in XLP1. Ref.19

VAR_048013

Natural variant

53

1

T → I in XLP1; loss of interaction with CD48 and reduced affinity for SLAMF1 and loss of interaction with non-phosphorylated SLAMF1. Ref.14 Ref.17 Ref.20

VAR_048014

Natural variant

54

1

Y → C in XLP1; reduced protein stability and reduced affinity for SLAMF1 and FYN. Ref.17 Ref.21 Ref.24

VAR_048015

Natural variant

55

1

R → L in XLP1; reduced affinity for SLAMF1 and FYN. Ref.18 Ref.21

VAR_018307

Natural variant

57

1

S → P in one XLP1 patient; unknown pathological significance. Ref.22

VAR_048016

Natural variant

68

1

T → I in XLP1; loss of interaction with CD48 and strongly reduced affinity for SLAMF1. Ref.1 Ref.14 Ref.20

VAR_005613

Natural variant

84

1

I → T in XLP1; reduced protein stability. Ref.24

VAR_048017

Natural variant

87

1

F → S in XLP1; reduced protein stability and reduced affinity for SLAMF1 and FYN. Ref.17 Ref.21 Ref.24

VAR_048018

Natural variant

99

1

Q → P in XLP1; reduced protein stability and strongly reduced affinity for SLAMF1. Ref.14 Ref.17 Ref.20

VAR_048019

Natural variant

101

1

P → L in XLP1; reduced protein stability and reduced affinity for SLAMF1. Ref.1 Ref.14 Ref.20
Corresponds to variant rs28935184 [ dbSNP | Ensembl ].

VAR_005614

Natural variant

102

1

V → G in XLP1; reduced protein stability and strongly reduced affinity for SLAMF1. Ref.14 Ref.17 Ref.20

VAR_048020

Experimental info

Mutagenesis

32

1

R → Q: Strongly reduced affinity for SLAMF1. Ref.14

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

128

Helix Strand Turn

Details...

Beta strand

5 – 7

3

Helix

13 – 23

11

Beta strand

28 – 33

6

Beta strand

35 – 37

3

Beta strand

41 – 47

7

Beta strand

50 – 58

9

Beta strand

64 – 66

3

Beta strand

77 – 79

3

Helix

80 – 87

8

Beta strand

89 – 96

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 90234E7A6614EE3D	FASTA	128	14,187
	10 20 30 40 50 60 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLYHGY IYTYRVSQTE 70 80 90 100 110 120 TGSWSAETAP GVHKRYFRKI KNLISAFQKP DQGIVIPLQY PVEKKSSARS TQGTTGIRED PDVCLKAP
	Isoform B [UniParc]. Checksum: 49A81B180192072A	FASTA	75	8,392
	10 20 30 40 50 60 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLYHGY IYTYRVSQTE 70 TGSWSAEHFR SQIKA
	Isoform C [UniParc]. Checksum: 39720893ACB3518A	FASTA	58	6,284
	10 20 30 40 50 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLQHLG YIKDISGK
	Isoform D [UniParc]. Checksum: 1E5EE8978D67E5D6	FASTA	125	13,928
	10 20 30 40 50 60 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLYHGY IYTYRVSQTE 70 80 90 100 110 120 TGSWSAETAP GVHKRYFRKI KNLISAFQKP DQGIVIPLQY PVEKKSSARS TQGIREDPDV CLKAP
	Isoform E [UniParc]. Checksum: 5BA2292A94518C00	FASTA	76	8,188
	10 20 30 40 50 60 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGI TVTFIHTECP RQKQVLGVLS 70 ISEARSRHCN TSAVSS
	Isoform F [UniParc]. Checksum: 51B125509F7EB9C4	FASTA	62	6,631
	10 20 30 40 50 60 MDAVAVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLISEA RSRHCNTSAV SS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene." Coffey A.J., Brooksbank R.A., Brandau O., Oohashi T., Howell G.R., Bye J.M., Cahn A.P., Durham J., Heath P., Wray P., Pavitt R., Wilkinson J., Leversha M., Huckle E., Shaw-Smith C.J., Dunham A., Rhodes S., Schuster V. , Porta G., Yin L., Serafini P., Sylla B., Zollo M., Franco B., Bentley D.R. Nat. Genet. 20:129-135(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS XLP1 THR-32; ILE-68 AND LEU-101.
[2]	"The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM." Sayos J., Wu C., Morra M., Wang N., Zhang X., Allen D., van Schaik S., Notarangelo L., Geha R., Roncarolo M.G., Oettgen H., de Vries J.E., Aversa G., Terhorst C. Nature 395:462-469(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis." Takei M., Ishiwata T., Mitamura K., Fujiwara S., Sasaki K., Nishi T., Kuga T., Ookubo T., Horie T., Ryu J., Ohi H., Sawada S. Int. Immunol. 13:559-565(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[4]	"The Duncan's disease gene is preferentially expressed in lymphoid cell lineages and undergoes high levels of alternative splicing." Amemiya C.T., Halevi A. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[5]	"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].
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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].
[9]	"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 A). Tissue: Lung.
[10]	"Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP." Sayos J., Martin M., Chen A., Simarro M., Howie D., Morra M., Engel P., Terhorst C. Blood 97:3867-3874(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD84.
[11]	"CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2." Tangye S.G., van de Weerdt B.C.M., Avery D.T., Hodgkin P.D. Eur. J. Immunol. 32:1640-1649(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD84.
[12]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89, MASS SPECTROMETRY.
[13]	"Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition." Poy F., Yaffe M.B., Sayos J., Saxena K., Morra M., Sumegi J., Cantley L.C., Terhorst C., Eck M.J. Mol. Cell 4:555-561(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 1-104.
[14]	"A 'three-pronged' binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome." Hwang P.M., Li C., Morra M., Lillywhite J., Muhandiram D.R., Gertler F., Terhorst C., Kay L.E., Pawson T., Forman-Kay J.D., Li S.-C. EMBO J. 21:314-323(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR IN COMPLEX WITH SLAMF1, CHARACTERIZATION OF VARIANTS XLP1 CYS-7; ARG-28; ILE-53; ILE-68; PRO-99; LEU-101 AND GLY-102, MUTAGENESIS OF ARG-32.
[15]	"SAP couples Fyn to SLAM immune receptors." Chan B., Lanyi A., Song H.K., Griesbach J., Simarro-Grande M., Poy F., Howie D., Sumegi J., Terhorst C., Eck M.J. Nat. Cell Biol. 5:155-160(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-104 IN COMPLEX WITH SLAMF1 AND FYN.
[16]	"SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients." Yin L., Ferrand V., Lavoue M.-F., Hayoz D., Philippe N., Souillet G., Seri M., Giacchino R., Castagnola E., Hodgson S., Sylla B.S., Romeo G. Hum. Genet. 105:501-505(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XLP1 THR-32.
[17]	"Correlation of mutations of the SH2D1A gene and Epstein-Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease." Sumegi J., Huang D., Lanyi A., Davis J.D., Seemayer T.A., Maeda A., Klein G., Seri M., Wakiguchi H., Purtilo D.T., Gross T.G. Blood 96:3118-3125(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XLP1 CYS-7; ARG-28; PRO-31; TRP-42; ILE-53; CYS-54; SER-87; PRO-99 AND GLY-102.
[18]	"Defective NK cell activation in X-linked lymphoproliferative disease." Benoit L., Wang X., Pabst H.F., Dutz J., Tan R. J. Immunol. 165:3549-3553(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XLP1 LEU-55.
[19]	"SH2D1A mutations in Japanese males with severe Epstein-Barr virus-associated illnesses." Sumazaki R., Kanegane H., Osaki M., Fukushima T., Tsuchida M., Matsukura H., Shinozaki K., Kimura H., Matsui A., Miyawaki T. Blood 98:1268-1270(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XLP1 ASP-8; SER-27; TYR-33 AND VAL-49.
[20]	"Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients." Morra M., Simarro-Grande M., Martin M., Chen A.S.-I., Lanyi A., Silander O., Calpe S., Davis J., Pawson T., Eck M.J., Sumegi J., Engel P., Li S.-C., Terhorst C. J. Biol. Chem. 276:36809-36816(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS XLP1 CYS-7; ARG-28; TRP-42; ILE-53; ILE-68; PRO-99; LEU-101 AND GLY-102, INTERACTION WITH CD244; SLAMF1; CD48 AND LY9.
[21]	"Disease-causing SAP mutants are defective in ligand binding and protein folding." Li C., Iosef C., Jia C.Y.H., Gkourasas T., Han V.K.M., Li S.-C. Biochemistry 42:14885-14892(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS XLP1 PRO-31; CYS-54; LEU-55 AND SER-87.
[22]	"Fatal hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection in a patient with a novel mutation in the signaling lymphocytic activation molecule-associated protein." Halasa N.B., Whitlock J.A., McCurley T.L., Smith J.A., Zhu Q., Ochs H., Dermody T.S., Crowe J.E. Jr. Clin. Infect. Dis. 37:E136-E141(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PRO-57.
[23]	"Characterization of a new disease-causing mutation of SH2D1A in a family with X-linked lymphoproliferative disease." Erdos M., Uzvoelgyi E., Nemes Z., Toeroek O., Rakoczi E., Went-Suemegi N., Suemegi J., Marodi L. Hum. Mutat. 25:506-506(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XLP1 ASP-16, CHARACTERIZATION OF VARIANT XLP1 ASP-16.
[24]	"Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP." Hare N.J., Ma C.S., Alvaro F., Nichols K.E., Tangye S.G. Int. Immunol. 18:1055-1065(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XLP1 CYS-54; THR-84 AND SER-87, CHARACTERIZATION OF VARIANTS XLP1 CYS-54; THR-84 AND SER-87.
+	Additional computationally mapped references.

Web resources

SH2D1Abase

SH2D1A mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL023657 mRNA. Translation: CAA19222.1.
AF073019 mRNA. Translation: AAC62631.1.
AF072930 mRNA. Translation: AAC62630.1.
AB586694 mRNA. Translation: BAJ19023.1.
AF100539 mRNA. Translation: AAC79712.1.
AF100540 mRNA. Translation: AAC79713.1.
AF100541 mRNA. Translation: AAC79714.1.
AF100542 mRNA. Translation: AAC79715.1.
AF100543 mRNA. Translation: AAC79716.1.
AK311911 mRNA. Translation: BAG34852.1.
CR542031 mRNA. Translation: CAG46828.1.
CR542043 mRNA. Translation: CAG46840.1.
AL022718 Genomic DNA. Translation: CAA18777.1.
CH471107 Genomic DNA. Translation: EAX11848.1.
CH471107 Genomic DNA. Translation: EAX11849.1.
BC020732 mRNA. Translation: AAH20732.1.

IPI

IPI00032401.
IPI00216635.
IPI00216636.
IPI00216637.
IPI00216639.
IPI00873008.

RefSeq

NP_001108409.1. NM_001114937.2.
NP_002342.1. NM_002351.4.

UniGene

Hs.349094.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D1Z	X-ray	1.40	A/B/C/D	1-104	[»]
1D4T	X-ray	1.10	A	1-104	[»]
1D4W	X-ray	1.80	A/B	1-104	[»]
1KA6	NMR	-	A	1-128	[»]
1KA7	NMR	-	A	1-128	[»]
1M27	X-ray	2.50	A	1-104	[»]

ProteinModelPortal

O60880.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-113697.

STRING

9606.ENSP00000360181.

PTM databases

PhosphoSite

O60880.

Proteomic databases

PaxDb

O60880.

PRIDE

O60880.

Protocols and materials databases

DNASU

4068.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360027; ENSP00000353126; ENSG00000183918.
ENST00000371139; ENSP00000360181; ENSG00000183918.

GeneID

4068.

KEGG

hsa:4068.

UCSC

uc004euf.4. human.
uc004euh.4. human.

Organism-specific databases

CTD

4068.

GeneCards

GC0XP123480.

HGNC

HGNC:10820. SH2D1A.

MIM

300490. gene.
308240. phenotype.

neXtProt

NX_O60880.

Orphanet

2442. X-linked lymphoproliferative disease.

PharmGKB

PA35728.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG298713.

HOVERGEN

HBG003702.

InParanoid

O60880.

KO

K07990.

OMA

TQGTTGR.

OrthoDB

EOG4HHP3S.

PhylomeDB

O60880.

Gene expression databases

Bgee

O60880.

CleanEx

HS_SH2D1A.

Genevestigator

O60880.

GermOnline

ENSG00000183918. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
IPR017289. SH2_prot_1A.
[Graphical view]

PANTHER

PTHR11200:SF1. PTHR11200:SF1. 1 hit.

Pfam

PF00017. SH2. 1 hit.
[Graphical view]

PIRSF

PIRSF037828. SH2_p1A. 1 hit.

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O60880.

GenomeRNAi

4068.

NextBio

15948.

SOURCE

Search...

Entry information

Entry name

SH21A_HUMAN

Accession

Primary (citable) accession number: O60880
Secondary accession number(s): A8MSW0 , O95383, O95384, O95385, O95386, Q6FGS6, Q9UNR0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 114 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.